Geriatrics

When I read the news that Bruce Willis had disclosed his diagnosis of frontotemporal dementia (FTD), I was reminded that all of us are at risk for spending our final epoch lost in a neurologic swamp. What is remarkable about the swamp that we call FTD is that it’s a somewhat rare and unusual type of dementia. We tend to characterize dementia as the erosion of memory, but FTD is more characterized by the loss of control over emotions and other cognitive functions. What›s especially tragic for performers like Mr. Willis is the loss of the verbal fluency required for delivering one’s lines.

Frontotemporal dementia

To this casual observer, Bruce Willis was an almost invincible force, vigorous, vital, one of the “immortals.” Alas, with his FTD diagnosis, we know that even a die-hard like Mr. Willis, now only 67 years of age, may have to endure years of progressive decline. If the disease follows its typical path, that will probably include slowly disconnecting and progressively losing emotional judgment and control as well as losing a reasonable understanding of what or why any of it is happening. He may also experience a progressive deterioration of the control of bodily functions and general health.

Most people with dementia lose their neurocognitive abilities through a number of different pathways, all of which result in brain shrinkage, disconnection, evident neuropathology, neurobehavioral expressions of loss, and forms of befuddlement. Alzheimer’s disease leads the list as the most common form of dementia, but vascular dementias; dementia with Lewy bodies; “mixed” dementias; dementias associated with Parkinson’s, Huntington’s, or other diseases; dementia rising from alcoholic or other brain poisoning, HIV, Lyme disease, or a host of other brain infections; or from traumatic encephalopathy (chronic or more current) may present at any active neurology clinic. These are what you might think of as your “grandpa’s dementia” – the common types often associated with old age.

FTD is a particularly interesting variant for several reasons. First, it usually arises in relatively young individuals, with initial symptoms emerging in one’s 50s or 60s. In most cases, there is no genetic and, with rare exception, any other explanation of origin – except that old medical standby, bad luck.

Second, FTD has little initial impact on a patient’s broader memory and associated cognitive abilities. The patient will stumble to come up with that next word and ultimately slow down their speech as their brain struggles with verbal fluency; they will struggle with translating their feelings and emotions into fast and appropriate actions expressed in their mind and their physical body while their memory will appear intact.

In all other dementias, cognitive losses can be profound, whereas social and emotional control and voluble speech production are generally better sustained. Imagine the impact that these struggles in verbal fluency and in emotional calibration and response must have for an established actor. By all reports, Mr. Willis vigorously pursued the work that he loved right up until the time of his dementia diagnosis, even as his colleagues would almost certainly have seen that he was struggling. Sadly, a lack of that type of self-awareness is an expected consequence of FTD.
 

The salience network and von Economo neurons

Third and most intriguing to a neuroscientific nerd like me is that patients with FTD experience an initial loss of a special population of cortical neurons located within the salience network in our brains, called the von Economo neurons. That salience network is designed to quickly read and evaluate our complex thoughts and emotions and via those Economo neurons, initiate appropriate neurologic and physical responses.

We share this special von Economo machinery with great apes, whales, elephants, and a handful of other especially social mammalian species.

When we see or hear or otherwise sense something that induces fear, alarm, or a potential reward, the salience network in our brain acts as a kind of gatekeeper. First, it assesses the emergent or changing situation, then it rapidly initiates an emotional and physical response. As I sit with a patient in obvious distress in my office, my salience network turns on an empathetic alarm. My brain and body immediately adjust to initiate appropriately sympathetic reactions. The von Economo neurons – those very neurons that have substantially died off in a brain with FTD – are the linchpins in this fast-response emotion and complex body signal-informed system.

Controlled emotional response is at the heart of our humanity. It’s a sad day when we lose it.

In other neurologic clinical conditions marked by the loss of specific brain cells, different forms of “disuse atrophy” are partly the cause. We don’t know whether that’s the case for FTD. Scientists have shown that specific forms of computerized brain exercises can sharply increase activity levels in the salience network which is linked to improvements in the regulatory control of the autonomic nervous system – one of the key response-mediating targets of the network’s von Economo neurons.

Interestingly, superagers who sustain body and brain health into their 90s (and beyond) die with a full complement of von Economo neurons operating happily in a still-vigorous salience network.

This neuroscientist can foresee a day when we routinely assess the integrity of this important brain system and more reliably maintain its good health. Keeping those very special neurons alive would have probably allowed Mr. Willis to sustain himself on the soundstage and on the grander stage of life for a long time to come. Alas, like so many things in medicine, there is promise. But at this moment for this famous patient, our current medical science appears to be a day late, and a dollar short.

Dr. Merzenichis is professor emeritus at the University of California, San Francisco, and a Kavli Laureate in Neuroscience. He reported conflicts of interest with the National Institutes of Health, Stronger Brains, and Posit Science.
 

A version of this article first appeared on Medscape.com.

When I read the news that Bruce Willis had disclosed his diagnosis of frontotemporal dementia (FTD), I was reminded that all of us are at risk for spending our final epoch lost in a neurologic swamp. What is remarkable about the swamp that we call FTD is that it’s a somewhat rare and unusual type of dementia. We tend to characterize dementia as the erosion of memory, but FTD is more characterized by the loss of control over emotions and other cognitive functions. What›s especially tragic for performers like Mr. Willis is the loss of the verbal fluency required for delivering one’s lines.

Frontotemporal dementia

To this casual observer, Bruce Willis was an almost invincible force, vigorous, vital, one of the “immortals.” Alas, with his FTD diagnosis, we know that even a die-hard like Mr. Willis, now only 67 years of age, may have to endure years of progressive decline. If the disease follows its typical path, that will probably include slowly disconnecting and progressively losing emotional judgment and control as well as losing a reasonable understanding of what or why any of it is happening. He may also experience a progressive deterioration of the control of bodily functions and general health.

Most people with dementia lose their neurocognitive abilities through a number of different pathways, all of which result in brain shrinkage, disconnection, evident neuropathology, neurobehavioral expressions of loss, and forms of befuddlement. Alzheimer’s disease leads the list as the most common form of dementia, but vascular dementias; dementia with Lewy bodies; “mixed” dementias; dementias associated with Parkinson’s, Huntington’s, or other diseases; dementia rising from alcoholic or other brain poisoning, HIV, Lyme disease, or a host of other brain infections; or from traumatic encephalopathy (chronic or more current) may present at any active neurology clinic. These are what you might think of as your “grandpa’s dementia” – the common types often associated with old age.

FTD is a particularly interesting variant for several reasons. First, it usually arises in relatively young individuals, with initial symptoms emerging in one’s 50s or 60s. In most cases, there is no genetic and, with rare exception, any other explanation of origin – except that old medical standby, bad luck.

Second, FTD has little initial impact on a patient’s broader memory and associated cognitive abilities. The patient will stumble to come up with that next word and ultimately slow down their speech as their brain struggles with verbal fluency; they will struggle with translating their feelings and emotions into fast and appropriate actions expressed in their mind and their physical body while their memory will appear intact.

In all other dementias, cognitive losses can be profound, whereas social and emotional control and voluble speech production are generally better sustained. Imagine the impact that these struggles in verbal fluency and in emotional calibration and response must have for an established actor. By all reports, Mr. Willis vigorously pursued the work that he loved right up until the time of his dementia diagnosis, even as his colleagues would almost certainly have seen that he was struggling. Sadly, a lack of that type of self-awareness is an expected consequence of FTD.
 

The salience network and von Economo neurons

Third and most intriguing to a neuroscientific nerd like me is that patients with FTD experience an initial loss of a special population of cortical neurons located within the salience network in our brains, called the von Economo neurons. That salience network is designed to quickly read and evaluate our complex thoughts and emotions and via those Economo neurons, initiate appropriate neurologic and physical responses.

We share this special von Economo machinery with great apes, whales, elephants, and a handful of other especially social mammalian species.

When we see or hear or otherwise sense something that induces fear, alarm, or a potential reward, the salience network in our brain acts as a kind of gatekeeper. First, it assesses the emergent or changing situation, then it rapidly initiates an emotional and physical response. As I sit with a patient in obvious distress in my office, my salience network turns on an empathetic alarm. My brain and body immediately adjust to initiate appropriately sympathetic reactions. The von Economo neurons – those very neurons that have substantially died off in a brain with FTD – are the linchpins in this fast-response emotion and complex body signal-informed system.

Controlled emotional response is at the heart of our humanity. It’s a sad day when we lose it.

In other neurologic clinical conditions marked by the loss of specific brain cells, different forms of “disuse atrophy” are partly the cause. We don’t know whether that’s the case for FTD. Scientists have shown that specific forms of computerized brain exercises can sharply increase activity levels in the salience network which is linked to improvements in the regulatory control of the autonomic nervous system – one of the key response-mediating targets of the network’s von Economo neurons.

Interestingly, superagers who sustain body and brain health into their 90s (and beyond) die with a full complement of von Economo neurons operating happily in a still-vigorous salience network.

This neuroscientist can foresee a day when we routinely assess the integrity of this important brain system and more reliably maintain its good health. Keeping those very special neurons alive would have probably allowed Mr. Willis to sustain himself on the soundstage and on the grander stage of life for a long time to come. Alas, like so many things in medicine, there is promise. But at this moment for this famous patient, our current medical science appears to be a day late, and a dollar short.

Dr. Merzenichis is professor emeritus at the University of California, San Francisco, and a Kavli Laureate in Neuroscience. He reported conflicts of interest with the National Institutes of Health, Stronger Brains, and Posit Science.
 

A version of this article first appeared on Medscape.com.

When I read the news that Bruce Willis had disclosed his diagnosis of frontotemporal dementia (FTD), I was reminded that all of us are at risk for spending our final epoch lost in a neurologic swamp. What is remarkable about the swamp that we call FTD is that it’s a somewhat rare and unusual type of dementia. We tend to characterize dementia as the erosion of memory, but FTD is more characterized by the loss of control over emotions and other cognitive functions. What›s especially tragic for performers like Mr. Willis is the loss of the verbal fluency required for delivering one’s lines.

Frontotemporal dementia

To this casual observer, Bruce Willis was an almost invincible force, vigorous, vital, one of the “immortals.” Alas, with his FTD diagnosis, we know that even a die-hard like Mr. Willis, now only 67 years of age, may have to endure years of progressive decline. If the disease follows its typical path, that will probably include slowly disconnecting and progressively losing emotional judgment and control as well as losing a reasonable understanding of what or why any of it is happening. He may also experience a progressive deterioration of the control of bodily functions and general health.

Most people with dementia lose their neurocognitive abilities through a number of different pathways, all of which result in brain shrinkage, disconnection, evident neuropathology, neurobehavioral expressions of loss, and forms of befuddlement. Alzheimer’s disease leads the list as the most common form of dementia, but vascular dementias; dementia with Lewy bodies; “mixed” dementias; dementias associated with Parkinson’s, Huntington’s, or other diseases; dementia rising from alcoholic or other brain poisoning, HIV, Lyme disease, or a host of other brain infections; or from traumatic encephalopathy (chronic or more current) may present at any active neurology clinic. These are what you might think of as your “grandpa’s dementia” – the common types often associated with old age.

FTD is a particularly interesting variant for several reasons. First, it usually arises in relatively young individuals, with initial symptoms emerging in one’s 50s or 60s. In most cases, there is no genetic and, with rare exception, any other explanation of origin – except that old medical standby, bad luck.

Second, FTD has little initial impact on a patient’s broader memory and associated cognitive abilities. The patient will stumble to come up with that next word and ultimately slow down their speech as their brain struggles with verbal fluency; they will struggle with translating their feelings and emotions into fast and appropriate actions expressed in their mind and their physical body while their memory will appear intact.

In all other dementias, cognitive losses can be profound, whereas social and emotional control and voluble speech production are generally better sustained. Imagine the impact that these struggles in verbal fluency and in emotional calibration and response must have for an established actor. By all reports, Mr. Willis vigorously pursued the work that he loved right up until the time of his dementia diagnosis, even as his colleagues would almost certainly have seen that he was struggling. Sadly, a lack of that type of self-awareness is an expected consequence of FTD.
 

The salience network and von Economo neurons

Third and most intriguing to a neuroscientific nerd like me is that patients with FTD experience an initial loss of a special population of cortical neurons located within the salience network in our brains, called the von Economo neurons. That salience network is designed to quickly read and evaluate our complex thoughts and emotions and via those Economo neurons, initiate appropriate neurologic and physical responses.

We share this special von Economo machinery with great apes, whales, elephants, and a handful of other especially social mammalian species.

When we see or hear or otherwise sense something that induces fear, alarm, or a potential reward, the salience network in our brain acts as a kind of gatekeeper. First, it assesses the emergent or changing situation, then it rapidly initiates an emotional and physical response. As I sit with a patient in obvious distress in my office, my salience network turns on an empathetic alarm. My brain and body immediately adjust to initiate appropriately sympathetic reactions. The von Economo neurons – those very neurons that have substantially died off in a brain with FTD – are the linchpins in this fast-response emotion and complex body signal-informed system.

Controlled emotional response is at the heart of our humanity. It’s a sad day when we lose it.

In other neurologic clinical conditions marked by the loss of specific brain cells, different forms of “disuse atrophy” are partly the cause. We don’t know whether that’s the case for FTD. Scientists have shown that specific forms of computerized brain exercises can sharply increase activity levels in the salience network which is linked to improvements in the regulatory control of the autonomic nervous system – one of the key response-mediating targets of the network’s von Economo neurons.

Interestingly, superagers who sustain body and brain health into their 90s (and beyond) die with a full complement of von Economo neurons operating happily in a still-vigorous salience network.

This neuroscientist can foresee a day when we routinely assess the integrity of this important brain system and more reliably maintain its good health. Keeping those very special neurons alive would have probably allowed Mr. Willis to sustain himself on the soundstage and on the grander stage of life for a long time to come. Alas, like so many things in medicine, there is promise. But at this moment for this famous patient, our current medical science appears to be a day late, and a dollar short.

Dr. Merzenichis is professor emeritus at the University of California, San Francisco, and a Kavli Laureate in Neuroscience. He reported conflicts of interest with the National Institutes of Health, Stronger Brains, and Posit Science.
 

A version of this article first appeared on Medscape.com.

When Senate Minority Leader Mitch McConnell (R-Ky.) fell recently at a dinner event in Washington, he unfortunately joined a large group of his senior citizen peers. 

This wasn’t the first tumble the 81-year-old has taken. In 2019, he fell in his home, fracturing his shoulder. This time, he got a concussion and was recently released to an in-patient rehabilitation facility. While Sen. McConnell didn’t fracture his skull, in falling and hitting his head, he became part of an emerging statistic: One that reveals falls are more dangerous for senior men than senior women. 

This new research, which appeared in the American Journal of Emergency Medicine, came as a surprise to lead researcher Scott Alter, MD, associate professor of emergency medicine at the Florida Atlantic University, Boca Raton. 

“We always hear about lower bone density rates among females, so we didn’t expect to see males with more skull fractures,” he said. 

Dr. Alter said that as a clinician in a southern Florida facility, his emergency department was the perfect study grounds to evaluate incoming geriatric patients due to falls. Older “patients are at higher risk of skull fractures and intercranial bleeding, and we wanted to look at any patient presenting with a head injury. Some 80% were fall related, however.” 

The statistics bear out the fact that falls of all types are common among the elderly: Some 800,000 seniors wind up in the hospital each year because of falls.

The numbers show death rates from falls are on the rise in the senior citizen age group, too, up 30% from 2007 to 2016. Falls account for 70% of accidental deaths in people 75 and older. They are the leading cause of injury-related visits to emergency departments in the country, too. 

