Alzheimer's & Cognition

A first stroke in older adults is associated with substantial immediate and accelerated long-term cognitive decline, suggested a new study that underscores the need for continuous cognitive monitoring in this patient population.

Results from the study, which included 14 international cohorts of older adults, showed that stroke was associated with a significant acute decline in global cognition and a small, but significant, acceleration in the rate of cognitive decline over time.

Cognitive assessments in primary care are “crucial, especially since cognitive impairment is frequently missed or undiagnosed in hospitals,” lead author Jessica Lo, MSc, biostatistician and research associate with the Center for Healthy Brain Aging, University of New South Wales, Sydney, Australia, told this news organization.

She suggested clinicians incorporate long-term cognitive assessments into care plans, using more sensitive neuropsychological tests in primary care to detect early signs of cognitive impairment. “Early detection would enable timely interventions to improve outcomes,” Lo said.

She also noted that poststroke care typically includes physical rehabilitation but not cognitive rehabilitation, which many rehabilitation centers aren’t equipped to provide.

The study was published online in JAMA Network Open.
 

Mapping Cognitive Decline Trajectory

Cognitive impairment after stroke is common, but the trajectory of cognitive decline following a first stroke, relative to prestroke cognitive function, remains unclear.

The investigators leveraged data from 14 population-based cohort studies of 20,860 adults (mean age, 73 years; 59% women) to map the trajectory of cognitive function before and after a first stroke.

The primary outcome was global cognition, defined as the standardized average of four cognitive domains (language, memory, processing speed, and executive function).

During a mean follow-up of 7.5 years, 1041 (5%) adults (mean age, 79 years) experienced a first stroke, a mean of 4.5 years after study entry.

In adjusted analyses, stroke was associated with a significant acute decline of 0.25 SD in global cognition and a “small but significant” acceleration in the rate of decline of −0.038 SD per year, the authors reported.

Stroke was also associated with acute decline in all individual cognitive domains except for memory, with effect sizes ranging from −0.17 to −0.22 SD. Poststroke declines in Mini-Mental State Examination scores (−0.36 SD) were also noted.

In terms of cognitive trajectory, the rate of decline before stroke in survivors was similar to that seen in peers who didn’t have a stroke (−0.048 and −0.049 SD per year in global cognition, respectively).

The researchers did not identify any vascular risk factors moderating cognitive decline following a stroke, consistent with prior research. However, cognitive decline was significantly more rapid in individuals without stroke, regardless of any future stroke, who had a history of diabetes, hypertension, high cholesterol, cardiovascular disease, depression, smoking, or were APOE4 carriers.

“Targeting modifiable vascular risk factors at an early stage may reduce the risk of stroke but also subsequent risk of stroke-related cognitive decline and cognitive impairment,” the researchers noted.
 

A ‘Major Step’ in the Right Direction

As previously reported by this news organization, in 2023 the American Heart Association (AHA) issued a statement noting that screening for cognitive impairment should be part of multidisciplinary care for stroke survivors.

Commenting for this news organization, Mitchell Elkind, MD, MS, AHA chief clinical science officer, said these new data are consistent with current AHA guidelines and statements that “support screening for cognitive and functional decline in patients both acutely and over the long term after stroke.”

Elkind noted that the 2022 guideline for intracerebral hemorrhage states that cognitive screening should occur “across the continuum of inpatient care and at intervals in the outpatient setting” and provides recommendations for cognitive therapy.

“Our 2021 scientific statement on the primary care of patients after stroke also recommends screening for both depression and cognitive impairment over both the short- and long-term,” said Elkind, professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City.

“These documents recognize the fact that function and cognition can continue to decline years after stroke and that patients’ rehabilitation and support needs may therefore change over time after stroke,” Elkind added.

The authors of an accompanying commentary called it a “major step” in the right direction for the future of long-term stroke outcome assessment.

“As we develop new devices, indications, and time windows for stroke treatment, it may perhaps be wise to ensure trials steer away from simpler outcomes to more complex, granular ones,” wrote Yasmin Sadigh, MSc, and Victor Volovici, MD, PhD, with Erasmus University Medical Center, Rotterdam, the Netherlands.

The study had no commercial funding. The authors and commentary writers and Elkind have declared no conflicts of interest.

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

A first stroke in older adults is associated with substantial immediate and accelerated long-term cognitive decline, suggested a new study that underscores the need for continuous cognitive monitoring in this patient population.

Results from the study, which included 14 international cohorts of older adults, showed that stroke was associated with a significant acute decline in global cognition and a small, but significant, acceleration in the rate of cognitive decline over time.

Cognitive assessments in primary care are “crucial, especially since cognitive impairment is frequently missed or undiagnosed in hospitals,” lead author Jessica Lo, MSc, biostatistician and research associate with the Center for Healthy Brain Aging, University of New South Wales, Sydney, Australia, told this news organization.

She suggested clinicians incorporate long-term cognitive assessments into care plans, using more sensitive neuropsychological tests in primary care to detect early signs of cognitive impairment. “Early detection would enable timely interventions to improve outcomes,” Lo said.

She also noted that poststroke care typically includes physical rehabilitation but not cognitive rehabilitation, which many rehabilitation centers aren’t equipped to provide.

The study was published online in JAMA Network Open.
 

Mapping Cognitive Decline Trajectory

Cognitive impairment after stroke is common, but the trajectory of cognitive decline following a first stroke, relative to prestroke cognitive function, remains unclear.

The investigators leveraged data from 14 population-based cohort studies of 20,860 adults (mean age, 73 years; 59% women) to map the trajectory of cognitive function before and after a first stroke.

The primary outcome was global cognition, defined as the standardized average of four cognitive domains (language, memory, processing speed, and executive function).

During a mean follow-up of 7.5 years, 1041 (5%) adults (mean age, 79 years) experienced a first stroke, a mean of 4.5 years after study entry.

In adjusted analyses, stroke was associated with a significant acute decline of 0.25 SD in global cognition and a “small but significant” acceleration in the rate of decline of −0.038 SD per year, the authors reported.

Stroke was also associated with acute decline in all individual cognitive domains except for memory, with effect sizes ranging from −0.17 to −0.22 SD. Poststroke declines in Mini-Mental State Examination scores (−0.36 SD) were also noted.

In terms of cognitive trajectory, the rate of decline before stroke in survivors was similar to that seen in peers who didn’t have a stroke (−0.048 and −0.049 SD per year in global cognition, respectively).

The researchers did not identify any vascular risk factors moderating cognitive decline following a stroke, consistent with prior research. However, cognitive decline was significantly more rapid in individuals without stroke, regardless of any future stroke, who had a history of diabetes, hypertension, high cholesterol, cardiovascular disease, depression, smoking, or were APOE4 carriers.

“Targeting modifiable vascular risk factors at an early stage may reduce the risk of stroke but also subsequent risk of stroke-related cognitive decline and cognitive impairment,” the researchers noted.
 

A ‘Major Step’ in the Right Direction

As previously reported by this news organization, in 2023 the American Heart Association (AHA) issued a statement noting that screening for cognitive impairment should be part of multidisciplinary care for stroke survivors.

Commenting for this news organization, Mitchell Elkind, MD, MS, AHA chief clinical science officer, said these new data are consistent with current AHA guidelines and statements that “support screening for cognitive and functional decline in patients both acutely and over the long term after stroke.”

Elkind noted that the 2022 guideline for intracerebral hemorrhage states that cognitive screening should occur “across the continuum of inpatient care and at intervals in the outpatient setting” and provides recommendations for cognitive therapy.

“Our 2021 scientific statement on the primary care of patients after stroke also recommends screening for both depression and cognitive impairment over both the short- and long-term,” said Elkind, professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City.

“These documents recognize the fact that function and cognition can continue to decline years after stroke and that patients’ rehabilitation and support needs may therefore change over time after stroke,” Elkind added.

The authors of an accompanying commentary called it a “major step” in the right direction for the future of long-term stroke outcome assessment.

“As we develop new devices, indications, and time windows for stroke treatment, it may perhaps be wise to ensure trials steer away from simpler outcomes to more complex, granular ones,” wrote Yasmin Sadigh, MSc, and Victor Volovici, MD, PhD, with Erasmus University Medical Center, Rotterdam, the Netherlands.

The study had no commercial funding. The authors and commentary writers and Elkind have declared no conflicts of interest.

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

A first stroke in older adults is associated with substantial immediate and accelerated long-term cognitive decline, suggested a new study that underscores the need for continuous cognitive monitoring in this patient population.

Results from the study, which included 14 international cohorts of older adults, showed that stroke was associated with a significant acute decline in global cognition and a small, but significant, acceleration in the rate of cognitive decline over time.

Cognitive assessments in primary care are “crucial, especially since cognitive impairment is frequently missed or undiagnosed in hospitals,” lead author Jessica Lo, MSc, biostatistician and research associate with the Center for Healthy Brain Aging, University of New South Wales, Sydney, Australia, told this news organization.

She suggested clinicians incorporate long-term cognitive assessments into care plans, using more sensitive neuropsychological tests in primary care to detect early signs of cognitive impairment. “Early detection would enable timely interventions to improve outcomes,” Lo said.

She also noted that poststroke care typically includes physical rehabilitation but not cognitive rehabilitation, which many rehabilitation centers aren’t equipped to provide.

The study was published online in JAMA Network Open.
 

Mapping Cognitive Decline Trajectory

Cognitive impairment after stroke is common, but the trajectory of cognitive decline following a first stroke, relative to prestroke cognitive function, remains unclear.

The investigators leveraged data from 14 population-based cohort studies of 20,860 adults (mean age, 73 years; 59% women) to map the trajectory of cognitive function before and after a first stroke.

The primary outcome was global cognition, defined as the standardized average of four cognitive domains (language, memory, processing speed, and executive function).

During a mean follow-up of 7.5 years, 1041 (5%) adults (mean age, 79 years) experienced a first stroke, a mean of 4.5 years after study entry.

In adjusted analyses, stroke was associated with a significant acute decline of 0.25 SD in global cognition and a “small but significant” acceleration in the rate of decline of −0.038 SD per year, the authors reported.

Stroke was also associated with acute decline in all individual cognitive domains except for memory, with effect sizes ranging from −0.17 to −0.22 SD. Poststroke declines in Mini-Mental State Examination scores (−0.36 SD) were also noted.

In terms of cognitive trajectory, the rate of decline before stroke in survivors was similar to that seen in peers who didn’t have a stroke (−0.048 and −0.049 SD per year in global cognition, respectively).

The researchers did not identify any vascular risk factors moderating cognitive decline following a stroke, consistent with prior research. However, cognitive decline was significantly more rapid in individuals without stroke, regardless of any future stroke, who had a history of diabetes, hypertension, high cholesterol, cardiovascular disease, depression, smoking, or were APOE4 carriers.

“Targeting modifiable vascular risk factors at an early stage may reduce the risk of stroke but also subsequent risk of stroke-related cognitive decline and cognitive impairment,” the researchers noted.
 

A ‘Major Step’ in the Right Direction

As previously reported by this news organization, in 2023 the American Heart Association (AHA) issued a statement noting that screening for cognitive impairment should be part of multidisciplinary care for stroke survivors.

Commenting for this news organization, Mitchell Elkind, MD, MS, AHA chief clinical science officer, said these new data are consistent with current AHA guidelines and statements that “support screening for cognitive and functional decline in patients both acutely and over the long term after stroke.”

Elkind noted that the 2022 guideline for intracerebral hemorrhage states that cognitive screening should occur “across the continuum of inpatient care and at intervals in the outpatient setting” and provides recommendations for cognitive therapy.

“Our 2021 scientific statement on the primary care of patients after stroke also recommends screening for both depression and cognitive impairment over both the short- and long-term,” said Elkind, professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City.

“These documents recognize the fact that function and cognition can continue to decline years after stroke and that patients’ rehabilitation and support needs may therefore change over time after stroke,” Elkind added.

The authors of an accompanying commentary called it a “major step” in the right direction for the future of long-term stroke outcome assessment.

“As we develop new devices, indications, and time windows for stroke treatment, it may perhaps be wise to ensure trials steer away from simpler outcomes to more complex, granular ones,” wrote Yasmin Sadigh, MSc, and Victor Volovici, MD, PhD, with Erasmus University Medical Center, Rotterdam, the Netherlands.

The study had no commercial funding. The authors and commentary writers and Elkind have declared no conflicts of interest.

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

Getting drugs to the brain is difficult. The very thing designed to protect the brain’s environment — the blood-brain barrier (BBB) — is one of the main reasons diseases like Alzheimer’s are so hard to treat.

And even if a drug can cross the BBB, it’s difficult to ensure it reaches specific areas of the brain like the hippocampus, which is located deep within the brain and notoriously difficult to target with conventional drugs.

However, new research shows that novel bioengineered proteins can target neurons in the hippocampus. Using a mouse model, the researchers found that these proteins could be delivered to the hippocampus intranasally — through the nose via a spray.

“This is an urgent topic because many potential therapeutic agents do not readily cross the blood-brain barrier or have limited effects even after intranasal delivery,” said Konrad Talbot, PhD, professor of neurosurgery and pathology at Loma Linda University, Loma Linda, California, who was not involved in the study.

This is the first time a protein drug, which is larger than many drug molecules, has been specifically delivered to the hippocampus, said Noriyasu Kamei, PhD, a professor of pharmaceutical science at Kobe Gakuin University in Kobe, Japan, and lead author of the study.
 

How Did They Do It?

“Smuggle” may be a flip term, but it’s not inaccurate.

Insulin has the ability to cross the BBB, so the team began with insulin as the vehicle. By attaching other molecules to an insulin fragment, researchers theorized they could create an insulin fusion protein that can be transported across the BBB and into the brain via a process called macropinocytosis.

