Alzheimer's & Cognition

BARCELONA – Amyloid PET brain imaging changed clinical management in 60% of patients with a diagnosis of mild cognitive impairment or dementia and confirmed a presumptive Alzheimer’s diagnosis in 95% of those with positive scans.

But the scans also benefited amyloid-negative patients, Gil Rabinovici, MD, said at the Clinical Trials on Alzheimer’s Disease conference. Before the test, 71% carried an Alzheimer’s disease (AD) diagnosis; after the test, just 10% did, opening the way for an accurate diagnosis and more effective treatment.

“These patients were saved from unnecessary treatment for Alzheimer’s,” said Dr. Rabinovici, the Edward Fein and Pearl Landrith Endowed Professor in Memory & Aging at the University of California, San Francisco. They received more suitable care plans because of the confirmation.

He presented final results of aim one of the IDEAS (Imaging Dementia–Evidence for Amyloid Scanning) study, which seeks to prove that amyloid imaging changes clinical management and improves health outcomes in Medicare beneficiaries who have been diagnosed with mild cognitive impairment (MCI) or dementia of uncertain cause. Its two aims are to show that amyloid PET imaging affects a patient’s care plan within 3 months of the scan and that this impacts major medical outcomes 12 months later. In diagnostically uncertain cases, investigators theorized, amyloid PET imaging would lead to significant changes in patient management, which would then translate into improved medical outcomes.

Ultimately, investigators hope the U.S.-wide, open-label study will prove the clinical value of amyloid PET scanning and convince the Centers for Medicare & Medicaid Services to make the test a fully covered service.

So far, IDEAS has accrued data on 11,409 patients and is quickly closing in on the 18,000-patient target. The patients reported on at CTAD were aged a mean of 75 years and were largely white; only 4% were black and 4% Hispanic. The mean Mini-Mental Scale Exam score was 26. AD was the leading suspect pathology in 73% of the 6,905 with MCI and in 83% of those with dementia of uncertain etiology. Overall, 44% were taking AD medications at baseline.

Scans were positive in 55% of those with MCI and in 70% of those with dementia. Overall, the scans changed clinical management in 61% (7,018), including 60% of those with MCI and 63% of those with dementia.

“We also asked physicians how much the scan results contributed to these changes, and 86.7% replied that they ‘contributed significantly,’ ” Dr. Rabinovici said.

Most changes involved adjustments to medication. AD drugs were started in 44% of MCI patients and in 45% of dementia patients, and non-AD drugs started in 22% and 25%, respectively. About a fifth of the patients received counseling in wake of the scan results.

Medication adjustments also varied by scan result. Among amyloid-positive MCI patients, AD drug use increased from 40% before imaging to 81% after; among amyloid-negative MCI patients, drug use decreased slightly from 27% to 24%. Among amyloid-positive dementia patients, AD drug use increased from 63% to 91%, and among amyloid-negative patients, it dropped from 50% to 44%. All these changes were statistically significant.

The primary diagnosis changed from AD to non-AD in 25%, and from non-AD to AD in 10%. Among amyloid-positive patients, the diagnosis prevalence jumped from 80.0% to 95.5%; among amyloid-negative patients, it dropped from 71% to just 10%.

“IDEAS now provides the strongest data we have supporting the beneficial impact of amyloid PET on patient management,” said Dr. Rabinovici. “Aim two, which is the 12-month health outcomes, we expect to be completed by the end of next year.”

The IDEAS team is also looking at a furthering the investigation with a study called, aptly, “NEW IDEAS.” That would reach out to recruit the minorities that were so underrepresented in the main study and include patients with early-onset MCI or dementia. Building up a library of DNA and blood plasma samples might also fit into the new project.

IDEAS is a funding collaboration of the CMS, the Alzheimer’s Association, Avid Radiopharmaceuticals/Eli Lilly, General Electric Healthcare, Piramal Imaging, and the American College of Radiology. Dr. Rabinovici had no financial disclosures.

[email protected]

BARCELONA – Amyloid PET brain imaging changed clinical management in 60% of patients with a diagnosis of mild cognitive impairment or dementia and confirmed a presumptive Alzheimer’s diagnosis in 95% of those with positive scans.

But the scans also benefited amyloid-negative patients, Gil Rabinovici, MD, said at the Clinical Trials on Alzheimer’s Disease conference. Before the test, 71% carried an Alzheimer’s disease (AD) diagnosis; after the test, just 10% did, opening the way for an accurate diagnosis and more effective treatment.

“These patients were saved from unnecessary treatment for Alzheimer’s,” said Dr. Rabinovici, the Edward Fein and Pearl Landrith Endowed Professor in Memory & Aging at the University of California, San Francisco. They received more suitable care plans because of the confirmation.

He presented final results of aim one of the IDEAS (Imaging Dementia–Evidence for Amyloid Scanning) study, which seeks to prove that amyloid imaging changes clinical management and improves health outcomes in Medicare beneficiaries who have been diagnosed with mild cognitive impairment (MCI) or dementia of uncertain cause. Its two aims are to show that amyloid PET imaging affects a patient’s care plan within 3 months of the scan and that this impacts major medical outcomes 12 months later. In diagnostically uncertain cases, investigators theorized, amyloid PET imaging would lead to significant changes in patient management, which would then translate into improved medical outcomes.

Ultimately, investigators hope the U.S.-wide, open-label study will prove the clinical value of amyloid PET scanning and convince the Centers for Medicare & Medicaid Services to make the test a fully covered service.

So far, IDEAS has accrued data on 11,409 patients and is quickly closing in on the 18,000-patient target. The patients reported on at CTAD were aged a mean of 75 years and were largely white; only 4% were black and 4% Hispanic. The mean Mini-Mental Scale Exam score was 26. AD was the leading suspect pathology in 73% of the 6,905 with MCI and in 83% of those with dementia of uncertain etiology. Overall, 44% were taking AD medications at baseline.

Scans were positive in 55% of those with MCI and in 70% of those with dementia. Overall, the scans changed clinical management in 61% (7,018), including 60% of those with MCI and 63% of those with dementia.

“We also asked physicians how much the scan results contributed to these changes, and 86.7% replied that they ‘contributed significantly,’ ” Dr. Rabinovici said.

Most changes involved adjustments to medication. AD drugs were started in 44% of MCI patients and in 45% of dementia patients, and non-AD drugs started in 22% and 25%, respectively. About a fifth of the patients received counseling in wake of the scan results.

Medication adjustments also varied by scan result. Among amyloid-positive MCI patients, AD drug use increased from 40% before imaging to 81% after; among amyloid-negative MCI patients, drug use decreased slightly from 27% to 24%. Among amyloid-positive dementia patients, AD drug use increased from 63% to 91%, and among amyloid-negative patients, it dropped from 50% to 44%. All these changes were statistically significant.

The primary diagnosis changed from AD to non-AD in 25%, and from non-AD to AD in 10%. Among amyloid-positive patients, the diagnosis prevalence jumped from 80.0% to 95.5%; among amyloid-negative patients, it dropped from 71% to just 10%.

“IDEAS now provides the strongest data we have supporting the beneficial impact of amyloid PET on patient management,” said Dr. Rabinovici. “Aim two, which is the 12-month health outcomes, we expect to be completed by the end of next year.”

The IDEAS team is also looking at a furthering the investigation with a study called, aptly, “NEW IDEAS.” That would reach out to recruit the minorities that were so underrepresented in the main study and include patients with early-onset MCI or dementia. Building up a library of DNA and blood plasma samples might also fit into the new project.

IDEAS is a funding collaboration of the CMS, the Alzheimer’s Association, Avid Radiopharmaceuticals/Eli Lilly, General Electric Healthcare, Piramal Imaging, and the American College of Radiology. Dr. Rabinovici had no financial disclosures.

[email protected]

BARCELONA – Amyloid PET brain imaging changed clinical management in 60% of patients with a diagnosis of mild cognitive impairment or dementia and confirmed a presumptive Alzheimer’s diagnosis in 95% of those with positive scans.

But the scans also benefited amyloid-negative patients, Gil Rabinovici, MD, said at the Clinical Trials on Alzheimer’s Disease conference. Before the test, 71% carried an Alzheimer’s disease (AD) diagnosis; after the test, just 10% did, opening the way for an accurate diagnosis and more effective treatment.

“These patients were saved from unnecessary treatment for Alzheimer’s,” said Dr. Rabinovici, the Edward Fein and Pearl Landrith Endowed Professor in Memory & Aging at the University of California, San Francisco. They received more suitable care plans because of the confirmation.

He presented final results of aim one of the IDEAS (Imaging Dementia–Evidence for Amyloid Scanning) study, which seeks to prove that amyloid imaging changes clinical management and improves health outcomes in Medicare beneficiaries who have been diagnosed with mild cognitive impairment (MCI) or dementia of uncertain cause. Its two aims are to show that amyloid PET imaging affects a patient’s care plan within 3 months of the scan and that this impacts major medical outcomes 12 months later. In diagnostically uncertain cases, investigators theorized, amyloid PET imaging would lead to significant changes in patient management, which would then translate into improved medical outcomes.

Ultimately, investigators hope the U.S.-wide, open-label study will prove the clinical value of amyloid PET scanning and convince the Centers for Medicare & Medicaid Services to make the test a fully covered service.

So far, IDEAS has accrued data on 11,409 patients and is quickly closing in on the 18,000-patient target. The patients reported on at CTAD were aged a mean of 75 years and were largely white; only 4% were black and 4% Hispanic. The mean Mini-Mental Scale Exam score was 26. AD was the leading suspect pathology in 73% of the 6,905 with MCI and in 83% of those with dementia of uncertain etiology. Overall, 44% were taking AD medications at baseline.

Scans were positive in 55% of those with MCI and in 70% of those with dementia. Overall, the scans changed clinical management in 61% (7,018), including 60% of those with MCI and 63% of those with dementia.

“We also asked physicians how much the scan results contributed to these changes, and 86.7% replied that they ‘contributed significantly,’ ” Dr. Rabinovici said.

Most changes involved adjustments to medication. AD drugs were started in 44% of MCI patients and in 45% of dementia patients, and non-AD drugs started in 22% and 25%, respectively. About a fifth of the patients received counseling in wake of the scan results.

Medication adjustments also varied by scan result. Among amyloid-positive MCI patients, AD drug use increased from 40% before imaging to 81% after; among amyloid-negative MCI patients, drug use decreased slightly from 27% to 24%. Among amyloid-positive dementia patients, AD drug use increased from 63% to 91%, and among amyloid-negative patients, it dropped from 50% to 44%. All these changes were statistically significant.

The primary diagnosis changed from AD to non-AD in 25%, and from non-AD to AD in 10%. Among amyloid-positive patients, the diagnosis prevalence jumped from 80.0% to 95.5%; among amyloid-negative patients, it dropped from 71% to just 10%.

“IDEAS now provides the strongest data we have supporting the beneficial impact of amyloid PET on patient management,” said Dr. Rabinovici. “Aim two, which is the 12-month health outcomes, we expect to be completed by the end of next year.”

The IDEAS team is also looking at a furthering the investigation with a study called, aptly, “NEW IDEAS.” That would reach out to recruit the minorities that were so underrepresented in the main study and include patients with early-onset MCI or dementia. Building up a library of DNA and blood plasma samples might also fit into the new project.

IDEAS is a funding collaboration of the CMS, the Alzheimer’s Association, Avid Radiopharmaceuticals/Eli Lilly, General Electric Healthcare, Piramal Imaging, and the American College of Radiology. Dr. Rabinovici had no financial disclosures.

[email protected]

ATLANTA – Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, results from a long-term analysis showed.

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” lead study author Keenan Walker, PhD, said in an interview in advance of the annual meeting of the American Neurological Association. “For example, several studies have found higher levels of inflammatory markers in the blood and cerebral spinal fluid of patients with dementia, compared to nondemented individuals of a comparable age. What is less clear, however, is whether inflammation actually promotes cognitive decline or occurs simply as a result of the brain changes underlying dementia.”

To help answer this question, Dr. Walker, of Johns Hopkins University, Baltimore, and his colleagues evaluated blood biomarkers of inflammation in 12,727 middle-aged participants during visits one and two of the Atherosclerosis Risk in Communities (ARIC) study, a prospective epidemiologic analysis conducted in four U.S. communities and funded by the National Heart, Lung, and Blood Institute. Visit one occurred between 1987 and 1989, while visit two took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at visit one, and measured C-reactive protein (CRP) at visit two. Next, they used measures of memory, executive function, and language assess cognition over three visits spanning 20 years.

The average age of study participants at first cognitive assessment was 57 years, 56% were women, and 21% were black. After controlling for differences in demographic variables, vascular risk factors and comorbidities, the researchers observed that each standard deviation (SD) increase in the midlife inflammation composite score was associated with an additional 20-year global cognitive decline of –0.035 SD (P less than .01). They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (–0.038 SD; P less than .01). In addition, study participants with a midlife inflammation composite score in the top quartile had a 7.6% steeper decline in global cognition, compared with participants in the lowest quartile; a similar association was observed for CRP.

“We were surprised at what we found when we looked at inflammation’s effect on individual cognitive domains,” Dr. Walker said. “Specifically, we found that inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language. One possible interpretation for these findings is that inflammation may selectively influence brain regions such as the hippocampus, which are necessary for memory consolidation and are also most vulnerable to Alzheimer’s disease.” He added that the current findings “provide support for the idea that systemic inflammation may have an early pathogenic role in the cognitive decline that occurs in the decades leading up to older adulthood.”

Dr. Walker acknowledged certain limitations of the study, including the attrition of participants because of deaths and dropouts over the 20-year follow-up period. “Because high levels of inflammation and comorbid disease are related to death and risk of study dropout, the sample of participants who completed the entirety of the study may represent a group that is healthier overall than the general population,” he said. “However, we took several steps to reduce any potential attrition bias using advanced statistical techniques.”

Dr. Walker disclosed that he receives funding support from the National Institutes of Health.
 

[email protected]

Source: Walker et al. ANA 2018, Abstract 305.

ATLANTA – Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, results from a long-term analysis showed.

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” lead study author Keenan Walker, PhD, said in an interview in advance of the annual meeting of the American Neurological Association. “For example, several studies have found higher levels of inflammatory markers in the blood and cerebral spinal fluid of patients with dementia, compared to nondemented individuals of a comparable age. What is less clear, however, is whether inflammation actually promotes cognitive decline or occurs simply as a result of the brain changes underlying dementia.”

To help answer this question, Dr. Walker, of Johns Hopkins University, Baltimore, and his colleagues evaluated blood biomarkers of inflammation in 12,727 middle-aged participants during visits one and two of the Atherosclerosis Risk in Communities (ARIC) study, a prospective epidemiologic analysis conducted in four U.S. communities and funded by the National Heart, Lung, and Blood Institute. Visit one occurred between 1987 and 1989, while visit two took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at visit one, and measured C-reactive protein (CRP) at visit two. Next, they used measures of memory, executive function, and language assess cognition over three visits spanning 20 years.

