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Acute kidney injury linked to later dementia
SAN DIEGO –
That’s according to a new study offering more evidence of a link between kidney disease and neurological problems.
“Clinicians should know that AKI is associated with poor long-term outcomes,” said lead author Jessica B. Kendrick MD, associate professor of medicine at the University of Colorado, Aurora. “We need to identify ways to prevent these long-term consequences.”
The findings were presented at Kidney Week 2018, sponsored by the American Society of Nephrology.
According to Dr. Kendrick, the acute neurological effects of AKI are well known. But no previous studies have examined the potential long-term cerebrovascular complications of AKI.
For the new study, Dr. Kendrick and her colleagues retrospectively analyzed 2,082 hospitalized patients in Utah from 1999 to 2009: 1,041 who completely recovered from AKI by discharge, and 1,041 who did not have AKI.
The average age was 61 years, and the average baseline creatinine was 0.9 ± 0.2 mg/dL. Over a median follow-up of 6 years, 97 patients developed dementia.
Those with AKI were more likely to develop dementia compared with the control group: 7% vs. 2% (hazard ratio, 3.4; 95% confidence interval, 2.14-5.40).
Other studies have linked kidney disease to cognitive impairment.
“There are a lot of theories as to why this is,” nephrologist Daniel Weiner, MD, of Tufts University, Boston, said in an interview. “It is most likely that the presence of kidney disease identifies individuals with a high burden of vascular disease, and that vascular disease, particularly of the small blood vessels, is an important contributor to cognitive impairment and dementia.”
That appears to be most notable in people who have protein in their urine, Dr. Weiner added. “The presence of protein in the urine identifies a severe enough process to affect the blood vessels in the kidney, and there is no reason to think that blood vessels elsewhere in the body, including in the brain, are not similarly affected.”
As for the current study, Dr. Weiner said it could support the vascular disease theory.
“People with vulnerable kidneys to acute injury also have vulnerable brains to acute injury,” he said. “People who get AKI usually have susceptibility to perfusion-related kidney injury. In other words, the small blood vessels that supply the kidney are unable to compensate to maintain sufficient blood flow during a time of low blood pressure or other systemic illness.”
That vulnerability “suggests to me that small blood vessels elsewhere in the body are less likely to be able to respond to challenges like low blood pressure,” Dr. Weiner explained. “If this occurs in the brain, it leads to microvascular disease and greater abnormal white-matter burden. This change in the brain anatomy is highly correlated with cognitive impairment.”
How can physicians put these finding to use? “These patients may require more monitoring,” Dr. Kendrick said. “For example, patients with AKI and complete recovery may not have any follow-up with a nephrologist, and perhaps they should.”
Moving forward, she said, “we are examining the association of AKI with cognitive dysfunction in different patient populations.” Researchers also are planning studies to better understand the mechanisms that are at work, she said.
The National Heart, Lung, and Blood Institute funded the study. The study authors had no disclosures.
SOURCE: Kendrick JB et al. Kidney Week 2018. Abstract TH-OR116.
SAN DIEGO –
That’s according to a new study offering more evidence of a link between kidney disease and neurological problems.
“Clinicians should know that AKI is associated with poor long-term outcomes,” said lead author Jessica B. Kendrick MD, associate professor of medicine at the University of Colorado, Aurora. “We need to identify ways to prevent these long-term consequences.”
The findings were presented at Kidney Week 2018, sponsored by the American Society of Nephrology.
According to Dr. Kendrick, the acute neurological effects of AKI are well known. But no previous studies have examined the potential long-term cerebrovascular complications of AKI.
For the new study, Dr. Kendrick and her colleagues retrospectively analyzed 2,082 hospitalized patients in Utah from 1999 to 2009: 1,041 who completely recovered from AKI by discharge, and 1,041 who did not have AKI.
The average age was 61 years, and the average baseline creatinine was 0.9 ± 0.2 mg/dL. Over a median follow-up of 6 years, 97 patients developed dementia.