They executed this technique in mice by fusing florescent proteins to insulin. To treat Alzheimer’s or other diseases, they would want to fuse therapeutic molecules to the insulin for brain delivery — a future step for their research.

Other groups are studying a similar approach using transferrin receptor instead of insulin to shuttle molecules across the BBB. However, the transferrin receptor doesn’t make it to the hippocampus, Kamei said.

A benefit of their system, Kamei pointed out, is that because the method just requires a small piece of insulin to work, it’s straightforward to produce in bacteria. Importantly, he said, the insulin fusion protein should not affect blood glucose levels.
 

Why Insulin?

Aside from its ability to cross the BBB, the team thought to use insulin as the basis of a fusion protein because of their previous work.

“I found that insulin has the unique characteristics to be accumulated specifically in the hippocampal neuronal layers,” Kamei explained. That potential for accumulation is key, as they can deliver more of a drug that way.

In their past work, Kamei and colleagues also found that it could be delivered from the nose to the brain, indicating that it may be possible to use a simple nasal spray.

“The potential for noninvasive delivery of proteins by intranasal administration to the hippocampal neurons is novel,” said John Varghese, PhD, professor of neurology at University of California Los Angeles (he was not involved in the study). He noted that it’s also possible that this method could be harnessed to treat other brain diseases.

There are other drugs that treat central nervous system diseases, such as desmopressin and buserelin, which are available as nasal sprays. However, these drugs are synthetic hormones, and though relatively small molecules, they do not cross the BBB.

There are also antibody treatments for Alzheimer’s, such as aducanumab (which will soon be discontinued), lecanemab, and donanemab; however, they aren’t always effective and they require an intravenous infusion, and while they cross the BBB to a degree, to bolster delivery to the brain, studies have proposed additional methods like focused ultrasound.

“Neuronal uptake of drugs potentially therapeutic for Alzheimer’s may be significantly enhanced by fusion of those drugs with insulin. This should be a research priority,” said Talbot.

While this is exciting and has potential, such drugs won’t be available anytime soon. Kamei would like to complete the research at a basic level in 5 years, including testing insulin fused with larger proteins such as therapeutic antibodies. If all goes well, they’ll move on to testing insulin fusion drugs in people.
 

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

Getting drugs to the brain is difficult. The very thing designed to protect the brain’s environment — the blood-brain barrier (BBB) — is one of the main reasons diseases like Alzheimer’s are so hard to treat.

And even if a drug can cross the BBB, it’s difficult to ensure it reaches specific areas of the brain like the hippocampus, which is located deep within the brain and notoriously difficult to target with conventional drugs.

However, new research shows that novel bioengineered proteins can target neurons in the hippocampus. Using a mouse model, the researchers found that these proteins could be delivered to the hippocampus intranasally — through the nose via a spray.

“This is an urgent topic because many potential therapeutic agents do not readily cross the blood-brain barrier or have limited effects even after intranasal delivery,” said Konrad Talbot, PhD, professor of neurosurgery and pathology at Loma Linda University, Loma Linda, California, who was not involved in the study.

This is the first time a protein drug, which is larger than many drug molecules, has been specifically delivered to the hippocampus, said Noriyasu Kamei, PhD, a professor of pharmaceutical science at Kobe Gakuin University in Kobe, Japan, and lead author of the study.
 

How Did They Do It?

“Smuggle” may be a flip term, but it’s not inaccurate.

Insulin has the ability to cross the BBB, so the team began with insulin as the vehicle. By attaching other molecules to an insulin fragment, researchers theorized they could create an insulin fusion protein that can be transported across the BBB and into the brain via a process called macropinocytosis.

They executed this technique in mice by fusing florescent proteins to insulin. To treat Alzheimer’s or other diseases, they would want to fuse therapeutic molecules to the insulin for brain delivery — a future step for their research.

Other groups are studying a similar approach using transferrin receptor instead of insulin to shuttle molecules across the BBB. However, the transferrin receptor doesn’t make it to the hippocampus, Kamei said.

A benefit of their system, Kamei pointed out, is that because the method just requires a small piece of insulin to work, it’s straightforward to produce in bacteria. Importantly, he said, the insulin fusion protein should not affect blood glucose levels.
 

Why Insulin?

Aside from its ability to cross the BBB, the team thought to use insulin as the basis of a fusion protein because of their previous work.

“I found that insulin has the unique characteristics to be accumulated specifically in the hippocampal neuronal layers,” Kamei explained. That potential for accumulation is key, as they can deliver more of a drug that way.

In their past work, Kamei and colleagues also found that it could be delivered from the nose to the brain, indicating that it may be possible to use a simple nasal spray.

“The potential for noninvasive delivery of proteins by intranasal administration to the hippocampal neurons is novel,” said John Varghese, PhD, professor of neurology at University of California Los Angeles (he was not involved in the study). He noted that it’s also possible that this method could be harnessed to treat other brain diseases.

There are other drugs that treat central nervous system diseases, such as desmopressin and buserelin, which are available as nasal sprays. However, these drugs are synthetic hormones, and though relatively small molecules, they do not cross the BBB.

There are also antibody treatments for Alzheimer’s, such as aducanumab (which will soon be discontinued), lecanemab, and donanemab; however, they aren’t always effective and they require an intravenous infusion, and while they cross the BBB to a degree, to bolster delivery to the brain, studies have proposed additional methods like focused ultrasound.

“Neuronal uptake of drugs potentially therapeutic for Alzheimer’s may be significantly enhanced by fusion of those drugs with insulin. This should be a research priority,” said Talbot.

While this is exciting and has potential, such drugs won’t be available anytime soon. Kamei would like to complete the research at a basic level in 5 years, including testing insulin fused with larger proteins such as therapeutic antibodies. If all goes well, they’ll move on to testing insulin fusion drugs in people.
 

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

Getting drugs to the brain is difficult. The very thing designed to protect the brain’s environment — the blood-brain barrier (BBB) — is one of the main reasons diseases like Alzheimer’s are so hard to treat.

And even if a drug can cross the BBB, it’s difficult to ensure it reaches specific areas of the brain like the hippocampus, which is located deep within the brain and notoriously difficult to target with conventional drugs.

However, new research shows that novel bioengineered proteins can target neurons in the hippocampus. Using a mouse model, the researchers found that these proteins could be delivered to the hippocampus intranasally — through the nose via a spray.

“This is an urgent topic because many potential therapeutic agents do not readily cross the blood-brain barrier or have limited effects even after intranasal delivery,” said Konrad Talbot, PhD, professor of neurosurgery and pathology at Loma Linda University, Loma Linda, California, who was not involved in the study.

This is the first time a protein drug, which is larger than many drug molecules, has been specifically delivered to the hippocampus, said Noriyasu Kamei, PhD, a professor of pharmaceutical science at Kobe Gakuin University in Kobe, Japan, and lead author of the study.
 

How Did They Do It?

“Smuggle” may be a flip term, but it’s not inaccurate.

Insulin has the ability to cross the BBB, so the team began with insulin as the vehicle. By attaching other molecules to an insulin fragment, researchers theorized they could create an insulin fusion protein that can be transported across the BBB and into the brain via a process called macropinocytosis.

They executed this technique in mice by fusing florescent proteins to insulin. To treat Alzheimer’s or other diseases, they would want to fuse therapeutic molecules to the insulin for brain delivery — a future step for their research.

Other groups are studying a similar approach using transferrin receptor instead of insulin to shuttle molecules across the BBB. However, the transferrin receptor doesn’t make it to the hippocampus, Kamei said.

A benefit of their system, Kamei pointed out, is that because the method just requires a small piece of insulin to work, it’s straightforward to produce in bacteria. Importantly, he said, the insulin fusion protein should not affect blood glucose levels.
 

Why Insulin?

Aside from its ability to cross the BBB, the team thought to use insulin as the basis of a fusion protein because of their previous work.

“I found that insulin has the unique characteristics to be accumulated specifically in the hippocampal neuronal layers,” Kamei explained. That potential for accumulation is key, as they can deliver more of a drug that way.

In their past work, Kamei and colleagues also found that it could be delivered from the nose to the brain, indicating that it may be possible to use a simple nasal spray.

“The potential for noninvasive delivery of proteins by intranasal administration to the hippocampal neurons is novel,” said John Varghese, PhD, professor of neurology at University of California Los Angeles (he was not involved in the study). He noted that it’s also possible that this method could be harnessed to treat other brain diseases.

There are other drugs that treat central nervous system diseases, such as desmopressin and buserelin, which are available as nasal sprays. However, these drugs are synthetic hormones, and though relatively small molecules, they do not cross the BBB.

There are also antibody treatments for Alzheimer’s, such as aducanumab (which will soon be discontinued), lecanemab, and donanemab; however, they aren’t always effective and they require an intravenous infusion, and while they cross the BBB to a degree, to bolster delivery to the brain, studies have proposed additional methods like focused ultrasound.

“Neuronal uptake of drugs potentially therapeutic for Alzheimer’s may be significantly enhanced by fusion of those drugs with insulin. This should be a research priority,” said Talbot.

While this is exciting and has potential, such drugs won’t be available anytime soon. Kamei would like to complete the research at a basic level in 5 years, including testing insulin fused with larger proteins such as therapeutic antibodies. If all goes well, they’ll move on to testing insulin fusion drugs in people.
 

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

TOPLINE:

High levels of urinary cadmium are associated with double the risk for global cognitive impairment in White adults, a new study shows. There was no such association between the heavy metal and cognitive function in Black adults.

METHODOLOGY:

• Investigators reviewed data on 2172 adults (mean age, 64 years; 61% White; 39% Black; 55% women) from the ongoing REGARDS population-based prospective cohort study in the United States who were free of cognitive impairment or stroke at baseline.
• Global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment was assessed every 2 years using the Enhanced Cognitive Battery.
• Blood and urine samples were collected from the participants at baseline, and levels of urinary cadmium were assessed using a urinary creatinine-correction method.
• Covariates included participants’ age, sex, smoking pack-years, alcohol consumption, and education level.
• Mean follow-up was 10 years.

TAKEAWAY:

• Global cognitive impairment was observed in 195 cases and domain-based cognitive impairment in 53 cases.
• High levels of urinary cadmium were associated with double the risk of developing global cognitive impairment in White adults (odds ratio [OR], 2.07; 95% CI, 1.18-3.64).
• No association was observed between urinary cadmium and global cognitive impairment in the overall cohort or in Black adults.
• Median smoking pack-years — a significant source of cadmium exposure for the US population — was significantly higher in White participants than Black participants (P = .001 for the highest tertile of urinary cadmium concentration).

IN PRACTICE:

“These results need to be confirmed with studies that measure cadmium levels over time, include more people and follow people over a longer time, but there are many reasons to reduce exposure to cadmium, whether it’s through implementing policies and regulations for air pollution and drinking water or people changing their behaviors by stopping smoking or being around cigarette smoke,” lead author Liping Lu, MD, PhD, MS, Columbia University, New York City, said in a press release.

SOURCE:

The study was published online in Neurology.

LIMITATIONS:

Urinary cadmium levels were tested only at baseline, which may not have captured changes in exposure over time. A limited number of patients with cognitive impairment used the Enhanced Cognitive Battery. The study did not include occupational information, and the potential for residual confounding from smoking could not be completely excluded. The follow-up time may have been insufficient for observing a significant effect on cognition, and competing risks for mortality associated with cadmium exposure could also have affected the findings.

DISCLOSURES:

The study was co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health (NIH). Several authors were partially supported by the NIH. Detailed disclosures are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

High levels of urinary cadmium are associated with double the risk for global cognitive impairment in White adults, a new study shows. There was no such association between the heavy metal and cognitive function in Black adults.

METHODOLOGY:

• Investigators reviewed data on 2172 adults (mean age, 64 years; 61% White; 39% Black; 55% women) from the ongoing REGARDS population-based prospective cohort study in the United States who were free of cognitive impairment or stroke at baseline.
• Global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment was assessed every 2 years using the Enhanced Cognitive Battery.
• Blood and urine samples were collected from the participants at baseline, and levels of urinary cadmium were assessed using a urinary creatinine-correction method.
• Covariates included participants’ age, sex, smoking pack-years, alcohol consumption, and education level.
• Mean follow-up was 10 years.

TAKEAWAY:

• Global cognitive impairment was observed in 195 cases and domain-based cognitive impairment in 53 cases.
• High levels of urinary cadmium were associated with double the risk of developing global cognitive impairment in White adults (odds ratio [OR], 2.07; 95% CI, 1.18-3.64).
• No association was observed between urinary cadmium and global cognitive impairment in the overall cohort or in Black adults.
• Median smoking pack-years — a significant source of cadmium exposure for the US population — was significantly higher in White participants than Black participants (P = .001 for the highest tertile of urinary cadmium concentration).

IN PRACTICE:

“These results need to be confirmed with studies that measure cadmium levels over time, include more people and follow people over a longer time, but there are many reasons to reduce exposure to cadmium, whether it’s through implementing policies and regulations for air pollution and drinking water or people changing their behaviors by stopping smoking or being around cigarette smoke,” lead author Liping Lu, MD, PhD, MS, Columbia University, New York City, said in a press release.

SOURCE:

The study was published online in Neurology.

LIMITATIONS:

Urinary cadmium levels were tested only at baseline, which may not have captured changes in exposure over time. A limited number of patients with cognitive impairment used the Enhanced Cognitive Battery. The study did not include occupational information, and the potential for residual confounding from smoking could not be completely excluded. The follow-up time may have been insufficient for observing a significant effect on cognition, and competing risks for mortality associated with cadmium exposure could also have affected the findings.