The average age of study participants at first cognitive assessment was 57 years, 56% were women, and 21% were black. After controlling for differences in demographic variables, vascular risk factors and comorbidities, the researchers observed that each standard deviation (SD) increase in the midlife inflammation composite score was associated with an additional 20-year global cognitive decline of –0.035 SD (P less than .01). They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (–0.038 SD; P less than .01). In addition, study participants with a midlife inflammation composite score in the top quartile had a 7.6% steeper decline in global cognition, compared with participants in the lowest quartile; a similar association was observed for CRP.

“We were surprised at what we found when we looked at inflammation’s effect on individual cognitive domains,” Dr. Walker said. “Specifically, we found that inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language. One possible interpretation for these findings is that inflammation may selectively influence brain regions such as the hippocampus, which are necessary for memory consolidation and are also most vulnerable to Alzheimer’s disease.” He added that the current findings “provide support for the idea that systemic inflammation may have an early pathogenic role in the cognitive decline that occurs in the decades leading up to older adulthood.”

Dr. Walker acknowledged certain limitations of the study, including the attrition of participants because of deaths and dropouts over the 20-year follow-up period. “Because high levels of inflammation and comorbid disease are related to death and risk of study dropout, the sample of participants who completed the entirety of the study may represent a group that is healthier overall than the general population,” he said. “However, we took several steps to reduce any potential attrition bias using advanced statistical techniques.”

Dr. Walker disclosed that he receives funding support from the National Institutes of Health.
 

[email protected]

Source: Walker et al. ANA 2018, Abstract 305.

ATLANTA – Individuals with higher levels of systemic inflammation during midlife experience greater rates of cognitive decline over the subsequent 20-year period, results from a long-term analysis showed.

“There is considerable evidence suggesting that abnormal immune functioning and inflammation may influence cognitive functioning and promote dementia,” lead study author Keenan Walker, PhD, said in an interview in advance of the annual meeting of the American Neurological Association. “For example, several studies have found higher levels of inflammatory markers in the blood and cerebral spinal fluid of patients with dementia, compared to nondemented individuals of a comparable age. What is less clear, however, is whether inflammation actually promotes cognitive decline or occurs simply as a result of the brain changes underlying dementia.”

To help answer this question, Dr. Walker, of Johns Hopkins University, Baltimore, and his colleagues evaluated blood biomarkers of inflammation in 12,727 middle-aged participants during visits one and two of the Atherosclerosis Risk in Communities (ARIC) study, a prospective epidemiologic analysis conducted in four U.S. communities and funded by the National Heart, Lung, and Blood Institute. Visit one occurred between 1987 and 1989, while visit two took place between 1990 and 1992. The researchers related these markers to cognitive change over the subsequent decades. Specifically, they used four biomarkers (fibrinogen, white blood cell count, von Willebrand factor, and Factor VIII) to create an inflammation composite score at visit one, and measured C-reactive protein (CRP) at visit two. Next, they used measures of memory, executive function, and language assess cognition over three visits spanning 20 years.

The average age of study participants at first cognitive assessment was 57 years, 56% were women, and 21% were black. After controlling for differences in demographic variables, vascular risk factors and comorbidities, the researchers observed that each standard deviation (SD) increase in the midlife inflammation composite score was associated with an additional 20-year global cognitive decline of –0.035 SD (P less than .01). They found a similar association between each SD higher midlife CRP level and additional 20-year decline in global cognition (–0.038 SD; P less than .01). In addition, study participants with a midlife inflammation composite score in the top quartile had a 7.6% steeper decline in global cognition, compared with participants in the lowest quartile; a similar association was observed for CRP.

“We were surprised at what we found when we looked at inflammation’s effect on individual cognitive domains,” Dr. Walker said. “Specifically, we found that inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language. One possible interpretation for these findings is that inflammation may selectively influence brain regions such as the hippocampus, which are necessary for memory consolidation and are also most vulnerable to Alzheimer’s disease.” He added that the current findings “provide support for the idea that systemic inflammation may have an early pathogenic role in the cognitive decline that occurs in the decades leading up to older adulthood.”

Dr. Walker acknowledged certain limitations of the study, including the attrition of participants because of deaths and dropouts over the 20-year follow-up period. “Because high levels of inflammation and comorbid disease are related to death and risk of study dropout, the sample of participants who completed the entirety of the study may represent a group that is healthier overall than the general population,” he said. “However, we took several steps to reduce any potential attrition bias using advanced statistical techniques.”

Dr. Walker disclosed that he receives funding support from the National Institutes of Health.
 

[email protected]

Source: Walker et al. ANA 2018, Abstract 305.

NEW YORK – As part of a comprehensive support program, a computer program administered to patients with cognitive impairment, including those with Alzheimer’s disease, has been associated with preserved cognitive function.

“Based on this series of cases, we believe that the brain in patients with dementia can maintain cognitive function for up to 8 years when an integrative rehabilitation program is employed,” reported Valentin I. Bragin, MD, PhD, of the Stress and Pain Relief Memory Training Center, New York.

While the integrative program involves other types of supportive care, including physical exercises and pharmacologic treatments, the focus of this case series was on the contribution of a computer program for cognitive training. As described by Dr. Bragin, it consists of tasks aimed at training working memory, selective attention, visual field expansion, and eye-hand coordination.

The computer program is designed to improve or maintain motor speed and reaction time. The aim is a rehabilitation process to activate the brain via sensory motor and other bodily systems to prevent patients with Alzheimer’s disease from decline, according to Dr. Bragin. He explained that the computer program is augmented with pen and paper tasks, such as clock drawing, that also stimulate cognitive function.

“The theory behind this treatment is the notion that increased cerebral blood flow is a highly modifiable factor in the risk of cognitive decline,” Dr. Bragin explained at the International Conference on Parkinson’s Disease and Movement Disorders. This premise is supported by a case series of four patients. The shortest duration of treatment was 4 years, but two patients were treated for 7 years and one for 8 years. In this series, motor speed has remained stable in all four patients throughout follow-up. Reaction time remained stable over the period of study in three of four patients, while working memory remained stable in two of the four. Although there was no control group, this persistence of cognitive function is longer than that expected in patients with progressive dementia, according to Dr. Bragin.

“Previously, we demonstrated an improvement and stabilization of cognitive functions in people with mild dementia and depression for periods of up to 6 years by using pen and paper tests,” Dr. Bragin reported. He explained that the computer program expands on this approach.

“We believe that cerebral blood flow is a highly modifiable factor that is a crucial element for reducing hypoxia, improving energy production, and increasing protein synthesis to prevent dementia,” Dr. Bragin said.

Although Dr. Bragin acknowledged that the findings from this case series are preliminary and need to be replicated in a large and controlled trial, he considers it a reasonable empirical strategy, particularly when employed as part of an integrative rehabilitation program like the one now in place at his center.

“This could be a feasible treatment option for dementia patients to stabilize their cognition and improve their quality of life until newer effective approaches become available,” Dr. Bragin said. He noted in the absence of a clear understanding of the pathology of Alzheimer’s disease and other progressive disorders involving cognitive decline, “the most successful treatment model is integrative care.”

NEW YORK – As part of a comprehensive support program, a computer program administered to patients with cognitive impairment, including those with Alzheimer’s disease, has been associated with preserved cognitive function.

“Based on this series of cases, we believe that the brain in patients with dementia can maintain cognitive function for up to 8 years when an integrative rehabilitation program is employed,” reported Valentin I. Bragin, MD, PhD, of the Stress and Pain Relief Memory Training Center, New York.

While the integrative program involves other types of supportive care, including physical exercises and pharmacologic treatments, the focus of this case series was on the contribution of a computer program for cognitive training. As described by Dr. Bragin, it consists of tasks aimed at training working memory, selective attention, visual field expansion, and eye-hand coordination.

The computer program is designed to improve or maintain motor speed and reaction time. The aim is a rehabilitation process to activate the brain via sensory motor and other bodily systems to prevent patients with Alzheimer’s disease from decline, according to Dr. Bragin. He explained that the computer program is augmented with pen and paper tasks, such as clock drawing, that also stimulate cognitive function.

“The theory behind this treatment is the notion that increased cerebral blood flow is a highly modifiable factor in the risk of cognitive decline,” Dr. Bragin explained at the International Conference on Parkinson’s Disease and Movement Disorders. This premise is supported by a case series of four patients. The shortest duration of treatment was 4 years, but two patients were treated for 7 years and one for 8 years. In this series, motor speed has remained stable in all four patients throughout follow-up. Reaction time remained stable over the period of study in three of four patients, while working memory remained stable in two of the four. Although there was no control group, this persistence of cognitive function is longer than that expected in patients with progressive dementia, according to Dr. Bragin.

“Previously, we demonstrated an improvement and stabilization of cognitive functions in people with mild dementia and depression for periods of up to 6 years by using pen and paper tests,” Dr. Bragin reported. He explained that the computer program expands on this approach.

“We believe that cerebral blood flow is a highly modifiable factor that is a crucial element for reducing hypoxia, improving energy production, and increasing protein synthesis to prevent dementia,” Dr. Bragin said.

Although Dr. Bragin acknowledged that the findings from this case series are preliminary and need to be replicated in a large and controlled trial, he considers it a reasonable empirical strategy, particularly when employed as part of an integrative rehabilitation program like the one now in place at his center.

“This could be a feasible treatment option for dementia patients to stabilize their cognition and improve their quality of life until newer effective approaches become available,” Dr. Bragin said. He noted in the absence of a clear understanding of the pathology of Alzheimer’s disease and other progressive disorders involving cognitive decline, “the most successful treatment model is integrative care.”

NEW YORK – As part of a comprehensive support program, a computer program administered to patients with cognitive impairment, including those with Alzheimer’s disease, has been associated with preserved cognitive function.

“Based on this series of cases, we believe that the brain in patients with dementia can maintain cognitive function for up to 8 years when an integrative rehabilitation program is employed,” reported Valentin I. Bragin, MD, PhD, of the Stress and Pain Relief Memory Training Center, New York.

While the integrative program involves other types of supportive care, including physical exercises and pharmacologic treatments, the focus of this case series was on the contribution of a computer program for cognitive training. As described by Dr. Bragin, it consists of tasks aimed at training working memory, selective attention, visual field expansion, and eye-hand coordination.

The computer program is designed to improve or maintain motor speed and reaction time. The aim is a rehabilitation process to activate the brain via sensory motor and other bodily systems to prevent patients with Alzheimer’s disease from decline, according to Dr. Bragin. He explained that the computer program is augmented with pen and paper tasks, such as clock drawing, that also stimulate cognitive function.

“The theory behind this treatment is the notion that increased cerebral blood flow is a highly modifiable factor in the risk of cognitive decline,” Dr. Bragin explained at the International Conference on Parkinson’s Disease and Movement Disorders. This premise is supported by a case series of four patients. The shortest duration of treatment was 4 years, but two patients were treated for 7 years and one for 8 years. In this series, motor speed has remained stable in all four patients throughout follow-up. Reaction time remained stable over the period of study in three of four patients, while working memory remained stable in two of the four. Although there was no control group, this persistence of cognitive function is longer than that expected in patients with progressive dementia, according to Dr. Bragin.

“Previously, we demonstrated an improvement and stabilization of cognitive functions in people with mild dementia and depression for periods of up to 6 years by using pen and paper tests,” Dr. Bragin reported. He explained that the computer program expands on this approach.

“We believe that cerebral blood flow is a highly modifiable factor that is a crucial element for reducing hypoxia, improving energy production, and increasing protein synthesis to prevent dementia,” Dr. Bragin said.

Although Dr. Bragin acknowledged that the findings from this case series are preliminary and need to be replicated in a large and controlled trial, he considers it a reasonable empirical strategy, particularly when employed as part of an integrative rehabilitation program like the one now in place at his center.

“This could be a feasible treatment option for dementia patients to stabilize their cognition and improve their quality of life until newer effective approaches become available,” Dr. Bragin said. He noted in the absence of a clear understanding of the pathology of Alzheimer’s disease and other progressive disorders involving cognitive decline, “the most successful treatment model is integrative care.”

BERLIN—Cognitive impairment in patients with multiple sclerosis (MS) varies in presence and degree in a manner that is neither identified nor quantified by the Symbol Digit Modalities Test (SDMT), according to a study presented at ECTRIMS 2018. “A unidimensional score or measure is insufficient to adequately identify and appreciate the richness and variation of the combinations and degrees of cognitive impairment that occur in patients with MS and impact the appearance of meaningful cognitive-related disability,” said Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues. “Better screening tools are required for evaluation of cognitive impairment in patients with MS.”

Cognitive impairment is common in people with MS. This impairment impacts economically important milestones and patient quality of life. Clinician and patient perceptions of the presence and degree of cognitive impairment are insufficiently sensitive measures, according to Dr. Gudesblatt. An increasing number of cognitive domains impaired greater than 1 standard deviation below age- and education-matched persons with MS has been shown to progressively impact self-reported driving, employment, and fall risk in patients with an EDSS score less than 6. Important cognitive disability in patients with MS can be unrelated to visible physical disability. Variability in the location and degree of MS plaque burden may differentially affect cognitive and physical ability, and many other factors may influence cognitive impairment in patients with MS. Routine cognitive screening in MS care is uncommon, Dr. Gudesblatt said. The SDMT, although frequently recommended, provides a single screening score that does not provide information about individual cognitive domains or the presence and degree of impairment across multiple cognitive domains or the accumulation of cognitive impairment.

Dr. Gudesblatt and colleagues conducted a retrospective review of consecutive patients with MS referred for screening with a multidomain computerized screening cognitive assessment battery (CAB) in the course of routine care who also underwent testing with the oral version of the SDMT on the same day. Their study included 113 patients with MS. The cohort had a mean age of 48.9, and 85% were female.

Within this patient sample, the SDMT defined cognitive function as follows: 68% normal classification, 14% low, 5% moderately low, and 12% very low. In this same patient group, the multidomain screening CAB identified the following domains of cognitive impairment greater than 1 standard deviation below normal values: memory (32%), executive function (25%), attention (28%), information processing speed (30%), visuospatial processing (20%), verbal function (23%), motor skills (20%), and a global summary screening score (24%). The multidimensional screening CAB in this same patient population further identified the number of cognitive domains impaired: zero domains, 36%; one domain, 24%; two domains, 11.5%; and three or more domains, 28%.

BERLIN—Cognitive impairment in patients with multiple sclerosis (MS) varies in presence and degree in a manner that is neither identified nor quantified by the Symbol Digit Modalities Test (SDMT), according to a study presented at ECTRIMS 2018. “A unidimensional score or measure is insufficient to adequately identify and appreciate the richness and variation of the combinations and degrees of cognitive impairment that occur in patients with MS and impact the appearance of meaningful cognitive-related disability,” said Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues. “Better screening tools are required for evaluation of cognitive impairment in patients with MS.”