Jennifer Stevens, MD, a gerontologist and executive director at Florida-based Abbey Delray South, is aware of the dire numbers and sees their consequences regularly. “The reasons seniors are at a high fall risk are many,” she said. “They include balance issues, declining strength, diseases like Parkinson’s and Alzheimer’s, side effects of their medications, and more.”

In addition, many seniors live in spaces that are not necessarily equipped for their limitations, and hazards exist all over their homes. Put together, and the risks for falls are everywhere. But there are steps seniors, their families, and even middle-aged people can take to mitigate and hopefully prevent dangerous falls.  
 

Starting early

While in many cases the journey to lessen fall risks begins after a fall, the time to begin addressing the issue is long before you hit your senior years. Mary Therese Cole, a physical therapist and certified dementia practitioner at Manual Edge Physical Therapy in Colorado Springs, Colo., says that age 50 is a good time to start paying attention and addressing physical declines. 

“This is an age where your vision might begin deteriorating,” she said. “It’s a big reason why elderly people trip and fall.” 

As our brains begin to age in our middle years, the neural pathways from brain to extremities start to decline, too. The result is that many people stop picking up their feet as well as they used to do, making them more likely to trip. 

“You’re not elderly yet, but you’re not a spring chicken, either,” Ms. Cole said. “Any issues you have now will only get worse if you’re not working on them.” 

A good starting point in middle age, then, is to work on both strength training and balance exercises. A certified personal trainer or physical therapist can help get you on a program to ward off many of these declines.

If you’ve reached your later years, however, and are experiencing physical declines, it’s smart to check in with your primary care doctor for an assessment. “He or she can get your started on regular PT to evaluate any shortcomings and then address them,” Ms. Cole said. 

She noted that when she’s working with senior patients, she’ll test their strength getting into and out of a chair, do a manual strength test to check on lower extremities, check their walking stride, and ask about conditions such as diabetes, former surgeries, and other conditions. 

From there, Ms. Cole said she can write up a plan for the patient. Likewise, Dr. Stevens uses a program called Be Active that allows her to test seniors on a variety of measurements, including flexibility, balance, hand strength, and more. 

“Then we match them with classes to address their shortcomings,” she said. “It’s critical that seniors have the ability to recover and not fall if they get knocked off balance.”

Beyond working on your physical limitations, taking a good look at your home is essential, too. “You can have an occupational therapist come to your home and do an evaluation,” Dr. Stevens said. “They can help you rearrange and reorganize for a safer environment.” 

Big, common household fall hazards include throw rugs, lack of nightlights for middle-of-the-night visits to the bathroom, a lack of grab bars in the shower/bathtub, and furniture that blocks pathways. 

For his part, Dr. Alter likes to point seniors and their doctors to the CDC’s STEADI program, which is aimed at stopping elderly accidents, deaths, and injuries. 

“It includes screening for fall risk, assessing factors you can modify or improve, and more tools,” he said. 

Dr. Alter also recommended seniors talk to their doctors about medications, particularly blood thinners. 

“At a certain point, you need to weigh the benefits of disease prevention with the risk of injury if you fall,” he said. “The bleeding risk might be too high if the patient is at a high risk of falls.”
 

A version of this article originally appeared on WebMD.com. 

When Senate Minority Leader Mitch McConnell (R-Ky.) fell recently at a dinner event in Washington, he unfortunately joined a large group of his senior citizen peers. 

This wasn’t the first tumble the 81-year-old has taken. In 2019, he fell in his home, fracturing his shoulder. This time, he got a concussion and was recently released to an in-patient rehabilitation facility. While Sen. McConnell didn’t fracture his skull, in falling and hitting his head, he became part of an emerging statistic: One that reveals falls are more dangerous for senior men than senior women. 

This new research, which appeared in the American Journal of Emergency Medicine, came as a surprise to lead researcher Scott Alter, MD, associate professor of emergency medicine at the Florida Atlantic University, Boca Raton. 

“We always hear about lower bone density rates among females, so we didn’t expect to see males with more skull fractures,” he said. 

Dr. Alter said that as a clinician in a southern Florida facility, his emergency department was the perfect study grounds to evaluate incoming geriatric patients due to falls. Older “patients are at higher risk of skull fractures and intercranial bleeding, and we wanted to look at any patient presenting with a head injury. Some 80% were fall related, however.” 

The statistics bear out the fact that falls of all types are common among the elderly: Some 800,000 seniors wind up in the hospital each year because of falls.

The numbers show death rates from falls are on the rise in the senior citizen age group, too, up 30% from 2007 to 2016. Falls account for 70% of accidental deaths in people 75 and older. They are the leading cause of injury-related visits to emergency departments in the country, too. 

Jennifer Stevens, MD, a gerontologist and executive director at Florida-based Abbey Delray South, is aware of the dire numbers and sees their consequences regularly. “The reasons seniors are at a high fall risk are many,” she said. “They include balance issues, declining strength, diseases like Parkinson’s and Alzheimer’s, side effects of their medications, and more.”

In addition, many seniors live in spaces that are not necessarily equipped for their limitations, and hazards exist all over their homes. Put together, and the risks for falls are everywhere. But there are steps seniors, their families, and even middle-aged people can take to mitigate and hopefully prevent dangerous falls.  
 

Starting early

While in many cases the journey to lessen fall risks begins after a fall, the time to begin addressing the issue is long before you hit your senior years. Mary Therese Cole, a physical therapist and certified dementia practitioner at Manual Edge Physical Therapy in Colorado Springs, Colo., says that age 50 is a good time to start paying attention and addressing physical declines. 

“This is an age where your vision might begin deteriorating,” she said. “It’s a big reason why elderly people trip and fall.” 

As our brains begin to age in our middle years, the neural pathways from brain to extremities start to decline, too. The result is that many people stop picking up their feet as well as they used to do, making them more likely to trip. 

“You’re not elderly yet, but you’re not a spring chicken, either,” Ms. Cole said. “Any issues you have now will only get worse if you’re not working on them.” 

A good starting point in middle age, then, is to work on both strength training and balance exercises. A certified personal trainer or physical therapist can help get you on a program to ward off many of these declines.

If you’ve reached your later years, however, and are experiencing physical declines, it’s smart to check in with your primary care doctor for an assessment. “He or she can get your started on regular PT to evaluate any shortcomings and then address them,” Ms. Cole said. 

She noted that when she’s working with senior patients, she’ll test their strength getting into and out of a chair, do a manual strength test to check on lower extremities, check their walking stride, and ask about conditions such as diabetes, former surgeries, and other conditions. 

From there, Ms. Cole said she can write up a plan for the patient. Likewise, Dr. Stevens uses a program called Be Active that allows her to test seniors on a variety of measurements, including flexibility, balance, hand strength, and more. 

“Then we match them with classes to address their shortcomings,” she said. “It’s critical that seniors have the ability to recover and not fall if they get knocked off balance.”

Beyond working on your physical limitations, taking a good look at your home is essential, too. “You can have an occupational therapist come to your home and do an evaluation,” Dr. Stevens said. “They can help you rearrange and reorganize for a safer environment.” 

Big, common household fall hazards include throw rugs, lack of nightlights for middle-of-the-night visits to the bathroom, a lack of grab bars in the shower/bathtub, and furniture that blocks pathways. 

For his part, Dr. Alter likes to point seniors and their doctors to the CDC’s STEADI program, which is aimed at stopping elderly accidents, deaths, and injuries. 

“It includes screening for fall risk, assessing factors you can modify or improve, and more tools,” he said. 

Dr. Alter also recommended seniors talk to their doctors about medications, particularly blood thinners. 

“At a certain point, you need to weigh the benefits of disease prevention with the risk of injury if you fall,” he said. “The bleeding risk might be too high if the patient is at a high risk of falls.”
 

A version of this article originally appeared on WebMD.com. 

When Senate Minority Leader Mitch McConnell (R-Ky.) fell recently at a dinner event in Washington, he unfortunately joined a large group of his senior citizen peers. 

This wasn’t the first tumble the 81-year-old has taken. In 2019, he fell in his home, fracturing his shoulder. This time, he got a concussion and was recently released to an in-patient rehabilitation facility. While Sen. McConnell didn’t fracture his skull, in falling and hitting his head, he became part of an emerging statistic: One that reveals falls are more dangerous for senior men than senior women. 

This new research, which appeared in the American Journal of Emergency Medicine, came as a surprise to lead researcher Scott Alter, MD, associate professor of emergency medicine at the Florida Atlantic University, Boca Raton. 

“We always hear about lower bone density rates among females, so we didn’t expect to see males with more skull fractures,” he said. 

Dr. Alter said that as a clinician in a southern Florida facility, his emergency department was the perfect study grounds to evaluate incoming geriatric patients due to falls. Older “patients are at higher risk of skull fractures and intercranial bleeding, and we wanted to look at any patient presenting with a head injury. Some 80% were fall related, however.” 

The statistics bear out the fact that falls of all types are common among the elderly: Some 800,000 seniors wind up in the hospital each year because of falls.

The numbers show death rates from falls are on the rise in the senior citizen age group, too, up 30% from 2007 to 2016. Falls account for 70% of accidental deaths in people 75 and older. They are the leading cause of injury-related visits to emergency departments in the country, too. 

Jennifer Stevens, MD, a gerontologist and executive director at Florida-based Abbey Delray South, is aware of the dire numbers and sees their consequences regularly. “The reasons seniors are at a high fall risk are many,” she said. “They include balance issues, declining strength, diseases like Parkinson’s and Alzheimer’s, side effects of their medications, and more.”

In addition, many seniors live in spaces that are not necessarily equipped for their limitations, and hazards exist all over their homes. Put together, and the risks for falls are everywhere. But there are steps seniors, their families, and even middle-aged people can take to mitigate and hopefully prevent dangerous falls.  
 

Starting early

While in many cases the journey to lessen fall risks begins after a fall, the time to begin addressing the issue is long before you hit your senior years. Mary Therese Cole, a physical therapist and certified dementia practitioner at Manual Edge Physical Therapy in Colorado Springs, Colo., says that age 50 is a good time to start paying attention and addressing physical declines. 

“This is an age where your vision might begin deteriorating,” she said. “It’s a big reason why elderly people trip and fall.” 

As our brains begin to age in our middle years, the neural pathways from brain to extremities start to decline, too. The result is that many people stop picking up their feet as well as they used to do, making them more likely to trip. 

“You’re not elderly yet, but you’re not a spring chicken, either,” Ms. Cole said. “Any issues you have now will only get worse if you’re not working on them.” 

A good starting point in middle age, then, is to work on both strength training and balance exercises. A certified personal trainer or physical therapist can help get you on a program to ward off many of these declines.

If you’ve reached your later years, however, and are experiencing physical declines, it’s smart to check in with your primary care doctor for an assessment. “He or she can get your started on regular PT to evaluate any shortcomings and then address them,” Ms. Cole said. 

She noted that when she’s working with senior patients, she’ll test their strength getting into and out of a chair, do a manual strength test to check on lower extremities, check their walking stride, and ask about conditions such as diabetes, former surgeries, and other conditions. 

From there, Ms. Cole said she can write up a plan for the patient. Likewise, Dr. Stevens uses a program called Be Active that allows her to test seniors on a variety of measurements, including flexibility, balance, hand strength, and more. 

“Then we match them with classes to address their shortcomings,” she said. “It’s critical that seniors have the ability to recover and not fall if they get knocked off balance.”

Beyond working on your physical limitations, taking a good look at your home is essential, too. “You can have an occupational therapist come to your home and do an evaluation,” Dr. Stevens said. “They can help you rearrange and reorganize for a safer environment.” 

Big, common household fall hazards include throw rugs, lack of nightlights for middle-of-the-night visits to the bathroom, a lack of grab bars in the shower/bathtub, and furniture that blocks pathways. 

For his part, Dr. Alter likes to point seniors and their doctors to the CDC’s STEADI program, which is aimed at stopping elderly accidents, deaths, and injuries. 

“It includes screening for fall risk, assessing factors you can modify or improve, and more tools,” he said. 

Dr. Alter also recommended seniors talk to their doctors about medications, particularly blood thinners. 

“At a certain point, you need to weigh the benefits of disease prevention with the risk of injury if you fall,” he said. “The bleeding risk might be too high if the patient is at a high risk of falls.”
 

A version of this article originally appeared on WebMD.com. 

A common chemical that is used in correction fluid, paint removers, gun cleaners, aerosol cleaning products, and dry cleaning may be the key culprit behind the dramatic increase in Parkinson’s disease (PD), researchers say.

An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).

Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”

“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”

The paper was published online in the Journal of Parkinson’s Disease.
 

Invisible, ubiquitous

TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.

“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.

In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”

Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.

TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.

“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”

Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”

To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.

“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.

TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”

Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.

The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.

People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”

They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”

Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.

The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.

Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.

All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.

The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.

They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
 

Recall bias?

Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”

Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”

Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”

In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.

These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.

Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
 

A version of this article first appeared on Medscape.com.

A common chemical that is used in correction fluid, paint removers, gun cleaners, aerosol cleaning products, and dry cleaning may be the key culprit behind the dramatic increase in Parkinson’s disease (PD), researchers say.

An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).

Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”

“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”

The paper was published online in the Journal of Parkinson’s Disease.
 

Invisible, ubiquitous

TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.

“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.

In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”

Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.

TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.

“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”

Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”

To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.

“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.

TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”

Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.

The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.

People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”

They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”

Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.

The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.

Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.

All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.

The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.

They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
 

Recall bias?

Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”

Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”

Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”

In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.

These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.

Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
 

A version of this article first appeared on Medscape.com.

A common chemical that is used in correction fluid, paint removers, gun cleaners, aerosol cleaning products, and dry cleaning may be the key culprit behind the dramatic increase in Parkinson’s disease (PD), researchers say.

An international team of researchers reviewed previous research and cited data that suggest the chemical trichloroethylene (TCE) is associated with as much as a 500% increased risk for Parkinson’s disease (PD).

Lead investigator Ray Dorsey, MD, professor of neurology, University of Rochester, N.Y., called PD “the world’s fastest-growing brain disease,” and told this news organization that it “may be largely preventable.”

“Countless people have died over generations from cancer and other disease linked to TCE [and] Parkinson’s may be the latest,” he said. “Banning these chemicals, containing contaminated sites, and protecting homes, schools, and buildings at risk may all create a world where Parkinson’s is increasingly rare, not common.”

The paper was published online in the Journal of Parkinson’s Disease.
 

Invisible, ubiquitous

TCE was first synthesized in a lab in 1864, with commercial production beginning in 1920, the researchers noted.

“Because of its unique properties, TCE has had countless industrial, commercial, military, and medical applications,” including producing refrigerants, cleaning electronics, and degreasing engine parts.

In addition, it’s been used in dry cleaning, although a similar chemical (perchloroethylene [PCE]) is currently more widely used for that purpose. Nevertheless, the authors noted, in anaerobic conditions, perchloroethylene often transforms into TCE “and their toxicity may be similar.”

Consumer products in which TCE is found include typewriter correction fluid, paint removers, gun cleaners, and aerosol cleaning products. Up until the 1970s, it was used to decaffeinate coffee.

TCE exposure isn’t confined to those who work with it. It also pollutes outdoor air, taints groundwater, and contaminates indoor air. It’s present in a substantial amount of groundwater in the United States and it “evaporates from underlying soil and groundwater and enters homes, workplaces, or schools, often undetected,” the researchers noted.

“Exposure can come via occupation or the environment and is often largely unknown at the time it occurs,” Dr. Dorsey said.

He noted that the rapid increase in PD incidence cannot be explained by genetic factors alone, which affect only about 15% of patients with PD, nor can it be explained by aging alone. “Certain pesticides ... are likely causes but would not explain the high prevalence of PD in urban areas, as is the case in the U.S.” Rather, “other factors” are involved, and “TCE is likely one such factor.”