DISCLOSURES:

The study was co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health (NIH). Several authors were partially supported by the NIH. Detailed disclosures are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

High levels of urinary cadmium are associated with double the risk for global cognitive impairment in White adults, a new study shows. There was no such association between the heavy metal and cognitive function in Black adults.

METHODOLOGY:

• Investigators reviewed data on 2172 adults (mean age, 64 years; 61% White; 39% Black; 55% women) from the ongoing REGARDS population-based prospective cohort study in the United States who were free of cognitive impairment or stroke at baseline.
• Global cognitive impairment was assessed annually using the Six-Item Screener, and domain-based cognitive impairment was assessed every 2 years using the Enhanced Cognitive Battery.
• Blood and urine samples were collected from the participants at baseline, and levels of urinary cadmium were assessed using a urinary creatinine-correction method.
• Covariates included participants’ age, sex, smoking pack-years, alcohol consumption, and education level.
• Mean follow-up was 10 years.

TAKEAWAY:

• Global cognitive impairment was observed in 195 cases and domain-based cognitive impairment in 53 cases.
• High levels of urinary cadmium were associated with double the risk of developing global cognitive impairment in White adults (odds ratio [OR], 2.07; 95% CI, 1.18-3.64).
• No association was observed between urinary cadmium and global cognitive impairment in the overall cohort or in Black adults.
• Median smoking pack-years — a significant source of cadmium exposure for the US population — was significantly higher in White participants than Black participants (P = .001 for the highest tertile of urinary cadmium concentration).

IN PRACTICE:

“These results need to be confirmed with studies that measure cadmium levels over time, include more people and follow people over a longer time, but there are many reasons to reduce exposure to cadmium, whether it’s through implementing policies and regulations for air pollution and drinking water or people changing their behaviors by stopping smoking or being around cigarette smoke,” lead author Liping Lu, MD, PhD, MS, Columbia University, New York City, said in a press release.

SOURCE:

The study was published online in Neurology.

LIMITATIONS:

Urinary cadmium levels were tested only at baseline, which may not have captured changes in exposure over time. A limited number of patients with cognitive impairment used the Enhanced Cognitive Battery. The study did not include occupational information, and the potential for residual confounding from smoking could not be completely excluded. The follow-up time may have been insufficient for observing a significant effect on cognition, and competing risks for mortality associated with cadmium exposure could also have affected the findings.

DISCLOSURES:

The study was co-funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health (NIH). Several authors were partially supported by the NIH. Detailed disclosures are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

DUBLIN – As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities. 

This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.

“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”

Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.

“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
 

The Case of Jay

Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”

Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently. 

During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings. 
 

Legal and Cultural Variations Across Europe

The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments. 

In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.

In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy. 

In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized. 

In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.

Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
 

Family Doctors, a Growing Responsibility

“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”

The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.

“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”

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

DUBLIN – As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities. 

This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.

“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”

Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.

“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
 

The Case of Jay

Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”

Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently. 

During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings. 
 

Legal and Cultural Variations Across Europe

The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments. 

In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.

In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy. 

In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized. 

In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.

Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
 

Family Doctors, a Growing Responsibility

“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”

The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.

“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”

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

DUBLIN – As healthcare systems across Europe deal with an increasing prevalence of cognitive impairment, family doctors are emerging as key players in assessing and supporting patients’ decision-making capacities. 

This was a central theme at the 29th WONCA Europe Conference, where the European Young Family Doctors Movement (EYFDM) presented insights from a project conducted across Europe, involving young general practitioners who participated in workshops held in multiple countries.

“Family doctors are the linchpin in these decisions,” said Alina Zidaru, MD, from the Irish College of Physicians, Dublin. “They understand the patient’s history, build long-term relationships, and are best positioned to ensure that decisions reflect the patient’s values, not just what the law or the family might say.”

Dr. Zidaru and her colleague, Nick Mamo, MD, member of EYFDM in Glasgow, Scotland, emphasized the central role family doctors play in ensuring that patient rights and preferences are respected, regardless of their cognitive state. They are often the first to identify cognitive impairments and must carefully navigate the legal and ethical landscape of decision-making support.

“Often, we focus too much on avoiding harm and overlook the principle of autonomy,” said Dr. Mamo. “But it’s essential to give patients the right to make their own decisions, even when those decisions might seem unwise to us.”
 

The Case of Jay

Dr. Zidaru said: “We’ve conducted workshops in Brussels, Vienna, and Sydney, focusing on how to build habits that support patients. We presented real-life cases, like Jay, a 43-year-old man with trisomy and a moderate intellectual disability who must decide whether to undergo surgery for a hernia. The most significant challenge was ensuring continuity of care and respecting his autonomy, despite cognitive limitations.”

Jay’s case illustrates the complex ethical dilemmas faced by family doctors when balancing autonomy with patient safety. In many cases, cognitive impairments raise concerns about whether a patient can make decisions independently. 

During the session, the audience was asked to share their thoughts on the case and to indicate whether they would allow Jay to make his own decision, and if they felt confident in assessing his cognitive capacity. The responses revealed a range of mixed feelings. 
 

Legal and Cultural Variations Across Europe

The session also explored how different European countries approach decision-making for cognitively impaired individuals. A clear divide exists between nations that give family members automatic decision-making rights and those that require legal appointments. 

In the United Kingdom, the Mental Capacity Act 2005 presumes capacity unless proven otherwise. Family doctors can assess patients’ decision-making abilities using any validated tool they find suitable. They should also aim to ensure that decisions are made in the patient’s best interests if they lack capacity. Family members only have legal authority if appointed through formal means, such as a lasting power of attorney.

In Spain and Italy, functional assessments are performed when patients retain decision-making authority in areas where they demonstrate competence. Legal guardianship can be appointed by the courts, sometimes limited to specific areas, but it is intended to support rather than replace the patient’s autonomy. 

In France and Portugal, guardianship may be implemented in specific domains, but the patient’s ability to participate in decisions is always prioritized. 

In Turkey, according to Turkish general practitioners in the audience, the courts and close family members often share the decision-making responsibility.

Dr. Zidaru added that Ireland’s Assisted Decision-Making (Capacity) Act 2015 introduced significant changes to how cognitive impairment is managed there. “Ireland adopted a standardized functional test of capacity, used by any doctor. A person can still make decisions as long as they understand, retain, and weigh the information needed to make that choice. If their capacity diminishes, a decision-making assistant, co–decision-maker, or representative can be appointed, but the patient’s will and preferences always come first.”
 

Family Doctors, a Growing Responsibility

“It’s not just about the legal framework: it’s about cultural awareness and early communication,” added Dr. Mamo. “We have to ask ourselves: Do patients have the right to make bad decisions? And how do we, as family doctors, respect that while still ensuring their safety?”

The session concluded with a discussion on how the role of family doctors in decision-making for cognitively impaired patients will evolve as populations age and the incidence of conditions like dementia increases. The workload is rising, and the need for clear, consistent guidelines is critical.

“Family doctors will continue to play a central role in managing these challenges,” Dr. Zidaru emphasized. “But we need more resources, more education, and more support to ensure we can respect patient autonomy without compromising their well-being.”

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

Alzheimer’s disease (AD), the most common cause of dementia, is the fifth leading cause of death in the United States. An estimated 6.9 million Americans aged 65 years or older have AD. Comorbid conditions in AD may exacerbate the progression of dementia and negatively affect overall health.

Although the exact mechanisms remain unclear, systemic inflammation is thought to play a significant role in the development of many common comorbidities associated with AD. Among the most frequently observed comorbid conditions are hypertension, diabetes, and depression. The presence of these comorbidities affects the treatment and management of AD, underscoring the need to understand the mechanisms of their interrelationship and develop effective management strategies. 
 

Hypertension 

Hypertension is a well-established risk factor for numerous health conditions, including AD. A comprehensive review of five meta-analyses and 52 primary studies revealed that elevated systolic blood pressure (SBP) correlates with an 11 % increased risk of developing AD, raising the question of whether early intervention and control of blood pressure would mitigate the risk for AD later in life. 

Findings from the Northern Manhattan Study suggest that although elevated SBP contributes to cognitive decline in older patients, the use of antihypertensive medications can neutralize the effects of high SBP on certain cognitive functions. Furthermore, a systematic review and meta-analysis comprising 12 trials (92,135 participants) demonstrated a significant reduction in the risk for dementia and cognitive impairment with antihypertensive treatment.

Notably, a retrospective cohort study involving 69,081 participants treated with beta-blockers for hypertension found that beta-blockers with high blood-brain barrier permeability were associated with a reduced risk for AD compared with those with low blood-brain barrier permeability. Additionally, a secondary analysis of the SPRINT trial found antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors were associated with a lower incidence of cognitive impairment. Although further clinical trials are necessary to directly assess specific medications, these findings emphasize the potential of antihypertensive treatment as a strategic approach to reduce the risk for AD.
 

Type 2 Diabetes 

The connection between AD and type 2 diabetes is such that AD is sometimes referred to as “type 3 diabetes.” Both diseases share some of the same underlying pathophysiologic mechanisms, particularly the development of insulin resistance and oxidative stress. A prospective cohort study of 10,095 participants showed that diabetes was significantly associated with a higher risk of developing dementia; this risk is even greater in patients who develop diabetes at an earlier age.

In an interview with this news organization, Alvaro Pascual-Leone, MD, PhD, a professor of neurology at Harvard Medical School, Boston, said, “In addition to being a comorbidity factor, diabetes appears to be a predisposing risk factor for AD.” This is supported by a comprehensive literature review showing an increased progression from mild cognitive impairment (MCI) to dementia in patients with diabetes, prediabetes, or metabolic syndrome, with a pooled odds ratio for dementia progression in individuals with diabetes of 1.53.

Owing to the overlapping pathophysiologic mechanisms in AD and diabetes, treating one condition may have beneficial effects on the other. A systematic umbrella review and meta-analysis that included 10 meta-analyses across nine classes of diabetes drugs found a protective effect against dementia with the use of metformin, thiazolidinediones (including pioglitazone), glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Moreover, a cohort study of 12,220 patients who discontinued metformin early (ie, stopped using metformin without a prior history of abnormal kidney function) and 29,126 patients considered routine users found an increased risk for dementia in the early terminator group. Although further research is warranted, the concurrent treatment of AD and diabetes with antidiabetic agents holds considerable promise.
 

Depression and Anxiety

Anxiety and depression are significant risk factors for AD, and conversely, AD increases the likelihood of developing these psychiatric conditions. A systematic review of 14,760 studies showed dysthymia often emerges during the early stages of AD as an emotional response to cognitive decline. 

Data from the Australian Imaging Biomarkers and Lifestyle study showed a markedly elevated risk for AD and MCI among individuals with preexisting anxiety or depression. This study also found that age, sex, and marital status are important determinants, with men and single individuals with depression being particularly susceptible to developing AD. Conversely, a cohort study of 129,410 AD patients with AD, 390,088 patients with all-cause dementia, and 3,900,880 age-matched controls without a history of depression showed a cumulative incidence of depression of 13% in the AD group vs 3% in the control group, suggesting a heightened risk for depression following an AD diagnosis. 

These findings underscore the importance of targeted screening and assessment for patients with anxiety and depression who may be at risk for AD or those diagnosed with AD who are at risk for subsequent depression and anxiety. Although antidepressants are effective in treating depression in general, their efficacy in AD-related depression is of variable quality, probably owing to differing pathophysiologic mechanisms of the disease. Further research is necessary to explore both pharmacologic and nonpharmacologic interventions for treating depression in AD patients. Some studies have found that cognitive behavioral-therapy can be effective in improving depression in patients with AD.
 

Sleep Disorders

Research has shown a strong correlation between AD and sleep disorders, particularly obstructive sleep apnea, insomnia, and circadian rhythm disruptions. Additionally, studies suggest that insomnia and sleep deprivation contribute to increased amyloid beta production and tau pathology, hallmark features of AD. A scoping review of 70 studies proposed that this relationship is mediated by the glymphatic system (glial-dependent waste clearance pathway in the central nervous system), and that sleep deprivation disrupts its function, leading to protein accumulation and subsequent neurologic symptoms of AD. Another study showed that sleep deprivation triggers glial cell activation, initiating an inflammatory cascade that accelerates AD progression.

Given that the gold standard treatment for obstructive sleep apnea is continuous positive airway pressure (CPAP), it has been hypothesized that CPAP could also alleviate AD symptoms owing to shared pathophysiologic mechanisms of these conditions. A large systemic review found that CPAP use improved AD symptoms in patients with mild AD or MCI, though other sleep interventions, such as cognitive-behavioral therapy and melatonin supplementation, have yielded mixed outcomes. However, most studies in this area are small in scale, and there remains a paucity of research on treating sleep disorders in AD patients, indicating a need for further investigation.
 

Musculoskeletal Disorders

Although no direct causative link has been established, research indicates an association between osteoarthritis (OA) and dementia, likely because of similar pathophysiologic mechanisms, including systemic inflammation. Longitudinal analyses of data from the Alzheimer’s Disease Neuroimaging Initiative study found cognitively normal older individuals with OA experience more rapid declines in hippocampal volumes compared to those without OA, suggesting that OA may elevate the risk of cognitive impairment. Current treatments for OA, such as nonsteroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying OA drugs, might also help alleviate AD symptoms related to inflammation, though the research in this area is limited.

AD has also been linked to osteoporosis. In a longitudinal follow-up study involving 78,994 patients with osteoporosis and 78,994 controls, AD developed in 5856 patients with osteoporosis compared with 3761 patients in the control group. These findings represent a 1.27-fold higher incidence of AD in patients with osteoporosis than in the control group, suggesting that osteoporosis might be a risk factor for AD.