Cognitive impairment is common in people with MS. This impairment impacts economically important milestones and patient quality of life. Clinician and patient perceptions of the presence and degree of cognitive impairment are insufficiently sensitive measures, according to Dr. Gudesblatt. An increasing number of cognitive domains impaired greater than 1 standard deviation below age- and education-matched persons with MS has been shown to progressively impact self-reported driving, employment, and fall risk in patients with an EDSS score less than 6. Important cognitive disability in patients with MS can be unrelated to visible physical disability. Variability in the location and degree of MS plaque burden may differentially affect cognitive and physical ability, and many other factors may influence cognitive impairment in patients with MS. Routine cognitive screening in MS care is uncommon, Dr. Gudesblatt said. The SDMT, although frequently recommended, provides a single screening score that does not provide information about individual cognitive domains or the presence and degree of impairment across multiple cognitive domains or the accumulation of cognitive impairment.

Dr. Gudesblatt and colleagues conducted a retrospective review of consecutive patients with MS referred for screening with a multidomain computerized screening cognitive assessment battery (CAB) in the course of routine care who also underwent testing with the oral version of the SDMT on the same day. Their study included 113 patients with MS. The cohort had a mean age of 48.9, and 85% were female.

Within this patient sample, the SDMT defined cognitive function as follows: 68% normal classification, 14% low, 5% moderately low, and 12% very low. In this same patient group, the multidomain screening CAB identified the following domains of cognitive impairment greater than 1 standard deviation below normal values: memory (32%), executive function (25%), attention (28%), information processing speed (30%), visuospatial processing (20%), verbal function (23%), motor skills (20%), and a global summary screening score (24%). The multidimensional screening CAB in this same patient population further identified the number of cognitive domains impaired: zero domains, 36%; one domain, 24%; two domains, 11.5%; and three or more domains, 28%.

BERLIN—Cognitive impairment in patients with multiple sclerosis (MS) varies in presence and degree in a manner that is neither identified nor quantified by the Symbol Digit Modalities Test (SDMT), according to a study presented at ECTRIMS 2018. “A unidimensional score or measure is insufficient to adequately identify and appreciate the richness and variation of the combinations and degrees of cognitive impairment that occur in patients with MS and impact the appearance of meaningful cognitive-related disability,” said Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, New York, and colleagues. “Better screening tools are required for evaluation of cognitive impairment in patients with MS.”

Cognitive impairment is common in people with MS. This impairment impacts economically important milestones and patient quality of life. Clinician and patient perceptions of the presence and degree of cognitive impairment are insufficiently sensitive measures, according to Dr. Gudesblatt. An increasing number of cognitive domains impaired greater than 1 standard deviation below age- and education-matched persons with MS has been shown to progressively impact self-reported driving, employment, and fall risk in patients with an EDSS score less than 6. Important cognitive disability in patients with MS can be unrelated to visible physical disability. Variability in the location and degree of MS plaque burden may differentially affect cognitive and physical ability, and many other factors may influence cognitive impairment in patients with MS. Routine cognitive screening in MS care is uncommon, Dr. Gudesblatt said. The SDMT, although frequently recommended, provides a single screening score that does not provide information about individual cognitive domains or the presence and degree of impairment across multiple cognitive domains or the accumulation of cognitive impairment.

Dr. Gudesblatt and colleagues conducted a retrospective review of consecutive patients with MS referred for screening with a multidomain computerized screening cognitive assessment battery (CAB) in the course of routine care who also underwent testing with the oral version of the SDMT on the same day. Their study included 113 patients with MS. The cohort had a mean age of 48.9, and 85% were female.

Within this patient sample, the SDMT defined cognitive function as follows: 68% normal classification, 14% low, 5% moderately low, and 12% very low. In this same patient group, the multidomain screening CAB identified the following domains of cognitive impairment greater than 1 standard deviation below normal values: memory (32%), executive function (25%), attention (28%), information processing speed (30%), visuospatial processing (20%), verbal function (23%), motor skills (20%), and a global summary screening score (24%). The multidimensional screening CAB in this same patient population further identified the number of cognitive domains impaired: zero domains, 36%; one domain, 24%; two domains, 11.5%; and three or more domains, 28%.

Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, based on results from the population-based Rotterdam study published in the Oct. 1 online edition of the Journal of Neurology, Neurosurgery & Psychiatry.

The study involved 12,102 individuals (57.7% women) who were aged 45 years or older and free from neurologic disease at baseline who were followed for 26 years.

Silvan Licher, MD, and colleagues from the University Medical Center Rotterdam (the Netherlands) found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.

“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet, a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”

Women aged 45 years had a significantly higher lifetime risk than men of developing dementia (31.4% vs. 18.6% respectively) and stroke (21.6% vs. 19.3%), but the risk of parkinsonism was similar between the sexes.

Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs. 3.1%, P less than .001), largely because of the overlap between dementia and stroke.

At age 45 women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85 years, 66.6% of first diagnoses in women and 55.6% in men were dementia.

By comparison, first manifestation of stroke was the greatest threat to men aged 45. Men were also at a significantly higher risk for stroke at a younger age – before age 75 years – than were women (8.4% vs. 5.8%).

In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke, and was relatively low after the age of 85 years, with no significant differences in risk between men and women.

The authors also considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a 1, 2, or 3-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals aged 45 years or older, and a greater than 50% reduction in risk in the very oldest.

A 3-year delay in the onset of dementia reduced the lifetime risk by 15% for both men and women aged 45 years and granted a 30% reduction in risk to those aged 45 years or older.

The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam, the Netherlands Consortium for Healthy Ageing, and the Dutch Heart Foundation. No conflicts of interest were declared.

SOURCE: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.

Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, based on results from the population-based Rotterdam study published in the Oct. 1 online edition of the Journal of Neurology, Neurosurgery & Psychiatry.

The study involved 12,102 individuals (57.7% women) who were aged 45 years or older and free from neurologic disease at baseline who were followed for 26 years.

Silvan Licher, MD, and colleagues from the University Medical Center Rotterdam (the Netherlands) found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.

“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet, a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”

Women aged 45 years had a significantly higher lifetime risk than men of developing dementia (31.4% vs. 18.6% respectively) and stroke (21.6% vs. 19.3%), but the risk of parkinsonism was similar between the sexes.

Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs. 3.1%, P less than .001), largely because of the overlap between dementia and stroke.

At age 45 women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85 years, 66.6% of first diagnoses in women and 55.6% in men were dementia.

By comparison, first manifestation of stroke was the greatest threat to men aged 45. Men were also at a significantly higher risk for stroke at a younger age – before age 75 years – than were women (8.4% vs. 5.8%).

In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke, and was relatively low after the age of 85 years, with no significant differences in risk between men and women.

The authors also considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a 1, 2, or 3-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals aged 45 years or older, and a greater than 50% reduction in risk in the very oldest.

A 3-year delay in the onset of dementia reduced the lifetime risk by 15% for both men and women aged 45 years and granted a 30% reduction in risk to those aged 45 years or older.

The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam, the Netherlands Consortium for Healthy Ageing, and the Dutch Heart Foundation. No conflicts of interest were declared.

SOURCE: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.

Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, based on results from the population-based Rotterdam study published in the Oct. 1 online edition of the Journal of Neurology, Neurosurgery & Psychiatry.

The study involved 12,102 individuals (57.7% women) who were aged 45 years or older and free from neurologic disease at baseline who were followed for 26 years.

Silvan Licher, MD, and colleagues from the University Medical Center Rotterdam (the Netherlands) found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.

“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet, a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”

Women aged 45 years had a significantly higher lifetime risk than men of developing dementia (31.4% vs. 18.6% respectively) and stroke (21.6% vs. 19.3%), but the risk of parkinsonism was similar between the sexes.

Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs. 3.1%, P less than .001), largely because of the overlap between dementia and stroke.

At age 45 women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85 years, 66.6% of first diagnoses in women and 55.6% in men were dementia.

By comparison, first manifestation of stroke was the greatest threat to men aged 45. Men were also at a significantly higher risk for stroke at a younger age – before age 75 years – than were women (8.4% vs. 5.8%).

In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke, and was relatively low after the age of 85 years, with no significant differences in risk between men and women.

The authors also considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a 1, 2, or 3-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals aged 45 years or older, and a greater than 50% reduction in risk in the very oldest.

A 3-year delay in the onset of dementia reduced the lifetime risk by 15% for both men and women aged 45 years and granted a 30% reduction in risk to those aged 45 years or older.

The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam, the Netherlands Consortium for Healthy Ageing, and the Dutch Heart Foundation. No conflicts of interest were declared.

SOURCE: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.

Nearly half of Medicare beneficiaries with Parkinson’s disease were concurrently prescribed a high-potency anticholinergic medication and an acetylcholinesterase inhibitor, with higher rates of potential prescribing errors seen among women and Hispanic patients, according to a cross-sectional analysis of Centers for Medicare & Medicaid Services data published in JAMA Neurology.

tupungato/Thinkstock

“Coadministration of a drug with high anticholinergic activity and an [acetylcholinesterase inhibitor] represents a frank prescribing error because these drugs have opposing pharmacologic effects,” wrote Sneha Mantri, MD, of the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia VA Medical Center, and her colleagues. “In patients with Parkinson disease, who bear additional risks of cognitive impairment and vulnerability to anticholinergic activity, coprescribing of an [acetylcholinesterase inhibitor] and a high-potency anticholinergic medication can be considered a never event because it is a medication error likely to contribute to disability.”

Dr. Mantri and her colleagues analyzed the inpatient, outpatient, and prescription data of 268,407 Medicare beneficiaries with Parkinson’s, of whom 73,093 patients (27.2%) were prescribed a minimum of one antidementia medication fill. Patients were mean 78.9 years old, and the demographics of the Medicare beneficiaries were 50.1% male, 86.7% white, 5.5% black, 2.7% Hispanic, 2.7% Asian, and 0.7% Native American. The most common antidementia prescriptions were donepezil hydrochloride (63.0%), memantine hydrochloride (41.8%), and rivastigmine tartrate (26.4%). The researchers measured medications in cases of coprescription with potential anticholinergic (ACH) activity using the Anticholinergic Cognitive Burden Scale.

They found antidementia medication use was associated with patients who were black (adjusted odds ratio, 1.33; 95% confidence interval, 1.28-1.38) and Hispanic (aOR, 1.28; 95% CI, 1.22-1.35). Meanwhile, a negative association was found between Native American patients and antidementia medication use (aOR, 0.62; 95% CI, 0.51-0.74) compared with white patients and women (aOR, 0.85; 95% CI, 0.84-0.87) compared with men. The researchers noted that 28,495 patients (44.5%) were prescribed concurrently one high-potency anticholinergic and acetylcholinesterase inhibitors, with higher rates of prescribing seen for Hispanic (aOR, 1.11; 95% CI, 1.00-1.23) and women (aOR, 1.30; 95% CI, 1.25-1.35). High prevalence clusters of this type of prescribing were statistically high in the Southern and Midwestern states, they added.

Limitations included the study of a single year of data and the absence of conclusive data of dementia prevalence among Parkinson’s patients based on antidementia medication use alone and potential off-label use of antidementia medication analyzed in the study, the researchers said.

“In determining whether anticholinergic drug exposure has a causal role in clinical dementia in Parkinson disease, future studies may take a clinical trial approach, in which high-potency anticholinergic medications are replaced with lower-potency alternatives, and the change in cognitive testing and cognitive trajectory are measured,” Dr. Mantri and her colleagues wrote. “Such an approach will allow the calculation of anticholinergic drug safety in terms that are easily understood, such as number needed to harm.”

This study was funded by a grant from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health. The authors report no relevant conflicts of interest.
 

SOURCE: Mantri S et al. JAMA Neurol. 2018 Oct 1. doi: 10.1001/jamaneurol.2018.2820.

Nearly half of Medicare beneficiaries with Parkinson’s disease were concurrently prescribed a high-potency anticholinergic medication and an acetylcholinesterase inhibitor, with higher rates of potential prescribing errors seen among women and Hispanic patients, according to a cross-sectional analysis of Centers for Medicare & Medicaid Services data published in JAMA Neurology.

tupungato/Thinkstock

“Coadministration of a drug with high anticholinergic activity and an [acetylcholinesterase inhibitor] represents a frank prescribing error because these drugs have opposing pharmacologic effects,” wrote Sneha Mantri, MD, of the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia VA Medical Center, and her colleagues. “In patients with Parkinson disease, who bear additional risks of cognitive impairment and vulnerability to anticholinergic activity, coprescribing of an [acetylcholinesterase inhibitor] and a high-potency anticholinergic medication can be considered a never event because it is a medication error likely to contribute to disability.”

Dr. Mantri and her colleagues analyzed the inpatient, outpatient, and prescription data of 268,407 Medicare beneficiaries with Parkinson’s, of whom 73,093 patients (27.2%) were prescribed a minimum of one antidementia medication fill. Patients were mean 78.9 years old, and the demographics of the Medicare beneficiaries were 50.1% male, 86.7% white, 5.5% black, 2.7% Hispanic, 2.7% Asian, and 0.7% Native American. The most common antidementia prescriptions were donepezil hydrochloride (63.0%), memantine hydrochloride (41.8%), and rivastigmine tartrate (26.4%). The researchers measured medications in cases of coprescription with potential anticholinergic (ACH) activity using the Anticholinergic Cognitive Burden Scale.

They found antidementia medication use was associated with patients who were black (adjusted odds ratio, 1.33; 95% confidence interval, 1.28-1.38) and Hispanic (aOR, 1.28; 95% CI, 1.22-1.35). Meanwhile, a negative association was found between Native American patients and antidementia medication use (aOR, 0.62; 95% CI, 0.51-0.74) compared with white patients and women (aOR, 0.85; 95% CI, 0.84-0.87) compared with men. The researchers noted that 28,495 patients (44.5%) were prescribed concurrently one high-potency anticholinergic and acetylcholinesterase inhibitors, with higher rates of prescribing seen for Hispanic (aOR, 1.11; 95% CI, 1.00-1.23) and women (aOR, 1.30; 95% CI, 1.25-1.35). High prevalence clusters of this type of prescribing were statistically high in the Southern and Midwestern states, they added.

Limitations included the study of a single year of data and the absence of conclusive data of dementia prevalence among Parkinson’s patients based on antidementia medication use alone and potential off-label use of antidementia medication analyzed in the study, the researchers said.

“In determining whether anticholinergic drug exposure has a causal role in clinical dementia in Parkinson disease, future studies may take a clinical trial approach, in which high-potency anticholinergic medications are replaced with lower-potency alternatives, and the change in cognitive testing and cognitive trajectory are measured,” Dr. Mantri and her colleagues wrote. “Such an approach will allow the calculation of anticholinergic drug safety in terms that are easily understood, such as number needed to harm.”

This study was funded by a grant from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health. The authors report no relevant conflicts of interest.
 

SOURCE: Mantri S et al. JAMA Neurol. 2018 Oct 1. doi: 10.1001/jamaneurol.2018.2820.