Those with AKI were more likely to develop dementia compared with the control group: 7% vs. 2% (hazard ratio, 3.4; 95% confidence interval, 2.14-5.40).
Other studies have linked kidney disease to cognitive impairment.
“There are a lot of theories as to why this is,” nephrologist Daniel Weiner, MD, of Tufts University, Boston, said in an interview. “It is most likely that the presence of kidney disease identifies individuals with a high burden of vascular disease, and that vascular disease, particularly of the small blood vessels, is an important contributor to cognitive impairment and dementia.”
That appears to be most notable in people who have protein in their urine, Dr. Weiner added. “The presence of protein in the urine identifies a severe enough process to affect the blood vessels in the kidney, and there is no reason to think that blood vessels elsewhere in the body, including in the brain, are not similarly affected.”
As for the current study, Dr. Weiner said it could support the vascular disease theory.
“People with vulnerable kidneys to acute injury also have vulnerable brains to acute injury,” he said. “People who get AKI usually have susceptibility to perfusion-related kidney injury. In other words, the small blood vessels that supply the kidney are unable to compensate to maintain sufficient blood flow during a time of low blood pressure or other systemic illness.”
That vulnerability “suggests to me that small blood vessels elsewhere in the body are less likely to be able to respond to challenges like low blood pressure,” Dr. Weiner explained. “If this occurs in the brain, it leads to microvascular disease and greater abnormal white-matter burden. This change in the brain anatomy is highly correlated with cognitive impairment.”
How can physicians put these finding to use? “These patients may require more monitoring,” Dr. Kendrick said. “For example, patients with AKI and complete recovery may not have any follow-up with a nephrologist, and perhaps they should.”
Moving forward, she said, “we are examining the association of AKI with cognitive dysfunction in different patient populations.” Researchers also are planning studies to better understand the mechanisms that are at work, she said.
The National Heart, Lung, and Blood Institute funded the study. The study authors had no disclosures.
SOURCE: Kendrick JB et al. Kidney Week 2018. Abstract TH-OR116.
SAN DIEGO –
That’s according to a new study offering more evidence of a link between kidney disease and neurological problems.
“Clinicians should know that AKI is associated with poor long-term outcomes,” said lead author Jessica B. Kendrick MD, associate professor of medicine at the University of Colorado, Aurora. “We need to identify ways to prevent these long-term consequences.”
The findings were presented at Kidney Week 2018, sponsored by the American Society of Nephrology.
According to Dr. Kendrick, the acute neurological effects of AKI are well known. But no previous studies have examined the potential long-term cerebrovascular complications of AKI.
For the new study, Dr. Kendrick and her colleagues retrospectively analyzed 2,082 hospitalized patients in Utah from 1999 to 2009: 1,041 who completely recovered from AKI by discharge, and 1,041 who did not have AKI.
The average age was 61 years, and the average baseline creatinine was 0.9 ± 0.2 mg/dL. Over a median follow-up of 6 years, 97 patients developed dementia.
Those with AKI were more likely to develop dementia compared with the control group: 7% vs. 2% (hazard ratio, 3.4; 95% confidence interval, 2.14-5.40).
Other studies have linked kidney disease to cognitive impairment.
“There are a lot of theories as to why this is,” nephrologist Daniel Weiner, MD, of Tufts University, Boston, said in an interview. “It is most likely that the presence of kidney disease identifies individuals with a high burden of vascular disease, and that vascular disease, particularly of the small blood vessels, is an important contributor to cognitive impairment and dementia.”
That appears to be most notable in people who have protein in their urine, Dr. Weiner added. “The presence of protein in the urine identifies a severe enough process to affect the blood vessels in the kidney, and there is no reason to think that blood vessels elsewhere in the body, including in the brain, are not similarly affected.”
As for the current study, Dr. Weiner said it could support the vascular disease theory.
“People with vulnerable kidneys to acute injury also have vulnerable brains to acute injury,” he said. “People who get AKI usually have susceptibility to perfusion-related kidney injury. In other words, the small blood vessels that supply the kidney are unable to compensate to maintain sufficient blood flow during a time of low blood pressure or other systemic illness.”