Additionally, research has identified a relationship between AD and increased fracture risk and decreased bone mineral density, with AD patients exhibiting a significantly higher likelihood of bone fractures compared with those without AD. “Falls and fractures, aside from the risk they pose in all geriatric patients, in individuals with cognitive impairment — whether due to AD or another cause — have higher risk to cause delirium and that can result in greater morbidity and mortality and a lasting increase in cognitive disability,” stated Dr. Pascual-Leone. Current recommendations emphasize exercise and fall prevention strategies to reduce fracture risk in patients with AD, but there is a lack of comprehensive research on the safety and efficacy of osteoporosis medications in this population.
 

Implications for Clinical Practice

The intricate interplay between AD and its comorbidities highlights the need for a comprehensive and integrated approach to patient care. The overlapping pathophysiologic mechanisms suggest that these comorbidities can contribute to the evolution and progression of AD. Likewise, AD can exacerbate comorbid conditions. As such, a holistic assessment strategy that prioritizes early detection and management of comorbid conditions to mitigate their impact on AD progression would be beneficial. Dr. Pascual-Leone added, “The presence of any of these comorbidities suggests a need to screen for MCI earlier than might otherwise be indicated or as part of the treatment for the comorbid condition. In many cases, patients can make lifestyle modifications that improve not only the comorbid condition but also reduce its effect on dementia.” In doing so, healthcare providers can help improve patient outcomes and enhance the overall quality of life for individuals living with AD.

Alissa Hershberger, Professor of Nursing, University of Central Missouri, Lee’s Summit, Missouri, has disclosed no relevant financial relationships.

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

Alzheimer’s disease (AD), the most common cause of dementia, is the fifth leading cause of death in the United States. An estimated 6.9 million Americans aged 65 years or older have AD. Comorbid conditions in AD may exacerbate the progression of dementia and negatively affect overall health.

Although the exact mechanisms remain unclear, systemic inflammation is thought to play a significant role in the development of many common comorbidities associated with AD. Among the most frequently observed comorbid conditions are hypertension, diabetes, and depression. The presence of these comorbidities affects the treatment and management of AD, underscoring the need to understand the mechanisms of their interrelationship and develop effective management strategies. 
 

Hypertension 

Hypertension is a well-established risk factor for numerous health conditions, including AD. A comprehensive review of five meta-analyses and 52 primary studies revealed that elevated systolic blood pressure (SBP) correlates with an 11 % increased risk of developing AD, raising the question of whether early intervention and control of blood pressure would mitigate the risk for AD later in life. 

Findings from the Northern Manhattan Study suggest that although elevated SBP contributes to cognitive decline in older patients, the use of antihypertensive medications can neutralize the effects of high SBP on certain cognitive functions. Furthermore, a systematic review and meta-analysis comprising 12 trials (92,135 participants) demonstrated a significant reduction in the risk for dementia and cognitive impairment with antihypertensive treatment.

Notably, a retrospective cohort study involving 69,081 participants treated with beta-blockers for hypertension found that beta-blockers with high blood-brain barrier permeability were associated with a reduced risk for AD compared with those with low blood-brain barrier permeability. Additionally, a secondary analysis of the SPRINT trial found antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors were associated with a lower incidence of cognitive impairment. Although further clinical trials are necessary to directly assess specific medications, these findings emphasize the potential of antihypertensive treatment as a strategic approach to reduce the risk for AD.
 

Type 2 Diabetes 

The connection between AD and type 2 diabetes is such that AD is sometimes referred to as “type 3 diabetes.” Both diseases share some of the same underlying pathophysiologic mechanisms, particularly the development of insulin resistance and oxidative stress. A prospective cohort study of 10,095 participants showed that diabetes was significantly associated with a higher risk of developing dementia; this risk is even greater in patients who develop diabetes at an earlier age.

In an interview with this news organization, Alvaro Pascual-Leone, MD, PhD, a professor of neurology at Harvard Medical School, Boston, said, “In addition to being a comorbidity factor, diabetes appears to be a predisposing risk factor for AD.” This is supported by a comprehensive literature review showing an increased progression from mild cognitive impairment (MCI) to dementia in patients with diabetes, prediabetes, or metabolic syndrome, with a pooled odds ratio for dementia progression in individuals with diabetes of 1.53.

Owing to the overlapping pathophysiologic mechanisms in AD and diabetes, treating one condition may have beneficial effects on the other. A systematic umbrella review and meta-analysis that included 10 meta-analyses across nine classes of diabetes drugs found a protective effect against dementia with the use of metformin, thiazolidinediones (including pioglitazone), glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Moreover, a cohort study of 12,220 patients who discontinued metformin early (ie, stopped using metformin without a prior history of abnormal kidney function) and 29,126 patients considered routine users found an increased risk for dementia in the early terminator group. Although further research is warranted, the concurrent treatment of AD and diabetes with antidiabetic agents holds considerable promise.
 

Depression and Anxiety

Anxiety and depression are significant risk factors for AD, and conversely, AD increases the likelihood of developing these psychiatric conditions. A systematic review of 14,760 studies showed dysthymia often emerges during the early stages of AD as an emotional response to cognitive decline. 

Data from the Australian Imaging Biomarkers and Lifestyle study showed a markedly elevated risk for AD and MCI among individuals with preexisting anxiety or depression. This study also found that age, sex, and marital status are important determinants, with men and single individuals with depression being particularly susceptible to developing AD. Conversely, a cohort study of 129,410 AD patients with AD, 390,088 patients with all-cause dementia, and 3,900,880 age-matched controls without a history of depression showed a cumulative incidence of depression of 13% in the AD group vs 3% in the control group, suggesting a heightened risk for depression following an AD diagnosis. 

These findings underscore the importance of targeted screening and assessment for patients with anxiety and depression who may be at risk for AD or those diagnosed with AD who are at risk for subsequent depression and anxiety. Although antidepressants are effective in treating depression in general, their efficacy in AD-related depression is of variable quality, probably owing to differing pathophysiologic mechanisms of the disease. Further research is necessary to explore both pharmacologic and nonpharmacologic interventions for treating depression in AD patients. Some studies have found that cognitive behavioral-therapy can be effective in improving depression in patients with AD.
 

Sleep Disorders

Research has shown a strong correlation between AD and sleep disorders, particularly obstructive sleep apnea, insomnia, and circadian rhythm disruptions. Additionally, studies suggest that insomnia and sleep deprivation contribute to increased amyloid beta production and tau pathology, hallmark features of AD. A scoping review of 70 studies proposed that this relationship is mediated by the glymphatic system (glial-dependent waste clearance pathway in the central nervous system), and that sleep deprivation disrupts its function, leading to protein accumulation and subsequent neurologic symptoms of AD. Another study showed that sleep deprivation triggers glial cell activation, initiating an inflammatory cascade that accelerates AD progression.

Given that the gold standard treatment for obstructive sleep apnea is continuous positive airway pressure (CPAP), it has been hypothesized that CPAP could also alleviate AD symptoms owing to shared pathophysiologic mechanisms of these conditions. A large systemic review found that CPAP use improved AD symptoms in patients with mild AD or MCI, though other sleep interventions, such as cognitive-behavioral therapy and melatonin supplementation, have yielded mixed outcomes. However, most studies in this area are small in scale, and there remains a paucity of research on treating sleep disorders in AD patients, indicating a need for further investigation.
 

Musculoskeletal Disorders

Although no direct causative link has been established, research indicates an association between osteoarthritis (OA) and dementia, likely because of similar pathophysiologic mechanisms, including systemic inflammation. Longitudinal analyses of data from the Alzheimer’s Disease Neuroimaging Initiative study found cognitively normal older individuals with OA experience more rapid declines in hippocampal volumes compared to those without OA, suggesting that OA may elevate the risk of cognitive impairment. Current treatments for OA, such as nonsteroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying OA drugs, might also help alleviate AD symptoms related to inflammation, though the research in this area is limited.

AD has also been linked to osteoporosis. In a longitudinal follow-up study involving 78,994 patients with osteoporosis and 78,994 controls, AD developed in 5856 patients with osteoporosis compared with 3761 patients in the control group. These findings represent a 1.27-fold higher incidence of AD in patients with osteoporosis than in the control group, suggesting that osteoporosis might be a risk factor for AD.

Additionally, research has identified a relationship between AD and increased fracture risk and decreased bone mineral density, with AD patients exhibiting a significantly higher likelihood of bone fractures compared with those without AD. “Falls and fractures, aside from the risk they pose in all geriatric patients, in individuals with cognitive impairment — whether due to AD or another cause — have higher risk to cause delirium and that can result in greater morbidity and mortality and a lasting increase in cognitive disability,” stated Dr. Pascual-Leone. Current recommendations emphasize exercise and fall prevention strategies to reduce fracture risk in patients with AD, but there is a lack of comprehensive research on the safety and efficacy of osteoporosis medications in this population.
 

Implications for Clinical Practice

The intricate interplay between AD and its comorbidities highlights the need for a comprehensive and integrated approach to patient care. The overlapping pathophysiologic mechanisms suggest that these comorbidities can contribute to the evolution and progression of AD. Likewise, AD can exacerbate comorbid conditions. As such, a holistic assessment strategy that prioritizes early detection and management of comorbid conditions to mitigate their impact on AD progression would be beneficial. Dr. Pascual-Leone added, “The presence of any of these comorbidities suggests a need to screen for MCI earlier than might otherwise be indicated or as part of the treatment for the comorbid condition. In many cases, patients can make lifestyle modifications that improve not only the comorbid condition but also reduce its effect on dementia.” In doing so, healthcare providers can help improve patient outcomes and enhance the overall quality of life for individuals living with AD.

Alissa Hershberger, Professor of Nursing, University of Central Missouri, Lee’s Summit, Missouri, has disclosed no relevant financial relationships.

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

Alzheimer’s disease (AD), the most common cause of dementia, is the fifth leading cause of death in the United States. An estimated 6.9 million Americans aged 65 years or older have AD. Comorbid conditions in AD may exacerbate the progression of dementia and negatively affect overall health.

Although the exact mechanisms remain unclear, systemic inflammation is thought to play a significant role in the development of many common comorbidities associated with AD. Among the most frequently observed comorbid conditions are hypertension, diabetes, and depression. The presence of these comorbidities affects the treatment and management of AD, underscoring the need to understand the mechanisms of their interrelationship and develop effective management strategies. 
 

Hypertension 

Hypertension is a well-established risk factor for numerous health conditions, including AD. A comprehensive review of five meta-analyses and 52 primary studies revealed that elevated systolic blood pressure (SBP) correlates with an 11 % increased risk of developing AD, raising the question of whether early intervention and control of blood pressure would mitigate the risk for AD later in life. 

Findings from the Northern Manhattan Study suggest that although elevated SBP contributes to cognitive decline in older patients, the use of antihypertensive medications can neutralize the effects of high SBP on certain cognitive functions. Furthermore, a systematic review and meta-analysis comprising 12 trials (92,135 participants) demonstrated a significant reduction in the risk for dementia and cognitive impairment with antihypertensive treatment.

Notably, a retrospective cohort study involving 69,081 participants treated with beta-blockers for hypertension found that beta-blockers with high blood-brain barrier permeability were associated with a reduced risk for AD compared with those with low blood-brain barrier permeability. Additionally, a secondary analysis of the SPRINT trial found antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors were associated with a lower incidence of cognitive impairment. Although further clinical trials are necessary to directly assess specific medications, these findings emphasize the potential of antihypertensive treatment as a strategic approach to reduce the risk for AD.
 

Type 2 Diabetes 

The connection between AD and type 2 diabetes is such that AD is sometimes referred to as “type 3 diabetes.” Both diseases share some of the same underlying pathophysiologic mechanisms, particularly the development of insulin resistance and oxidative stress. A prospective cohort study of 10,095 participants showed that diabetes was significantly associated with a higher risk of developing dementia; this risk is even greater in patients who develop diabetes at an earlier age.

In an interview with this news organization, Alvaro Pascual-Leone, MD, PhD, a professor of neurology at Harvard Medical School, Boston, said, “In addition to being a comorbidity factor, diabetes appears to be a predisposing risk factor for AD.” This is supported by a comprehensive literature review showing an increased progression from mild cognitive impairment (MCI) to dementia in patients with diabetes, prediabetes, or metabolic syndrome, with a pooled odds ratio for dementia progression in individuals with diabetes of 1.53.

Owing to the overlapping pathophysiologic mechanisms in AD and diabetes, treating one condition may have beneficial effects on the other. A systematic umbrella review and meta-analysis that included 10 meta-analyses across nine classes of diabetes drugs found a protective effect against dementia with the use of metformin, thiazolidinediones (including pioglitazone), glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Moreover, a cohort study of 12,220 patients who discontinued metformin early (ie, stopped using metformin without a prior history of abnormal kidney function) and 29,126 patients considered routine users found an increased risk for dementia in the early terminator group. Although further research is warranted, the concurrent treatment of AD and diabetes with antidiabetic agents holds considerable promise.
 

Depression and Anxiety

Anxiety and depression are significant risk factors for AD, and conversely, AD increases the likelihood of developing these psychiatric conditions. A systematic review of 14,760 studies showed dysthymia often emerges during the early stages of AD as an emotional response to cognitive decline. 

Data from the Australian Imaging Biomarkers and Lifestyle study showed a markedly elevated risk for AD and MCI among individuals with preexisting anxiety or depression. This study also found that age, sex, and marital status are important determinants, with men and single individuals with depression being particularly susceptible to developing AD. Conversely, a cohort study of 129,410 AD patients with AD, 390,088 patients with all-cause dementia, and 3,900,880 age-matched controls without a history of depression showed a cumulative incidence of depression of 13% in the AD group vs 3% in the control group, suggesting a heightened risk for depression following an AD diagnosis. 