Nearly half of Medicare beneficiaries with Parkinson’s disease were concurrently prescribed a high-potency anticholinergic medication and an acetylcholinesterase inhibitor, with higher rates of potential prescribing errors seen among women and Hispanic patients, according to a cross-sectional analysis of Centers for Medicare & Medicaid Services data published in JAMA Neurology.

tupungato/Thinkstock

“Coadministration of a drug with high anticholinergic activity and an [acetylcholinesterase inhibitor] represents a frank prescribing error because these drugs have opposing pharmacologic effects,” wrote Sneha Mantri, MD, of the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia VA Medical Center, and her colleagues. “In patients with Parkinson disease, who bear additional risks of cognitive impairment and vulnerability to anticholinergic activity, coprescribing of an [acetylcholinesterase inhibitor] and a high-potency anticholinergic medication can be considered a never event because it is a medication error likely to contribute to disability.”

Dr. Mantri and her colleagues analyzed the inpatient, outpatient, and prescription data of 268,407 Medicare beneficiaries with Parkinson’s, of whom 73,093 patients (27.2%) were prescribed a minimum of one antidementia medication fill. Patients were mean 78.9 years old, and the demographics of the Medicare beneficiaries were 50.1% male, 86.7% white, 5.5% black, 2.7% Hispanic, 2.7% Asian, and 0.7% Native American. The most common antidementia prescriptions were donepezil hydrochloride (63.0%), memantine hydrochloride (41.8%), and rivastigmine tartrate (26.4%). The researchers measured medications in cases of coprescription with potential anticholinergic (ACH) activity using the Anticholinergic Cognitive Burden Scale.

They found antidementia medication use was associated with patients who were black (adjusted odds ratio, 1.33; 95% confidence interval, 1.28-1.38) and Hispanic (aOR, 1.28; 95% CI, 1.22-1.35). Meanwhile, a negative association was found between Native American patients and antidementia medication use (aOR, 0.62; 95% CI, 0.51-0.74) compared with white patients and women (aOR, 0.85; 95% CI, 0.84-0.87) compared with men. The researchers noted that 28,495 patients (44.5%) were prescribed concurrently one high-potency anticholinergic and acetylcholinesterase inhibitors, with higher rates of prescribing seen for Hispanic (aOR, 1.11; 95% CI, 1.00-1.23) and women (aOR, 1.30; 95% CI, 1.25-1.35). High prevalence clusters of this type of prescribing were statistically high in the Southern and Midwestern states, they added.

Limitations included the study of a single year of data and the absence of conclusive data of dementia prevalence among Parkinson’s patients based on antidementia medication use alone and potential off-label use of antidementia medication analyzed in the study, the researchers said.

“In determining whether anticholinergic drug exposure has a causal role in clinical dementia in Parkinson disease, future studies may take a clinical trial approach, in which high-potency anticholinergic medications are replaced with lower-potency alternatives, and the change in cognitive testing and cognitive trajectory are measured,” Dr. Mantri and her colleagues wrote. “Such an approach will allow the calculation of anticholinergic drug safety in terms that are easily understood, such as number needed to harm.”

This study was funded by a grant from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health. The authors report no relevant conflicts of interest.
 

SOURCE: Mantri S et al. JAMA Neurol. 2018 Oct 1. doi: 10.1001/jamaneurol.2018.2820.

Optimal measures of cardiovascular health are associated with brain health in adults, according to two studies published in the August 21 issue of JAMA.

In a French population-based cohort study, adults ages 65 and older with more cardiovascular health measures at ideal levels had a lower risk of dementia and lower rates of cognitive decline than did those with fewer optimal cardiovascular measures, such as blood pressure and physical activity.

In addition, a preliminary, cross-sectional study of younger adults found that the number of modifiable cardiovascular risk factors at recommended levels was associated with brain vessel structure and function and the number of white matter hyperintensities.

Cardiovascular Health in Older Age

Vascular dementia is the second most common neuropathologic basis of dementia, after Alzheimer’s disease, and “most cases of dementia arise from a combination of [Alzheimer’s disease] and cerebrovascular pathology,” the editorialists noted. Studies have suggested a connection between cardiovascular health and dementia, but the evidence is limited.

Cécilia Samieri, PhD, a Senior Researcher at the Bordeaux Population Health Research Center at the Université de Bordeaux in France, and colleagues studied people age 65 and older from Bordeaux, Dijon, and Montpellier, France, to examine the association between cardiovascular health level and risk of dementia and cognitive decline in older adults.

Cerebrovascular Structure and Function in Young Adults

Wilby Williamson, BMBS, Sports and Exercise Medicine Physician and Clinical Research Fellow in Cardiovascular Medicine at the University of Oxford, United Kingdom, and colleagues conducted a cross-sectional, observational study to examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function, and white matter integrity in young adults. The study included 125 adults ages 18 to 40 without clinical evidence of cerebrovascular disease. Participants had a mean age of 25, and 49% were women.

The researchers assessed patients’ cerebral vessel density, caliber, and tortuosity and brain white matter hyperintensity lesion count. In a subgroup of 52 participants, they assessed cerebral blood flow.

The researchers determined for each participant how many of eight modifiable risk factors were at recommended levels (ie, BMI < 25, highest tertile of cardiovascular fitness or physical activity, alcohol consumption < eight drinks per week, nonsmoker for more than six months, blood pressure on awake ambulatory monitoring < 130/80 mm Hg, a nonhypertensive diastolic response to exercise [ie, peak diastolic blood pressure < 90 mm Hg], total cholesterol < 200 mg/dL, and fasting glucose < 100 mg/dL).

On average, participants had six of the eight modifiable cardiovascular risk factors at recommended levels.

In multivariable models, cardiovascular risk factors were associated with cerebrovascular structure and the number of white matter hyperintensities. “For each additional modifiable risk factor categorized as healthy, vessel density was greater by 0.3 vessels/cm³, vessel caliber was greater by 8 μm, and white matter hyperintensity lesions were fewer by 1.6 lesions. Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor,” Dr. Williamson and colleagues said.

The findings suggest that “some individuals may be starting to diverge to different risk trajectories for brain vascular health in early adulthood,” the researchers said. The study was exploratory, however, and follow-up studies are needed to determine the clinical significance of these findings, they said.

“The magnitude of changes was generally much less than would be expected to produce clinical symptoms such as cognitive impairment or gait difficulty,” said Drs. Saver and Cushman. The changes, however, “may portend more substantial abnormalities later in life,” they said. “Even during the late-life period, when septuagenarians become octogenarians, cardiovascular health is associated with substantial differences in cognitive trajectory and dementia onset.”

—Jake Remaly

Suggested Reading

Samieri C, Perier MC, Gaye B, et al. Association of cardiovascular health level in older age with cognitive decline and incident dementia. JAMA. 2018;320(7):657-664.

Saver JL, Cushman M. Striving for ideal cardiovascular and brain health: It is never too early or too late. JAMA. 2018; 320(7):645-647.

Williamson W, Lewandowski AJ, Forkert ND, et al. Association of cardiovascular risk factors with MRI indices of cerebrovascular structure and function and white matter hyperintensities in young adults. JAMA. 2018;320(7):665-673.

Optimal measures of cardiovascular health are associated with brain health in adults, according to two studies published in the August 21 issue of JAMA.

In a French population-based cohort study, adults ages 65 and older with more cardiovascular health measures at ideal levels had a lower risk of dementia and lower rates of cognitive decline than did those with fewer optimal cardiovascular measures, such as blood pressure and physical activity.

In addition, a preliminary, cross-sectional study of younger adults found that the number of modifiable cardiovascular risk factors at recommended levels was associated with brain vessel structure and function and the number of white matter hyperintensities.

Cardiovascular Health in Older Age

Vascular dementia is the second most common neuropathologic basis of dementia, after Alzheimer’s disease, and “most cases of dementia arise from a combination of [Alzheimer’s disease] and cerebrovascular pathology,” the editorialists noted. Studies have suggested a connection between cardiovascular health and dementia, but the evidence is limited.

Cécilia Samieri, PhD, a Senior Researcher at the Bordeaux Population Health Research Center at the Université de Bordeaux in France, and colleagues studied people age 65 and older from Bordeaux, Dijon, and Montpellier, France, to examine the association between cardiovascular health level and risk of dementia and cognitive decline in older adults.

Cerebrovascular Structure and Function in Young Adults

Wilby Williamson, BMBS, Sports and Exercise Medicine Physician and Clinical Research Fellow in Cardiovascular Medicine at the University of Oxford, United Kingdom, and colleagues conducted a cross-sectional, observational study to examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function, and white matter integrity in young adults. The study included 125 adults ages 18 to 40 without clinical evidence of cerebrovascular disease. Participants had a mean age of 25, and 49% were women.

The researchers assessed patients’ cerebral vessel density, caliber, and tortuosity and brain white matter hyperintensity lesion count. In a subgroup of 52 participants, they assessed cerebral blood flow.

The researchers determined for each participant how many of eight modifiable risk factors were at recommended levels (ie, BMI < 25, highest tertile of cardiovascular fitness or physical activity, alcohol consumption < eight drinks per week, nonsmoker for more than six months, blood pressure on awake ambulatory monitoring < 130/80 mm Hg, a nonhypertensive diastolic response to exercise [ie, peak diastolic blood pressure < 90 mm Hg], total cholesterol < 200 mg/dL, and fasting glucose < 100 mg/dL).

On average, participants had six of the eight modifiable cardiovascular risk factors at recommended levels.

In multivariable models, cardiovascular risk factors were associated with cerebrovascular structure and the number of white matter hyperintensities. “For each additional modifiable risk factor categorized as healthy, vessel density was greater by 0.3 vessels/cm³, vessel caliber was greater by 8 μm, and white matter hyperintensity lesions were fewer by 1.6 lesions. Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor,” Dr. Williamson and colleagues said.

The findings suggest that “some individuals may be starting to diverge to different risk trajectories for brain vascular health in early adulthood,” the researchers said. The study was exploratory, however, and follow-up studies are needed to determine the clinical significance of these findings, they said.

“The magnitude of changes was generally much less than would be expected to produce clinical symptoms such as cognitive impairment or gait difficulty,” said Drs. Saver and Cushman. The changes, however, “may portend more substantial abnormalities later in life,” they said. “Even during the late-life period, when septuagenarians become octogenarians, cardiovascular health is associated with substantial differences in cognitive trajectory and dementia onset.”

—Jake Remaly

Suggested Reading

Samieri C, Perier MC, Gaye B, et al. Association of cardiovascular health level in older age with cognitive decline and incident dementia. JAMA. 2018;320(7):657-664.

Saver JL, Cushman M. Striving for ideal cardiovascular and brain health: It is never too early or too late. JAMA. 2018; 320(7):645-647.

Williamson W, Lewandowski AJ, Forkert ND, et al. Association of cardiovascular risk factors with MRI indices of cerebrovascular structure and function and white matter hyperintensities in young adults. JAMA. 2018;320(7):665-673.

Optimal measures of cardiovascular health are associated with brain health in adults, according to two studies published in the August 21 issue of JAMA.

In a French population-based cohort study, adults ages 65 and older with more cardiovascular health measures at ideal levels had a lower risk of dementia and lower rates of cognitive decline than did those with fewer optimal cardiovascular measures, such as blood pressure and physical activity.

In addition, a preliminary, cross-sectional study of younger adults found that the number of modifiable cardiovascular risk factors at recommended levels was associated with brain vessel structure and function and the number of white matter hyperintensities.

Cardiovascular Health in Older Age

Vascular dementia is the second most common neuropathologic basis of dementia, after Alzheimer’s disease, and “most cases of dementia arise from a combination of [Alzheimer’s disease] and cerebrovascular pathology,” the editorialists noted. Studies have suggested a connection between cardiovascular health and dementia, but the evidence is limited.

Cécilia Samieri, PhD, a Senior Researcher at the Bordeaux Population Health Research Center at the Université de Bordeaux in France, and colleagues studied people age 65 and older from Bordeaux, Dijon, and Montpellier, France, to examine the association between cardiovascular health level and risk of dementia and cognitive decline in older adults.

Cerebrovascular Structure and Function in Young Adults

Wilby Williamson, BMBS, Sports and Exercise Medicine Physician and Clinical Research Fellow in Cardiovascular Medicine at the University of Oxford, United Kingdom, and colleagues conducted a cross-sectional, observational study to examine relationships between modifiable cardiovascular risk factors and cerebrovascular structure, function, and white matter integrity in young adults. The study included 125 adults ages 18 to 40 without clinical evidence of cerebrovascular disease. Participants had a mean age of 25, and 49% were women.

The researchers assessed patients’ cerebral vessel density, caliber, and tortuosity and brain white matter hyperintensity lesion count. In a subgroup of 52 participants, they assessed cerebral blood flow.

The researchers determined for each participant how many of eight modifiable risk factors were at recommended levels (ie, BMI < 25, highest tertile of cardiovascular fitness or physical activity, alcohol consumption < eight drinks per week, nonsmoker for more than six months, blood pressure on awake ambulatory monitoring < 130/80 mm Hg, a nonhypertensive diastolic response to exercise [ie, peak diastolic blood pressure < 90 mm Hg], total cholesterol < 200 mg/dL, and fasting glucose < 100 mg/dL).

On average, participants had six of the eight modifiable cardiovascular risk factors at recommended levels.

In multivariable models, cardiovascular risk factors were associated with cerebrovascular structure and the number of white matter hyperintensities. “For each additional modifiable risk factor categorized as healthy, vessel density was greater by 0.3 vessels/cm³, vessel caliber was greater by 8 μm, and white matter hyperintensity lesions were fewer by 1.6 lesions. Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor,” Dr. Williamson and colleagues said.

The findings suggest that “some individuals may be starting to diverge to different risk trajectories for brain vascular health in early adulthood,” the researchers said. The study was exploratory, however, and follow-up studies are needed to determine the clinical significance of these findings, they said.

“The magnitude of changes was generally much less than would be expected to produce clinical symptoms such as cognitive impairment or gait difficulty,” said Drs. Saver and Cushman. The changes, however, “may portend more substantial abnormalities later in life,” they said. “Even during the late-life period, when septuagenarians become octogenarians, cardiovascular health is associated with substantial differences in cognitive trajectory and dementia onset.”

—Jake Remaly

Suggested Reading

Samieri C, Perier MC, Gaye B, et al. Association of cardiovascular health level in older age with cognitive decline and incident dementia. JAMA. 2018;320(7):657-664.

Saver JL, Cushman M. Striving for ideal cardiovascular and brain health: It is never too early or too late. JAMA. 2018; 320(7):645-647.

Williamson W, Lewandowski AJ, Forkert ND, et al. Association of cardiovascular risk factors with MRI indices of cerebrovascular structure and function and white matter hyperintensities in young adults. JAMA. 2018;320(7):665-673.

CHICAGO—The first large-scale analysis of dementia prevalence among sexual minorities found a rate of 8% in adults age 60 or older who are lesbian, gay, or bisexual (LGB), according to research presented at AAIC 2018.

The crude dementia prevalence was lower than the 9% prevalence among a heterosexual comparator group. Subjects in the LGB group, however, were younger, more likely to be male, and more likely to have a college education, compared with subjects in the heterosexual group, said Jason Flatt, PhD.