Yet, “despite widespread contamination and increasing industrial, commercial, and military use, clinical investigations of TCE and PD have been limited.”

To fill this knowledge gap, Dr. Dorsey and his coauthors of the book, “Ending Parkinson’s Disease: A Prescription for Action,” took a deep dive into studies focusing on the potential association of TCE and PD and presented seven cases to illustrate the association.

“Like many genetic mutations (e.g., Parkin) and other environmental toxicants ... TCE damages the energy-producing parts of cells, i.e., the mitochondria,” said Dr. Dorsey.

TCE and PCE “likely mediate their toxicity through a common metabolite.” Because both are lipophilic, they “readily distribute in the brain and body tissues and appear to cause mitochondrial dysfunction at high doses,” the researchers hypothesized.

Dopaminergic neurons are particularly sensitive to mitochondrial neurotoxicants, so this might “partially explain the link to PD.”

Animal studies have shown that TCE “caused selective loss of dopaminergic neurons.” Moreover, PD-related neuropathology was found in the substantia nigra of rodents exposed to TCE over time. In addition, studies as early as 1960 were showing an association between TCE and parkinsonism.

The authors describe TCE as “ubiquitous” in the 1970s, with 10 million Americans working with the chemical or other organic solvents daily. The review details an extensive list of industries and occupations in which TCE exposure continues to occur.

People working with TCE might inhale it or touch it; but “millions more encounter the chemical unknowingly through outdoor air, contaminated groundwater, and indoor air pollution.”

They noted that TCE contaminates up to one-third of U.S. drinking water, has polluted the groundwater in more than 20 different countries on five continents, and is found in half of the 1,300 most toxic “Superfund” sites that are “part of a federal clean-up program, including 15 in California’s Silicon Valley, where TCE was used to clean electronics.”

Although the U.S. military stopped using TCE, numerous sites have been contaminated, including Marine Corps Base Camp Lejeune in North Carolina, where TCE and PCE were found in drinking water at 280 times the recommended safety standards.

The researchers highlighted seven cases of individuals who developed PD after likely exposure to TCE, including NBA basketball player Brian Grant, who developed symptoms of PD in 2006 at the age of 34.

Mr. Grant and his family had lived in Camp Lejeune when he was a child, during which time he drank, bathed, and swam in contaminated water, “unaware of its toxicity.” His father also died of esophageal cancer, “which is linked to TCE,” the authors of the study wrote. Mr. Grant has created a foundation to inspire and support patients with PD.

All of the individuals either grew up in or spent time in an area where they were extensively exposed to TCE, PCE, or other chemicals, or experienced occupational exposure.

The authors acknowledged that the role of TCE in PD, as illustrated by the cases, is “far from definitive.” For example, exposure to TCE is often combined with exposure to other toxins, or with unmeasured genetic risk factors.

They highlighted the need for more research and called for cleaning and containing contaminated sites, monitoring TCE levels, and publicly communicating risk and a ban on TCE.
 

Recall bias?

Commenting for this news organization, Rebecca Gilbert, MD, PhD, chief scientific officer, American Parkinson Disease Association (APDA), noted that the authors “are very frank about the limitations of this approach [illustrative cases] as proof of causation between PD and TCE exposure.”

Another limitation is that TCE exposure is very common, “as argued in the paper.” But “most people with exposure do not develop PD,” Dr. Gilbert pointed out. “By probing the TCE exposure of those who already have PD, there is a danger of recall bias.”

Dr. Gilbert, associate professor of neurology at NYU Langone Health, who was not involved with the study, acknowledged that the authors “present their work as hypothesis and clearly state that more work is needed to understand the connection between TCE and PD.”

In the meantime, however, there are “well-established health risks of TCE exposure, including development of various cancers,” she said. Therefore, the authors’ goals appear to be educating the public about known health risks, working to clean up known sites of contamination, and advocating to ban future use of TCE.

These goals “do not need to wait for [proof of] firm causation between TCE and PD,” she stated.

Dr. Dorsey reported he has received honoraria for speaking at the American Academy of Neurology and at multiple other societies and foundations and has received compensation for consulting services from pharmaceutical companies, foundations, medical education companies, and medical publications; he owns stock in several companies. The other authors’ disclosures can be found in the original paper. Dr. Gilbert is employed by the American Parkinson Disease Association and Bellevue Hospital Center in New York City.
 

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Cognitive behavioral therapy (CBT) should be the first-line therapy for insomnia in seniors, but many clinicians are unaware of its benefits, experts say.

Rajesh R. Tampi

“The lack of awareness among clinicians who take care of older adults that CBT for insomnia (CBT-I) is an effective treatment for insomnia is an issue,” Rajesh R. Tampi, MD, professor and chairman of the department of psychiatry, Creighton University, Omaha, Neb., told this news organization.

Dr. Tampi was among the speakers during a session as part of the American Association for Geriatric Psychiatry annual meeting addressing the complex challenges of treating insomnia in older patients, who tend to have higher rates of insomnia than their younger counterparts.

The prevalence of insomnia in older adults is estimated to be 20%-40%, and medication is frequently the first treatment choice, a less than ideal approach, said Dr. Tampi.

“Prescribing sedatives and hypnotics, which can cause severe adverse effects, without a thorough assessment that includes comorbidities that may be causing the insomnia” is among the biggest mistakes clinicians make in the treatment of insomnia in older patients, Dr. Tampi said in an interview.

“It’s our duty as providers to first take a good assessment, talk about polymorbidity, and try to address those conditions, and judiciously use medications in conjunction with at least components of CBT-I,” he said.
 

Long-term safety, efficacy unclear

About one-third of older adults take at least one form of pharmacological treatment for insomnia symptoms, said Ebony Dix, MD, assistant professor of psychiatry at Yale University, New Haven, Conn., in a separate talk during the session. This, despite the low-risk profile of CBT and recommendations from various medical societies that CBT should be tried first.

Dr. Dix noted that medications approved for insomnia by the U.S. Food and Drug Administration, including melatonin receptor agonists, heterocyclics, and dual orexin receptor antagonists (DORAs), can play an important role in the short-term management of insomnia, but their long-term effects are unknown.

“Pharmacotherapeutic agents may be effective in the short term, but there is a lack of sufficient, statistically significant data to support the long-term safety and efficacy of any [sleep] medication, especially in aging adults, due to the impact of hypnotic drugs on sleep architecture, the impact of aging on pharmacokinetics, as well as polypharmacy and drug-to-drug interactions,” Dr. Dix said. She noted that clinical trials of insomnia drugs rarely include geriatric patients.

University of South Carolina

The American Academy of Sleep Medicine recommends CBT-I as first-line treatment for insomnia, with the key benefit being its exemplary safety profile, said Shilpa Srinivasan, MD, a professor of clinical psychiatry at the University of South Carolina, Columbia, who also presented during the session.

“The biggest [attribute] of CBT-I management strategies is the low risk of side effects,” she said. “How many medications can we say that about?”

The CBT-I intervention includes a focus on key components of lifestyle and mental health issues to improve sleep. These include the following:

• Strictly restricting sleep hours for bedtime and arising (with napping discouraged).
• Control of stimulus to disrupt falling asleep.
• Cognitive therapy to identify and replace maladaptive beliefs.
• Control of sleep hygiene for optimal sleep.
• Relaxation training.

Keys to success

Dr. Srinivasan noted one recent study of CBT-I among patients aged 60 and older with insomnia and depression. The 156 participants randomized to receive weekly 120-minute CBT-I sessions over 2 months were significantly less likely to develop new or recurrent major depression versus their counterparts randomized to receive sleep education (hazard ratio, 0.51; P = .02).

However, CBT-I is more labor intensive than medication and requires provider training and motivation, and commitment on the part of the patient, to be successful.

“We really need to ensure that even when patients are receiving pharmacologic interventions for insomnia that we provide psychoeducation. At the end of the day, some of these nonpharmacologic components can make or break the success of pharmacotherapy,” said Dr. Srinivasan.

Whether using CBT-I alone or in combination with pharmacotherapy, the intervention does not necessarily have to include all components to be beneficial, she said.

“I think one of the challenges in incorporating CBT-I is the misconception that it is an all-or-nothing approach wherein every modality must be utilized,” she said. “While multicomponent CBT-I has been shown to be effective, the individual components can be incorporated into patient encounters in a stepped approach.”

Informing patients that they have options other than medications and involving them in decision-making is key, she added.

“In the case of insomnia, this is particularly relevant because of the physical and emotional distress that it causes,” Dr. Srinivasan said. “Patients often seek over-the-counter medications or other nonprescribed agents to try to obtain relief even before seeking treatment in a health care setting. There is less awareness about evidence-based and effective nonpharmacologic treatments such as CBT-I.”

Dr. Tampi, Dr. Dix, and Dr. Srinivasan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Cognitive behavioral therapy (CBT) should be the first-line therapy for insomnia in seniors, but many clinicians are unaware of its benefits, experts say.

Rajesh R. Tampi

“The lack of awareness among clinicians who take care of older adults that CBT for insomnia (CBT-I) is an effective treatment for insomnia is an issue,” Rajesh R. Tampi, MD, professor and chairman of the department of psychiatry, Creighton University, Omaha, Neb., told this news organization.

Dr. Tampi was among the speakers during a session as part of the American Association for Geriatric Psychiatry annual meeting addressing the complex challenges of treating insomnia in older patients, who tend to have higher rates of insomnia than their younger counterparts.

The prevalence of insomnia in older adults is estimated to be 20%-40%, and medication is frequently the first treatment choice, a less than ideal approach, said Dr. Tampi.

“Prescribing sedatives and hypnotics, which can cause severe adverse effects, without a thorough assessment that includes comorbidities that may be causing the insomnia” is among the biggest mistakes clinicians make in the treatment of insomnia in older patients, Dr. Tampi said in an interview.

“It’s our duty as providers to first take a good assessment, talk about polymorbidity, and try to address those conditions, and judiciously use medications in conjunction with at least components of CBT-I,” he said.
 

Long-term safety, efficacy unclear

About one-third of older adults take at least one form of pharmacological treatment for insomnia symptoms, said Ebony Dix, MD, assistant professor of psychiatry at Yale University, New Haven, Conn., in a separate talk during the session. This, despite the low-risk profile of CBT and recommendations from various medical societies that CBT should be tried first.

Dr. Dix noted that medications approved for insomnia by the U.S. Food and Drug Administration, including melatonin receptor agonists, heterocyclics, and dual orexin receptor antagonists (DORAs), can play an important role in the short-term management of insomnia, but their long-term effects are unknown.

“Pharmacotherapeutic agents may be effective in the short term, but there is a lack of sufficient, statistically significant data to support the long-term safety and efficacy of any [sleep] medication, especially in aging adults, due to the impact of hypnotic drugs on sleep architecture, the impact of aging on pharmacokinetics, as well as polypharmacy and drug-to-drug interactions,” Dr. Dix said. She noted that clinical trials of insomnia drugs rarely include geriatric patients.

University of South Carolina

The American Academy of Sleep Medicine recommends CBT-I as first-line treatment for insomnia, with the key benefit being its exemplary safety profile, said Shilpa Srinivasan, MD, a professor of clinical psychiatry at the University of South Carolina, Columbia, who also presented during the session.

“The biggest [attribute] of CBT-I management strategies is the low risk of side effects,” she said. “How many medications can we say that about?”

The CBT-I intervention includes a focus on key components of lifestyle and mental health issues to improve sleep. These include the following:

• Strictly restricting sleep hours for bedtime and arising (with napping discouraged).
• Control of stimulus to disrupt falling asleep.
• Cognitive therapy to identify and replace maladaptive beliefs.
• Control of sleep hygiene for optimal sleep.
• Relaxation training.

Keys to success

Dr. Srinivasan noted one recent study of CBT-I among patients aged 60 and older with insomnia and depression. The 156 participants randomized to receive weekly 120-minute CBT-I sessions over 2 months were significantly less likely to develop new or recurrent major depression versus their counterparts randomized to receive sleep education (hazard ratio, 0.51; P = .02).

However, CBT-I is more labor intensive than medication and requires provider training and motivation, and commitment on the part of the patient, to be successful.

“We really need to ensure that even when patients are receiving pharmacologic interventions for insomnia that we provide psychoeducation. At the end of the day, some of these nonpharmacologic components can make or break the success of pharmacotherapy,” said Dr. Srinivasan.

Whether using CBT-I alone or in combination with pharmacotherapy, the intervention does not necessarily have to include all components to be beneficial, she said.

“I think one of the challenges in incorporating CBT-I is the misconception that it is an all-or-nothing approach wherein every modality must be utilized,” she said. “While multicomponent CBT-I has been shown to be effective, the individual components can be incorporated into patient encounters in a stepped approach.”

Informing patients that they have options other than medications and involving them in decision-making is key, she added.

“In the case of insomnia, this is particularly relevant because of the physical and emotional distress that it causes,” Dr. Srinivasan said. “Patients often seek over-the-counter medications or other nonprescribed agents to try to obtain relief even before seeking treatment in a health care setting. There is less awareness about evidence-based and effective nonpharmacologic treatments such as CBT-I.”

Dr. Tampi, Dr. Dix, and Dr. Srinivasan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Cognitive behavioral therapy (CBT) should be the first-line therapy for insomnia in seniors, but many clinicians are unaware of its benefits, experts say.

Rajesh R. Tampi

“The lack of awareness among clinicians who take care of older adults that CBT for insomnia (CBT-I) is an effective treatment for insomnia is an issue,” Rajesh R. Tampi, MD, professor and chairman of the department of psychiatry, Creighton University, Omaha, Neb., told this news organization.

Dr. Tampi was among the speakers during a session as part of the American Association for Geriatric Psychiatry annual meeting addressing the complex challenges of treating insomnia in older patients, who tend to have higher rates of insomnia than their younger counterparts.

The prevalence of insomnia in older adults is estimated to be 20%-40%, and medication is frequently the first treatment choice, a less than ideal approach, said Dr. Tampi.

“Prescribing sedatives and hypnotics, which can cause severe adverse effects, without a thorough assessment that includes comorbidities that may be causing the insomnia” is among the biggest mistakes clinicians make in the treatment of insomnia in older patients, Dr. Tampi said in an interview.

“It’s our duty as providers to first take a good assessment, talk about polymorbidity, and try to address those conditions, and judiciously use medications in conjunction with at least components of CBT-I,” he said.
 

Long-term safety, efficacy unclear

About one-third of older adults take at least one form of pharmacological treatment for insomnia symptoms, said Ebony Dix, MD, assistant professor of psychiatry at Yale University, New Haven, Conn., in a separate talk during the session. This, despite the low-risk profile of CBT and recommendations from various medical societies that CBT should be tried first.

Dr. Dix noted that medications approved for insomnia by the U.S. Food and Drug Administration, including melatonin receptor agonists, heterocyclics, and dual orexin receptor antagonists (DORAs), can play an important role in the short-term management of insomnia, but their long-term effects are unknown.

“Pharmacotherapeutic agents may be effective in the short term, but there is a lack of sufficient, statistically significant data to support the long-term safety and efficacy of any [sleep] medication, especially in aging adults, due to the impact of hypnotic drugs on sleep architecture, the impact of aging on pharmacokinetics, as well as polypharmacy and drug-to-drug interactions,” Dr. Dix said. She noted that clinical trials of insomnia drugs rarely include geriatric patients.

University of South Carolina

The American Academy of Sleep Medicine recommends CBT-I as first-line treatment for insomnia, with the key benefit being its exemplary safety profile, said Shilpa Srinivasan, MD, a professor of clinical psychiatry at the University of South Carolina, Columbia, who also presented during the session.