These findings underscore the importance of targeted screening and assessment for patients with anxiety and depression who may be at risk for AD or those diagnosed with AD who are at risk for subsequent depression and anxiety. Although antidepressants are effective in treating depression in general, their efficacy in AD-related depression is of variable quality, probably owing to differing pathophysiologic mechanisms of the disease. Further research is necessary to explore both pharmacologic and nonpharmacologic interventions for treating depression in AD patients. Some studies have found that cognitive behavioral-therapy can be effective in improving depression in patients with AD.
 

Sleep Disorders

Research has shown a strong correlation between AD and sleep disorders, particularly obstructive sleep apnea, insomnia, and circadian rhythm disruptions. Additionally, studies suggest that insomnia and sleep deprivation contribute to increased amyloid beta production and tau pathology, hallmark features of AD. A scoping review of 70 studies proposed that this relationship is mediated by the glymphatic system (glial-dependent waste clearance pathway in the central nervous system), and that sleep deprivation disrupts its function, leading to protein accumulation and subsequent neurologic symptoms of AD. Another study showed that sleep deprivation triggers glial cell activation, initiating an inflammatory cascade that accelerates AD progression.

Given that the gold standard treatment for obstructive sleep apnea is continuous positive airway pressure (CPAP), it has been hypothesized that CPAP could also alleviate AD symptoms owing to shared pathophysiologic mechanisms of these conditions. A large systemic review found that CPAP use improved AD symptoms in patients with mild AD or MCI, though other sleep interventions, such as cognitive-behavioral therapy and melatonin supplementation, have yielded mixed outcomes. However, most studies in this area are small in scale, and there remains a paucity of research on treating sleep disorders in AD patients, indicating a need for further investigation.
 

Musculoskeletal Disorders

Although no direct causative link has been established, research indicates an association between osteoarthritis (OA) and dementia, likely because of similar pathophysiologic mechanisms, including systemic inflammation. Longitudinal analyses of data from the Alzheimer’s Disease Neuroimaging Initiative study found cognitively normal older individuals with OA experience more rapid declines in hippocampal volumes compared to those without OA, suggesting that OA may elevate the risk of cognitive impairment. Current treatments for OA, such as nonsteroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying OA drugs, might also help alleviate AD symptoms related to inflammation, though the research in this area is limited.

AD has also been linked to osteoporosis. In a longitudinal follow-up study involving 78,994 patients with osteoporosis and 78,994 controls, AD developed in 5856 patients with osteoporosis compared with 3761 patients in the control group. These findings represent a 1.27-fold higher incidence of AD in patients with osteoporosis than in the control group, suggesting that osteoporosis might be a risk factor for AD.

Additionally, research has identified a relationship between AD and increased fracture risk and decreased bone mineral density, with AD patients exhibiting a significantly higher likelihood of bone fractures compared with those without AD. “Falls and fractures, aside from the risk they pose in all geriatric patients, in individuals with cognitive impairment — whether due to AD or another cause — have higher risk to cause delirium and that can result in greater morbidity and mortality and a lasting increase in cognitive disability,” stated Dr. Pascual-Leone. Current recommendations emphasize exercise and fall prevention strategies to reduce fracture risk in patients with AD, but there is a lack of comprehensive research on the safety and efficacy of osteoporosis medications in this population.
 

Implications for Clinical Practice

The intricate interplay between AD and its comorbidities highlights the need for a comprehensive and integrated approach to patient care. The overlapping pathophysiologic mechanisms suggest that these comorbidities can contribute to the evolution and progression of AD. Likewise, AD can exacerbate comorbid conditions. As such, a holistic assessment strategy that prioritizes early detection and management of comorbid conditions to mitigate their impact on AD progression would be beneficial. Dr. Pascual-Leone added, “The presence of any of these comorbidities suggests a need to screen for MCI earlier than might otherwise be indicated or as part of the treatment for the comorbid condition. In many cases, patients can make lifestyle modifications that improve not only the comorbid condition but also reduce its effect on dementia.” In doing so, healthcare providers can help improve patient outcomes and enhance the overall quality of life for individuals living with AD.

Alissa Hershberger, Professor of Nursing, University of Central Missouri, Lee’s Summit, Missouri, has disclosed no relevant financial relationships.

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

MILAN — Antidepressants escitalopram and duloxetine have been shown to improve verbal memory in moderate to severe depression, a clinical effect linked to changes in serotonin 4 (5-HT4) receptor levels in the brain, as shown on PET.

These findings suggested there is a role for specifically targeting the 5-HT4 receptor to improve verbal memory in depression, said investigator Vibeke H. Dam, PhD, from Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

“Verbal memory is often impaired in depression, and this has a lot of impact on patients’ ability to work and have a normal life. That’s why we’re so excited about this receptor in particular,” Dr. Dam said.

“If we can find a way to activate it more directly, we’re thinking this could be a way to treat this memory symptom that a lot of patients have and that currently we don’t really have a treatment for,” she added.

The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and recently published in Biological Psychiatry .
 

Largest Trial of Its Kind

The study is the largest single-site PET trial investigating serotonergic neurotransmission in major depressive disorder over the course of antidepressant treatment to date. It included 90 patients with moderate to severe depression who underwent baseline cognitive tests and brain scans to measure 5-HT4 receptor levels before starting their treatment with the selective serotonin reuptake inhibitor escitalopram.

Patients who showed no improvement in depressive symptoms after 4 weeks (n = 14), as assessed by the Hamilton Depression Rating Scale 6 (HAMD6), were switched to the serotonin-norepinephrine reuptake inhibitor duloxetine.

Both escitalopram and duloxetine inhibit the reuptake of 5-HT4, enhancing neurotransmitter activity; escitalopram primarily increases serotonin levels, while duloxetine increases both serotonin and norepinephrine levels.

The primary cognitive outcome measure was change in the Verbal Affective Memory Task 26. Secondary cognitive outcomes were change in working memory, reaction time, emotion recognition bias, and negative social emotion.

After 8 weeks of treatment, a subset of 40 patients repeated PET scans, and at 12 weeks, all patients repeated cognitive testing.

Matching neuroimaging and cognitive data were available for 88 patients at baseline and for 39 patients with rescan.

As expected, the study showed that antidepressant treatment resulted in the downregulation of 5-HT4 receptor levels. “One hypothesis is that if we increase the availability of serotonin [with treatment], downregulation of the receptors might be a response,” said Dr. Dam.

“What was interesting was that this was the effect across all patients, whether they [clinically] responded or not. So we see the medication does what it’s supposed to do in the brain.” But, she said, there was no association between 5-HT4 receptor levels and HAMD6 scores.
 

Gains in Verbal Memory

Although the downregulation of 5-HT4 did not correlate with somatic or mood symptoms, it did correlate with cognitive symptoms.

Interestingly, while most patients showed improvement in depressive symptoms — many reaching remission or recovery — they also experienced gains in verbal memory. However, these improvements were not correlated. It was possible for one to improve more than the other, with no apparent link between the two, said Dr. Dam.

“What was linked was how the brain responded to the medication for this particular receptor. So even though there is this downregulation of the receptor, there’s still a lot of activation of it, and our thinking is that it’s activation of the receptor that is the important bit.”

Work by other groups has shown that another medication, prucalopride, which is used to treat gastroparesis, can more directly activate the 5-HT4 receptor, and that the treatment of healthy volunteers with this medication can boost memory and learning, said Dr. Dam.

“We could repurpose this drug, and we’re currently looking for funding to test this in a wide variety of different groups such as concussion, diabetes, and depression.”

The study’s coinvestigator, Vibe G. Frokjaer, MD, said more research is required to understand the potential implications of the findings.

“Poor cognitive function is very hard to treat efficiently and may require extra treatment. This work points to the possibility of stimulating this specific receptor so that we can treat cognitive problems, even aside from whether or not the patient has overcome the core symptoms of depression,” she said in a release.

Commenting on the research, Philip Cowen, MD, professor of psychopharmacology at the University of Oxford, England, said in a release that in light of “recent controversies about the role of brain serotonin in clinical depression, it is noteworthy that the PET studies of the Copenhagen Group provide unequivocal evidence that brain 5-HT4 receptors are decreased in unmedicated depressed patients.

“Their work also demonstrates the intimate role of brain 5-HT4 receptors in cognitive function,” he added. “This confirms recent work from Oxford, showing that the 5-HT4 receptor stimulant, prucalopride — a drug licensed for the treatment of constipation — improves memory in both healthy participants and people at risk of depression,” he added.

The study was funded by the Innovation Fund Denmark, Research Fund of the Mental Health Services – Capital Region of Denmark, Independent Research Fund Denmark, Global Justice Foundation, Research Council of Rigshospitalet, Augustinus Foundation, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, Lundbeck Foundation, and H. Lundbeck A/S.

Dr. Dam reported serving as a speaker for H. Lundbeck. Frokjaer reported serving as a consultant for Sage Therapeutics and lecturer for H. Lundbeck, Janssen-Cilag, and Gedeon Richter. Study investigator Martin B. Jørgensen has given talks sponsored by Boehringer Ingelheim and Lundbeck Pharma. All other investigators reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

MILAN — Antidepressants escitalopram and duloxetine have been shown to improve verbal memory in moderate to severe depression, a clinical effect linked to changes in serotonin 4 (5-HT4) receptor levels in the brain, as shown on PET.

These findings suggested there is a role for specifically targeting the 5-HT4 receptor to improve verbal memory in depression, said investigator Vibeke H. Dam, PhD, from Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

“Verbal memory is often impaired in depression, and this has a lot of impact on patients’ ability to work and have a normal life. That’s why we’re so excited about this receptor in particular,” Dr. Dam said.

“If we can find a way to activate it more directly, we’re thinking this could be a way to treat this memory symptom that a lot of patients have and that currently we don’t really have a treatment for,” she added.

The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and recently published in Biological Psychiatry .
 

Largest Trial of Its Kind

The study is the largest single-site PET trial investigating serotonergic neurotransmission in major depressive disorder over the course of antidepressant treatment to date. It included 90 patients with moderate to severe depression who underwent baseline cognitive tests and brain scans to measure 5-HT4 receptor levels before starting their treatment with the selective serotonin reuptake inhibitor escitalopram.

Patients who showed no improvement in depressive symptoms after 4 weeks (n = 14), as assessed by the Hamilton Depression Rating Scale 6 (HAMD6), were switched to the serotonin-norepinephrine reuptake inhibitor duloxetine.

Both escitalopram and duloxetine inhibit the reuptake of 5-HT4, enhancing neurotransmitter activity; escitalopram primarily increases serotonin levels, while duloxetine increases both serotonin and norepinephrine levels.

The primary cognitive outcome measure was change in the Verbal Affective Memory Task 26. Secondary cognitive outcomes were change in working memory, reaction time, emotion recognition bias, and negative social emotion.

After 8 weeks of treatment, a subset of 40 patients repeated PET scans, and at 12 weeks, all patients repeated cognitive testing.

Matching neuroimaging and cognitive data were available for 88 patients at baseline and for 39 patients with rescan.

As expected, the study showed that antidepressant treatment resulted in the downregulation of 5-HT4 receptor levels. “One hypothesis is that if we increase the availability of serotonin [with treatment], downregulation of the receptors might be a response,” said Dr. Dam.

“What was interesting was that this was the effect across all patients, whether they [clinically] responded or not. So we see the medication does what it’s supposed to do in the brain.” But, she said, there was no association between 5-HT4 receptor levels and HAMD6 scores.
 

Gains in Verbal Memory

Although the downregulation of 5-HT4 did not correlate with somatic or mood symptoms, it did correlate with cognitive symptoms.

Interestingly, while most patients showed improvement in depressive symptoms — many reaching remission or recovery — they also experienced gains in verbal memory. However, these improvements were not correlated. It was possible for one to improve more than the other, with no apparent link between the two, said Dr. Dam.

“What was linked was how the brain responded to the medication for this particular receptor. So even though there is this downregulation of the receptor, there’s still a lot of activation of it, and our thinking is that it’s activation of the receptor that is the important bit.”

Work by other groups has shown that another medication, prucalopride, which is used to treat gastroparesis, can more directly activate the 5-HT4 receptor, and that the treatment of healthy volunteers with this medication can boost memory and learning, said Dr. Dam.

“We could repurpose this drug, and we’re currently looking for funding to test this in a wide variety of different groups such as concussion, diabetes, and depression.”

The study’s coinvestigator, Vibe G. Frokjaer, MD, said more research is required to understand the potential implications of the findings.

“Poor cognitive function is very hard to treat efficiently and may require extra treatment. This work points to the possibility of stimulating this specific receptor so that we can treat cognitive problems, even aside from whether or not the patient has overcome the core symptoms of depression,” she said in a release.

Commenting on the research, Philip Cowen, MD, professor of psychopharmacology at the University of Oxford, England, said in a release that in light of “recent controversies about the role of brain serotonin in clinical depression, it is noteworthy that the PET studies of the Copenhagen Group provide unequivocal evidence that brain 5-HT4 receptors are decreased in unmedicated depressed patients.

“Their work also demonstrates the intimate role of brain 5-HT4 receptors in cognitive function,” he added. “This confirms recent work from Oxford, showing that the 5-HT4 receptor stimulant, prucalopride — a drug licensed for the treatment of constipation — improves memory in both healthy participants and people at risk of depression,” he added.

The study was funded by the Innovation Fund Denmark, Research Fund of the Mental Health Services – Capital Region of Denmark, Independent Research Fund Denmark, Global Justice Foundation, Research Council of Rigshospitalet, Augustinus Foundation, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, Lundbeck Foundation, and H. Lundbeck A/S.