A Gap in the Literature

Between two million and three million people age 60 or older in the United States identify as LGB. “With the continued aging of our entire population, we expect this number to increase to about six million by 2040,” Dr. Flatt said. “Given the gaps in collection of sexual orientation and gender identification, we have not been able to look at this issue before.”

Sexual minorities may face unique dementia risks. They are less likely to marry and have children than are heterosexuals, and twice as likely to live alone. “They often have little or no caregiver support, and are likely to have experienced stigma, discrimination, trauma, and high lifelong stress,” he said. These experiences make the LGB population less likely to seek out medical care. “All of these things impact health over the life course,” he said.

To examine the prevalence of dementia and potential risk factors in a sample of LGB older adults, Dr. Flatt and his colleagues analyzed data from the Kaiser Permanente Research Program on Genes, Environment, and Health. Their study examined dementia prevalence and comorbidities among 4,337 LGB subjects and 195,264 heterosexual subjects aged 60 or older. Dementia diagnoses occurred between 1996 and 2015, and the mean follow-up time was nine years. A quarter of the LGB sample identified as lesbian, 37% identified as gay men, and 38% identified as bisexual. Depression was more common in the LGB group (35% vs 28%), as was posttraumatic stress disorder (1.9% vs 1%). Both are well-documented risk factors for dementia.

The LGB group had a younger mean age, compared with the heterosexual group (69 vs 71). In addition, a greater percentage of LGB subjects identified as male (63% vs 44%) and had a college education (62% vs 40%).

Other risk factors such as hypertension, stroke, and heart disease did not significantly differ between the groups. Dr. Flatt and his associates plan to examine midlife obesity, physical inactivity, and low educational attainment in a future analysis.

Depression Nearly Tripled the Risk

A dementia diagnosis occurred in 343 subjects (7.9%) in the LGB group and in 18,060 subjects (9.2%) in the heterosexual group.

Higher education did not seem to be as protective in the LGB population, Dr. Flatt said.

In a regression analysis that adjusted for age and education, depression almost tripled the risk of dementia among sexual minorities (odds ratio, 2.7). Depression was also a significant dementia risk factor for heterosexual subjects (odds ratio, 2.5).

These initial findings highlight the need for more research into this population, Dr. Flatt said.

“We need to provide more LGB-affirming health care services, and this means training health care providers to meet these needs,” he said. Such efforts might include improved community outreach that could result in earlier detection and treatment, as well as training medical staff to provide more culturally sensitive care.

—Michele G. Sullivan

CHICAGO—The first large-scale analysis of dementia prevalence among sexual minorities found a rate of 8% in adults age 60 or older who are lesbian, gay, or bisexual (LGB), according to research presented at AAIC 2018.

The crude dementia prevalence was lower than the 9% prevalence among a heterosexual comparator group. Subjects in the LGB group, however, were younger, more likely to be male, and more likely to have a college education, compared with subjects in the heterosexual group, said Jason Flatt, PhD.

A Gap in the Literature

Between two million and three million people age 60 or older in the United States identify as LGB. “With the continued aging of our entire population, we expect this number to increase to about six million by 2040,” Dr. Flatt said. “Given the gaps in collection of sexual orientation and gender identification, we have not been able to look at this issue before.”

Sexual minorities may face unique dementia risks. They are less likely to marry and have children than are heterosexuals, and twice as likely to live alone. “They often have little or no caregiver support, and are likely to have experienced stigma, discrimination, trauma, and high lifelong stress,” he said. These experiences make the LGB population less likely to seek out medical care. “All of these things impact health over the life course,” he said.

To examine the prevalence of dementia and potential risk factors in a sample of LGB older adults, Dr. Flatt and his colleagues analyzed data from the Kaiser Permanente Research Program on Genes, Environment, and Health. Their study examined dementia prevalence and comorbidities among 4,337 LGB subjects and 195,264 heterosexual subjects aged 60 or older. Dementia diagnoses occurred between 1996 and 2015, and the mean follow-up time was nine years. A quarter of the LGB sample identified as lesbian, 37% identified as gay men, and 38% identified as bisexual. Depression was more common in the LGB group (35% vs 28%), as was posttraumatic stress disorder (1.9% vs 1%). Both are well-documented risk factors for dementia.

The LGB group had a younger mean age, compared with the heterosexual group (69 vs 71). In addition, a greater percentage of LGB subjects identified as male (63% vs 44%) and had a college education (62% vs 40%).

Other risk factors such as hypertension, stroke, and heart disease did not significantly differ between the groups. Dr. Flatt and his associates plan to examine midlife obesity, physical inactivity, and low educational attainment in a future analysis.

Depression Nearly Tripled the Risk

A dementia diagnosis occurred in 343 subjects (7.9%) in the LGB group and in 18,060 subjects (9.2%) in the heterosexual group.

Higher education did not seem to be as protective in the LGB population, Dr. Flatt said.

In a regression analysis that adjusted for age and education, depression almost tripled the risk of dementia among sexual minorities (odds ratio, 2.7). Depression was also a significant dementia risk factor for heterosexual subjects (odds ratio, 2.5).

These initial findings highlight the need for more research into this population, Dr. Flatt said.

“We need to provide more LGB-affirming health care services, and this means training health care providers to meet these needs,” he said. Such efforts might include improved community outreach that could result in earlier detection and treatment, as well as training medical staff to provide more culturally sensitive care.

—Michele G. Sullivan

CHICAGO—The first large-scale analysis of dementia prevalence among sexual minorities found a rate of 8% in adults age 60 or older who are lesbian, gay, or bisexual (LGB), according to research presented at AAIC 2018.

The crude dementia prevalence was lower than the 9% prevalence among a heterosexual comparator group. Subjects in the LGB group, however, were younger, more likely to be male, and more likely to have a college education, compared with subjects in the heterosexual group, said Jason Flatt, PhD.

A Gap in the Literature

Between two million and three million people age 60 or older in the United States identify as LGB. “With the continued aging of our entire population, we expect this number to increase to about six million by 2040,” Dr. Flatt said. “Given the gaps in collection of sexual orientation and gender identification, we have not been able to look at this issue before.”

Sexual minorities may face unique dementia risks. They are less likely to marry and have children than are heterosexuals, and twice as likely to live alone. “They often have little or no caregiver support, and are likely to have experienced stigma, discrimination, trauma, and high lifelong stress,” he said. These experiences make the LGB population less likely to seek out medical care. “All of these things impact health over the life course,” he said.

To examine the prevalence of dementia and potential risk factors in a sample of LGB older adults, Dr. Flatt and his colleagues analyzed data from the Kaiser Permanente Research Program on Genes, Environment, and Health. Their study examined dementia prevalence and comorbidities among 4,337 LGB subjects and 195,264 heterosexual subjects aged 60 or older. Dementia diagnoses occurred between 1996 and 2015, and the mean follow-up time was nine years. A quarter of the LGB sample identified as lesbian, 37% identified as gay men, and 38% identified as bisexual. Depression was more common in the LGB group (35% vs 28%), as was posttraumatic stress disorder (1.9% vs 1%). Both are well-documented risk factors for dementia.

The LGB group had a younger mean age, compared with the heterosexual group (69 vs 71). In addition, a greater percentage of LGB subjects identified as male (63% vs 44%) and had a college education (62% vs 40%).

Other risk factors such as hypertension, stroke, and heart disease did not significantly differ between the groups. Dr. Flatt and his associates plan to examine midlife obesity, physical inactivity, and low educational attainment in a future analysis.

Depression Nearly Tripled the Risk

A dementia diagnosis occurred in 343 subjects (7.9%) in the LGB group and in 18,060 subjects (9.2%) in the heterosexual group.

Higher education did not seem to be as protective in the LGB population, Dr. Flatt said.

In a regression analysis that adjusted for age and education, depression almost tripled the risk of dementia among sexual minorities (odds ratio, 2.7). Depression was also a significant dementia risk factor for heterosexual subjects (odds ratio, 2.5).

These initial findings highlight the need for more research into this population, Dr. Flatt said.

“We need to provide more LGB-affirming health care services, and this means training health care providers to meet these needs,” he said. Such efforts might include improved community outreach that could result in earlier detection and treatment, as well as training medical staff to provide more culturally sensitive care.

—Michele G. Sullivan

Patients With High Blood Pressure Should Undergo Clock Drawing Test

A clock drawing test for detecting cognitive dysfunction should be conducted routinely in patients with high blood pressure, according to researchers.

Patients with high blood pressure who have impaired cognitive function are at increased risk of developing dementia within five years. Despite this known link, cognitive function is not routinely measured in patients with high blood pressure.

“The ability to draw the numbers of a clock and a particular time is an easy way to find out if a patient with high blood pressure has cognitive impairment,” said Augusto Vicario, MD, a cardiologist at the Cardiovascular Institute of Buenos Aires. “Identifying these patients provides the opportunity to intervene before dementia develops.”

The Heart-Brain Study in Argentina evaluated the usefulness of the clock drawing test, compared with the Mini-Mental State Examination (MMSE), to detect cognitive impairment in 1,414 adults with high blood pressure recruited from 18 cardiology centers in Argentina. The population’s average blood pressure was 144/84 mm Hg, average age was 60, and 62% were women.

For the clock drawing test, patients were given a piece of paper with a circle on it (diameter, 10 cm). They were asked to write the numbers of the clock in the correct positions inside the circle and draw hands on the clock indicating the time “20 to four.” Patients were scored as having normal cognition or moderate or severe cognitive impairment.

The researchers found a higher prevalence of cognitive impairment with the clock drawing test (36%), compared with the MMSE (21%). Three of 10 patients who had a normal MMSE score had an abnormal clock drawing result. The disparity in results between the two tests was greatest in middle-aged patients.

“Untreated high blood pressure silently and progressively damages the arteries in the subcortex of the brain and stops communication between the subcortex and frontal lobe,” said Dr. Vicario. “This disconnect leads to impaired executive functions such as planning, visuospatial abilities, remembering details, and decision-making. The clock drawing test is known to evaluate executive functions. The MMSE evaluates several other cognitive abilities but is weakly correlated with executive functions.

“Our study suggests that the clock drawing test should be preferred over the MMSE for early detection of executive dysfunction in patients with high blood pressure, particularly in middle age. We think the score on the clock drawing test can be considered a surrogate measure of silent vascular damage in the brain and identifies patients at greater risk of developing dementia. In our study, more than one-third of patients were at risk.

“The clock drawing test should be adopted as a routine screening tool for cognitive decline in patients with high blood pressure. Further studies are needed to determine whether lowering blood pressure can prevent progression to dementia,” Dr. Vicario concluded.

Short Sleep Associated With Doubled Risk of Cardiovascular Disease

Middle-aged men who sleep for five hours or fewer per night have twice the risk of developing a major cardiovascular event during the following two decades, compared with men who sleep for seven to eight hours, according to a study.

“For people with busy lives, sleeping may feel like a waste of time, but our study suggests that short sleep could be linked with future cardiovascular disease,” said Moa Bengtsson of the University of Gothenburg, Sweden.

Previous studies have generated conflicting evidence on whether short sleep is associated with a greater chance of having a future cardiovascular event. This study investigated this relationship in 50-year-old men.

In 1993, 50% of all men born in 1943 and living in Gothenburg were randomly selected to participate in the study. Of the 1,463 invited, 798 (55%) men agreed to take part. Participants underwent a physical examination and completed a questionnaire on current health conditions, average sleep duration, physical activity, and smoking. The men were divided into four groups according to their self-estimated average sleep duration at the start of the study: five or fewer hours, six hours, seven to eight hours (considered normal sleep duration), and more than eight hours.

Participants were followed up for 21 years for the occurrence of major cardiovascular events, which included heart attack, stroke, hospitalization due to heart failure, coronary revascularization, or death from cardiovascular disease. Data on cardiovascular events were collected from medical records, the Swedish Hospital Discharge Registry, and the Swedish Cause of Death Register.

Men with incomplete data on sleep duration, incomplete follow-up information, or who had a major cardiovascular event before the start of the study were excluded, leaving a total of 759 men for the analyses.

High blood pressure, diabetes, obesity, current smoking, low physical activity, and poor sleep quality were more common in men who slept for five or fewer hours per night, compared with those who slept for seven to eight hours.

Compared with those with normal sleep duration, men who slept for five or fewer hours per night had a twofold higher risk of having a major cardiovascular event by age 71. The risk remained doubled after adjusting for cardiovascular risk factors at the start of the study, including obesity, diabetes, and smoking.

“Men with the shortest sleep duration at the age of 50 were twice as likely to have had a cardiovascular event by age 71 as those who slept a normal amount, even when other risk factors were taken into account,” said Ms. Bengtsson.

“In our study, the magnitude of increased cardiovascular risk associated with insufficient sleep is similar to that of smoking or having diabetes at age 50. This was an observational study, so, based on our findings, we cannot conclude that short sleep causes cardiovascular disease or say definitively that sleeping more will reduce risk. However, the findings do suggest that sleep is important, and that should be a wake-up call to all of us.”

How Long Is a Good Night’s Sleep?

Researchers have found that a sweet spot of six to eight hours’ sleep per night is most beneficial for heart health. More or less sleep is detrimental.

“We spend one-third of our lives sleeping, yet we know little about the impact of this biologic need on the cardiovascular system,” said Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Centre in Athens.

The study investigated the relationship between sleep duration and cardiovascular disease using a meta-analysis that included 11 prospective studies published within the past five years of more than one million adults without cardiovascular disease.

Two groups, one with short (ie, fewer than six hours) and another with long (ie, more than eight hours) nightly sleep duration, were compared with the reference group (ie, six to eight hours’ sleep).

Short and long sleepers had a greater risk of developing or dying from coronary artery disease or stroke. Compared with adults who slept for six to eight hours per night, short and long sleepers had 11% and 33% greater risks, respectively, of developing or dying from coronary artery disease or stroke during an average follow-up of 9.3 years.

“Our findings suggest that too much or too little sleep may be bad for the heart,” said Dr. Fountas. “More research is needed to clarify exactly why, but we do know that sleep influences biologic processes like glucose metabolism, blood pressure, and inflammation, all of which have an impact on cardiovascular disease.”

A strength of the current analysis is that only prospective studies were included, noted Dr. Fountas. This technique avoids recall bias.

“Having the odd short night or lie-in is unlikely to be detrimental to health, but evidence is accumulating that prolonged nightly sleep deprivation or excessive sleeping should be avoided,” said Dr. Fountas. “The good news is that there are plenty of ways to get into the habit of getting six to eight hours a night: for example, by going to bed and getting up at the same time every day, avoiding alcohol and caffeine before bed, eating healthily, and being physically active. Getting the right amount of sleep is an important part of a healthy lifestyle.”

Four in 10 Patients With Atrial Fibrillation Have Unrecognized Brain Damage

Four out of 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack have previously unrecognized brain damage, according to the first results of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF).

“Our results suggest that clinically unrecognized brain damage may explain the association between dementia and atrial fibrillation in patients without prior stroke,” said David Conen, MD, MPH, Associate Professor of Cardiology at McMaster University in Hamilton, Canada.