“The biggest [attribute] of CBT-I management strategies is the low risk of side effects,” she said. “How many medications can we say that about?”

The CBT-I intervention includes a focus on key components of lifestyle and mental health issues to improve sleep. These include the following:

• Strictly restricting sleep hours for bedtime and arising (with napping discouraged).
• Control of stimulus to disrupt falling asleep.
• Cognitive therapy to identify and replace maladaptive beliefs.
• Control of sleep hygiene for optimal sleep.
• Relaxation training.

Keys to success

Dr. Srinivasan noted one recent study of CBT-I among patients aged 60 and older with insomnia and depression. The 156 participants randomized to receive weekly 120-minute CBT-I sessions over 2 months were significantly less likely to develop new or recurrent major depression versus their counterparts randomized to receive sleep education (hazard ratio, 0.51; P = .02).

However, CBT-I is more labor intensive than medication and requires provider training and motivation, and commitment on the part of the patient, to be successful.

“We really need to ensure that even when patients are receiving pharmacologic interventions for insomnia that we provide psychoeducation. At the end of the day, some of these nonpharmacologic components can make or break the success of pharmacotherapy,” said Dr. Srinivasan.

Whether using CBT-I alone or in combination with pharmacotherapy, the intervention does not necessarily have to include all components to be beneficial, she said.

“I think one of the challenges in incorporating CBT-I is the misconception that it is an all-or-nothing approach wherein every modality must be utilized,” she said. “While multicomponent CBT-I has been shown to be effective, the individual components can be incorporated into patient encounters in a stepped approach.”

Informing patients that they have options other than medications and involving them in decision-making is key, she added.

“In the case of insomnia, this is particularly relevant because of the physical and emotional distress that it causes,” Dr. Srinivasan said. “Patients often seek over-the-counter medications or other nonprescribed agents to try to obtain relief even before seeking treatment in a health care setting. There is less awareness about evidence-based and effective nonpharmacologic treatments such as CBT-I.”

Dr. Tampi, Dr. Dix, and Dr. Srinivasan have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Intravenous (IV) ketamine is effective for geriatric patients with treatment-resistant depression (TRD), and the response rate was similar to that observed in younger adult patients, two new studies suggest.

“These were patients with depression who had not responded even to intensive therapies or procedures, and we found that after a 6-week ketamine infusion regimen, there was no difference in the response to the treatment between the treatment-resistant geriatric and nongeriatric patients,” study investigator Jonathan Kim, of Emory University, Atlanta, the first author of one of two studies presented as part of the American Association for Geriatric Psychiatry annual meeting, said in an interview.

The findings are important because research on the effects of IV ketamine have not been well documented in geriatric patients, who have high rates of depression and TRD.

“There is a lack of data on IV ketamine in older adults with treatment-resistant depression, and there are some safety and tolerability concerns which may lead some older adults and their clinicians to be reluctant to pursue IV ketamine treatment,” study coinvestigator Hanadi Ajam Oughli, MD, a health sciences assistant clinical professor in the department of psychiatry and biobehavioral sciences, University of California, Los Angeles, told this news organization.

Nasal vs. IV administration

Ketamine has traditionally been used as an anesthetic that blocks N-methyl-D-aspartate (NMDA) glutamate receptors, Dr. Oughli and colleagues note.

In the treatment of TRD, an infusion of 0.5 mg/kg is typically administered over 40 minutes, producing a rapid antidepressant response. Recent research shows the drug reduces suicidality and improves mood and quality of life.

A more recent intranasal formulation of ketamine, esketamine, was approved by the U.S. Food and Drug Administration for TRD in 2019, and some experts questioned its path to approval. In addition, the drug’s high cost and poor bioavailability in comparison with IV ketamine remains an issue, said Dr. Oughli.

In the previous TRANSFORM-3 study, a placebo-controlled randomized trial, there was no difference between esketamine, used in conjunction with an antidepressant, and placebo for geriatric patients.

To better understand the effects of IV ketamine in this patient population, Mr. Kim’s team conducted a retrospective chart review of 91 older patients with TRD who received IV ketamine treatment between October 2016 and August 2022.

Patients were divided into two groups – those older than 60 years (n = 36; 44% women; mean age, 68.86) and those younger than 60 (n = 55; 49% women; mean age, 41.05). Participants in each age group received six ketamine infusions over 6 weeks.

Results showed that with regard to depression severity, as assessed using Beck Depression Inventory (BDI-II) scores, 27.8% of patients in the geriatric group had a 50% or greater improvement, vs. 25.4% of those younger than 60.

The average BDI-II scores represented a significant improvement for both groups (P < .01), and the difference in scores between the groups was not statistically significant (P = .973).

“It is important to note that our study was conducted in a real-world clinical setting with a treatment-resistant population; other clinical studies may not have such sick patients in their trials. Additional studies are therefore warranted to establish further treatment guidelines in this area,” Mr. Kim said.

Open-label trial results

In the second study, Dr. Oughli and colleagues evaluated additional key outcomes in geriatric patients treated with IV ketamine as part of a larger open-label late-life trial on TRD.

The secondary analysis of the trial focused on 23 patients (mean age, 71.5 years) who had been initially treated with twice-a-week IV ketamine for 4 weeks.

After the first 4 weeks, patients who had experienced a partial response received an additional 4 weeks of once-weekly IV ketamine.

Overall, 48% of participants achieved a response, and 24% achieved remission of depressive symptoms following the first 4 weeks of twice-weekly treatment. This effect was maintained during the continuation phase of the study.

These findings are consistent with research in younger adults and demonstrate that twice-weekly infusions yield a more sustained antidepressant response than once-weekly infusions, the authors note.

The analysis also showed important increases in psychological well-being scores on the Scale for Suicidal Ideation, improved sleep quality as measured by the Pittsburgh Sleep Quality Index, and overall psychological well-being as shown on the NIH Toolbox Positive Affect on happiness/contentment and the NIH Toolbox General Life Satisfaction scales.

In a previous analysis, published in The American Journal of Geriatric Psychiatry, the researchers also evaluated cognitive function using the NIH Cognitive Battery, which showed that geriatric patients with TRD had significant improvements in a composite of executive functioning and fluid cognition during the 4-week acute treatment period of twice-weekly IV ketamine infusions (Cohen’s d = 0.61) and that those improvements were sustained in the continuation phase of once-weekly infusions for 4 more weeks.

Those results are consistent with ketamine’s known potential procognitive effects in TRD, due to a putative antidepressant mechanism that rescues prefrontal circuit dysfunction through synaptogenesis, the researchers note.

Dr. Oughli said that in both analyses, patients tolerated ketamine well, and there were no serious adverse events.

“Adverse events, including hypertension, dissociated effects, and cravings, were rare and did not prevent the continued use of IV ketamine by older adults. We were able to use clonidine to help manage blood pressure changes seen during the infusions,” she noted.

“These findings are very promising and will need to be confirmed and extended in a larger randomized controlled trial.”

Unsettling for some older patients

George T. Grossberg, MD, director, geriatric psychiatry, Saint Louis University, noted that in his experience, IV ketamine treatment can be unsettling for some older geriatric patients, such as those in their 80s.

“Particularly with some of my older patients, the kind of psychotomimetic properties of ketamine and the out-of-body experiences [with the initial treatment] can be frightening,” he said. “They may be willing to try, but I’ve had more than one patient quit after one treatment because they became so frightened.”

However, the dire nature of TRD and failure to respond to multiple medications and combinations and other strategies may prompt patients to try ketamine as a measure with at least some potential, he noted.

“But there is a high bar for acceptance, especially on the part of older adults and their families, more than for younger people,” he said.

The investigators have disclosed no relevant financial relationships. Dr. Grossberg has received consulting fees from Acadia, Avanir, Biogen, BioXcel, Genentech, Karuna, Lundbeck, Otsuka, Roche, and Takeda.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Intravenous (IV) ketamine is effective for geriatric patients with treatment-resistant depression (TRD), and the response rate was similar to that observed in younger adult patients, two new studies suggest.

“These were patients with depression who had not responded even to intensive therapies or procedures, and we found that after a 6-week ketamine infusion regimen, there was no difference in the response to the treatment between the treatment-resistant geriatric and nongeriatric patients,” study investigator Jonathan Kim, of Emory University, Atlanta, the first author of one of two studies presented as part of the American Association for Geriatric Psychiatry annual meeting, said in an interview.

The findings are important because research on the effects of IV ketamine have not been well documented in geriatric patients, who have high rates of depression and TRD.

“There is a lack of data on IV ketamine in older adults with treatment-resistant depression, and there are some safety and tolerability concerns which may lead some older adults and their clinicians to be reluctant to pursue IV ketamine treatment,” study coinvestigator Hanadi Ajam Oughli, MD, a health sciences assistant clinical professor in the department of psychiatry and biobehavioral sciences, University of California, Los Angeles, told this news organization.

Nasal vs. IV administration

Ketamine has traditionally been used as an anesthetic that blocks N-methyl-D-aspartate (NMDA) glutamate receptors, Dr. Oughli and colleagues note.

In the treatment of TRD, an infusion of 0.5 mg/kg is typically administered over 40 minutes, producing a rapid antidepressant response. Recent research shows the drug reduces suicidality and improves mood and quality of life.

A more recent intranasal formulation of ketamine, esketamine, was approved by the U.S. Food and Drug Administration for TRD in 2019, and some experts questioned its path to approval. In addition, the drug’s high cost and poor bioavailability in comparison with IV ketamine remains an issue, said Dr. Oughli.

In the previous TRANSFORM-3 study, a placebo-controlled randomized trial, there was no difference between esketamine, used in conjunction with an antidepressant, and placebo for geriatric patients.

To better understand the effects of IV ketamine in this patient population, Mr. Kim’s team conducted a retrospective chart review of 91 older patients with TRD who received IV ketamine treatment between October 2016 and August 2022.

Patients were divided into two groups – those older than 60 years (n = 36; 44% women; mean age, 68.86) and those younger than 60 (n = 55; 49% women; mean age, 41.05). Participants in each age group received six ketamine infusions over 6 weeks.

Results showed that with regard to depression severity, as assessed using Beck Depression Inventory (BDI-II) scores, 27.8% of patients in the geriatric group had a 50% or greater improvement, vs. 25.4% of those younger than 60.

The average BDI-II scores represented a significant improvement for both groups (P < .01), and the difference in scores between the groups was not statistically significant (P = .973).

“It is important to note that our study was conducted in a real-world clinical setting with a treatment-resistant population; other clinical studies may not have such sick patients in their trials. Additional studies are therefore warranted to establish further treatment guidelines in this area,” Mr. Kim said.

Open-label trial results

In the second study, Dr. Oughli and colleagues evaluated additional key outcomes in geriatric patients treated with IV ketamine as part of a larger open-label late-life trial on TRD.

The secondary analysis of the trial focused on 23 patients (mean age, 71.5 years) who had been initially treated with twice-a-week IV ketamine for 4 weeks.

After the first 4 weeks, patients who had experienced a partial response received an additional 4 weeks of once-weekly IV ketamine.

Overall, 48% of participants achieved a response, and 24% achieved remission of depressive symptoms following the first 4 weeks of twice-weekly treatment. This effect was maintained during the continuation phase of the study.

These findings are consistent with research in younger adults and demonstrate that twice-weekly infusions yield a more sustained antidepressant response than once-weekly infusions, the authors note.

The analysis also showed important increases in psychological well-being scores on the Scale for Suicidal Ideation, improved sleep quality as measured by the Pittsburgh Sleep Quality Index, and overall psychological well-being as shown on the NIH Toolbox Positive Affect on happiness/contentment and the NIH Toolbox General Life Satisfaction scales.

In a previous analysis, published in The American Journal of Geriatric Psychiatry, the researchers also evaluated cognitive function using the NIH Cognitive Battery, which showed that geriatric patients with TRD had significant improvements in a composite of executive functioning and fluid cognition during the 4-week acute treatment period of twice-weekly IV ketamine infusions (Cohen’s d = 0.61) and that those improvements were sustained in the continuation phase of once-weekly infusions for 4 more weeks.

Those results are consistent with ketamine’s known potential procognitive effects in TRD, due to a putative antidepressant mechanism that rescues prefrontal circuit dysfunction through synaptogenesis, the researchers note.

Dr. Oughli said that in both analyses, patients tolerated ketamine well, and there were no serious adverse events.

“Adverse events, including hypertension, dissociated effects, and cravings, were rare and did not prevent the continued use of IV ketamine by older adults. We were able to use clonidine to help manage blood pressure changes seen during the infusions,” she noted.

“These findings are very promising and will need to be confirmed and extended in a larger randomized controlled trial.”

Unsettling for some older patients

George T. Grossberg, MD, director, geriatric psychiatry, Saint Louis University, noted that in his experience, IV ketamine treatment can be unsettling for some older geriatric patients, such as those in their 80s.

“Particularly with some of my older patients, the kind of psychotomimetic properties of ketamine and the out-of-body experiences [with the initial treatment] can be frightening,” he said. “They may be willing to try, but I’ve had more than one patient quit after one treatment because they became so frightened.”

However, the dire nature of TRD and failure to respond to multiple medications and combinations and other strategies may prompt patients to try ketamine as a measure with at least some potential, he noted.

“But there is a high bar for acceptance, especially on the part of older adults and their families, more than for younger people,” he said.

The investigators have disclosed no relevant financial relationships. Dr. Grossberg has received consulting fees from Acadia, Avanir, Biogen, BioXcel, Genentech, Karuna, Lundbeck, Otsuka, Roche, and Takeda.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Intravenous (IV) ketamine is effective for geriatric patients with treatment-resistant depression (TRD), and the response rate was similar to that observed in younger adult patients, two new studies suggest.

“These were patients with depression who had not responded even to intensive therapies or procedures, and we found that after a 6-week ketamine infusion regimen, there was no difference in the response to the treatment between the treatment-resistant geriatric and nongeriatric patients,” study investigator Jonathan Kim, of Emory University, Atlanta, the first author of one of two studies presented as part of the American Association for Geriatric Psychiatry annual meeting, said in an interview.

The findings are important because research on the effects of IV ketamine have not been well documented in geriatric patients, who have high rates of depression and TRD.

“There is a lack of data on IV ketamine in older adults with treatment-resistant depression, and there are some safety and tolerability concerns which may lead some older adults and their clinicians to be reluctant to pursue IV ketamine treatment,” study coinvestigator Hanadi Ajam Oughli, MD, a health sciences assistant clinical professor in the department of psychiatry and biobehavioral sciences, University of California, Los Angeles, told this news organization.

Nasal vs. IV administration

Ketamine has traditionally been used as an anesthetic that blocks N-methyl-D-aspartate (NMDA) glutamate receptors, Dr. Oughli and colleagues note.

In the treatment of TRD, an infusion of 0.5 mg/kg is typically administered over 40 minutes, producing a rapid antidepressant response. Recent research shows the drug reduces suicidality and improves mood and quality of life.

A more recent intranasal formulation of ketamine, esketamine, was approved by the U.S. Food and Drug Administration for TRD in 2019, and some experts questioned its path to approval. In addition, the drug’s high cost and poor bioavailability in comparison with IV ketamine remains an issue, said Dr. Oughli.

In the previous TRANSFORM-3 study, a placebo-controlled randomized trial, there was no difference between esketamine, used in conjunction with an antidepressant, and placebo for geriatric patients.

To better understand the effects of IV ketamine in this patient population, Mr. Kim’s team conducted a retrospective chart review of 91 older patients with TRD who received IV ketamine treatment between October 2016 and August 2022.

Patients were divided into two groups – those older than 60 years (n = 36; 44% women; mean age, 68.86) and those younger than 60 (n = 55; 49% women; mean age, 41.05). Participants in each age group received six ketamine infusions over 6 weeks.