That vulnerability “suggests to me that small blood vessels elsewhere in the body are less likely to be able to respond to challenges like low blood pressure,” Dr. Weiner explained. “If this occurs in the brain, it leads to microvascular disease and greater abnormal white-matter burden. This change in the brain anatomy is highly correlated with cognitive impairment.”
How can physicians put these finding to use? “These patients may require more monitoring,” Dr. Kendrick said. “For example, patients with AKI and complete recovery may not have any follow-up with a nephrologist, and perhaps they should.”
Moving forward, she said, “we are examining the association of AKI with cognitive dysfunction in different patient populations.” Researchers also are planning studies to better understand the mechanisms that are at work, she said.
The National Heart, Lung, and Blood Institute funded the study. The study authors had no disclosures.
SOURCE: Kendrick JB et al. Kidney Week 2018. Abstract TH-OR116.
REPORTING FROM KIDNEY WEEK 2018
Key clinical point: Patients with acute kidney injury seem to face a much higher risk of dementia.
Major finding: Hospitalized patients with AKI were 3.4 times more likely to develop dementia within a median of 6 years, compared with other hospitalized patients.
Study details: A retrospective study of 2,082 propensity-matched hospitalized patients, 1,041 who had AKI and fully recovered, and 1,041 who did not have AKI.
Disclosures: The National Heart, Lung, and Blood Institute funded the study. The authors had no disclosures.
Source: Kendrick JB et al. Kidney Week 2018. Abstract No. TH-OR116.
Antipsychotic drugs failed to shorten ICU delirium
The antipsychotic medications in patients in intensive care, new research has found.
In a paper published in the New England Journal of Medicine, researchers reported the results of a randomized, double-blind, placebo-controlled trial in 566 patients with acute respiratory failure or shock and hypoactive or hyperactive delirium. Participants were randomized either to a maximum of 20 mg IV haloperidol daily, maximum 40 mg ziprasidone daily, or placebo.
At the end of the 14-day intervention period, the placebo group had a median of 8.5 days alive without delirium or coma, the haloperidol group had a median of 7.9 days, and the ziprasidone group had a median of 8.7 days. The difference between groups was not statistically significant.
There were also no significant differences between the three groups in the secondary end point of duration of delirium and coma, 30-day and 90-day survival, time to freedom from mechanical ventilation, ICU discharge, ICU readmission, or hospital discharge.
Timothy D. Girard, MD, from the department of critical care at the University of Pittsburgh, and his coauthors wrote that their findings echoed those of two previous placebo-controlled trials in smaller numbers of ICU patients.
“One possible reason that we found no evidence that the use of haloperidol or ziprasidone resulted in a fewer days with delirium or coma than placebo is that the mechanism of brain dysfunction that is considered to be targeted by antipsychotic medications – increased dopamine signaling – may not play a major role in the pathogenesis of delirium during critical illness,” they wrote.
“In the current trial, approximately 90% of the patients received one or more doses of sedatives or analgesics, and the doses of sedatives and offtrial antipsychotic medications and the durations of exposures to those agents were similar in all trial groups,” the authors added.
Most of the patients in the trial had hypotensive delirium, which made it difficult to assess the effects of antipsychotics on hypertensive delirium.
The authors also commented that the patients enrolled were a mixed group, so their findings did not rule out the possibility that certain subgroups of patients – such as nonintubated patients with hyperactive delirium, those with alcohol withdrawal, or with other delirium phenotypes – may still benefit from antipsychotics.
Patients treated with ziprasidone were more likely to experience prolongation of the corrected QT interval. Two patients in the haloperidol group developed torsades de pointes but neither had received haloperidol in the 4 days preceding the onset of the arrhythmia.
One patient in each group – including the placebo group – experienced extrapyramidal symptoms and had treatment withheld. One patient in the haloperidol group also had the trial drug withheld because of suspected neuroleptic malignant syndrome, but this was later ruled out, and one patient had haloperidol withheld because of dystonia.