Patients with atrial fibrillation have a significantly increased risk of stroke, which is why most are treated with oral anticoagulation. This increased stroke risk is probably the main reason why patients with atrial fibrillation also face an increased risk of cognitive dysfunction and dementia. The relationship between atrial fibrillation and dementia has also been shown among patients without prior strokes, however, meaning that additional mechanisms must be involved. Clarifying the mechanisms by which atrial fibrillation increases the risk of cognitive dysfunction and dementia is a first step towards developing preventive measures.

Swiss-AF is a prospective, observational study designed to pinpoint the mechanisms of cognitive decline in patients with atrial fibrillation. Dr. Conen’s analysis investigated the prevalence of silent brain damage in patients with atrial fibrillation.

The study enrolled 2,415 patients older than 65 with atrial fibrillation between 2014 and 2017 from 14 centers in Switzerland. All patients without contraindications underwent standardized brain MRI, and the images were analyzed in a central core laboratory. Scans were available in 1,736 patients. Of those patients, 347 (20%) had a history of stroke or transient ischemic attack and were excluded from the analysis.

The final analysis included 1,389 patients with atrial fibrillation but no history of stroke or transient ischemic attack. The average age of participants was 72, and 26% were women. The scans showed that 569 (41%) patients had at least one type of previously unrecognized brain damage: 207 (15%) had a cerebral infarct, 269 (19%) had microbleeds, and 222 (16%) had lacunes.

“Four in 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack had clinically unrecognized silent brain lesions,” said Dr. Conen. “This brain damage could trigger cognitive decline.”

Most study participants (1,234; 89%) were treated with oral anticoagulants. Stefan Osswald, MD, Chief of Cardiology at University Hospital Basel in Switzerland, noted that the cross-sectional analysis looked at the data at a single point in time and cannot address the question of whether the cerebral infarcts and other brain lesions occurred before or after initiation of oral anticoagulation. “The findings nevertheless raise the issue that oral anticoagulation might not prevent all brain damage in patients with atrial fibrillation,” he said.

“All Swiss-AF participants underwent extensive cognitive testing. These data will be analyzed to see whether patients with silent brain lesions also have impaired cognitive function,” said Dr. Conen. Collaborations with other study groups will help determine whether these findings are specific to patients with atrial fibrillation.

Impaired Mental Status Doubles Elderly’s Risk of Death After Heart Attack

Impaired mental status is associated with a doubled risk of death one year after a heart attack in elderly patients, according to researchers.

“Cardiologists should consider conducting simple tests to assess mental status in elderly people after a heart attack,” said Farzin Beygui, MD, hospital practitioner at Caen University Hospital in France. “Patients with reduced mental status can then receive more intensive management such as regular follow-up appointments with their general practitioners or nurses, more specific assessment for an early diagnosis of dementia, and tailored therapy.”

The risks of dementia, Alzheimer’s disease, confusion, and delirium increase with age. Elderly people are also at higher risk of having a heart attack and dying afterwards. People aged 75 and older account for approximately one-third of heart attack admissions and more than half of those dying in the hospital after admission for a heart attack. Until now, it was not known whether impaired mental status affected the prognosis of elderly patients with heart attack.

This study assessed the impact of mental status on the risk of death in 600 patients age 75 and above consecutively admitted for heart attack and followed up for at least one year. Mental status was assessed using the Mini-Mental State Examination (MMSE) and the Confusion Assessment Method (CAM).Cognitive impairment was detected in 174 (29%) patients. Patients with impaired mental function were more than twice as likely to be dead one year after their heart attack than those with healthy mental function. The association was independent of other potential predictors of death such as age, sex, invasive treatment, type of myocardial infarction, heart failure, and severity of the heart attack.

Impaired mental status was also associated with a nearly fourfold higher rate of bleeding complications while in the hospital and a more than twofold higher risk of being readmitted to the hospital for cardiovascular causes within three months after discharge.

“Almost one-third of elderly heart attack patients in our study had reduced mental capacity,” said Dr. Beygui. “These patients had higher risks of bleeding, rehospitalization, and death. This may be because they forget to take their medicines or take them more than prescribed, rather than because of poor cognitive function itself.

“Assessing mental status is a simple way to identify elderly patients at particularly high risk of poor outcomes following a heart attack. Identifying these patients may help us target treatment to those who need it most.”

Patients With High Blood Pressure Should Undergo Clock Drawing Test

A clock drawing test for detecting cognitive dysfunction should be conducted routinely in patients with high blood pressure, according to researchers.

Patients with high blood pressure who have impaired cognitive function are at increased risk of developing dementia within five years. Despite this known link, cognitive function is not routinely measured in patients with high blood pressure.

“The ability to draw the numbers of a clock and a particular time is an easy way to find out if a patient with high blood pressure has cognitive impairment,” said Augusto Vicario, MD, a cardiologist at the Cardiovascular Institute of Buenos Aires. “Identifying these patients provides the opportunity to intervene before dementia develops.”

The Heart-Brain Study in Argentina evaluated the usefulness of the clock drawing test, compared with the Mini-Mental State Examination (MMSE), to detect cognitive impairment in 1,414 adults with high blood pressure recruited from 18 cardiology centers in Argentina. The population’s average blood pressure was 144/84 mm Hg, average age was 60, and 62% were women.

For the clock drawing test, patients were given a piece of paper with a circle on it (diameter, 10 cm). They were asked to write the numbers of the clock in the correct positions inside the circle and draw hands on the clock indicating the time “20 to four.” Patients were scored as having normal cognition or moderate or severe cognitive impairment.

The researchers found a higher prevalence of cognitive impairment with the clock drawing test (36%), compared with the MMSE (21%). Three of 10 patients who had a normal MMSE score had an abnormal clock drawing result. The disparity in results between the two tests was greatest in middle-aged patients.

“Untreated high blood pressure silently and progressively damages the arteries in the subcortex of the brain and stops communication between the subcortex and frontal lobe,” said Dr. Vicario. “This disconnect leads to impaired executive functions such as planning, visuospatial abilities, remembering details, and decision-making. The clock drawing test is known to evaluate executive functions. The MMSE evaluates several other cognitive abilities but is weakly correlated with executive functions.

“Our study suggests that the clock drawing test should be preferred over the MMSE for early detection of executive dysfunction in patients with high blood pressure, particularly in middle age. We think the score on the clock drawing test can be considered a surrogate measure of silent vascular damage in the brain and identifies patients at greater risk of developing dementia. In our study, more than one-third of patients were at risk.

“The clock drawing test should be adopted as a routine screening tool for cognitive decline in patients with high blood pressure. Further studies are needed to determine whether lowering blood pressure can prevent progression to dementia,” Dr. Vicario concluded.

Short Sleep Associated With Doubled Risk of Cardiovascular Disease

Middle-aged men who sleep for five hours or fewer per night have twice the risk of developing a major cardiovascular event during the following two decades, compared with men who sleep for seven to eight hours, according to a study.

“For people with busy lives, sleeping may feel like a waste of time, but our study suggests that short sleep could be linked with future cardiovascular disease,” said Moa Bengtsson of the University of Gothenburg, Sweden.

Previous studies have generated conflicting evidence on whether short sleep is associated with a greater chance of having a future cardiovascular event. This study investigated this relationship in 50-year-old men.

In 1993, 50% of all men born in 1943 and living in Gothenburg were randomly selected to participate in the study. Of the 1,463 invited, 798 (55%) men agreed to take part. Participants underwent a physical examination and completed a questionnaire on current health conditions, average sleep duration, physical activity, and smoking. The men were divided into four groups according to their self-estimated average sleep duration at the start of the study: five or fewer hours, six hours, seven to eight hours (considered normal sleep duration), and more than eight hours.

Participants were followed up for 21 years for the occurrence of major cardiovascular events, which included heart attack, stroke, hospitalization due to heart failure, coronary revascularization, or death from cardiovascular disease. Data on cardiovascular events were collected from medical records, the Swedish Hospital Discharge Registry, and the Swedish Cause of Death Register.

Men with incomplete data on sleep duration, incomplete follow-up information, or who had a major cardiovascular event before the start of the study were excluded, leaving a total of 759 men for the analyses.

High blood pressure, diabetes, obesity, current smoking, low physical activity, and poor sleep quality were more common in men who slept for five or fewer hours per night, compared with those who slept for seven to eight hours.

Compared with those with normal sleep duration, men who slept for five or fewer hours per night had a twofold higher risk of having a major cardiovascular event by age 71. The risk remained doubled after adjusting for cardiovascular risk factors at the start of the study, including obesity, diabetes, and smoking.

“Men with the shortest sleep duration at the age of 50 were twice as likely to have had a cardiovascular event by age 71 as those who slept a normal amount, even when other risk factors were taken into account,” said Ms. Bengtsson.

“In our study, the magnitude of increased cardiovascular risk associated with insufficient sleep is similar to that of smoking or having diabetes at age 50. This was an observational study, so, based on our findings, we cannot conclude that short sleep causes cardiovascular disease or say definitively that sleeping more will reduce risk. However, the findings do suggest that sleep is important, and that should be a wake-up call to all of us.”

How Long Is a Good Night’s Sleep?

Researchers have found that a sweet spot of six to eight hours’ sleep per night is most beneficial for heart health. More or less sleep is detrimental.

“We spend one-third of our lives sleeping, yet we know little about the impact of this biologic need on the cardiovascular system,” said Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Centre in Athens.

The study investigated the relationship between sleep duration and cardiovascular disease using a meta-analysis that included 11 prospective studies published within the past five years of more than one million adults without cardiovascular disease.

Two groups, one with short (ie, fewer than six hours) and another with long (ie, more than eight hours) nightly sleep duration, were compared with the reference group (ie, six to eight hours’ sleep).

Short and long sleepers had a greater risk of developing or dying from coronary artery disease or stroke. Compared with adults who slept for six to eight hours per night, short and long sleepers had 11% and 33% greater risks, respectively, of developing or dying from coronary artery disease or stroke during an average follow-up of 9.3 years.

“Our findings suggest that too much or too little sleep may be bad for the heart,” said Dr. Fountas. “More research is needed to clarify exactly why, but we do know that sleep influences biologic processes like glucose metabolism, blood pressure, and inflammation, all of which have an impact on cardiovascular disease.”

A strength of the current analysis is that only prospective studies were included, noted Dr. Fountas. This technique avoids recall bias.

“Having the odd short night or lie-in is unlikely to be detrimental to health, but evidence is accumulating that prolonged nightly sleep deprivation or excessive sleeping should be avoided,” said Dr. Fountas. “The good news is that there are plenty of ways to get into the habit of getting six to eight hours a night: for example, by going to bed and getting up at the same time every day, avoiding alcohol and caffeine before bed, eating healthily, and being physically active. Getting the right amount of sleep is an important part of a healthy lifestyle.”

Four in 10 Patients With Atrial Fibrillation Have Unrecognized Brain Damage

Four out of 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack have previously unrecognized brain damage, according to the first results of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF).

“Our results suggest that clinically unrecognized brain damage may explain the association between dementia and atrial fibrillation in patients without prior stroke,” said David Conen, MD, MPH, Associate Professor of Cardiology at McMaster University in Hamilton, Canada.

Patients with atrial fibrillation have a significantly increased risk of stroke, which is why most are treated with oral anticoagulation. This increased stroke risk is probably the main reason why patients with atrial fibrillation also face an increased risk of cognitive dysfunction and dementia. The relationship between atrial fibrillation and dementia has also been shown among patients without prior strokes, however, meaning that additional mechanisms must be involved. Clarifying the mechanisms by which atrial fibrillation increases the risk of cognitive dysfunction and dementia is a first step towards developing preventive measures.

Swiss-AF is a prospective, observational study designed to pinpoint the mechanisms of cognitive decline in patients with atrial fibrillation. Dr. Conen’s analysis investigated the prevalence of silent brain damage in patients with atrial fibrillation.

The study enrolled 2,415 patients older than 65 with atrial fibrillation between 2014 and 2017 from 14 centers in Switzerland. All patients without contraindications underwent standardized brain MRI, and the images were analyzed in a central core laboratory. Scans were available in 1,736 patients. Of those patients, 347 (20%) had a history of stroke or transient ischemic attack and were excluded from the analysis.

The final analysis included 1,389 patients with atrial fibrillation but no history of stroke or transient ischemic attack. The average age of participants was 72, and 26% were women. The scans showed that 569 (41%) patients had at least one type of previously unrecognized brain damage: 207 (15%) had a cerebral infarct, 269 (19%) had microbleeds, and 222 (16%) had lacunes.

“Four in 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack had clinically unrecognized silent brain lesions,” said Dr. Conen. “This brain damage could trigger cognitive decline.”

Most study participants (1,234; 89%) were treated with oral anticoagulants. Stefan Osswald, MD, Chief of Cardiology at University Hospital Basel in Switzerland, noted that the cross-sectional analysis looked at the data at a single point in time and cannot address the question of whether the cerebral infarcts and other brain lesions occurred before or after initiation of oral anticoagulation. “The findings nevertheless raise the issue that oral anticoagulation might not prevent all brain damage in patients with atrial fibrillation,” he said.

“All Swiss-AF participants underwent extensive cognitive testing. These data will be analyzed to see whether patients with silent brain lesions also have impaired cognitive function,” said Dr. Conen. Collaborations with other study groups will help determine whether these findings are specific to patients with atrial fibrillation.

Impaired Mental Status Doubles Elderly’s Risk of Death After Heart Attack

Impaired mental status is associated with a doubled risk of death one year after a heart attack in elderly patients, according to researchers.

“Cardiologists should consider conducting simple tests to assess mental status in elderly people after a heart attack,” said Farzin Beygui, MD, hospital practitioner at Caen University Hospital in France. “Patients with reduced mental status can then receive more intensive management such as regular follow-up appointments with their general practitioners or nurses, more specific assessment for an early diagnosis of dementia, and tailored therapy.”

The risks of dementia, Alzheimer’s disease, confusion, and delirium increase with age. Elderly people are also at higher risk of having a heart attack and dying afterwards. People aged 75 and older account for approximately one-third of heart attack admissions and more than half of those dying in the hospital after admission for a heart attack. Until now, it was not known whether impaired mental status affected the prognosis of elderly patients with heart attack.

This study assessed the impact of mental status on the risk of death in 600 patients age 75 and above consecutively admitted for heart attack and followed up for at least one year. Mental status was assessed using the Mini-Mental State Examination (MMSE) and the Confusion Assessment Method (CAM).Cognitive impairment was detected in 174 (29%) patients. Patients with impaired mental function were more than twice as likely to be dead one year after their heart attack than those with healthy mental function. The association was independent of other potential predictors of death such as age, sex, invasive treatment, type of myocardial infarction, heart failure, and severity of the heart attack.

Impaired mental status was also associated with a nearly fourfold higher rate of bleeding complications while in the hospital and a more than twofold higher risk of being readmitted to the hospital for cardiovascular causes within three months after discharge.

“Almost one-third of elderly heart attack patients in our study had reduced mental capacity,” said Dr. Beygui. “These patients had higher risks of bleeding, rehospitalization, and death. This may be because they forget to take their medicines or take them more than prescribed, rather than because of poor cognitive function itself.