Results showed that with regard to depression severity, as assessed using Beck Depression Inventory (BDI-II) scores, 27.8% of patients in the geriatric group had a 50% or greater improvement, vs. 25.4% of those younger than 60.

The average BDI-II scores represented a significant improvement for both groups (P < .01), and the difference in scores between the groups was not statistically significant (P = .973).

“It is important to note that our study was conducted in a real-world clinical setting with a treatment-resistant population; other clinical studies may not have such sick patients in their trials. Additional studies are therefore warranted to establish further treatment guidelines in this area,” Mr. Kim said.

Open-label trial results

In the second study, Dr. Oughli and colleagues evaluated additional key outcomes in geriatric patients treated with IV ketamine as part of a larger open-label late-life trial on TRD.

The secondary analysis of the trial focused on 23 patients (mean age, 71.5 years) who had been initially treated with twice-a-week IV ketamine for 4 weeks.

After the first 4 weeks, patients who had experienced a partial response received an additional 4 weeks of once-weekly IV ketamine.

Overall, 48% of participants achieved a response, and 24% achieved remission of depressive symptoms following the first 4 weeks of twice-weekly treatment. This effect was maintained during the continuation phase of the study.

These findings are consistent with research in younger adults and demonstrate that twice-weekly infusions yield a more sustained antidepressant response than once-weekly infusions, the authors note.

The analysis also showed important increases in psychological well-being scores on the Scale for Suicidal Ideation, improved sleep quality as measured by the Pittsburgh Sleep Quality Index, and overall psychological well-being as shown on the NIH Toolbox Positive Affect on happiness/contentment and the NIH Toolbox General Life Satisfaction scales.

In a previous analysis, published in The American Journal of Geriatric Psychiatry, the researchers also evaluated cognitive function using the NIH Cognitive Battery, which showed that geriatric patients with TRD had significant improvements in a composite of executive functioning and fluid cognition during the 4-week acute treatment period of twice-weekly IV ketamine infusions (Cohen’s d = 0.61) and that those improvements were sustained in the continuation phase of once-weekly infusions for 4 more weeks.

Those results are consistent with ketamine’s known potential procognitive effects in TRD, due to a putative antidepressant mechanism that rescues prefrontal circuit dysfunction through synaptogenesis, the researchers note.

Dr. Oughli said that in both analyses, patients tolerated ketamine well, and there were no serious adverse events.

“Adverse events, including hypertension, dissociated effects, and cravings, were rare and did not prevent the continued use of IV ketamine by older adults. We were able to use clonidine to help manage blood pressure changes seen during the infusions,” she noted.

“These findings are very promising and will need to be confirmed and extended in a larger randomized controlled trial.”

Unsettling for some older patients

George T. Grossberg, MD, director, geriatric psychiatry, Saint Louis University, noted that in his experience, IV ketamine treatment can be unsettling for some older geriatric patients, such as those in their 80s.

“Particularly with some of my older patients, the kind of psychotomimetic properties of ketamine and the out-of-body experiences [with the initial treatment] can be frightening,” he said. “They may be willing to try, but I’ve had more than one patient quit after one treatment because they became so frightened.”

However, the dire nature of TRD and failure to respond to multiple medications and combinations and other strategies may prompt patients to try ketamine as a measure with at least some potential, he noted.

“But there is a high bar for acceptance, especially on the part of older adults and their families, more than for younger people,” he said.

The investigators have disclosed no relevant financial relationships. Dr. Grossberg has received consulting fees from Acadia, Avanir, Biogen, BioXcel, Genentech, Karuna, Lundbeck, Otsuka, Roche, and Takeda.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – For older patients with resistant depression who fail to respond to antidepressant treatment, the addition of the atypical antipsychotic aripiprazole (Abilify) is superior to switching antidepressants, new research suggests.

“We found that adding aripiprazole led to higher rates of depression remission and greater improvements in psychological well-being – which means how positive and satisfied patients felt – and this is good news,” study investigator Eric J. Lenze, MD, of the department of psychiatry, Washington University, St. Louis, said in a press statement.

“However, even that approach helped only about 30% of people in the study with treatment-resistant depression, underscoring the need to find and develop more effective treatments that can help more people,” he added.

The findings were presented here as part of the American Association for Geriatric Psychiatry annual meeting, and published concurrently in the New England Journal of Medicine.
 

Need for safe treatment options

Treatment-resistant depression is common in older patients, but switching medications or adding other agents can be challenging. With higher rates of comorbidity and polypharmacy, treatment decisions in this patient population are more complex compared with those involving younger patients.

To compare the benefits of augmentation vs. drug-switching strategies, the researchers conducted a multicenter, two-step trial involving 619 patients with an average baseline age of 69 who had failed to respond to two courses of selective serotonin reuptake inhibitors (SSRIs).

Patients were randomly assigned to one of three groups. These included augmentation of existing antidepressant medication with either aripiprazole (n = 211) or the dopamine and norepinephrine–reuptake inhibitor bupropion (Wellbutrin, Zyban) (n = 206), or to taper off of their current antidepressant and switch to bupropion (n = 202).

After 10 weeks, patients’ psychological well-being was assessed via the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales. The researchers found patients in the aripiprazole and bupropion add-on groups improved by 4.83 points and 4.33 points, respectively. The bupropion switch group had a change of 2.04 points.

The difference between the aripiprazole augmentation group and the switch to bupropion group was significant (difference 2.79 points; P = .014). Other between-group differences were not significantly different.

Remission rates were similar in the aripiprazole and bupropion groups at 28.9% and 28.2%, respectively. The remission rate in the bupropion switch group was 19.3%.

The study results showed patients who received adjunctive bupropion had the highest fall rate at 0.55 falls per patient, vs. 0.33 falls per patient in the aripiprazole group, suggesting that among the three treatment options, adjunctive aripiprazole may be the best choice because of its superior efficacy and lower fall risk.

A total of 248 patients enrolled in the study showed no improvement and were further randomly assigned to receive adjunctive lithium (n = 127) or switch from current therapy to nortriptyline (n = 121).

Well-being scores in the lithium group improved by 3.17 points and 2.18 points in the nortriptyline group. Remission occurred in 18.9% of patients in the lithium group and 21.5% in the nortriptyline group. Fall rates were similar among the two groups.

Overall, “this large, randomized study demonstrated that adding aripiprazole was a superior option for older adults with treatment-resistant depression,” Dr. Lenze told this news organization.

“Since neither lithium nor nortriptyline were promising against treatment-resistant depression in older adults, those medications are unlikely to be helpful in most cases,” he added.
 

Practice changing?

In an accompanying editorial, Gemma Lewis, PhD, and Glyn Lewis, PhD, division of psychiatry, University of College London, noted the findings “support aripiprazole augmentation as a strategy for treatment-resistant depression in older persons, largely because of the lower risk of falls than with bupropion augmentation.”

However, “in clinical practice, [it] would be important to tailor treatment in light of potential adverse effects and the preferences of the patient,” they added.

Akathisia, for instance, is a common side effect of aripiprazole, shown in one recent trial to affect 11% of the patients. In addition, weight gain, though typically lower than seen with other antipsychotics, is a consideration with aripiprazole. 

With respect to fall risk, they noted that bupropion was largely used in relatively high doses of 300 mg and 450 mg, despite some recent research showing little clinical benefit from increasing antidepressant doses above minimum recommendations.

“It is possible that smaller doses of bupropion than those used in the current trial would retain effectiveness while minimizing adverse effects such as falls,” the editorialists noted.

Commenting on the study, Jennifer R. Gatchel, MD, PhD, assistant psychiatrist at Massachusetts General Hospital/McLean Hospital and assistant professor of psychiatry at Harvard Medical School, Boston, said the findings have high clinical significance in the treatment of geriatric depression. 

“These results are of great impact for clinicians managing older adults with treatment-resistant depression. They provide some of the first evidence of safety and efficacy of augmentation with aripiprazole as a strategy in clinical management of older adults who fail to initially respond to treatment,” said Dr. Gatchel, who was not associated with this research.

“Of particular significance, efficacy here is based on patient-centered outcomes and psychological well-being as a primary effectiveness outcome, which could translate into strengthened physician-patient alliance.”

While adjunctive aripiprazole is not necessarily a first-line strategy when older adults fail to respond to antidepressants, there is a lack of data on the risks and benefits of any other antipsychotic medications, she noted.

“Thus, this is evidence that will impact clinical practice and hopefully contribute to reduced societal burden of depression in older adults and the morbidity and mortality associated with it,” Dr. Gatchel said. 

The study received support from a Patient-Centered Outcomes Research Institute (PCORI) Award (TRD-1511-33321). Dr. Lenze received additional support from the Taylor Family Institute for Innovative Psychiatric Research at Washington University School of Medicine, as well as the Washington University Institute of Clinical and Translational Sciences grant (UL1TR002345) from the National Center for Advancing Translational Sciences of the National Institutes of Health. Dr. Gatchel reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – For older patients with resistant depression who fail to respond to antidepressant treatment, the addition of the atypical antipsychotic aripiprazole (Abilify) is superior to switching antidepressants, new research suggests.

“We found that adding aripiprazole led to higher rates of depression remission and greater improvements in psychological well-being – which means how positive and satisfied patients felt – and this is good news,” study investigator Eric J. Lenze, MD, of the department of psychiatry, Washington University, St. Louis, said in a press statement.

“However, even that approach helped only about 30% of people in the study with treatment-resistant depression, underscoring the need to find and develop more effective treatments that can help more people,” he added.

The findings were presented here as part of the American Association for Geriatric Psychiatry annual meeting, and published concurrently in the New England Journal of Medicine.
 

Need for safe treatment options

Treatment-resistant depression is common in older patients, but switching medications or adding other agents can be challenging. With higher rates of comorbidity and polypharmacy, treatment decisions in this patient population are more complex compared with those involving younger patients.

To compare the benefits of augmentation vs. drug-switching strategies, the researchers conducted a multicenter, two-step trial involving 619 patients with an average baseline age of 69 who had failed to respond to two courses of selective serotonin reuptake inhibitors (SSRIs).

Patients were randomly assigned to one of three groups. These included augmentation of existing antidepressant medication with either aripiprazole (n = 211) or the dopamine and norepinephrine–reuptake inhibitor bupropion (Wellbutrin, Zyban) (n = 206), or to taper off of their current antidepressant and switch to bupropion (n = 202).

After 10 weeks, patients’ psychological well-being was assessed via the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales. The researchers found patients in the aripiprazole and bupropion add-on groups improved by 4.83 points and 4.33 points, respectively. The bupropion switch group had a change of 2.04 points.

The difference between the aripiprazole augmentation group and the switch to bupropion group was significant (difference 2.79 points; P = .014). Other between-group differences were not significantly different.

Remission rates were similar in the aripiprazole and bupropion groups at 28.9% and 28.2%, respectively. The remission rate in the bupropion switch group was 19.3%.

The study results showed patients who received adjunctive bupropion had the highest fall rate at 0.55 falls per patient, vs. 0.33 falls per patient in the aripiprazole group, suggesting that among the three treatment options, adjunctive aripiprazole may be the best choice because of its superior efficacy and lower fall risk.

A total of 248 patients enrolled in the study showed no improvement and were further randomly assigned to receive adjunctive lithium (n = 127) or switch from current therapy to nortriptyline (n = 121).

Well-being scores in the lithium group improved by 3.17 points and 2.18 points in the nortriptyline group. Remission occurred in 18.9% of patients in the lithium group and 21.5% in the nortriptyline group. Fall rates were similar among the two groups.

Overall, “this large, randomized study demonstrated that adding aripiprazole was a superior option for older adults with treatment-resistant depression,” Dr. Lenze told this news organization.

“Since neither lithium nor nortriptyline were promising against treatment-resistant depression in older adults, those medications are unlikely to be helpful in most cases,” he added.
 

Practice changing?

In an accompanying editorial, Gemma Lewis, PhD, and Glyn Lewis, PhD, division of psychiatry, University of College London, noted the findings “support aripiprazole augmentation as a strategy for treatment-resistant depression in older persons, largely because of the lower risk of falls than with bupropion augmentation.”

However, “in clinical practice, [it] would be important to tailor treatment in light of potential adverse effects and the preferences of the patient,” they added.

Akathisia, for instance, is a common side effect of aripiprazole, shown in one recent trial to affect 11% of the patients. In addition, weight gain, though typically lower than seen with other antipsychotics, is a consideration with aripiprazole. 

With respect to fall risk, they noted that bupropion was largely used in relatively high doses of 300 mg and 450 mg, despite some recent research showing little clinical benefit from increasing antidepressant doses above minimum recommendations.

“It is possible that smaller doses of bupropion than those used in the current trial would retain effectiveness while minimizing adverse effects such as falls,” the editorialists noted.

Commenting on the study, Jennifer R. Gatchel, MD, PhD, assistant psychiatrist at Massachusetts General Hospital/McLean Hospital and assistant professor of psychiatry at Harvard Medical School, Boston, said the findings have high clinical significance in the treatment of geriatric depression. 

“These results are of great impact for clinicians managing older adults with treatment-resistant depression. They provide some of the first evidence of safety and efficacy of augmentation with aripiprazole as a strategy in clinical management of older adults who fail to initially respond to treatment,” said Dr. Gatchel, who was not associated with this research.

“Of particular significance, efficacy here is based on patient-centered outcomes and psychological well-being as a primary effectiveness outcome, which could translate into strengthened physician-patient alliance.”

While adjunctive aripiprazole is not necessarily a first-line strategy when older adults fail to respond to antidepressants, there is a lack of data on the risks and benefits of any other antipsychotic medications, she noted.

“Thus, this is evidence that will impact clinical practice and hopefully contribute to reduced societal burden of depression in older adults and the morbidity and mortality associated with it,” Dr. Gatchel said. 

The study received support from a Patient-Centered Outcomes Research Institute (PCORI) Award (TRD-1511-33321). Dr. Lenze received additional support from the Taylor Family Institute for Innovative Psychiatric Research at Washington University School of Medicine, as well as the Washington University Institute of Clinical and Translational Sciences grant (UL1TR002345) from the National Center for Advancing Translational Sciences of the National Institutes of Health. Dr. Gatchel reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – For older patients with resistant depression who fail to respond to antidepressant treatment, the addition of the atypical antipsychotic aripiprazole (Abilify) is superior to switching antidepressants, new research suggests.

“We found that adding aripiprazole led to higher rates of depression remission and greater improvements in psychological well-being – which means how positive and satisfied patients felt – and this is good news,” study investigator Eric J. Lenze, MD, of the department of psychiatry, Washington University, St. Louis, said in a press statement.

“However, even that approach helped only about 30% of people in the study with treatment-resistant depression, underscoring the need to find and develop more effective treatments that can help more people,” he added.

The findings were presented here as part of the American Association for Geriatric Psychiatry annual meeting, and published concurrently in the New England Journal of Medicine.
 

Need for safe treatment options

Treatment-resistant depression is common in older patients, but switching medications or adding other agents can be challenging. With higher rates of comorbidity and polypharmacy, treatment decisions in this patient population are more complex compared with those involving younger patients.

To compare the benefits of augmentation vs. drug-switching strategies, the researchers conducted a multicenter, two-step trial involving 619 patients with an average baseline age of 69 who had failed to respond to two courses of selective serotonin reuptake inhibitors (SSRIs).

Patients were randomly assigned to one of three groups. These included augmentation of existing antidepressant medication with either aripiprazole (n = 211) or the dopamine and norepinephrine–reuptake inhibitor bupropion (Wellbutrin, Zyban) (n = 206), or to taper off of their current antidepressant and switch to bupropion (n = 202).