Dr. Dam reported serving as a speaker for H. Lundbeck. Frokjaer reported serving as a consultant for Sage Therapeutics and lecturer for H. Lundbeck, Janssen-Cilag, and Gedeon Richter. Study investigator Martin B. Jørgensen has given talks sponsored by Boehringer Ingelheim and Lundbeck Pharma. All other investigators reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

MILAN — Antidepressants escitalopram and duloxetine have been shown to improve verbal memory in moderate to severe depression, a clinical effect linked to changes in serotonin 4 (5-HT4) receptor levels in the brain, as shown on PET.

These findings suggested there is a role for specifically targeting the 5-HT4 receptor to improve verbal memory in depression, said investigator Vibeke H. Dam, PhD, from Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

“Verbal memory is often impaired in depression, and this has a lot of impact on patients’ ability to work and have a normal life. That’s why we’re so excited about this receptor in particular,” Dr. Dam said.

“If we can find a way to activate it more directly, we’re thinking this could be a way to treat this memory symptom that a lot of patients have and that currently we don’t really have a treatment for,” she added.

The findings were presented at the 37th European College of Neuropsychopharmacology (ECNP) Congress and recently published in Biological Psychiatry .
 

Largest Trial of Its Kind

The study is the largest single-site PET trial investigating serotonergic neurotransmission in major depressive disorder over the course of antidepressant treatment to date. It included 90 patients with moderate to severe depression who underwent baseline cognitive tests and brain scans to measure 5-HT4 receptor levels before starting their treatment with the selective serotonin reuptake inhibitor escitalopram.

Patients who showed no improvement in depressive symptoms after 4 weeks (n = 14), as assessed by the Hamilton Depression Rating Scale 6 (HAMD6), were switched to the serotonin-norepinephrine reuptake inhibitor duloxetine.

Both escitalopram and duloxetine inhibit the reuptake of 5-HT4, enhancing neurotransmitter activity; escitalopram primarily increases serotonin levels, while duloxetine increases both serotonin and norepinephrine levels.

The primary cognitive outcome measure was change in the Verbal Affective Memory Task 26. Secondary cognitive outcomes were change in working memory, reaction time, emotion recognition bias, and negative social emotion.

After 8 weeks of treatment, a subset of 40 patients repeated PET scans, and at 12 weeks, all patients repeated cognitive testing.

Matching neuroimaging and cognitive data were available for 88 patients at baseline and for 39 patients with rescan.

As expected, the study showed that antidepressant treatment resulted in the downregulation of 5-HT4 receptor levels. “One hypothesis is that if we increase the availability of serotonin [with treatment], downregulation of the receptors might be a response,” said Dr. Dam.

“What was interesting was that this was the effect across all patients, whether they [clinically] responded or not. So we see the medication does what it’s supposed to do in the brain.” But, she said, there was no association between 5-HT4 receptor levels and HAMD6 scores.
 

Gains in Verbal Memory

Although the downregulation of 5-HT4 did not correlate with somatic or mood symptoms, it did correlate with cognitive symptoms.

Interestingly, while most patients showed improvement in depressive symptoms — many reaching remission or recovery — they also experienced gains in verbal memory. However, these improvements were not correlated. It was possible for one to improve more than the other, with no apparent link between the two, said Dr. Dam.

“What was linked was how the brain responded to the medication for this particular receptor. So even though there is this downregulation of the receptor, there’s still a lot of activation of it, and our thinking is that it’s activation of the receptor that is the important bit.”

Work by other groups has shown that another medication, prucalopride, which is used to treat gastroparesis, can more directly activate the 5-HT4 receptor, and that the treatment of healthy volunteers with this medication can boost memory and learning, said Dr. Dam.

“We could repurpose this drug, and we’re currently looking for funding to test this in a wide variety of different groups such as concussion, diabetes, and depression.”

The study’s coinvestigator, Vibe G. Frokjaer, MD, said more research is required to understand the potential implications of the findings.

“Poor cognitive function is very hard to treat efficiently and may require extra treatment. This work points to the possibility of stimulating this specific receptor so that we can treat cognitive problems, even aside from whether or not the patient has overcome the core symptoms of depression,” she said in a release.

Commenting on the research, Philip Cowen, MD, professor of psychopharmacology at the University of Oxford, England, said in a release that in light of “recent controversies about the role of brain serotonin in clinical depression, it is noteworthy that the PET studies of the Copenhagen Group provide unequivocal evidence that brain 5-HT4 receptors are decreased in unmedicated depressed patients.

“Their work also demonstrates the intimate role of brain 5-HT4 receptors in cognitive function,” he added. “This confirms recent work from Oxford, showing that the 5-HT4 receptor stimulant, prucalopride — a drug licensed for the treatment of constipation — improves memory in both healthy participants and people at risk of depression,” he added.

The study was funded by the Innovation Fund Denmark, Research Fund of the Mental Health Services – Capital Region of Denmark, Independent Research Fund Denmark, Global Justice Foundation, Research Council of Rigshospitalet, Augustinus Foundation, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, Lundbeck Foundation, and H. Lundbeck A/S.

Dr. Dam reported serving as a speaker for H. Lundbeck. Frokjaer reported serving as a consultant for Sage Therapeutics and lecturer for H. Lundbeck, Janssen-Cilag, and Gedeon Richter. Study investigator Martin B. Jørgensen has given talks sponsored by Boehringer Ingelheim and Lundbeck Pharma. All other investigators reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

MILAN — Recent research allaying concerns about suicidality linked to glucagon-like peptide 1 (GLP-1) receptor agonists, along with evidence of these agents’ potential psychiatric and cognitive benefits, has prompted the lead investigator of a major analysis to urge researchers to explore the potential of these drugs for mental illness.

“So far, we’ve been talking about the safety from a neuropsychiatric perspective in diabetes, but there is also the safety and benefit in people with mental disorders,” Riccardo De Giorgi, MD, PhD, from the Department of Psychiatry, University of Oxford in England, said in an interview.

The results of the meta-analysis were previously reported by this news organization and reviewed by Dr. De Giorgi at the 37th European College of Neuropsychopharmacology (ECNP) Congress. Dr. De Giorgi broached whether GLP-1 inhibitors such as semaglutide might also offer the same benefits in patients without diabetes as they do in those with diabetes, in terms of cognitive deficits and substance use or mood disorders.

Noting that GLP-1s are not approved for psychiatric disorders, Dr. De Giorgi said it can’t be assumed that the “metabolic or maybe even more general mechanisms that are being modified with these medications in diabetes or even in obesity are the same for people with psychiatric disorders. We’re talking about very different things. From a clinical perspective, you could do real harm,” he told this news organization.

Yet Dr. De Giorgi emphasized the importance of exploring the potential benefits of these medications in psychiatry.

“From a research perspective ... I am very worried about missing an opportunity here. This happened with rimonabant, a cannabis medication that was used for weight loss back in 2012 and was withdrawn quite dramatically in Europe immediately after licensing because it increased suicide risk. Since then, nobody has been touching the cannabinoid system, and that’s a shame because in psychiatry, we don’t have that much we can work on. So we don’t want to miss an opportunity with the GLP-1 system — that’s why we need to be cautious and look at safety first,” he said.
 

Signal of Efficacy?

Dr. De Giorgi’s research suggested several potential neurobiological effects of GLP-1 inhibition in diabetes research.

“There was a bit of a signal specifically for the big three dementias — vascular, Lewy Body, and frontotemporal — although there was not enough power,” he reported. “We also saw a reduced risk in nicotine misuse, especially amongst other substance use disorders ... and finally a more tentative association for reduced depression.”

He noted that GLP-1s for psychiatric illness likely have limitations and may not cure mental disorders but could help specific subsets of patients. Rather than aiming for large-scale studies, the focus should be on small, incremental studies to advance the research.

Asked by the session chair, John Cryan, PhD, from University College Cork in Ireland, and chair of the ECNP Scientific Committee whether improvement in patients’ mood could be attributed to weight loss, Dr. De Giorgi replied no.

“We now have quite a lot of studies that show that if there is an effect or association it is seen quite a bit earlier than any weight loss. Remember, weight loss takes quite a lot of time, and at quite high doses, but more provocatively, even if that’s the case, does it matter? We as psychiatrists do worry that we need to disentangle these things, but they don’t do that in cardiology, for example. If they see a benefit in mortality they don’t really care if it’s specifically an effect on heart failure or ischemic disease,” said Dr. De Giorgi.

Regardless of their neuropsychiatric potential, the cardiometabolic benefits of GLP-1 inhibitors are sorely needed in the psychiatric population, noted two experts in a recent JAMA Psychiatry viewpoint article.

Sri Mahavir Agarwal, MD, PhD, and Margaret Hahn, MD, PhD, from the University of Toronto and the Schizophrenia Division at the Centre for Addiction and Mental Health, in Toronto, Ontario, Canada, pointed out that “individuals with severe mental illness (SMI) have exceedingly high rates of metabolic comorbidity; three of four are overweight or obese, whereas the prevalence of type 2 diabetes (T2D) is several-fold higher than in the general population. Consequently, individuals with SMI die 15-20 years earlier from cardiovascular disease (CVD) than do those in the general population with CVD,” they noted.

“The arrival of semaglutide has infused significant enthusiasm in the field of mental health research. The proximal effects of weight and related CV comorbidities are significant in themselves. It is plausible that semaglutide could act through neurogenesis or secondary benefits of improving metabolic health on other important outcomes, such as cognitive health and quality of life, thereby filling an unmet need in the treatment of SMI,” Dr. Agarwal and Dr. Hahn added.
 

An Exciting Opportunity

Current research investigating GLP-1s in psychiatry and neurology is increasingly focused on neuroinflammation, said Dr. De Giorgi.

Research shows significant evidence that certain medications may help reduce dysfunctional inflammatory processes linked to various cognitive and psychiatric disorders, he added.

Many patients with established psychiatric conditions also have physical health issues, which contribute to increased mortality risk, said Dr. De Giorgi. It’s crucial to understand that, if these treatments improve mortality outcomes for psychiatric patients, the specific mechanisms involved are secondary to the results. Psychiatrists must be equipped to prescribe, manage, and initiate these therapies.

“While trials involving psychosis patients are ongoing, we are making progress and should seize this opportunity” said Dr. De Giorgi.

Dr. Cryan agreed: “I think we’ll get there. What these drugs have shown is that you can, through a single mechanism, have multitude effects related to brain-body interactions, and why not focus that on mood and anxiety and cognitive performance? It’s exciting no matter what. We now need to do longitudinal, cross-sectional, placebo-controlled trials in specific patient populations.”

This study received funding from the National Institute for Health and Care Research Oxford Health Biomedical Research Centre and Medical Research Council. Dr. De Giorgi’s coauthors reported receiving funding for other work from Novo Nordisk, Five Lives, Cognetivity Ltd., Cognex, P1vital, Lundbeck, Servier, UCB, Zogenix, Johnson & Johnson, and Syndesi. Dr. Cryan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

MILAN — Recent research allaying concerns about suicidality linked to glucagon-like peptide 1 (GLP-1) receptor agonists, along with evidence of these agents’ potential psychiatric and cognitive benefits, has prompted the lead investigator of a major analysis to urge researchers to explore the potential of these drugs for mental illness.

“So far, we’ve been talking about the safety from a neuropsychiatric perspective in diabetes, but there is also the safety and benefit in people with mental disorders,” Riccardo De Giorgi, MD, PhD, from the Department of Psychiatry, University of Oxford in England, said in an interview.

The results of the meta-analysis were previously reported by this news organization and reviewed by Dr. De Giorgi at the 37th European College of Neuropsychopharmacology (ECNP) Congress. Dr. De Giorgi broached whether GLP-1 inhibitors such as semaglutide might also offer the same benefits in patients without diabetes as they do in those with diabetes, in terms of cognitive deficits and substance use or mood disorders.

Noting that GLP-1s are not approved for psychiatric disorders, Dr. De Giorgi said it can’t be assumed that the “metabolic or maybe even more general mechanisms that are being modified with these medications in diabetes or even in obesity are the same for people with psychiatric disorders. We’re talking about very different things. From a clinical perspective, you could do real harm,” he told this news organization.

Yet Dr. De Giorgi emphasized the importance of exploring the potential benefits of these medications in psychiatry.

“From a research perspective ... I am very worried about missing an opportunity here. This happened with rimonabant, a cannabis medication that was used for weight loss back in 2012 and was withdrawn quite dramatically in Europe immediately after licensing because it increased suicide risk. Since then, nobody has been touching the cannabinoid system, and that’s a shame because in psychiatry, we don’t have that much we can work on. So we don’t want to miss an opportunity with the GLP-1 system — that’s why we need to be cautious and look at safety first,” he said.
 

Signal of Efficacy?

Dr. De Giorgi’s research suggested several potential neurobiological effects of GLP-1 inhibition in diabetes research.

“There was a bit of a signal specifically for the big three dementias — vascular, Lewy Body, and frontotemporal — although there was not enough power,” he reported. “We also saw a reduced risk in nicotine misuse, especially amongst other substance use disorders ... and finally a more tentative association for reduced depression.”

He noted that GLP-1s for psychiatric illness likely have limitations and may not cure mental disorders but could help specific subsets of patients. Rather than aiming for large-scale studies, the focus should be on small, incremental studies to advance the research.

Asked by the session chair, John Cryan, PhD, from University College Cork in Ireland, and chair of the ECNP Scientific Committee whether improvement in patients’ mood could be attributed to weight loss, Dr. De Giorgi replied no.

“We now have quite a lot of studies that show that if there is an effect or association it is seen quite a bit earlier than any weight loss. Remember, weight loss takes quite a lot of time, and at quite high doses, but more provocatively, even if that’s the case, does it matter? We as psychiatrists do worry that we need to disentangle these things, but they don’t do that in cardiology, for example. If they see a benefit in mortality they don’t really care if it’s specifically an effect on heart failure or ischemic disease,” said Dr. De Giorgi.