The dose of haloperidol used in the study was considered high, the authors said, but they left open the possibility that even higher doses might help. However, they also noted that doses of 25 mg and above were known to have adverse effects on cognition, which is why they chose the 20-mg dosage.
The study was supported by the National Institutes of Health and the Department of Veterans Affairs Geriatric Research Education and Clinical Center. Most authors declared support from the NIH or VA during the course of the study. Four authors also reported fees and grants from private industry outside the context of the study.
SOURCE: Girard TD et al. N Engl J Med.2018 Oct 22. doi: 10.1056/NEJMoa1808217.
In a comment published with this study, Thomas P. Bleck, MD, of the department of neurologic sciences at Rush Medical College, Chicago, wrote, “A change in mental status in a patient in intensive care can be one of the most vexing problems. In the past 2 decades, the idea has arisen that antipsychotic drugs – and particularly dopamine antagonists, which ameliorate thought disorders in psychotic patients – could help patients with disordered thinking in other contexts, such as the intensive care unit. However, yet another trial has now called this idea into question.”
He noted that, in the study group, a bolus of placebo was just as effective as a bolus of active medication, which may be because of the majority of patients having hypoactive delirium, which the active drugs may not impact.
“I would still consider using dopamine agonists in patients at imminent risk of injurious behaviors but have less confidence in their benefits than I once had,” Dr. Bleck wrote.
Dr. Bleck did not report any conflicts of interest.
In a comment published with this study, Thomas P. Bleck, MD, of the department of neurologic sciences at Rush Medical College, Chicago, wrote, “A change in mental status in a patient in intensive care can be one of the most vexing problems. In the past 2 decades, the idea has arisen that antipsychotic drugs – and particularly dopamine antagonists, which ameliorate thought disorders in psychotic patients – could help patients with disordered thinking in other contexts, such as the intensive care unit. However, yet another trial has now called this idea into question.”
He noted that, in the study group, a bolus of placebo was just as effective as a bolus of active medication, which may be because of the majority of patients having hypoactive delirium, which the active drugs may not impact.
“I would still consider using dopamine agonists in patients at imminent risk of injurious behaviors but have less confidence in their benefits than I once had,” Dr. Bleck wrote.
Dr. Bleck did not report any conflicts of interest.
In a comment published with this study, Thomas P. Bleck, MD, of the department of neurologic sciences at Rush Medical College, Chicago, wrote, “A change in mental status in a patient in intensive care can be one of the most vexing problems. In the past 2 decades, the idea has arisen that antipsychotic drugs – and particularly dopamine antagonists, which ameliorate thought disorders in psychotic patients – could help patients with disordered thinking in other contexts, such as the intensive care unit. However, yet another trial has now called this idea into question.”
He noted that, in the study group, a bolus of placebo was just as effective as a bolus of active medication, which may be because of the majority of patients having hypoactive delirium, which the active drugs may not impact.
“I would still consider using dopamine agonists in patients at imminent risk of injurious behaviors but have less confidence in their benefits than I once had,” Dr. Bleck wrote.
Dr. Bleck did not report any conflicts of interest.
The antipsychotic medications in patients in intensive care, new research has found.
In a paper published in the New England Journal of Medicine, researchers reported the results of a randomized, double-blind, placebo-controlled trial in 566 patients with acute respiratory failure or shock and hypoactive or hyperactive delirium. Participants were randomized either to a maximum of 20 mg IV haloperidol daily, maximum 40 mg ziprasidone daily, or placebo.
At the end of the 14-day intervention period, the placebo group had a median of 8.5 days alive without delirium or coma, the haloperidol group had a median of 7.9 days, and the ziprasidone group had a median of 8.7 days. The difference between groups was not statistically significant.
There were also no significant differences between the three groups in the secondary end point of duration of delirium and coma, 30-day and 90-day survival, time to freedom from mechanical ventilation, ICU discharge, ICU readmission, or hospital discharge.