After 10 weeks, patients’ psychological well-being was assessed via the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales. The researchers found patients in the aripiprazole and bupropion add-on groups improved by 4.83 points and 4.33 points, respectively. The bupropion switch group had a change of 2.04 points.

The difference between the aripiprazole augmentation group and the switch to bupropion group was significant (difference 2.79 points; P = .014). Other between-group differences were not significantly different.

Remission rates were similar in the aripiprazole and bupropion groups at 28.9% and 28.2%, respectively. The remission rate in the bupropion switch group was 19.3%.

The study results showed patients who received adjunctive bupropion had the highest fall rate at 0.55 falls per patient, vs. 0.33 falls per patient in the aripiprazole group, suggesting that among the three treatment options, adjunctive aripiprazole may be the best choice because of its superior efficacy and lower fall risk.

A total of 248 patients enrolled in the study showed no improvement and were further randomly assigned to receive adjunctive lithium (n = 127) or switch from current therapy to nortriptyline (n = 121).

Well-being scores in the lithium group improved by 3.17 points and 2.18 points in the nortriptyline group. Remission occurred in 18.9% of patients in the lithium group and 21.5% in the nortriptyline group. Fall rates were similar among the two groups.

Overall, “this large, randomized study demonstrated that adding aripiprazole was a superior option for older adults with treatment-resistant depression,” Dr. Lenze told this news organization.

“Since neither lithium nor nortriptyline were promising against treatment-resistant depression in older adults, those medications are unlikely to be helpful in most cases,” he added.
 

Practice changing?

In an accompanying editorial, Gemma Lewis, PhD, and Glyn Lewis, PhD, division of psychiatry, University of College London, noted the findings “support aripiprazole augmentation as a strategy for treatment-resistant depression in older persons, largely because of the lower risk of falls than with bupropion augmentation.”

However, “in clinical practice, [it] would be important to tailor treatment in light of potential adverse effects and the preferences of the patient,” they added.

Akathisia, for instance, is a common side effect of aripiprazole, shown in one recent trial to affect 11% of the patients. In addition, weight gain, though typically lower than seen with other antipsychotics, is a consideration with aripiprazole. 

With respect to fall risk, they noted that bupropion was largely used in relatively high doses of 300 mg and 450 mg, despite some recent research showing little clinical benefit from increasing antidepressant doses above minimum recommendations.

“It is possible that smaller doses of bupropion than those used in the current trial would retain effectiveness while minimizing adverse effects such as falls,” the editorialists noted.

Commenting on the study, Jennifer R. Gatchel, MD, PhD, assistant psychiatrist at Massachusetts General Hospital/McLean Hospital and assistant professor of psychiatry at Harvard Medical School, Boston, said the findings have high clinical significance in the treatment of geriatric depression. 

“These results are of great impact for clinicians managing older adults with treatment-resistant depression. They provide some of the first evidence of safety and efficacy of augmentation with aripiprazole as a strategy in clinical management of older adults who fail to initially respond to treatment,” said Dr. Gatchel, who was not associated with this research.

“Of particular significance, efficacy here is based on patient-centered outcomes and psychological well-being as a primary effectiveness outcome, which could translate into strengthened physician-patient alliance.”

While adjunctive aripiprazole is not necessarily a first-line strategy when older adults fail to respond to antidepressants, there is a lack of data on the risks and benefits of any other antipsychotic medications, she noted.

“Thus, this is evidence that will impact clinical practice and hopefully contribute to reduced societal burden of depression in older adults and the morbidity and mortality associated with it,” Dr. Gatchel said. 

The study received support from a Patient-Centered Outcomes Research Institute (PCORI) Award (TRD-1511-33321). Dr. Lenze received additional support from the Taylor Family Institute for Innovative Psychiatric Research at Washington University School of Medicine, as well as the Washington University Institute of Clinical and Translational Sciences grant (UL1TR002345) from the National Center for Advancing Translational Sciences of the National Institutes of Health. Dr. Gatchel reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

One morning I stepped into the elevator in the lobby of the US Department of Veterans Affairs (VA) medical center where I work, holding a cup of coffee, joining another staffer, a middle-aged man, wearing a veteran’s pin on his employee badge. An older veteran slowly approached the elevator doors, shuffling with each step, and since he was at the front of the elevator, he cheerfully bellowed “Which floor?” as he offered to push the button for us.

“What’s on 12?” he asked in a jovial voice. I smiled. “Aging research,” referring to the Geriatrics Research Education and Clinical Center where I work.¹

“I definitely need that—I forgot where I’m going!” he joked, his fingers hovering over the elevator buttons.

As we reached his floor, the doors opened, he waved with a smile and unsteadily made his way out of the elevator and down the hall to his appointment. As the elevator doors closed behind him, the other staffer turned to me and said with a shrug, “That’ll be me one day,” as he got off at the next floor.

When I got off the elevator and walked toward my office, I reflected on the care that I as a geriatrician and we at the VA hope to provide to aging veterans, now and in the future: Age-Friendly care. Age-Friendly means the compassionate care that we want for those who have served our country, for our loved ones, and for ourselves as we age. Age-Friendly means person-centered, evidence-based care that as we grow older will help us to address challenges that may come with older age, such as falls, cognitive impairment, and polypharmacy. Too often the health care system remains focused on the chief concern or on a clinician’s specialty and may not focus on those important areas where we can potentially intervene to support aging veterans.

The VA has set a goal to become the largest Age-Friendly Health System (AFHS) in the country.² Led by the Institute for Healthcare Improvement and funded by the John A. Hartford Foundation, the Age-Friendly Health Systems Initiative aims to help clinicians and care settings “follow an essential set of evidence-based practices; cause no harm; and align with what matters to the older adult and their family caregivers.”³ An AFHS cares for older adults with attention to the 4Ms—What Matters, Mobility, Mentation, and Medications.⁴ Specifically, in an AFHS, older adults are asked what matters to them so we can align their health care with their goals; clinicians evaluate veterans for safe mobility and fall risk reduction, cognitive impairment and mood disorders, and identify and avoid high-risk medications.⁵ In an AFHS, the 4Ms are practiced as a set, reliably, across settings, so that there should be no wrong door or wrong floor for an older veteran to receive Age-Friendly care within the VA health care system.⁶

Too often our health care system and health professions education have left clinicians unprepared to care for older adults using an Age-Friendly framework; rather, we have been trained in problem-based or disease-based care that can miss the forest for the trees in an older adult living with multiple chronic conditions and/or frailty. We may focus on providing evidence-based care for individual medical conditions while neglecting the often practical interventions that can help an older person age in place by focusing on what matters, supporting safe mobility, addressing cognition and mood, and optimizing medications.¹⁸

The vision of the VA as the largest AFHS in America is urgently needed; nearly half of the veteran population is aged 65 ≥ years, compared with 16% of the general population.¹⁹ Building on the VA’s legacy of creativity and innovation in geriatrics, and the VA’s goal of being a high reliability organization, becoming an AFHS will ensure that for that older veteran stepping off that elevator there is no wrong floor, and no wrong door to receive the Age-Friendly care he deserves and that we all hope for as we age.^1,5,19,20

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Boston Healthcare System and the New England Geriatric Research Education and Clinical Center. 

One morning I stepped into the elevator in the lobby of the US Department of Veterans Affairs (VA) medical center where I work, holding a cup of coffee, joining another staffer, a middle-aged man, wearing a veteran’s pin on his employee badge. An older veteran slowly approached the elevator doors, shuffling with each step, and since he was at the front of the elevator, he cheerfully bellowed “Which floor?” as he offered to push the button for us.

“What’s on 12?” he asked in a jovial voice. I smiled. “Aging research,” referring to the Geriatrics Research Education and Clinical Center where I work.¹

“I definitely need that—I forgot where I’m going!” he joked, his fingers hovering over the elevator buttons.

As we reached his floor, the doors opened, he waved with a smile and unsteadily made his way out of the elevator and down the hall to his appointment. As the elevator doors closed behind him, the other staffer turned to me and said with a shrug, “That’ll be me one day,” as he got off at the next floor.

When I got off the elevator and walked toward my office, I reflected on the care that I as a geriatrician and we at the VA hope to provide to aging veterans, now and in the future: Age-Friendly care. Age-Friendly means the compassionate care that we want for those who have served our country, for our loved ones, and for ourselves as we age. Age-Friendly means person-centered, evidence-based care that as we grow older will help us to address challenges that may come with older age, such as falls, cognitive impairment, and polypharmacy. Too often the health care system remains focused on the chief concern or on a clinician’s specialty and may not focus on those important areas where we can potentially intervene to support aging veterans.

The VA has set a goal to become the largest Age-Friendly Health System (AFHS) in the country.² Led by the Institute for Healthcare Improvement and funded by the John A. Hartford Foundation, the Age-Friendly Health Systems Initiative aims to help clinicians and care settings “follow an essential set of evidence-based practices; cause no harm; and align with what matters to the older adult and their family caregivers.”³ An AFHS cares for older adults with attention to the 4Ms—What Matters, Mobility, Mentation, and Medications.⁴ Specifically, in an AFHS, older adults are asked what matters to them so we can align their health care with their goals; clinicians evaluate veterans for safe mobility and fall risk reduction, cognitive impairment and mood disorders, and identify and avoid high-risk medications.⁵ In an AFHS, the 4Ms are practiced as a set, reliably, across settings, so that there should be no wrong door or wrong floor for an older veteran to receive Age-Friendly care within the VA health care system.⁶

Too often our health care system and health professions education have left clinicians unprepared to care for older adults using an Age-Friendly framework; rather, we have been trained in problem-based or disease-based care that can miss the forest for the trees in an older adult living with multiple chronic conditions and/or frailty. We may focus on providing evidence-based care for individual medical conditions while neglecting the often practical interventions that can help an older person age in place by focusing on what matters, supporting safe mobility, addressing cognition and mood, and optimizing medications.¹⁸

The vision of the VA as the largest AFHS in America is urgently needed; nearly half of the veteran population is aged 65 ≥ years, compared with 16% of the general population.¹⁹ Building on the VA’s legacy of creativity and innovation in geriatrics, and the VA’s goal of being a high reliability organization, becoming an AFHS will ensure that for that older veteran stepping off that elevator there is no wrong floor, and no wrong door to receive the Age-Friendly care he deserves and that we all hope for as we age.^1,5,19,20

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Boston Healthcare System and the New England Geriatric Research Education and Clinical Center. 

One morning I stepped into the elevator in the lobby of the US Department of Veterans Affairs (VA) medical center where I work, holding a cup of coffee, joining another staffer, a middle-aged man, wearing a veteran’s pin on his employee badge. An older veteran slowly approached the elevator doors, shuffling with each step, and since he was at the front of the elevator, he cheerfully bellowed “Which floor?” as he offered to push the button for us.

“What’s on 12?” he asked in a jovial voice. I smiled. “Aging research,” referring to the Geriatrics Research Education and Clinical Center where I work.¹

“I definitely need that—I forgot where I’m going!” he joked, his fingers hovering over the elevator buttons.

As we reached his floor, the doors opened, he waved with a smile and unsteadily made his way out of the elevator and down the hall to his appointment. As the elevator doors closed behind him, the other staffer turned to me and said with a shrug, “That’ll be me one day,” as he got off at the next floor.

When I got off the elevator and walked toward my office, I reflected on the care that I as a geriatrician and we at the VA hope to provide to aging veterans, now and in the future: Age-Friendly care. Age-Friendly means the compassionate care that we want for those who have served our country, for our loved ones, and for ourselves as we age. Age-Friendly means person-centered, evidence-based care that as we grow older will help us to address challenges that may come with older age, such as falls, cognitive impairment, and polypharmacy. Too often the health care system remains focused on the chief concern or on a clinician’s specialty and may not focus on those important areas where we can potentially intervene to support aging veterans.

The VA has set a goal to become the largest Age-Friendly Health System (AFHS) in the country.² Led by the Institute for Healthcare Improvement and funded by the John A. Hartford Foundation, the Age-Friendly Health Systems Initiative aims to help clinicians and care settings “follow an essential set of evidence-based practices; cause no harm; and align with what matters to the older adult and their family caregivers.”³ An AFHS cares for older adults with attention to the 4Ms—What Matters, Mobility, Mentation, and Medications.⁴ Specifically, in an AFHS, older adults are asked what matters to them so we can align their health care with their goals; clinicians evaluate veterans for safe mobility and fall risk reduction, cognitive impairment and mood disorders, and identify and avoid high-risk medications.⁵ In an AFHS, the 4Ms are practiced as a set, reliably, across settings, so that there should be no wrong door or wrong floor for an older veteran to receive Age-Friendly care within the VA health care system.⁶

Too often our health care system and health professions education have left clinicians unprepared to care for older adults using an Age-Friendly framework; rather, we have been trained in problem-based or disease-based care that can miss the forest for the trees in an older adult living with multiple chronic conditions and/or frailty. We may focus on providing evidence-based care for individual medical conditions while neglecting the often practical interventions that can help an older person age in place by focusing on what matters, supporting safe mobility, addressing cognition and mood, and optimizing medications.¹⁸

The vision of the VA as the largest AFHS in America is urgently needed; nearly half of the veteran population is aged 65 ≥ years, compared with 16% of the general population.¹⁹ Building on the VA’s legacy of creativity and innovation in geriatrics, and the VA’s goal of being a high reliability organization, becoming an AFHS will ensure that for that older veteran stepping off that elevator there is no wrong floor, and no wrong door to receive the Age-Friendly care he deserves and that we all hope for as we age.^1,5,19,20

Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Boston Healthcare System and the New England Geriatric Research Education and Clinical Center. 

Practicing yoga was associated with improvements in several frailty markers in previously inactive older adults, a multistudy review finds.

“Up to 50% of adults aged 80 years or older are estimated to be frail, and the global prevalence is expected to rise given the aging of our population,” therefore more interventions are needed to help with frailty, corresponding author Julia Loewenthal, MD, said in an interview.

Yoga integrates across multiple body systems including the musculoskeletal system, nervous system, and others, said Dr. Loewenthal of Brigham and Women’s Hospital, Boston. Previous research has shown that yoga has a positive effect on cardiovascular risk factors, mood, and quality of life, but the effects of yoga on frailty have not been well studied.

“We wanted to evaluate whether [yoga] might help with frailty, since it touches on so many systems, as frailty does,” she noted.

In a systematic review published in Annals of Internal Medicine, the researchers identified 33 randomized, controlled trials of yoga-based interventions including 2,384 adults aged 65 years and older. The studies mainly involved Iyengar or chair-based yoga methods. The study population included community-dwelling seniors, nursing home residents, and individuals with chronic diseases.

The studies assessed the effect of a range of yoga practices on frailty markers including gait speed, handgrip strength, balance, lower extremity strength and endurance, and multicomponent measures of physical performance.

Overall, individuals who were randomized to engage in a yoga practice showed improved gait speed and lower extremity strength, compared with controls who were inactive or received an education intervention, with moderate-certainty evidence. The researchers also found low-certainty evidence in favor of yoga for improved balance and for a composite measure of physical function, and low-certainty evidence in favor of yoga for improved handgrip strength.

The findings were limited by several factors, mainly the heterogenous study designs, populations, and yoga styles, the researchers noted. Other limitations included the small sample sizes, variation in descriptions of the studies’ randomizations, and a lack of data on race and ethnicity of the participants.
 

Yoga’s role in healthy aging

“Overall, we were not surprised by the results since we have seen similar findings from other mind-body practices such as tai chi,” Dr. Loewenthal said in an interview. “We were surprised by the degree of improvement many of the participants had with gait speed.

“Yoga practices usually include a mix of poses in the standing, seated, and lying-down positions,” Dr. Loewenthal said. Some of the studies in the review also involved chair-based methods with few standing poses, and some involved gentle or slow-paced practices. “We know that many of the practices helped with leg strength, and perhaps they are also helping with coordination between the brain and body for walking.”