“Assessing mental status is a simple way to identify elderly patients at particularly high risk of poor outcomes following a heart attack. Identifying these patients may help us target treatment to those who need it most.”

Patients With High Blood Pressure Should Undergo Clock Drawing Test

A clock drawing test for detecting cognitive dysfunction should be conducted routinely in patients with high blood pressure, according to researchers.

Patients with high blood pressure who have impaired cognitive function are at increased risk of developing dementia within five years. Despite this known link, cognitive function is not routinely measured in patients with high blood pressure.

“The ability to draw the numbers of a clock and a particular time is an easy way to find out if a patient with high blood pressure has cognitive impairment,” said Augusto Vicario, MD, a cardiologist at the Cardiovascular Institute of Buenos Aires. “Identifying these patients provides the opportunity to intervene before dementia develops.”

The Heart-Brain Study in Argentina evaluated the usefulness of the clock drawing test, compared with the Mini-Mental State Examination (MMSE), to detect cognitive impairment in 1,414 adults with high blood pressure recruited from 18 cardiology centers in Argentina. The population’s average blood pressure was 144/84 mm Hg, average age was 60, and 62% were women.

For the clock drawing test, patients were given a piece of paper with a circle on it (diameter, 10 cm). They were asked to write the numbers of the clock in the correct positions inside the circle and draw hands on the clock indicating the time “20 to four.” Patients were scored as having normal cognition or moderate or severe cognitive impairment.

The researchers found a higher prevalence of cognitive impairment with the clock drawing test (36%), compared with the MMSE (21%). Three of 10 patients who had a normal MMSE score had an abnormal clock drawing result. The disparity in results between the two tests was greatest in middle-aged patients.

“Untreated high blood pressure silently and progressively damages the arteries in the subcortex of the brain and stops communication between the subcortex and frontal lobe,” said Dr. Vicario. “This disconnect leads to impaired executive functions such as planning, visuospatial abilities, remembering details, and decision-making. The clock drawing test is known to evaluate executive functions. The MMSE evaluates several other cognitive abilities but is weakly correlated with executive functions.

“Our study suggests that the clock drawing test should be preferred over the MMSE for early detection of executive dysfunction in patients with high blood pressure, particularly in middle age. We think the score on the clock drawing test can be considered a surrogate measure of silent vascular damage in the brain and identifies patients at greater risk of developing dementia. In our study, more than one-third of patients were at risk.

“The clock drawing test should be adopted as a routine screening tool for cognitive decline in patients with high blood pressure. Further studies are needed to determine whether lowering blood pressure can prevent progression to dementia,” Dr. Vicario concluded.

Short Sleep Associated With Doubled Risk of Cardiovascular Disease

Middle-aged men who sleep for five hours or fewer per night have twice the risk of developing a major cardiovascular event during the following two decades, compared with men who sleep for seven to eight hours, according to a study.

“For people with busy lives, sleeping may feel like a waste of time, but our study suggests that short sleep could be linked with future cardiovascular disease,” said Moa Bengtsson of the University of Gothenburg, Sweden.

Previous studies have generated conflicting evidence on whether short sleep is associated with a greater chance of having a future cardiovascular event. This study investigated this relationship in 50-year-old men.

In 1993, 50% of all men born in 1943 and living in Gothenburg were randomly selected to participate in the study. Of the 1,463 invited, 798 (55%) men agreed to take part. Participants underwent a physical examination and completed a questionnaire on current health conditions, average sleep duration, physical activity, and smoking. The men were divided into four groups according to their self-estimated average sleep duration at the start of the study: five or fewer hours, six hours, seven to eight hours (considered normal sleep duration), and more than eight hours.

Participants were followed up for 21 years for the occurrence of major cardiovascular events, which included heart attack, stroke, hospitalization due to heart failure, coronary revascularization, or death from cardiovascular disease. Data on cardiovascular events were collected from medical records, the Swedish Hospital Discharge Registry, and the Swedish Cause of Death Register.

Men with incomplete data on sleep duration, incomplete follow-up information, or who had a major cardiovascular event before the start of the study were excluded, leaving a total of 759 men for the analyses.

High blood pressure, diabetes, obesity, current smoking, low physical activity, and poor sleep quality were more common in men who slept for five or fewer hours per night, compared with those who slept for seven to eight hours.

Compared with those with normal sleep duration, men who slept for five or fewer hours per night had a twofold higher risk of having a major cardiovascular event by age 71. The risk remained doubled after adjusting for cardiovascular risk factors at the start of the study, including obesity, diabetes, and smoking.

“Men with the shortest sleep duration at the age of 50 were twice as likely to have had a cardiovascular event by age 71 as those who slept a normal amount, even when other risk factors were taken into account,” said Ms. Bengtsson.

“In our study, the magnitude of increased cardiovascular risk associated with insufficient sleep is similar to that of smoking or having diabetes at age 50. This was an observational study, so, based on our findings, we cannot conclude that short sleep causes cardiovascular disease or say definitively that sleeping more will reduce risk. However, the findings do suggest that sleep is important, and that should be a wake-up call to all of us.”

How Long Is a Good Night’s Sleep?

Researchers have found that a sweet spot of six to eight hours’ sleep per night is most beneficial for heart health. More or less sleep is detrimental.

“We spend one-third of our lives sleeping, yet we know little about the impact of this biologic need on the cardiovascular system,” said Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Centre in Athens.

The study investigated the relationship between sleep duration and cardiovascular disease using a meta-analysis that included 11 prospective studies published within the past five years of more than one million adults without cardiovascular disease.

Two groups, one with short (ie, fewer than six hours) and another with long (ie, more than eight hours) nightly sleep duration, were compared with the reference group (ie, six to eight hours’ sleep).

Short and long sleepers had a greater risk of developing or dying from coronary artery disease or stroke. Compared with adults who slept for six to eight hours per night, short and long sleepers had 11% and 33% greater risks, respectively, of developing or dying from coronary artery disease or stroke during an average follow-up of 9.3 years.

“Our findings suggest that too much or too little sleep may be bad for the heart,” said Dr. Fountas. “More research is needed to clarify exactly why, but we do know that sleep influences biologic processes like glucose metabolism, blood pressure, and inflammation, all of which have an impact on cardiovascular disease.”

A strength of the current analysis is that only prospective studies were included, noted Dr. Fountas. This technique avoids recall bias.

“Having the odd short night or lie-in is unlikely to be detrimental to health, but evidence is accumulating that prolonged nightly sleep deprivation or excessive sleeping should be avoided,” said Dr. Fountas. “The good news is that there are plenty of ways to get into the habit of getting six to eight hours a night: for example, by going to bed and getting up at the same time every day, avoiding alcohol and caffeine before bed, eating healthily, and being physically active. Getting the right amount of sleep is an important part of a healthy lifestyle.”

Four in 10 Patients With Atrial Fibrillation Have Unrecognized Brain Damage

Four out of 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack have previously unrecognized brain damage, according to the first results of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF).

“Our results suggest that clinically unrecognized brain damage may explain the association between dementia and atrial fibrillation in patients without prior stroke,” said David Conen, MD, MPH, Associate Professor of Cardiology at McMaster University in Hamilton, Canada.

Patients with atrial fibrillation have a significantly increased risk of stroke, which is why most are treated with oral anticoagulation. This increased stroke risk is probably the main reason why patients with atrial fibrillation also face an increased risk of cognitive dysfunction and dementia. The relationship between atrial fibrillation and dementia has also been shown among patients without prior strokes, however, meaning that additional mechanisms must be involved. Clarifying the mechanisms by which atrial fibrillation increases the risk of cognitive dysfunction and dementia is a first step towards developing preventive measures.

Swiss-AF is a prospective, observational study designed to pinpoint the mechanisms of cognitive decline in patients with atrial fibrillation. Dr. Conen’s analysis investigated the prevalence of silent brain damage in patients with atrial fibrillation.

The study enrolled 2,415 patients older than 65 with atrial fibrillation between 2014 and 2017 from 14 centers in Switzerland. All patients without contraindications underwent standardized brain MRI, and the images were analyzed in a central core laboratory. Scans were available in 1,736 patients. Of those patients, 347 (20%) had a history of stroke or transient ischemic attack and were excluded from the analysis.

The final analysis included 1,389 patients with atrial fibrillation but no history of stroke or transient ischemic attack. The average age of participants was 72, and 26% were women. The scans showed that 569 (41%) patients had at least one type of previously unrecognized brain damage: 207 (15%) had a cerebral infarct, 269 (19%) had microbleeds, and 222 (16%) had lacunes.

“Four in 10 patients with atrial fibrillation but no history of stroke or transient ischemic attack had clinically unrecognized silent brain lesions,” said Dr. Conen. “This brain damage could trigger cognitive decline.”

Most study participants (1,234; 89%) were treated with oral anticoagulants. Stefan Osswald, MD, Chief of Cardiology at University Hospital Basel in Switzerland, noted that the cross-sectional analysis looked at the data at a single point in time and cannot address the question of whether the cerebral infarcts and other brain lesions occurred before or after initiation of oral anticoagulation. “The findings nevertheless raise the issue that oral anticoagulation might not prevent all brain damage in patients with atrial fibrillation,” he said.

“All Swiss-AF participants underwent extensive cognitive testing. These data will be analyzed to see whether patients with silent brain lesions also have impaired cognitive function,” said Dr. Conen. Collaborations with other study groups will help determine whether these findings are specific to patients with atrial fibrillation.

Impaired Mental Status Doubles Elderly’s Risk of Death After Heart Attack

Impaired mental status is associated with a doubled risk of death one year after a heart attack in elderly patients, according to researchers.

“Cardiologists should consider conducting simple tests to assess mental status in elderly people after a heart attack,” said Farzin Beygui, MD, hospital practitioner at Caen University Hospital in France. “Patients with reduced mental status can then receive more intensive management such as regular follow-up appointments with their general practitioners or nurses, more specific assessment for an early diagnosis of dementia, and tailored therapy.”

The risks of dementia, Alzheimer’s disease, confusion, and delirium increase with age. Elderly people are also at higher risk of having a heart attack and dying afterwards. People aged 75 and older account for approximately one-third of heart attack admissions and more than half of those dying in the hospital after admission for a heart attack. Until now, it was not known whether impaired mental status affected the prognosis of elderly patients with heart attack.

This study assessed the impact of mental status on the risk of death in 600 patients age 75 and above consecutively admitted for heart attack and followed up for at least one year. Mental status was assessed using the Mini-Mental State Examination (MMSE) and the Confusion Assessment Method (CAM).Cognitive impairment was detected in 174 (29%) patients. Patients with impaired mental function were more than twice as likely to be dead one year after their heart attack than those with healthy mental function. The association was independent of other potential predictors of death such as age, sex, invasive treatment, type of myocardial infarction, heart failure, and severity of the heart attack.

Impaired mental status was also associated with a nearly fourfold higher rate of bleeding complications while in the hospital and a more than twofold higher risk of being readmitted to the hospital for cardiovascular causes within three months after discharge.

“Almost one-third of elderly heart attack patients in our study had reduced mental capacity,” said Dr. Beygui. “These patients had higher risks of bleeding, rehospitalization, and death. This may be because they forget to take their medicines or take them more than prescribed, rather than because of poor cognitive function itself.

“Assessing mental status is a simple way to identify elderly patients at particularly high risk of poor outcomes following a heart attack. Identifying these patients may help us target treatment to those who need it most.”

HILTON HEAD, SC—Behavioral variant frontotemporal dementia (bvFTD), a clinically and pathologically heterogenous condition, can be difficult to distinguish from other forms of dementia or frontotemporal disease. “Although clinical symptoms vary based on which part of the brain is affected, there is a significant amount of overlap, with different pathologies causing the same type of syndrome,” said Richard Ryan Darby, MD, Assistant Professor of Neurology at Vanderbilt University Medical School in Nashville. “In a large proportion of patients, behavioral changes can lead to criminal behavior.” Future research examining brain lesion networks may shed light on this condition, said Dr. Darby at the 41st Annual Contemporary Clinical Neurology Symposium.

Clinical Features and Diagnosis

The incidence of bvFTD is equal to that of Alzheimer’s disease. However, patients with bvFTD tend to be younger: between the ages of 45 and 65. “Social and behavioral features predominate,” said Dr. Darby. “If a patient in this age range with no previous psychiatric history presents to you with a new psychiatric diagnosis such as schizophrenia or bipolar disease, this should raise your suspicion of bvFTD.” These psychiatric problems often cause considerable disruptions in patients’ lives. They often have problems at work and lose their source of income. “Patients often have no insight about their symptoms,” said Dr. Darby.

A differential diagnosis of bvFTD is possible in patients with three or more of the following six clinical features: socially inappropriate behavior (eg, eating from the trash or walking around naked at inappropriate times); lack of empathy; apathy; stereotyped or repetitive behavior (eg, saying things repeatedly, pacing); hyperorality (eg, eating uncontrollably, particularly sweet foods); and executive dysfunction, especially when memory is preserved.

“When you talk to caregivers, they often say, ‘This is not the person I married,’ or, ‘This is not my father. He seems like a different person,’” said Dr. Darby. An MRI or a PET scan showing changes in the frontotemporal lobes is a firm basis for a diagnosis of bvFTD, said Dr. Darby. Genetic testing for autosomal dominant mutation or pathology or an autopsy provides a definite diagnosis.

Pathology

Between 40% and 50% of patients with bvFTD have tau pathology, said Dr. Darby. This pathology includes the classic Pick body form of tau, tufted astrocytes (which are associated with clinical symptoms of progressive supranuclear palsy), and astrocytic plaques (which are associated with symptoms of corticobasal degeneration). Similarly, between 40% and 50% of patients with bvFTD have a TAR DNA-binding protein 43 (TDP-43) pathology. TDP-43 Type A pathology is associated with perirolandic seizures, Type B is associated with amyotrophic lateral sclerosis (ALS), and Type C is associated with semantic dementia. Between 5% and 10% of patients with bvFTD have fused-in sarcoma pathology, which is associated with ALS.

Mutations in C9orf72 occur in 13% to 50% of patients with bvFTD who have genetic mutations. ALS and parkinsonism are common clinical presentations in patients with this genetic mutation. MAPT and GRN mutations are present in 5% to 20% of cases, and each can present clinically as parkinsonism.

Treatment

SSRIs, antipsychotics, anticonvulsants, and stimulants have been used to treat apathy, disinhibition, compulsive behaviors, agitation, and inappropriate behavior in patients with bvFTD. “There are no FDA-approved treatments for bvFTD, and the evidence for [these agents] has been mostly reported in case studies and small clinical trials,” said Dr. Darby. Among the SSRIs, paroxetine improved repetitive behavior in open-label trials, but not in a randomized controlled trial. Sertraline and citalopram have been studied in open-label trials, and trazodone was examined in a randomized controlled crossover trial involving 26 patients.