Regardless of their neuropsychiatric potential, the cardiometabolic benefits of GLP-1 inhibitors are sorely needed in the psychiatric population, noted two experts in a recent JAMA Psychiatry viewpoint article.

Sri Mahavir Agarwal, MD, PhD, and Margaret Hahn, MD, PhD, from the University of Toronto and the Schizophrenia Division at the Centre for Addiction and Mental Health, in Toronto, Ontario, Canada, pointed out that “individuals with severe mental illness (SMI) have exceedingly high rates of metabolic comorbidity; three of four are overweight or obese, whereas the prevalence of type 2 diabetes (T2D) is several-fold higher than in the general population. Consequently, individuals with SMI die 15-20 years earlier from cardiovascular disease (CVD) than do those in the general population with CVD,” they noted.

“The arrival of semaglutide has infused significant enthusiasm in the field of mental health research. The proximal effects of weight and related CV comorbidities are significant in themselves. It is plausible that semaglutide could act through neurogenesis or secondary benefits of improving metabolic health on other important outcomes, such as cognitive health and quality of life, thereby filling an unmet need in the treatment of SMI,” Dr. Agarwal and Dr. Hahn added.
 

An Exciting Opportunity

Current research investigating GLP-1s in psychiatry and neurology is increasingly focused on neuroinflammation, said Dr. De Giorgi.

Research shows significant evidence that certain medications may help reduce dysfunctional inflammatory processes linked to various cognitive and psychiatric disorders, he added.

Many patients with established psychiatric conditions also have physical health issues, which contribute to increased mortality risk, said Dr. De Giorgi. It’s crucial to understand that, if these treatments improve mortality outcomes for psychiatric patients, the specific mechanisms involved are secondary to the results. Psychiatrists must be equipped to prescribe, manage, and initiate these therapies.

“While trials involving psychosis patients are ongoing, we are making progress and should seize this opportunity” said Dr. De Giorgi.

Dr. Cryan agreed: “I think we’ll get there. What these drugs have shown is that you can, through a single mechanism, have multitude effects related to brain-body interactions, and why not focus that on mood and anxiety and cognitive performance? It’s exciting no matter what. We now need to do longitudinal, cross-sectional, placebo-controlled trials in specific patient populations.”

This study received funding from the National Institute for Health and Care Research Oxford Health Biomedical Research Centre and Medical Research Council. Dr. De Giorgi’s coauthors reported receiving funding for other work from Novo Nordisk, Five Lives, Cognetivity Ltd., Cognex, P1vital, Lundbeck, Servier, UCB, Zogenix, Johnson & Johnson, and Syndesi. Dr. Cryan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

MILAN — Recent research allaying concerns about suicidality linked to glucagon-like peptide 1 (GLP-1) receptor agonists, along with evidence of these agents’ potential psychiatric and cognitive benefits, has prompted the lead investigator of a major analysis to urge researchers to explore the potential of these drugs for mental illness.

“So far, we’ve been talking about the safety from a neuropsychiatric perspective in diabetes, but there is also the safety and benefit in people with mental disorders,” Riccardo De Giorgi, MD, PhD, from the Department of Psychiatry, University of Oxford in England, said in an interview.

The results of the meta-analysis were previously reported by this news organization and reviewed by Dr. De Giorgi at the 37th European College of Neuropsychopharmacology (ECNP) Congress. Dr. De Giorgi broached whether GLP-1 inhibitors such as semaglutide might also offer the same benefits in patients without diabetes as they do in those with diabetes, in terms of cognitive deficits and substance use or mood disorders.

Noting that GLP-1s are not approved for psychiatric disorders, Dr. De Giorgi said it can’t be assumed that the “metabolic or maybe even more general mechanisms that are being modified with these medications in diabetes or even in obesity are the same for people with psychiatric disorders. We’re talking about very different things. From a clinical perspective, you could do real harm,” he told this news organization.

Yet Dr. De Giorgi emphasized the importance of exploring the potential benefits of these medications in psychiatry.

“From a research perspective ... I am very worried about missing an opportunity here. This happened with rimonabant, a cannabis medication that was used for weight loss back in 2012 and was withdrawn quite dramatically in Europe immediately after licensing because it increased suicide risk. Since then, nobody has been touching the cannabinoid system, and that’s a shame because in psychiatry, we don’t have that much we can work on. So we don’t want to miss an opportunity with the GLP-1 system — that’s why we need to be cautious and look at safety first,” he said.
 

Signal of Efficacy?

Dr. De Giorgi’s research suggested several potential neurobiological effects of GLP-1 inhibition in diabetes research.

“There was a bit of a signal specifically for the big three dementias — vascular, Lewy Body, and frontotemporal — although there was not enough power,” he reported. “We also saw a reduced risk in nicotine misuse, especially amongst other substance use disorders ... and finally a more tentative association for reduced depression.”

He noted that GLP-1s for psychiatric illness likely have limitations and may not cure mental disorders but could help specific subsets of patients. Rather than aiming for large-scale studies, the focus should be on small, incremental studies to advance the research.

Asked by the session chair, John Cryan, PhD, from University College Cork in Ireland, and chair of the ECNP Scientific Committee whether improvement in patients’ mood could be attributed to weight loss, Dr. De Giorgi replied no.

“We now have quite a lot of studies that show that if there is an effect or association it is seen quite a bit earlier than any weight loss. Remember, weight loss takes quite a lot of time, and at quite high doses, but more provocatively, even if that’s the case, does it matter? We as psychiatrists do worry that we need to disentangle these things, but they don’t do that in cardiology, for example. If they see a benefit in mortality they don’t really care if it’s specifically an effect on heart failure or ischemic disease,” said Dr. De Giorgi.

Regardless of their neuropsychiatric potential, the cardiometabolic benefits of GLP-1 inhibitors are sorely needed in the psychiatric population, noted two experts in a recent JAMA Psychiatry viewpoint article.

Sri Mahavir Agarwal, MD, PhD, and Margaret Hahn, MD, PhD, from the University of Toronto and the Schizophrenia Division at the Centre for Addiction and Mental Health, in Toronto, Ontario, Canada, pointed out that “individuals with severe mental illness (SMI) have exceedingly high rates of metabolic comorbidity; three of four are overweight or obese, whereas the prevalence of type 2 diabetes (T2D) is several-fold higher than in the general population. Consequently, individuals with SMI die 15-20 years earlier from cardiovascular disease (CVD) than do those in the general population with CVD,” they noted.

“The arrival of semaglutide has infused significant enthusiasm in the field of mental health research. The proximal effects of weight and related CV comorbidities are significant in themselves. It is plausible that semaglutide could act through neurogenesis or secondary benefits of improving metabolic health on other important outcomes, such as cognitive health and quality of life, thereby filling an unmet need in the treatment of SMI,” Dr. Agarwal and Dr. Hahn added.
 

An Exciting Opportunity

Current research investigating GLP-1s in psychiatry and neurology is increasingly focused on neuroinflammation, said Dr. De Giorgi.

Research shows significant evidence that certain medications may help reduce dysfunctional inflammatory processes linked to various cognitive and psychiatric disorders, he added.

Many patients with established psychiatric conditions also have physical health issues, which contribute to increased mortality risk, said Dr. De Giorgi. It’s crucial to understand that, if these treatments improve mortality outcomes for psychiatric patients, the specific mechanisms involved are secondary to the results. Psychiatrists must be equipped to prescribe, manage, and initiate these therapies.

“While trials involving psychosis patients are ongoing, we are making progress and should seize this opportunity” said Dr. De Giorgi.

Dr. Cryan agreed: “I think we’ll get there. What these drugs have shown is that you can, through a single mechanism, have multitude effects related to brain-body interactions, and why not focus that on mood and anxiety and cognitive performance? It’s exciting no matter what. We now need to do longitudinal, cross-sectional, placebo-controlled trials in specific patient populations.”

This study received funding from the National Institute for Health and Care Research Oxford Health Biomedical Research Centre and Medical Research Council. Dr. De Giorgi’s coauthors reported receiving funding for other work from Novo Nordisk, Five Lives, Cognetivity Ltd., Cognex, P1vital, Lundbeck, Servier, UCB, Zogenix, Johnson & Johnson, and Syndesi. Dr. Cryan reported no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Diabetes and prediabetes are associated with accelerated brain aging with brain age gaps of 2.29 and 0.50 years, respectively. This association is more pronounced in men and those with poor cardiometabolic health but may be mitigated by a healthy lifestyle.

METHODOLOGY:

• Diabetes is a known risk factor for cognitive impairment, dementia, and global brain atrophy but conflicting results have been reported for prediabetes, and it’s unknown whether a healthy lifestyle can counteract the negative impact of prediabetes.
• Researchers examined the cross-sectional and longitudinal relationship between hyperglycemia and brain aging, as well as the potential mitigating effect of a healthy lifestyle in 31,229 dementia-free adults (mean age, 54.8 years; 53% women) from the UK Biobank, including 13,518 participants with prediabetes and 1149 with diabetes.
• The glycemic status of the participants was determined by their medical history, medication use, and A1c levels.
• The brain age gap was calculated as a difference between chronologic age and brain age estimated from MRI data from six modalities vs several hundred brain MRI phenotypes that were modeled from a subset of healthy individuals.
• The role of sex, cardiometabolic risk factors, and a healthy lifestyle and their association with brain age was also explored, with a healthy lifestyle defined as never smoking, no or light or moderate alcohol consumption, and high physical activity.

TAKEAWAY:

• Prediabetes and diabetes were associated with a higher brain age gap than normoglycemia (beta-coefficient, 0.22 and 2.01; 95% CI, 0.10-0.34 and 1.70-2.32, respectively), and diabetes was more pronounced in men vs women and those with a higher vs lower burden of cardiometabolic risk factors.
• The brain ages of those with prediabetes and diabetes were 0.50 years and 2.29 years older on average than their respective chronologic ages.
• In an exploratory longitudinal analysis of the 2414 participants with two brain MRI scans, diabetes was linked to a 0.27-year annual increase in the brain age gap, and higher A1c, but not prediabetes, was associated with a significant increase in brain age gap.
• A healthy lifestyle attenuated the association between diabetes and a higher brain age gap (P = .003), reducing it by 1.68 years, also with a significant interaction between glycemic status and lifestyle.

IN PRACTICE:

“Our findings highlight diabetes and prediabetes as ideal targets for lifestyle-based interventions to promote brain health,” the authors wrote.

SOURCE:

This study, led by Abigail Dove, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, was published online in Diabetes Care.

LIMITATIONS:

The generalizability of the findings was limited due to a healthy volunteer bias in the UK Biobank. A high proportion of missing data prevented the inclusion of diet in the healthy lifestyle construct. Reverse causality may be possible as an older brain may contribute to the development of prediabetes by making it more difficult to manage medical conditions and adhere to a healthy lifestyle. A1c levels were measured only at baseline, preventing the assessment of changes in glycemic control over time.

DISCLOSURES:

The authors reported receiving funding from the Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Karolinska Institutet Board of Research; Riksbankens Jubileumsfond; Marianne and Marcus Wallenberg Foundation; Alzheimerfonden; and Demensfonden. They declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Diabetes and prediabetes are associated with accelerated brain aging with brain age gaps of 2.29 and 0.50 years, respectively. This association is more pronounced in men and those with poor cardiometabolic health but may be mitigated by a healthy lifestyle.

METHODOLOGY:

• Diabetes is a known risk factor for cognitive impairment, dementia, and global brain atrophy but conflicting results have been reported for prediabetes, and it’s unknown whether a healthy lifestyle can counteract the negative impact of prediabetes.
• Researchers examined the cross-sectional and longitudinal relationship between hyperglycemia and brain aging, as well as the potential mitigating effect of a healthy lifestyle in 31,229 dementia-free adults (mean age, 54.8 years; 53% women) from the UK Biobank, including 13,518 participants with prediabetes and 1149 with diabetes.
• The glycemic status of the participants was determined by their medical history, medication use, and A1c levels.
• The brain age gap was calculated as a difference between chronologic age and brain age estimated from MRI data from six modalities vs several hundred brain MRI phenotypes that were modeled from a subset of healthy individuals.
• The role of sex, cardiometabolic risk factors, and a healthy lifestyle and their association with brain age was also explored, with a healthy lifestyle defined as never smoking, no or light or moderate alcohol consumption, and high physical activity.

TAKEAWAY:

• Prediabetes and diabetes were associated with a higher brain age gap than normoglycemia (beta-coefficient, 0.22 and 2.01; 95% CI, 0.10-0.34 and 1.70-2.32, respectively), and diabetes was more pronounced in men vs women and those with a higher vs lower burden of cardiometabolic risk factors.
• The brain ages of those with prediabetes and diabetes were 0.50 years and 2.29 years older on average than their respective chronologic ages.
• In an exploratory longitudinal analysis of the 2414 participants with two brain MRI scans, diabetes was linked to a 0.27-year annual increase in the brain age gap, and higher A1c, but not prediabetes, was associated with a significant increase in brain age gap.
• A healthy lifestyle attenuated the association between diabetes and a higher brain age gap (P = .003), reducing it by 1.68 years, also with a significant interaction between glycemic status and lifestyle.

IN PRACTICE:

“Our findings highlight diabetes and prediabetes as ideal targets for lifestyle-based interventions to promote brain health,” the authors wrote.

SOURCE:

This study, led by Abigail Dove, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, was published online in Diabetes Care.

LIMITATIONS:

The generalizability of the findings was limited due to a healthy volunteer bias in the UK Biobank. A high proportion of missing data prevented the inclusion of diet in the healthy lifestyle construct. Reverse causality may be possible as an older brain may contribute to the development of prediabetes by making it more difficult to manage medical conditions and adhere to a healthy lifestyle. A1c levels were measured only at baseline, preventing the assessment of changes in glycemic control over time.