The findings suggest that clinicians can view yoga practice in general as part of a strategy to support healthy aging, Dr. Loewenthal said. “While our work looked at frailty markers and not overall frailty, I think it would be reasonable to offer yoga as a strategy along with already-established interventions such as resistance training and the Mediterranean diet, and if older adults are already practicing yoga, this could help them understand how the practice is impacting the aging process.”

There are many styles of yoga that overlap and are related to one another, so it is hard to make recommendations about a single type, said Dr. Loewenthal. Many of the studies in the review involved Iyengar yoga, named for yoga master B.K.S. Iyengar, which focuses on precise alignment and breath and seems to be conducive for older populations. Iyengar yoga also involves use of props such as blocks, bolsters, straps, and chairs, which makes it well suited for older individuals who may have a chronic condition or other limitations.

“Some styles of yoga are very physical and may reach energy expenditure and cardiovascular effects similar to aerobic exercise, but this is generally not the case for most styles of yoga,” she added.

As for additional research, “I think it is important that trials use a validated definition of frailty as an outcome; all of the trials in our study used markers of frailty but did not look at overall frailty,” said Dr. Loewenthal. In addition, it is important to understand how yoga affects people who have different levels of frailty, since previous research shows that those who are the most frail benefit most from physical activity interventions.
 

Yoga as an entry point for physical activity

With the increasing population of older adults in the United States and around the world, frailty is a major health concern because its association with significant declines in health and potential loss of independence, Amanda Paluch, PhD, said in an interview.

“Therefore, it is important to identify programs that can prevent frailty to support longevity and living independently for older adults. Yoga can be a feasible solution to promote movement and prevent frailty,” said Dr. Paluch, of the University of Massachusetts, Amherst, an assistant professor in the department of kinesiology and Institute for Applied Life Sciences.

“Other studies have demonstrated that light-intensity movement, as in yoga, may be particularly beneficial for older adults,” Dr. Paluch said. “Additionally, research has demonstrated that balance training activities are important to maintain physical function, prevent falls, and maintain their independence for older adults, so it makes sense that yoga was associated with lower likelihood of frailty.”

Although there may be additional benefits with higher intensity activity, “yoga could be a great place to start for older adults who are starting at low activity levels,” she said.

The takeaway for clinicians is to consider encouraging more physical activity for their patients to support healthy aging, including reducing the risk factors for frailty, said Dr. Paluch. “Particularly for older adults, physical activity may not need to be of high intensity for benefits. Activities such as yoga that focus on flexibility, balance, and movement at lower intensities can support healthy aging, and yoga may be a particularly good option for older adults who are least active.”

The study received no outside funding. The researchers and Dr. Paluch had no financial conflicts to disclose.

Practicing yoga was associated with improvements in several frailty markers in previously inactive older adults, a multistudy review finds.

“Up to 50% of adults aged 80 years or older are estimated to be frail, and the global prevalence is expected to rise given the aging of our population,” therefore more interventions are needed to help with frailty, corresponding author Julia Loewenthal, MD, said in an interview.

Yoga integrates across multiple body systems including the musculoskeletal system, nervous system, and others, said Dr. Loewenthal of Brigham and Women’s Hospital, Boston. Previous research has shown that yoga has a positive effect on cardiovascular risk factors, mood, and quality of life, but the effects of yoga on frailty have not been well studied.

“We wanted to evaluate whether [yoga] might help with frailty, since it touches on so many systems, as frailty does,” she noted.

In a systematic review published in Annals of Internal Medicine, the researchers identified 33 randomized, controlled trials of yoga-based interventions including 2,384 adults aged 65 years and older. The studies mainly involved Iyengar or chair-based yoga methods. The study population included community-dwelling seniors, nursing home residents, and individuals with chronic diseases.

The studies assessed the effect of a range of yoga practices on frailty markers including gait speed, handgrip strength, balance, lower extremity strength and endurance, and multicomponent measures of physical performance.

Overall, individuals who were randomized to engage in a yoga practice showed improved gait speed and lower extremity strength, compared with controls who were inactive or received an education intervention, with moderate-certainty evidence. The researchers also found low-certainty evidence in favor of yoga for improved balance and for a composite measure of physical function, and low-certainty evidence in favor of yoga for improved handgrip strength.

The findings were limited by several factors, mainly the heterogenous study designs, populations, and yoga styles, the researchers noted. Other limitations included the small sample sizes, variation in descriptions of the studies’ randomizations, and a lack of data on race and ethnicity of the participants.
 

Yoga’s role in healthy aging

“Overall, we were not surprised by the results since we have seen similar findings from other mind-body practices such as tai chi,” Dr. Loewenthal said in an interview. “We were surprised by the degree of improvement many of the participants had with gait speed.

“Yoga practices usually include a mix of poses in the standing, seated, and lying-down positions,” Dr. Loewenthal said. Some of the studies in the review also involved chair-based methods with few standing poses, and some involved gentle or slow-paced practices. “We know that many of the practices helped with leg strength, and perhaps they are also helping with coordination between the brain and body for walking.”

The findings suggest that clinicians can view yoga practice in general as part of a strategy to support healthy aging, Dr. Loewenthal said. “While our work looked at frailty markers and not overall frailty, I think it would be reasonable to offer yoga as a strategy along with already-established interventions such as resistance training and the Mediterranean diet, and if older adults are already practicing yoga, this could help them understand how the practice is impacting the aging process.”

There are many styles of yoga that overlap and are related to one another, so it is hard to make recommendations about a single type, said Dr. Loewenthal. Many of the studies in the review involved Iyengar yoga, named for yoga master B.K.S. Iyengar, which focuses on precise alignment and breath and seems to be conducive for older populations. Iyengar yoga also involves use of props such as blocks, bolsters, straps, and chairs, which makes it well suited for older individuals who may have a chronic condition or other limitations.

“Some styles of yoga are very physical and may reach energy expenditure and cardiovascular effects similar to aerobic exercise, but this is generally not the case for most styles of yoga,” she added.

As for additional research, “I think it is important that trials use a validated definition of frailty as an outcome; all of the trials in our study used markers of frailty but did not look at overall frailty,” said Dr. Loewenthal. In addition, it is important to understand how yoga affects people who have different levels of frailty, since previous research shows that those who are the most frail benefit most from physical activity interventions.
 

Yoga as an entry point for physical activity

With the increasing population of older adults in the United States and around the world, frailty is a major health concern because its association with significant declines in health and potential loss of independence, Amanda Paluch, PhD, said in an interview.

“Therefore, it is important to identify programs that can prevent frailty to support longevity and living independently for older adults. Yoga can be a feasible solution to promote movement and prevent frailty,” said Dr. Paluch, of the University of Massachusetts, Amherst, an assistant professor in the department of kinesiology and Institute for Applied Life Sciences.

“Other studies have demonstrated that light-intensity movement, as in yoga, may be particularly beneficial for older adults,” Dr. Paluch said. “Additionally, research has demonstrated that balance training activities are important to maintain physical function, prevent falls, and maintain their independence for older adults, so it makes sense that yoga was associated with lower likelihood of frailty.”

Although there may be additional benefits with higher intensity activity, “yoga could be a great place to start for older adults who are starting at low activity levels,” she said.

The takeaway for clinicians is to consider encouraging more physical activity for their patients to support healthy aging, including reducing the risk factors for frailty, said Dr. Paluch. “Particularly for older adults, physical activity may not need to be of high intensity for benefits. Activities such as yoga that focus on flexibility, balance, and movement at lower intensities can support healthy aging, and yoga may be a particularly good option for older adults who are least active.”

The study received no outside funding. The researchers and Dr. Paluch had no financial conflicts to disclose.

Practicing yoga was associated with improvements in several frailty markers in previously inactive older adults, a multistudy review finds.

“Up to 50% of adults aged 80 years or older are estimated to be frail, and the global prevalence is expected to rise given the aging of our population,” therefore more interventions are needed to help with frailty, corresponding author Julia Loewenthal, MD, said in an interview.

Yoga integrates across multiple body systems including the musculoskeletal system, nervous system, and others, said Dr. Loewenthal of Brigham and Women’s Hospital, Boston. Previous research has shown that yoga has a positive effect on cardiovascular risk factors, mood, and quality of life, but the effects of yoga on frailty have not been well studied.

“We wanted to evaluate whether [yoga] might help with frailty, since it touches on so many systems, as frailty does,” she noted.

In a systematic review published in Annals of Internal Medicine, the researchers identified 33 randomized, controlled trials of yoga-based interventions including 2,384 adults aged 65 years and older. The studies mainly involved Iyengar or chair-based yoga methods. The study population included community-dwelling seniors, nursing home residents, and individuals with chronic diseases.

The studies assessed the effect of a range of yoga practices on frailty markers including gait speed, handgrip strength, balance, lower extremity strength and endurance, and multicomponent measures of physical performance.

Overall, individuals who were randomized to engage in a yoga practice showed improved gait speed and lower extremity strength, compared with controls who were inactive or received an education intervention, with moderate-certainty evidence. The researchers also found low-certainty evidence in favor of yoga for improved balance and for a composite measure of physical function, and low-certainty evidence in favor of yoga for improved handgrip strength.

The findings were limited by several factors, mainly the heterogenous study designs, populations, and yoga styles, the researchers noted. Other limitations included the small sample sizes, variation in descriptions of the studies’ randomizations, and a lack of data on race and ethnicity of the participants.
 

Yoga’s role in healthy aging

“Overall, we were not surprised by the results since we have seen similar findings from other mind-body practices such as tai chi,” Dr. Loewenthal said in an interview. “We were surprised by the degree of improvement many of the participants had with gait speed.

“Yoga practices usually include a mix of poses in the standing, seated, and lying-down positions,” Dr. Loewenthal said. Some of the studies in the review also involved chair-based methods with few standing poses, and some involved gentle or slow-paced practices. “We know that many of the practices helped with leg strength, and perhaps they are also helping with coordination between the brain and body for walking.”

The findings suggest that clinicians can view yoga practice in general as part of a strategy to support healthy aging, Dr. Loewenthal said. “While our work looked at frailty markers and not overall frailty, I think it would be reasonable to offer yoga as a strategy along with already-established interventions such as resistance training and the Mediterranean diet, and if older adults are already practicing yoga, this could help them understand how the practice is impacting the aging process.”

There are many styles of yoga that overlap and are related to one another, so it is hard to make recommendations about a single type, said Dr. Loewenthal. Many of the studies in the review involved Iyengar yoga, named for yoga master B.K.S. Iyengar, which focuses on precise alignment and breath and seems to be conducive for older populations. Iyengar yoga also involves use of props such as blocks, bolsters, straps, and chairs, which makes it well suited for older individuals who may have a chronic condition or other limitations.

“Some styles of yoga are very physical and may reach energy expenditure and cardiovascular effects similar to aerobic exercise, but this is generally not the case for most styles of yoga,” she added.

As for additional research, “I think it is important that trials use a validated definition of frailty as an outcome; all of the trials in our study used markers of frailty but did not look at overall frailty,” said Dr. Loewenthal. In addition, it is important to understand how yoga affects people who have different levels of frailty, since previous research shows that those who are the most frail benefit most from physical activity interventions.
 

Yoga as an entry point for physical activity

With the increasing population of older adults in the United States and around the world, frailty is a major health concern because its association with significant declines in health and potential loss of independence, Amanda Paluch, PhD, said in an interview.

“Therefore, it is important to identify programs that can prevent frailty to support longevity and living independently for older adults. Yoga can be a feasible solution to promote movement and prevent frailty,” said Dr. Paluch, of the University of Massachusetts, Amherst, an assistant professor in the department of kinesiology and Institute for Applied Life Sciences.

“Other studies have demonstrated that light-intensity movement, as in yoga, may be particularly beneficial for older adults,” Dr. Paluch said. “Additionally, research has demonstrated that balance training activities are important to maintain physical function, prevent falls, and maintain their independence for older adults, so it makes sense that yoga was associated with lower likelihood of frailty.”

Although there may be additional benefits with higher intensity activity, “yoga could be a great place to start for older adults who are starting at low activity levels,” she said.

The takeaway for clinicians is to consider encouraging more physical activity for their patients to support healthy aging, including reducing the risk factors for frailty, said Dr. Paluch. “Particularly for older adults, physical activity may not need to be of high intensity for benefits. Activities such as yoga that focus on flexibility, balance, and movement at lower intensities can support healthy aging, and yoga may be a particularly good option for older adults who are least active.”

The study received no outside funding. The researchers and Dr. Paluch had no financial conflicts to disclose.

NEW ORLEANS - The antipsychotic brexpiprazole effectively improves agitation associated with Alzheimer’s disease (AD) with favorable tolerability, results of a phase 3 study suggest.

“In this phase 3 trial of patients with agitation in Alzheimer’s dementia, treatment with brexpiprazole 2 or 3 mg/day resulted in statistically significantly greater improvements in agitation versus placebo on the primary and key secondary endpoints,” said study investigator George Grossberg, MD, professor and director of the division of geriatric psychiatry, department of psychiatry & behavioral neuroscience, Saint Louis University.

Dr. Grossberg presented the findings as part of the annual meeting of the American Association for Geriatric Psychiatry.

Agitation common, distressing

With two previous studies also showing efficacy of brexpiprazole in AD-related agitation, Dr. Grossberg speculated that brexpiprazole will become the first drug to be approved for agitation in AD.

Agitation is one of the most common AD symptoms and is arguably the most distressing for patients and caregivers alike, Dr. Grossberg noted.

The drug was approved by the Food and Drug Administration in 2015 as an adjunctive therapy to antidepressants for adults with major depressive disorder and for adults with schizophrenia.

To investigate the drug at effective doses for AD-related agitation, the researchers conducted a phase 3 multicenter trial that included 345 patients with AD who met criteria for agitation and aggression.

Study participants had a mean Mini-Mental State Examination (MMSE) score between 5 and 22 at screening and baseline and a mean Cohen-Mansfield Agitation Inventory (CMAI) total score of about 79. A score above 45 is considered clinically significant agitation. Use of AD medications were permitted.

Patients had a mean age of 74 years and were randomly assigned in a 2:1 ratio to receive treatment with brexpiprazole 2 mg (n = 75) or 3 mg (n = 153) per day, or placebo (n = 117).

The study’s primary endpoint was improvement as assessed by the CMAI. Over 12 weeks, participants in the brexpiprazole group experienced greater improvement in agitation, with a mean change of –22.6 with brexpiprazole vs. –17.3 with placebo (P = .0026).

Brexpiprazole was also associated with significantly greater improvement in the secondary outcome of change from baseline to week 12 in agitation severity, as assessed using the Clinical Global Impression-Severity of Illness (CGI-S) score (mean change, –1.20 with brexpiprazole vs. –0.93 with placebo; P = .0078).

Specifically, treatment with the drug resulted in improvements in three key subscales of agitation, including aggressive behavior, such as physically striking out (P < .01 vs. placebo); physically nonaggressive; and verbally agitated, such as screaming or cursing (both P < .05).

Treatment-emergent adverse events (TEAEs) associated with brexpiprazole vs. placebo included somnolence (3.5% vs. 0.9%), nasopharyngitis (3.1% vs. 1.7%), dizziness (2.7% vs. 1.7%), diarrhea (2.2% vs. 0.9%), urinary tract infection (2.2% vs. 0.9%), and asthenia (2.2% vs. 0.0%).

“Aside from headache, no other TEAEs had an incidence of more than 5% in the brexpiprazole (2 or 3 mg) group, or in either dose group,” Dr. Grossberg said. “Cognition also remained stable,” he added.