The FDA issued a black box warning against the use of atypical antipsychotics in patients with dementia because they entail a risk of cardiac- and infection-related mortality. “For patients with bvFTD tau pathology in particular, there is a risk of extrapyramidal adverse effects,” said Dr. Darby. A series of case reports of risperidone and aripiprazole provided evidence of symptom improvement, as did an open label study of olanzapine. Quetiapine improved agitation in a case series but failed to show benefit in a double-blind crossover trial of eight patients with FTD.

Case series have shown evidence that antiepileptic drugs (eg, valproic acid, topiramate, and carbamazepine) have a stabilizing effect. “Stimulants are tried in some patients, but should be used with caution,” said Dr. Darby.

Criminality

Between 37% and 57% of patients with bvFTD engage in criminal behavior. “Approximately 10% to 15% of the time, a patient’s getting in trouble with the law is the reason for the initial presentation,” said Dr. Darby. The types of crimes described in case reports include pedophilia, public masturbation, hit and run, traffic violations, and theft.

“Murder and violent crimes occur but are rare. Crimes committed by patients with bvFTD are usually reactive,” said Dr. Darby. “When asked, they can tell you whether a specific act is right or wrong; however, they don’t show remorse for criminal behavior.” It is not clear whether executive dysfunction and the inability to reason, social perception and the inability to empathize, or differences in moral decision making are the reasons for changes in patients’ behavior, he said.

“One idea is that a network of brain regions, not just one part of the brain, is responsible for formulating the complex concept of morality.” In 2017, Dr. Darby and colleagues systematically mapped brain lesions with a documented temporal association with criminal behavior in 17 patients who were identified through a literature search. Criminal behavior included white collar crimes, and 12 of 17 patients had committed violent crimes. Fifteen cases had no history of criminal behavior before the lesion, and the behavior resolved following treatment of the lesion in two cases.

No single brain region had been damaged in all cases. Because lesion-induced symptoms can arise from sites connected to the lesion location, the investigators identified these sites in the cases. The network of these sites included regions involved in morality, value-based decision making, and theory of mind, but not regions involved in cognitive control or empathy. Darby and colleagues replicated these results in a separate cohort of 23 cases in which a temporal relationship between brain lesions and criminal behavior was plausible, but not definite.

Prior research suggests that the areas associated with criminal behavior in patients with brain lesions closely resemble the areas typically affected in patients with bvFTD. Prospective studies are needed to further elucidate these results, Dr. Darby concluded.

—Adriene Marshall

Suggested Reading

Darby RR, Horn A, Cushman F, Fox MD. Lesion network localization of criminal behavior. Proc Natl Acad Sci U S A. 2018;115(3):601-606.

Perry DC, Brown JA, Possin KL, et al. Clinicopathological correlations in behavioural variant frontotemporal dementia. Brain. 2017;140(12):3329-3345.

HILTON HEAD, SC—Behavioral variant frontotemporal dementia (bvFTD), a clinically and pathologically heterogenous condition, can be difficult to distinguish from other forms of dementia or frontotemporal disease. “Although clinical symptoms vary based on which part of the brain is affected, there is a significant amount of overlap, with different pathologies causing the same type of syndrome,” said Richard Ryan Darby, MD, Assistant Professor of Neurology at Vanderbilt University Medical School in Nashville. “In a large proportion of patients, behavioral changes can lead to criminal behavior.” Future research examining brain lesion networks may shed light on this condition, said Dr. Darby at the 41st Annual Contemporary Clinical Neurology Symposium.

Clinical Features and Diagnosis

The incidence of bvFTD is equal to that of Alzheimer’s disease. However, patients with bvFTD tend to be younger: between the ages of 45 and 65. “Social and behavioral features predominate,” said Dr. Darby. “If a patient in this age range with no previous psychiatric history presents to you with a new psychiatric diagnosis such as schizophrenia or bipolar disease, this should raise your suspicion of bvFTD.” These psychiatric problems often cause considerable disruptions in patients’ lives. They often have problems at work and lose their source of income. “Patients often have no insight about their symptoms,” said Dr. Darby.

A differential diagnosis of bvFTD is possible in patients with three or more of the following six clinical features: socially inappropriate behavior (eg, eating from the trash or walking around naked at inappropriate times); lack of empathy; apathy; stereotyped or repetitive behavior (eg, saying things repeatedly, pacing); hyperorality (eg, eating uncontrollably, particularly sweet foods); and executive dysfunction, especially when memory is preserved.

“When you talk to caregivers, they often say, ‘This is not the person I married,’ or, ‘This is not my father. He seems like a different person,’” said Dr. Darby. An MRI or a PET scan showing changes in the frontotemporal lobes is a firm basis for a diagnosis of bvFTD, said Dr. Darby. Genetic testing for autosomal dominant mutation or pathology or an autopsy provides a definite diagnosis.

Pathology

Between 40% and 50% of patients with bvFTD have tau pathology, said Dr. Darby. This pathology includes the classic Pick body form of tau, tufted astrocytes (which are associated with clinical symptoms of progressive supranuclear palsy), and astrocytic plaques (which are associated with symptoms of corticobasal degeneration). Similarly, between 40% and 50% of patients with bvFTD have a TAR DNA-binding protein 43 (TDP-43) pathology. TDP-43 Type A pathology is associated with perirolandic seizures, Type B is associated with amyotrophic lateral sclerosis (ALS), and Type C is associated with semantic dementia. Between 5% and 10% of patients with bvFTD have fused-in sarcoma pathology, which is associated with ALS.

Mutations in C9orf72 occur in 13% to 50% of patients with bvFTD who have genetic mutations. ALS and parkinsonism are common clinical presentations in patients with this genetic mutation. MAPT and GRN mutations are present in 5% to 20% of cases, and each can present clinically as parkinsonism.

Treatment

SSRIs, antipsychotics, anticonvulsants, and stimulants have been used to treat apathy, disinhibition, compulsive behaviors, agitation, and inappropriate behavior in patients with bvFTD. “There are no FDA-approved treatments for bvFTD, and the evidence for [these agents] has been mostly reported in case studies and small clinical trials,” said Dr. Darby. Among the SSRIs, paroxetine improved repetitive behavior in open-label trials, but not in a randomized controlled trial. Sertraline and citalopram have been studied in open-label trials, and trazodone was examined in a randomized controlled crossover trial involving 26 patients.

The FDA issued a black box warning against the use of atypical antipsychotics in patients with dementia because they entail a risk of cardiac- and infection-related mortality. “For patients with bvFTD tau pathology in particular, there is a risk of extrapyramidal adverse effects,” said Dr. Darby. A series of case reports of risperidone and aripiprazole provided evidence of symptom improvement, as did an open label study of olanzapine. Quetiapine improved agitation in a case series but failed to show benefit in a double-blind crossover trial of eight patients with FTD.

Case series have shown evidence that antiepileptic drugs (eg, valproic acid, topiramate, and carbamazepine) have a stabilizing effect. “Stimulants are tried in some patients, but should be used with caution,” said Dr. Darby.

Criminality

Between 37% and 57% of patients with bvFTD engage in criminal behavior. “Approximately 10% to 15% of the time, a patient’s getting in trouble with the law is the reason for the initial presentation,” said Dr. Darby. The types of crimes described in case reports include pedophilia, public masturbation, hit and run, traffic violations, and theft.

“Murder and violent crimes occur but are rare. Crimes committed by patients with bvFTD are usually reactive,” said Dr. Darby. “When asked, they can tell you whether a specific act is right or wrong; however, they don’t show remorse for criminal behavior.” It is not clear whether executive dysfunction and the inability to reason, social perception and the inability to empathize, or differences in moral decision making are the reasons for changes in patients’ behavior, he said.

“One idea is that a network of brain regions, not just one part of the brain, is responsible for formulating the complex concept of morality.” In 2017, Dr. Darby and colleagues systematically mapped brain lesions with a documented temporal association with criminal behavior in 17 patients who were identified through a literature search. Criminal behavior included white collar crimes, and 12 of 17 patients had committed violent crimes. Fifteen cases had no history of criminal behavior before the lesion, and the behavior resolved following treatment of the lesion in two cases.

No single brain region had been damaged in all cases. Because lesion-induced symptoms can arise from sites connected to the lesion location, the investigators identified these sites in the cases. The network of these sites included regions involved in morality, value-based decision making, and theory of mind, but not regions involved in cognitive control or empathy. Darby and colleagues replicated these results in a separate cohort of 23 cases in which a temporal relationship between brain lesions and criminal behavior was plausible, but not definite.

Prior research suggests that the areas associated with criminal behavior in patients with brain lesions closely resemble the areas typically affected in patients with bvFTD. Prospective studies are needed to further elucidate these results, Dr. Darby concluded.

—Adriene Marshall

Suggested Reading

Darby RR, Horn A, Cushman F, Fox MD. Lesion network localization of criminal behavior. Proc Natl Acad Sci U S A. 2018;115(3):601-606.

Perry DC, Brown JA, Possin KL, et al. Clinicopathological correlations in behavioural variant frontotemporal dementia. Brain. 2017;140(12):3329-3345.

HILTON HEAD, SC—Behavioral variant frontotemporal dementia (bvFTD), a clinically and pathologically heterogenous condition, can be difficult to distinguish from other forms of dementia or frontotemporal disease. “Although clinical symptoms vary based on which part of the brain is affected, there is a significant amount of overlap, with different pathologies causing the same type of syndrome,” said Richard Ryan Darby, MD, Assistant Professor of Neurology at Vanderbilt University Medical School in Nashville. “In a large proportion of patients, behavioral changes can lead to criminal behavior.” Future research examining brain lesion networks may shed light on this condition, said Dr. Darby at the 41st Annual Contemporary Clinical Neurology Symposium.

Clinical Features and Diagnosis

The incidence of bvFTD is equal to that of Alzheimer’s disease. However, patients with bvFTD tend to be younger: between the ages of 45 and 65. “Social and behavioral features predominate,” said Dr. Darby. “If a patient in this age range with no previous psychiatric history presents to you with a new psychiatric diagnosis such as schizophrenia or bipolar disease, this should raise your suspicion of bvFTD.” These psychiatric problems often cause considerable disruptions in patients’ lives. They often have problems at work and lose their source of income. “Patients often have no insight about their symptoms,” said Dr. Darby.

A differential diagnosis of bvFTD is possible in patients with three or more of the following six clinical features: socially inappropriate behavior (eg, eating from the trash or walking around naked at inappropriate times); lack of empathy; apathy; stereotyped or repetitive behavior (eg, saying things repeatedly, pacing); hyperorality (eg, eating uncontrollably, particularly sweet foods); and executive dysfunction, especially when memory is preserved.

“When you talk to caregivers, they often say, ‘This is not the person I married,’ or, ‘This is not my father. He seems like a different person,’” said Dr. Darby. An MRI or a PET scan showing changes in the frontotemporal lobes is a firm basis for a diagnosis of bvFTD, said Dr. Darby. Genetic testing for autosomal dominant mutation or pathology or an autopsy provides a definite diagnosis.

Pathology

Between 40% and 50% of patients with bvFTD have tau pathology, said Dr. Darby. This pathology includes the classic Pick body form of tau, tufted astrocytes (which are associated with clinical symptoms of progressive supranuclear palsy), and astrocytic plaques (which are associated with symptoms of corticobasal degeneration). Similarly, between 40% and 50% of patients with bvFTD have a TAR DNA-binding protein 43 (TDP-43) pathology. TDP-43 Type A pathology is associated with perirolandic seizures, Type B is associated with amyotrophic lateral sclerosis (ALS), and Type C is associated with semantic dementia. Between 5% and 10% of patients with bvFTD have fused-in sarcoma pathology, which is associated with ALS.

Mutations in C9orf72 occur in 13% to 50% of patients with bvFTD who have genetic mutations. ALS and parkinsonism are common clinical presentations in patients with this genetic mutation. MAPT and GRN mutations are present in 5% to 20% of cases, and each can present clinically as parkinsonism.

Treatment

SSRIs, antipsychotics, anticonvulsants, and stimulants have been used to treat apathy, disinhibition, compulsive behaviors, agitation, and inappropriate behavior in patients with bvFTD. “There are no FDA-approved treatments for bvFTD, and the evidence for [these agents] has been mostly reported in case studies and small clinical trials,” said Dr. Darby. Among the SSRIs, paroxetine improved repetitive behavior in open-label trials, but not in a randomized controlled trial. Sertraline and citalopram have been studied in open-label trials, and trazodone was examined in a randomized controlled crossover trial involving 26 patients.

The FDA issued a black box warning against the use of atypical antipsychotics in patients with dementia because they entail a risk of cardiac- and infection-related mortality. “For patients with bvFTD tau pathology in particular, there is a risk of extrapyramidal adverse effects,” said Dr. Darby. A series of case reports of risperidone and aripiprazole provided evidence of symptom improvement, as did an open label study of olanzapine. Quetiapine improved agitation in a case series but failed to show benefit in a double-blind crossover trial of eight patients with FTD.

Case series have shown evidence that antiepileptic drugs (eg, valproic acid, topiramate, and carbamazepine) have a stabilizing effect. “Stimulants are tried in some patients, but should be used with caution,” said Dr. Darby.

Criminality

Between 37% and 57% of patients with bvFTD engage in criminal behavior. “Approximately 10% to 15% of the time, a patient’s getting in trouble with the law is the reason for the initial presentation,” said Dr. Darby. The types of crimes described in case reports include pedophilia, public masturbation, hit and run, traffic violations, and theft.

“Murder and violent crimes occur but are rare. Crimes committed by patients with bvFTD are usually reactive,” said Dr. Darby. “When asked, they can tell you whether a specific act is right or wrong; however, they don’t show remorse for criminal behavior.” It is not clear whether executive dysfunction and the inability to reason, social perception and the inability to empathize, or differences in moral decision making are the reasons for changes in patients’ behavior, he said.

“One idea is that a network of brain regions, not just one part of the brain, is responsible for formulating the complex concept of morality.” In 2017, Dr. Darby and colleagues systematically mapped brain lesions with a documented temporal association with criminal behavior in 17 patients who were identified through a literature search. Criminal behavior included white collar crimes, and 12 of 17 patients had committed violent crimes. Fifteen cases had no history of criminal behavior before the lesion, and the behavior resolved following treatment of the lesion in two cases.

No single brain region had been damaged in all cases. Because lesion-induced symptoms can arise from sites connected to the lesion location, the investigators identified these sites in the cases. The network of these sites included regions involved in morality, value-based decision making, and theory of mind, but not regions involved in cognitive control or empathy. Darby and colleagues replicated these results in a separate cohort of 23 cases in which a temporal relationship between brain lesions and criminal behavior was plausible, but not definite.

Prior research suggests that the areas associated with criminal behavior in patients with brain lesions closely resemble the areas typically affected in patients with bvFTD. Prospective studies are needed to further elucidate these results, Dr. Darby concluded.

—Adriene Marshall

Suggested Reading

Darby RR, Horn A, Cushman F, Fox MD. Lesion network localization of criminal behavior. Proc Natl Acad Sci U S A. 2018;115(3):601-606.

Perry DC, Brown JA, Possin KL, et al. Clinicopathological correlations in behavioural variant frontotemporal dementia. Brain. 2017;140(12):3329-3345.