Timothy D. Girard, MD, from the department of critical care at the University of Pittsburgh, and his coauthors wrote that their findings echoed those of two previous placebo-controlled trials in smaller numbers of ICU patients.
“One possible reason that we found no evidence that the use of haloperidol or ziprasidone resulted in a fewer days with delirium or coma than placebo is that the mechanism of brain dysfunction that is considered to be targeted by antipsychotic medications – increased dopamine signaling – may not play a major role in the pathogenesis of delirium during critical illness,” they wrote.
“In the current trial, approximately 90% of the patients received one or more doses of sedatives or analgesics, and the doses of sedatives and offtrial antipsychotic medications and the durations of exposures to those agents were similar in all trial groups,” the authors added.
Most of the patients in the trial had hypotensive delirium, which made it difficult to assess the effects of antipsychotics on hypertensive delirium.
The authors also commented that the patients enrolled were a mixed group, so their findings did not rule out the possibility that certain subgroups of patients – such as nonintubated patients with hyperactive delirium, those with alcohol withdrawal, or with other delirium phenotypes – may still benefit from antipsychotics.
Patients treated with ziprasidone were more likely to experience prolongation of the corrected QT interval. Two patients in the haloperidol group developed torsades de pointes but neither had received haloperidol in the 4 days preceding the onset of the arrhythmia.
One patient in each group – including the placebo group – experienced extrapyramidal symptoms and had treatment withheld. One patient in the haloperidol group also had the trial drug withheld because of suspected neuroleptic malignant syndrome, but this was later ruled out, and one patient had haloperidol withheld because of dystonia.
The dose of haloperidol used in the study was considered high, the authors said, but they left open the possibility that even higher doses might help. However, they also noted that doses of 25 mg and above were known to have adverse effects on cognition, which is why they chose the 20-mg dosage.
The study was supported by the National Institutes of Health and the Department of Veterans Affairs Geriatric Research Education and Clinical Center. Most authors declared support from the NIH or VA during the course of the study. Four authors also reported fees and grants from private industry outside the context of the study.
SOURCE: Girard TD et al. N Engl J Med.2018 Oct 22. doi: 10.1056/NEJMoa1808217.
The antipsychotic medications in patients in intensive care, new research has found.
In a paper published in the New England Journal of Medicine, researchers reported the results of a randomized, double-blind, placebo-controlled trial in 566 patients with acute respiratory failure or shock and hypoactive or hyperactive delirium. Participants were randomized either to a maximum of 20 mg IV haloperidol daily, maximum 40 mg ziprasidone daily, or placebo.
At the end of the 14-day intervention period, the placebo group had a median of 8.5 days alive without delirium or coma, the haloperidol group had a median of 7.9 days, and the ziprasidone group had a median of 8.7 days. The difference between groups was not statistically significant.
There were also no significant differences between the three groups in the secondary end point of duration of delirium and coma, 30-day and 90-day survival, time to freedom from mechanical ventilation, ICU discharge, ICU readmission, or hospital discharge.
Timothy D. Girard, MD, from the department of critical care at the University of Pittsburgh, and his coauthors wrote that their findings echoed those of two previous placebo-controlled trials in smaller numbers of ICU patients.
“One possible reason that we found no evidence that the use of haloperidol or ziprasidone resulted in a fewer days with delirium or coma than placebo is that the mechanism of brain dysfunction that is considered to be targeted by antipsychotic medications – increased dopamine signaling – may not play a major role in the pathogenesis of delirium during critical illness,” they wrote.
“In the current trial, approximately 90% of the patients received one or more doses of sedatives or analgesics, and the doses of sedatives and offtrial antipsychotic medications and the durations of exposures to those agents were similar in all trial groups,” the authors added.
Most of the patients in the trial had hypotensive delirium, which made it difficult to assess the effects of antipsychotics on hypertensive delirium.
The authors also commented that the patients enrolled were a mixed group, so their findings did not rule out the possibility that certain subgroups of patients – such as nonintubated patients with hyperactive delirium, those with alcohol withdrawal, or with other delirium phenotypes – may still benefit from antipsychotics.