Boxed warnings

Adverse events commonly associated with brexpiprazole include weight change, extrapyramidal events, falls, cardiovascular events, and sedation. In the study, all occurred at an incidence of less than 2% in both study groups, he noted.

Compared with the antipsychotic aripiprazole, brexpiprazole is associated with lower weight gain and akathisia, or motor restlessness.

One death occurred in the brexpiprazole 3 mg group in a patient who had heart failure, pneumonia, and cachexia. At autopsy, it was found the patient had cerebral and coronary atherosclerosis. The death was considered to be unrelated to brexpiprazole, said Dr. Grossberg.

This finding is notable because a caveat is that brexpiprazole, like aripiprazole and other typical and atypical antipsychotics, carries an FDA boxed warning related to an increased risk for death in older patients when used for dementia-related psychosis.

Noting that a black box warning about mortality risk is not a minor issue, Dr. Grossberg added that the risks are relatively low, whereas the risks associated with agitation in dementia can be high.

“If it’s an emergency situation, you have to treat the patient because otherwise they may harm someone else, or harm the staff, or harm their loved ones or themselves, and in those cases, we want to treat the patient first, get them under control, and then we worry about the black box,” he said.

In addition, “the No. 1 reason for getting kicked out of a nursing home is agitation or severe behaviors in the context of a dementia or a major neurocognitive disorder that the facility cannot control,” Dr. Grossberg added.

In such cases, patients may wind up in an emergency department and may not be welcome back at the nursing home.

“There’s always a risk/benefit ratio, and I have that discussion with patients and their families, but I can tell you that I’ve never had a family ask me not to use a medication because of the black box warning, because they see how miserable and how out of control their loved one is and they’re miserable because they see the suffering and will ask that we do anything that we can to get this behavior under control,” Dr. Grossberg said.

Caution still warranted

Commenting on the study, Rajesh R. Tampi, MD, professor and chairman of the department of psychiatry and the Bhatia Family Endowed Chair in Psychiatry at Creighton University, Omaha, Neb., underscored that, owing to the concerns behind the FDA warnings, “nonpharmacologic management is the cornerstone of treating agitation in Alzheimer’s dementia.”

He noted that the lack of an FDA-approved drug for agitation with AD is the result of “the overall benefits of any of the drug classes or drugs trialed to treat agitation in Alzheimer’s dementia vs. their adverse effect profile,” he said.

Therefore, he continued, “any medication or medication class should be used with caution among these individuals who often have polymorbidity.”

Dr. Tampi agreed that “the use of each drug for agitation in AD should be on a case-by-case basis with a clear and documented risk/benefit discussion with the patient and their families.”

“These medications should only be used for refractory symptoms or emergency situations where the agitation is not managed adequately with nonpharmacologic techniques and with a clear and documented risk/benefit discussion with patients and their families,” Dr. Tampi said. 

The study was supported by Otsuka Pharmaceutical Development & Commercialization and H. Lundbeck. Dr. Grossberg has received consulting fees from Acadia, Avanir, Biogen, BioXcel, Genentech, Karuna, Lundbeck, Otsuka, Roche, and Takeda. Dr. Tampi had no disclosures to report.

A version of this article first appeared on Medscape.com.

This article was updated 3/14/23.

NEW ORLEANS - The antipsychotic brexpiprazole effectively improves agitation associated with Alzheimer’s disease (AD) with favorable tolerability, results of a phase 3 study suggest.

“In this phase 3 trial of patients with agitation in Alzheimer’s dementia, treatment with brexpiprazole 2 or 3 mg/day resulted in statistically significantly greater improvements in agitation versus placebo on the primary and key secondary endpoints,” said study investigator George Grossberg, MD, professor and director of the division of geriatric psychiatry, department of psychiatry & behavioral neuroscience, Saint Louis University.

Dr. Grossberg presented the findings as part of the annual meeting of the American Association for Geriatric Psychiatry.

Agitation common, distressing

With two previous studies also showing efficacy of brexpiprazole in AD-related agitation, Dr. Grossberg speculated that brexpiprazole will become the first drug to be approved for agitation in AD.

Agitation is one of the most common AD symptoms and is arguably the most distressing for patients and caregivers alike, Dr. Grossberg noted.

The drug was approved by the Food and Drug Administration in 2015 as an adjunctive therapy to antidepressants for adults with major depressive disorder and for adults with schizophrenia.

To investigate the drug at effective doses for AD-related agitation, the researchers conducted a phase 3 multicenter trial that included 345 patients with AD who met criteria for agitation and aggression.

Study participants had a mean Mini-Mental State Examination (MMSE) score between 5 and 22 at screening and baseline and a mean Cohen-Mansfield Agitation Inventory (CMAI) total score of about 79. A score above 45 is considered clinically significant agitation. Use of AD medications were permitted.

Patients had a mean age of 74 years and were randomly assigned in a 2:1 ratio to receive treatment with brexpiprazole 2 mg (n = 75) or 3 mg (n = 153) per day, or placebo (n = 117).

The study’s primary endpoint was improvement as assessed by the CMAI. Over 12 weeks, participants in the brexpiprazole group experienced greater improvement in agitation, with a mean change of –22.6 with brexpiprazole vs. –17.3 with placebo (P = .0026).

Brexpiprazole was also associated with significantly greater improvement in the secondary outcome of change from baseline to week 12 in agitation severity, as assessed using the Clinical Global Impression-Severity of Illness (CGI-S) score (mean change, –1.20 with brexpiprazole vs. –0.93 with placebo; P = .0078).

Specifically, treatment with the drug resulted in improvements in three key subscales of agitation, including aggressive behavior, such as physically striking out (P < .01 vs. placebo); physically nonaggressive; and verbally agitated, such as screaming or cursing (both P < .05).

Treatment-emergent adverse events (TEAEs) associated with brexpiprazole vs. placebo included somnolence (3.5% vs. 0.9%), nasopharyngitis (3.1% vs. 1.7%), dizziness (2.7% vs. 1.7%), diarrhea (2.2% vs. 0.9%), urinary tract infection (2.2% vs. 0.9%), and asthenia (2.2% vs. 0.0%).

“Aside from headache, no other TEAEs had an incidence of more than 5% in the brexpiprazole (2 or 3 mg) group, or in either dose group,” Dr. Grossberg said. “Cognition also remained stable,” he added.

Boxed warnings

Adverse events commonly associated with brexpiprazole include weight change, extrapyramidal events, falls, cardiovascular events, and sedation. In the study, all occurred at an incidence of less than 2% in both study groups, he noted.

Compared with the antipsychotic aripiprazole, brexpiprazole is associated with lower weight gain and akathisia, or motor restlessness.

One death occurred in the brexpiprazole 3 mg group in a patient who had heart failure, pneumonia, and cachexia. At autopsy, it was found the patient had cerebral and coronary atherosclerosis. The death was considered to be unrelated to brexpiprazole, said Dr. Grossberg.

This finding is notable because a caveat is that brexpiprazole, like aripiprazole and other typical and atypical antipsychotics, carries an FDA boxed warning related to an increased risk for death in older patients when used for dementia-related psychosis.

Noting that a black box warning about mortality risk is not a minor issue, Dr. Grossberg added that the risks are relatively low, whereas the risks associated with agitation in dementia can be high.

“If it’s an emergency situation, you have to treat the patient because otherwise they may harm someone else, or harm the staff, or harm their loved ones or themselves, and in those cases, we want to treat the patient first, get them under control, and then we worry about the black box,” he said.

In addition, “the No. 1 reason for getting kicked out of a nursing home is agitation or severe behaviors in the context of a dementia or a major neurocognitive disorder that the facility cannot control,” Dr. Grossberg added.

In such cases, patients may wind up in an emergency department and may not be welcome back at the nursing home.

“There’s always a risk/benefit ratio, and I have that discussion with patients and their families, but I can tell you that I’ve never had a family ask me not to use a medication because of the black box warning, because they see how miserable and how out of control their loved one is and they’re miserable because they see the suffering and will ask that we do anything that we can to get this behavior under control,” Dr. Grossberg said.

Caution still warranted

Commenting on the study, Rajesh R. Tampi, MD, professor and chairman of the department of psychiatry and the Bhatia Family Endowed Chair in Psychiatry at Creighton University, Omaha, Neb., underscored that, owing to the concerns behind the FDA warnings, “nonpharmacologic management is the cornerstone of treating agitation in Alzheimer’s dementia.”

He noted that the lack of an FDA-approved drug for agitation with AD is the result of “the overall benefits of any of the drug classes or drugs trialed to treat agitation in Alzheimer’s dementia vs. their adverse effect profile,” he said.

Therefore, he continued, “any medication or medication class should be used with caution among these individuals who often have polymorbidity.”

Dr. Tampi agreed that “the use of each drug for agitation in AD should be on a case-by-case basis with a clear and documented risk/benefit discussion with the patient and their families.”

“These medications should only be used for refractory symptoms or emergency situations where the agitation is not managed adequately with nonpharmacologic techniques and with a clear and documented risk/benefit discussion with patients and their families,” Dr. Tampi said. 

The study was supported by Otsuka Pharmaceutical Development & Commercialization and H. Lundbeck. Dr. Grossberg has received consulting fees from Acadia, Avanir, Biogen, BioXcel, Genentech, Karuna, Lundbeck, Otsuka, Roche, and Takeda. Dr. Tampi had no disclosures to report.

A version of this article first appeared on Medscape.com.

This article was updated 3/14/23.

NEW ORLEANS - The antipsychotic brexpiprazole effectively improves agitation associated with Alzheimer’s disease (AD) with favorable tolerability, results of a phase 3 study suggest.

“In this phase 3 trial of patients with agitation in Alzheimer’s dementia, treatment with brexpiprazole 2 or 3 mg/day resulted in statistically significantly greater improvements in agitation versus placebo on the primary and key secondary endpoints,” said study investigator George Grossberg, MD, professor and director of the division of geriatric psychiatry, department of psychiatry & behavioral neuroscience, Saint Louis University.

Dr. Grossberg presented the findings as part of the annual meeting of the American Association for Geriatric Psychiatry.

Agitation common, distressing

With two previous studies also showing efficacy of brexpiprazole in AD-related agitation, Dr. Grossberg speculated that brexpiprazole will become the first drug to be approved for agitation in AD.

Agitation is one of the most common AD symptoms and is arguably the most distressing for patients and caregivers alike, Dr. Grossberg noted.

The drug was approved by the Food and Drug Administration in 2015 as an adjunctive therapy to antidepressants for adults with major depressive disorder and for adults with schizophrenia.

To investigate the drug at effective doses for AD-related agitation, the researchers conducted a phase 3 multicenter trial that included 345 patients with AD who met criteria for agitation and aggression.

Study participants had a mean Mini-Mental State Examination (MMSE) score between 5 and 22 at screening and baseline and a mean Cohen-Mansfield Agitation Inventory (CMAI) total score of about 79. A score above 45 is considered clinically significant agitation. Use of AD medications were permitted.

Patients had a mean age of 74 years and were randomly assigned in a 2:1 ratio to receive treatment with brexpiprazole 2 mg (n = 75) or 3 mg (n = 153) per day, or placebo (n = 117).

The study’s primary endpoint was improvement as assessed by the CMAI. Over 12 weeks, participants in the brexpiprazole group experienced greater improvement in agitation, with a mean change of –22.6 with brexpiprazole vs. –17.3 with placebo (P = .0026).

Brexpiprazole was also associated with significantly greater improvement in the secondary outcome of change from baseline to week 12 in agitation severity, as assessed using the Clinical Global Impression-Severity of Illness (CGI-S) score (mean change, –1.20 with brexpiprazole vs. –0.93 with placebo; P = .0078).

Specifically, treatment with the drug resulted in improvements in three key subscales of agitation, including aggressive behavior, such as physically striking out (P < .01 vs. placebo); physically nonaggressive; and verbally agitated, such as screaming or cursing (both P < .05).

Treatment-emergent adverse events (TEAEs) associated with brexpiprazole vs. placebo included somnolence (3.5% vs. 0.9%), nasopharyngitis (3.1% vs. 1.7%), dizziness (2.7% vs. 1.7%), diarrhea (2.2% vs. 0.9%), urinary tract infection (2.2% vs. 0.9%), and asthenia (2.2% vs. 0.0%).

“Aside from headache, no other TEAEs had an incidence of more than 5% in the brexpiprazole (2 or 3 mg) group, or in either dose group,” Dr. Grossberg said. “Cognition also remained stable,” he added.

Boxed warnings

Adverse events commonly associated with brexpiprazole include weight change, extrapyramidal events, falls, cardiovascular events, and sedation. In the study, all occurred at an incidence of less than 2% in both study groups, he noted.

Compared with the antipsychotic aripiprazole, brexpiprazole is associated with lower weight gain and akathisia, or motor restlessness.

One death occurred in the brexpiprazole 3 mg group in a patient who had heart failure, pneumonia, and cachexia. At autopsy, it was found the patient had cerebral and coronary atherosclerosis. The death was considered to be unrelated to brexpiprazole, said Dr. Grossberg.

This finding is notable because a caveat is that brexpiprazole, like aripiprazole and other typical and atypical antipsychotics, carries an FDA boxed warning related to an increased risk for death in older patients when used for dementia-related psychosis.

Noting that a black box warning about mortality risk is not a minor issue, Dr. Grossberg added that the risks are relatively low, whereas the risks associated with agitation in dementia can be high.

“If it’s an emergency situation, you have to treat the patient because otherwise they may harm someone else, or harm the staff, or harm their loved ones or themselves, and in those cases, we want to treat the patient first, get them under control, and then we worry about the black box,” he said.

In addition, “the No. 1 reason for getting kicked out of a nursing home is agitation or severe behaviors in the context of a dementia or a major neurocognitive disorder that the facility cannot control,” Dr. Grossberg added.

In such cases, patients may wind up in an emergency department and may not be welcome back at the nursing home.

“There’s always a risk/benefit ratio, and I have that discussion with patients and their families, but I can tell you that I’ve never had a family ask me not to use a medication because of the black box warning, because they see how miserable and how out of control their loved one is and they’re miserable because they see the suffering and will ask that we do anything that we can to get this behavior under control,” Dr. Grossberg said.

Caution still warranted

Commenting on the study, Rajesh R. Tampi, MD, professor and chairman of the department of psychiatry and the Bhatia Family Endowed Chair in Psychiatry at Creighton University, Omaha, Neb., underscored that, owing to the concerns behind the FDA warnings, “nonpharmacologic management is the cornerstone of treating agitation in Alzheimer’s dementia.”

He noted that the lack of an FDA-approved drug for agitation with AD is the result of “the overall benefits of any of the drug classes or drugs trialed to treat agitation in Alzheimer’s dementia vs. their adverse effect profile,” he said.

Therefore, he continued, “any medication or medication class should be used with caution among these individuals who often have polymorbidity.”

Dr. Tampi agreed that “the use of each drug for agitation in AD should be on a case-by-case basis with a clear and documented risk/benefit discussion with the patient and their families.”

“These medications should only be used for refractory symptoms or emergency situations where the agitation is not managed adequately with nonpharmacologic techniques and with a clear and documented risk/benefit discussion with patients and their families,” Dr. Tampi said. 

The study was supported by Otsuka Pharmaceutical Development & Commercialization and H. Lundbeck. Dr. Grossberg has received consulting fees from Acadia, Avanir, Biogen, BioXcel, Genentech, Karuna, Lundbeck, Otsuka, Roche, and Takeda. Dr. Tampi had no disclosures to report.

A version of this article first appeared on Medscape.com.

This article was updated 3/14/23.

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

A version of this article first appeared on Medscape.com.

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

A version of this article first appeared on Medscape.com.

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

A version of this article first appeared on Medscape.com.