DISCLOSURES:

The authors reported receiving funding from the Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Karolinska Institutet Board of Research; Riksbankens Jubileumsfond; Marianne and Marcus Wallenberg Foundation; Alzheimerfonden; and Demensfonden. They declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Diabetes and prediabetes are associated with accelerated brain aging with brain age gaps of 2.29 and 0.50 years, respectively. This association is more pronounced in men and those with poor cardiometabolic health but may be mitigated by a healthy lifestyle.

METHODOLOGY:

• Diabetes is a known risk factor for cognitive impairment, dementia, and global brain atrophy but conflicting results have been reported for prediabetes, and it’s unknown whether a healthy lifestyle can counteract the negative impact of prediabetes.
• Researchers examined the cross-sectional and longitudinal relationship between hyperglycemia and brain aging, as well as the potential mitigating effect of a healthy lifestyle in 31,229 dementia-free adults (mean age, 54.8 years; 53% women) from the UK Biobank, including 13,518 participants with prediabetes and 1149 with diabetes.
• The glycemic status of the participants was determined by their medical history, medication use, and A1c levels.
• The brain age gap was calculated as a difference between chronologic age and brain age estimated from MRI data from six modalities vs several hundred brain MRI phenotypes that were modeled from a subset of healthy individuals.
• The role of sex, cardiometabolic risk factors, and a healthy lifestyle and their association with brain age was also explored, with a healthy lifestyle defined as never smoking, no or light or moderate alcohol consumption, and high physical activity.

TAKEAWAY:

• Prediabetes and diabetes were associated with a higher brain age gap than normoglycemia (beta-coefficient, 0.22 and 2.01; 95% CI, 0.10-0.34 and 1.70-2.32, respectively), and diabetes was more pronounced in men vs women and those with a higher vs lower burden of cardiometabolic risk factors.
• The brain ages of those with prediabetes and diabetes were 0.50 years and 2.29 years older on average than their respective chronologic ages.
• In an exploratory longitudinal analysis of the 2414 participants with two brain MRI scans, diabetes was linked to a 0.27-year annual increase in the brain age gap, and higher A1c, but not prediabetes, was associated with a significant increase in brain age gap.
• A healthy lifestyle attenuated the association between diabetes and a higher brain age gap (P = .003), reducing it by 1.68 years, also with a significant interaction between glycemic status and lifestyle.

IN PRACTICE:

“Our findings highlight diabetes and prediabetes as ideal targets for lifestyle-based interventions to promote brain health,” the authors wrote.

SOURCE:

This study, led by Abigail Dove, Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden, was published online in Diabetes Care.

LIMITATIONS:

The generalizability of the findings was limited due to a healthy volunteer bias in the UK Biobank. A high proportion of missing data prevented the inclusion of diet in the healthy lifestyle construct. Reverse causality may be possible as an older brain may contribute to the development of prediabetes by making it more difficult to manage medical conditions and adhere to a healthy lifestyle. A1c levels were measured only at baseline, preventing the assessment of changes in glycemic control over time.

DISCLOSURES:

The authors reported receiving funding from the Swedish Research Council; Swedish Research Council for Health, Working Life and Welfare; Karolinska Institutet Board of Research; Riksbankens Jubileumsfond; Marianne and Marcus Wallenberg Foundation; Alzheimerfonden; and Demensfonden. They declared no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

MADRID — Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) show significant reductions in the risk of developing neurodegenerative disorders including Alzheimer’s disease, vascular dementia, and Parkinson’s disease, compared with those treated with other antidiabetic drugs, results from a large population-based cohort show.

“This was the largest nationwide population-based longitudinal cohort study to investigate the association between the use of SGLT2 inhibitors and the incidence of all-cause dementia and Parkinson’s disease,” said first author Hae Kyung Kim, MD, of the Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, in presenting the findings at the annual meeting of the European Association for the Study of Diabetes.

Type 2 diabetes is known to increase the risk for neurodegenerative diseases such as dementia or Alzheimer’s disease, said Dr. Kim. Key factors attributed to the risk include shared pathophysiological mechanisms such as central nervous system insulin resistance and reduced cerebral glucose metabolism.

While research is lacking on the role of antidiabetic drugs in the treatment of neurodegenerative diseases, the researcher noted that “SGLT2 inhibitors, which have shown significant cardiorenal benefits and enhanced energy metabolism through ketogenesis, offer promise.”

To further investigate, Dr. Kim and her colleagues conducted the retrospective study, evaluating data on more than 1.3 million enrollees in Korea’s National Health Insurance Service Database who were aged 40 years or older, diagnosed with type 2 diabetes, and had initiated antidiabetic drugs between September 2014 and December 2019.

In the propensity score analysis, 358,862 patients were matched 1:1, in groups of 179,431 participants each, based on whether they were treated with SGLT2is or other oral antidiabetic drugs. Patients with a history of neurodegenerative disease, cancer, or use of glucagon-like peptide 1 receptor agonists were excluded.

The patients had a mean age of 57.8 years, 57.9% were men, and 6837 had incident dementia or Parkinson’s disease events reported.

With a mean follow-up of 2.88 years, after adjustment for key variables, those treated with SGLT2is had a 19% reduced risk of developing Alzheimer’s disease (adjusted hazard ratio [aHR], 0.81), a 31% reduced risk for vascular dementia (aHR, 0.69), and a 20% reduced risk for Parkinson’s disease (aHR, 0.80) compared with the non-SGLT2i group.

Furthermore, those receiving SGLT2i treatment had a 21% reduced risk for all-cause dementia (aHR, 0.79) and a 22% reduced risk for all-cause dementia and Parkinson’s disease compared with the oral antidiabetic drug group (aHR, 0.78) with a 6-month drug use lag period.

The association was observed regardless of SGLT2i exposure duration. Subgroup analyses indicated that the reductions in neurodegenerative disorders among those receiving SGLT2is were not associated with factors including age, sex, body mass index, blood pressure, glucose, lipid profiles, kidney function, health behaviors, comorbidities, diabetic complications, or other medication use.

Dr. Kim speculated that mechanisms underlying the reduced dementia risk could include SGLT2i effects of mitigating the common severe risk factors of type 2 diabetes and neurodegenerative diseases, including hypertension, heart failure, and chronic kidney disease, and improving hyperperfusion in the heart and cerebral vascular insufficiency.

Commenting on the study to this news organization, Erik H. Serné, MD, of the VU University Medical Centre, Amsterdam, the Netherlands, who comoderated the session, noted that “people with type 2 diabetes have a 50%-100% increased risk of developing dementia, particularly Alzheimer’s disease and vascular dementia.”

“The increasing prevalence of both conditions poses significant public health challenges, highlighting the need for effective prevention strategies and interventions.”

Currently, treatments for dementia are limited, with most primarily addressing symptoms and not the underlying cause of the neurodegenerative disease, he said.

He noted that, in addition to the effects mentioned by Dr. Kim, SGLT2is are also speculated to provide potential neuroprotective effects through improved glycemic control and insulin sensitivity, reduced inflammation and oxidative stress, enhanced mitochondrial function and energy metabolism, and reduced beta-amyloid and tau pathology.

“These mechanisms collectively may reduce the risk of cognitive decline, particularly in diabetic patients, and warrant further investigation in clinical trials to solidify the neuroprotective role of SGLT2 inhibitors,” said Dr. Serné.

In addition to their benefits in type 2 diabetes, SGLT2is “now offer hope in the prevention of dementia, a disease that has very limited therapeutic options thus far. The current data [presented by Dr. Kim] seem to corroborate this,” he added.

Dr. Kim and Dr. Serné had no disclosures to report.

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

Outside of caffeine, I have very few addictions. One of them is “Midnight Diner.”

“Midnight Diner” is a quirky, sometimes funny, sometimes bittersweet, Japanese series on Netflix. It’s about a small diner in Tokyo, open only in the wee hours of the morning, its enigmatic owner/cook, and the eclectic patrons that come and go. Each is seeking a dish that means something to them.

One episode (spoiler alert, in case you’re planning to watch it) deals with the regulars realizing a fellow who frequently comes in and orders potato salad is secretly Japan’s most famous porn actor, Erect Oki. This revelation garners him the respect, awe, and envy of the other male patrons, though Mr. Oki would rather be left to his potato salad.

The jokes are there ... but as things develop, we learn he has the potato salad because it reminds him of his mother’s potato salad — and that he’s been cut off from his family for more than 20 years because of his career path. The potato salad is all he has left.

While preparing for a shoot, he learns his mother has Alzheimer’s disease, and immediately returns home. As they sit talking on the patio of a care center, she tells him about her son, who lives in Tokyo, and loves her potato salad. The show doesn’t make it clear if she ever remembers who he is.

In the darkening hallways of her mind, she asks his sister for help in making potato salad for her visitor. It’s too salty, though whether this is from the ingredients or his tears is also never stated.

The episode is a poignant reminder of how Alzheimer’s disease is a worldwide human problem. Not American. Not western. Not restricted by race, or ethnicity, or continent. It effects us all as a species, as families, and as individuals. No matter what our jobs or backgrounds are.

For those of us on this side of the desk, it’s a reminder that effective treatments for Alzheimer’s disease are still not available. Yes, we have all kinds of new toys, but from a practical viewpoint it’s hard to say that we’ve made any major advances. I’m sure my drug reps will disagree with me, and I’m not saying any of the treatments of the last 28 years are worthless, but even now we’re still far from a cure, or even something that stops progression.

That’s not from lack of trying, either.

For all the jokes about his job, Mr. Oki is no different from any other children trying to hold onto their parents as the disease slowly takes them away.

I hope we have real answers, soon.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Outside of caffeine, I have very few addictions. One of them is “Midnight Diner.”

“Midnight Diner” is a quirky, sometimes funny, sometimes bittersweet, Japanese series on Netflix. It’s about a small diner in Tokyo, open only in the wee hours of the morning, its enigmatic owner/cook, and the eclectic patrons that come and go. Each is seeking a dish that means something to them.

One episode (spoiler alert, in case you’re planning to watch it) deals with the regulars realizing a fellow who frequently comes in and orders potato salad is secretly Japan’s most famous porn actor, Erect Oki. This revelation garners him the respect, awe, and envy of the other male patrons, though Mr. Oki would rather be left to his potato salad.

The jokes are there ... but as things develop, we learn he has the potato salad because it reminds him of his mother’s potato salad — and that he’s been cut off from his family for more than 20 years because of his career path. The potato salad is all he has left.

While preparing for a shoot, he learns his mother has Alzheimer’s disease, and immediately returns home. As they sit talking on the patio of a care center, she tells him about her son, who lives in Tokyo, and loves her potato salad. The show doesn’t make it clear if she ever remembers who he is.

In the darkening hallways of her mind, she asks his sister for help in making potato salad for her visitor. It’s too salty, though whether this is from the ingredients or his tears is also never stated.

The episode is a poignant reminder of how Alzheimer’s disease is a worldwide human problem. Not American. Not western. Not restricted by race, or ethnicity, or continent. It effects us all as a species, as families, and as individuals. No matter what our jobs or backgrounds are.

For those of us on this side of the desk, it’s a reminder that effective treatments for Alzheimer’s disease are still not available. Yes, we have all kinds of new toys, but from a practical viewpoint it’s hard to say that we’ve made any major advances. I’m sure my drug reps will disagree with me, and I’m not saying any of the treatments of the last 28 years are worthless, but even now we’re still far from a cure, or even something that stops progression.

That’s not from lack of trying, either.

For all the jokes about his job, Mr. Oki is no different from any other children trying to hold onto their parents as the disease slowly takes them away.

I hope we have real answers, soon.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

Outside of caffeine, I have very few addictions. One of them is “Midnight Diner.”

“Midnight Diner” is a quirky, sometimes funny, sometimes bittersweet, Japanese series on Netflix. It’s about a small diner in Tokyo, open only in the wee hours of the morning, its enigmatic owner/cook, and the eclectic patrons that come and go. Each is seeking a dish that means something to them.

One episode (spoiler alert, in case you’re planning to watch it) deals with the regulars realizing a fellow who frequently comes in and orders potato salad is secretly Japan’s most famous porn actor, Erect Oki. This revelation garners him the respect, awe, and envy of the other male patrons, though Mr. Oki would rather be left to his potato salad.

The jokes are there ... but as things develop, we learn he has the potato salad because it reminds him of his mother’s potato salad — and that he’s been cut off from his family for more than 20 years because of his career path. The potato salad is all he has left.

While preparing for a shoot, he learns his mother has Alzheimer’s disease, and immediately returns home. As they sit talking on the patio of a care center, she tells him about her son, who lives in Tokyo, and loves her potato salad. The show doesn’t make it clear if she ever remembers who he is.

In the darkening hallways of her mind, she asks his sister for help in making potato salad for her visitor. It’s too salty, though whether this is from the ingredients or his tears is also never stated.

The episode is a poignant reminder of how Alzheimer’s disease is a worldwide human problem. Not American. Not western. Not restricted by race, or ethnicity, or continent. It effects us all as a species, as families, and as individuals. No matter what our jobs or backgrounds are.

For those of us on this side of the desk, it’s a reminder that effective treatments for Alzheimer’s disease are still not available. Yes, we have all kinds of new toys, but from a practical viewpoint it’s hard to say that we’ve made any major advances. I’m sure my drug reps will disagree with me, and I’m not saying any of the treatments of the last 28 years are worthless, but even now we’re still far from a cure, or even something that stops progression.

That’s not from lack of trying, either.

For all the jokes about his job, Mr. Oki is no different from any other children trying to hold onto their parents as the disease slowly takes them away.

I hope we have real answers, soon.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.