Patients treated with ziprasidone were more likely to experience prolongation of the corrected QT interval. Two patients in the haloperidol group developed torsades de pointes but neither had received haloperidol in the 4 days preceding the onset of the arrhythmia.
One patient in each group – including the placebo group – experienced extrapyramidal symptoms and had treatment withheld. One patient in the haloperidol group also had the trial drug withheld because of suspected neuroleptic malignant syndrome, but this was later ruled out, and one patient had haloperidol withheld because of dystonia.
The dose of haloperidol used in the study was considered high, the authors said, but they left open the possibility that even higher doses might help. However, they also noted that doses of 25 mg and above were known to have adverse effects on cognition, which is why they chose the 20-mg dosage.
The study was supported by the National Institutes of Health and the Department of Veterans Affairs Geriatric Research Education and Clinical Center. Most authors declared support from the NIH or VA during the course of the study. Four authors also reported fees and grants from private industry outside the context of the study.
SOURCE: Girard TD et al. N Engl J Med.2018 Oct 22. doi: 10.1056/NEJMoa1808217.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Antipsychotics do not reduce the duration or incidence of delirium in intensive care.
Major finding: Patients treated with antipsychotics showed similar median days without delirium or coma, compared with those treated with placebo.
Study details: A randomized, double-blind, placebo-controlled trial in 566 intensive care patients.
Disclosures: The study was supported by the National Institutes of Health and the Department of Veterans Affairs Geriatric Research Education and Clinical Center. Most authors were supported by the NIH or VA during the course of the study. Four authors also reported fees and grants from private industry outside the context of the study.
Source: Girard TD et al. N Engl J Med. 2018 Oct 22. doi: 10.1056/NEJMoa1808217.
IDEAS study meets first aim of changing 3-month clinical management, health outcomes
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.
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.
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.
REPORTING FROM CTAD
Key clinical point: Amyloid PET imaging can refine equivocal dementia diagnoses.
Major finding:
Study details: The IDEAS study has thus far accrued data on 11,409 subjects.
Disclosures: IDEAS is a funding collaboration of the Centers for Medicare & Medicaid Services, 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.
High systemic inflammation at midlife portends cognitive changes in later life
ATLANTA – 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.
Source: Walker et al. ANA 2018, Abstract 305.
ATLANTA – 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.
Source: Walker et al. ANA 2018, Abstract 305.
ATLANTA – 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.
Source: Walker et al. ANA 2018, Abstract 305.
REPORTING FROM ANA 2018
Key clinical point: Inflammation was associated with declines in memory, but not declines in other domains, such as executive function or language.
Major finding: 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).
Study details: An evaluation of blood biomarkers of inflammation in 12,727 middle-aged participants in the Atherosclerosis Risk in Communities Study.
Disclosures: Dr. Walker disclosed that he receives funding support from the National Institutes of Health.
Source: Walker et al. ANA 2018, Abstract 305.
Computer program credited with cognitive stability in Alzheimer’s
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.”
REPORTING FROM ICPDMD 2018
Key clinical point: Patients with cognitive impairment can prevent loss with a computerized program with cognitive tasks.
Major finding: In all but one patient in a small series, reaction time remains stable throughout at least four years of follow-up.
Study details: Case series.
Disclosures: Dr. Bragin reported no financial relationships relevant to this study.
Is a Unidimensional Cognitive Screen Sufficient for Patients With MS?
A unidimensional approach to evaluating cognitive deficits misses the variability and impact of the disease.
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%.
A unidimensional approach to evaluating cognitive deficits misses the variability and impact of the disease.
A unidimensional approach to evaluating cognitive deficits misses the variability and impact of the disease.
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%.
Neurologic disease eventually affects half of women and one-third of men
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.
FROM JOURNAL OF NEUROLOGY, NEUROSURGERY & PSYCHIATRY
Major finding: A 45-year-old woman has a 48.2% lifetime risk of stroke, dementia, or parkinsonism, while a man has a 36.3% lifetime risk.
Study details: Population-based cohort study in 12,102 individuals.
Disclosures: 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 financial conflicts of interest were declared.
Source: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.
Concurrent ‘never event’ prescribing may worsen dementia in Parkinson’s
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.
“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.
Describing the prescribing patterns of antidementia medication for patients with Parkinson’s disease is useful, particularly with regard to black and Hispanic patients, but the analysis by Sneha Mantri, MD, and her colleagues has methodological issues that limit its impact, wrote Christopher W. Hess, MD, Michael S. Okun, MD, and Adolfo Ramirez-Zamora, MD, wrote in an editorial.
While the researchers used the Anticholinergic Cognitive Burden (ACB) Scale and graded acetylcholinesterase inhibitor and high anticholinergic (ACH) activity medication combinations with the highest ACB score (3 on a scale of 0 to 3) and labeled them as a prescribing error, the ACB scale score alone should not be the sole determination of whether a prescription combination is deemed an error, the authors said.
“A problem, however, arises in defining the coadministration of an antidementia drug and a medication with high ACH activity as a prescribing error or a never event in all clinical circumstances,” the authors wrote. “Across the literature in this area, the most important principle repeatedly emphasized was that these resources are intended to identify potentially inappropriate medication (not inappropriate medications), and the recommendations and ratings provided cannot replace patient-specific clinical judgment.”
Further, medications such as clozapine and quetiapine fumarate are often prescribed for patients with Parkinson’s disease–related psychosis as a standard of care; those medications also have an ACB score of 3, which would label them as prescribing errors and never events under the study by Mantri et al., the authors continued.
“Variability in ACH activity scoring methods is an additional concern, as no criterion standard exists for ranking relative ACH activity and the scores for medications to treat Parkinson disease (such as quetiapine for Parkinson disease psychosis) can markedly differ between the scales commonly used (such as the ACB Scale),” they wrote.
Christopher W. Hess, MD, Michael S. Okun, MD, and Adolfo Ramirez-Zamora, MD, are affiliated with the Fixel Center for Neurological Diseases in the department of neurology at the University of Florida in Gainesville. These comments summarize their editorial (JAMA Neurol. 2018 Oct 1 doi: 10.1001/jamaneurol.2018.2826).They reported no relevant conflicts of interest.
Describing the prescribing patterns of antidementia medication for patients with Parkinson’s disease is useful, particularly with regard to black and Hispanic patients, but the analysis by Sneha Mantri, MD, and her colleagues has methodological issues that limit its impact, wrote Christopher W. Hess, MD, Michael S. Okun, MD, and Adolfo Ramirez-Zamora, MD, wrote in an editorial.
While the researchers used the Anticholinergic Cognitive Burden (ACB) Scale and graded acetylcholinesterase inhibitor and high anticholinergic (ACH) activity medication combinations with the highest ACB score (3 on a scale of 0 to 3) and labeled them as a prescribing error, the ACB scale score alone should not be the sole determination of whether a prescription combination is deemed an error, the authors said.
“A problem, however, arises in defining the coadministration of an antidementia drug and a medication with high ACH activity as a prescribing error or a never event in all clinical circumstances,” the authors wrote. “Across the literature in this area, the most important principle repeatedly emphasized was that these resources are intended to identify potentially inappropriate medication (not inappropriate medications), and the recommendations and ratings provided cannot replace patient-specific clinical judgment.”
Further, medications such as clozapine and quetiapine fumarate are often prescribed for patients with Parkinson’s disease–related psychosis as a standard of care; those medications also have an ACB score of 3, which would label them as prescribing errors and never events under the study by Mantri et al., the authors continued.
“Variability in ACH activity scoring methods is an additional concern, as no criterion standard exists for ranking relative ACH activity and the scores for medications to treat Parkinson disease (such as quetiapine for Parkinson disease psychosis) can markedly differ between the scales commonly used (such as the ACB Scale),” they wrote.
Christopher W. Hess, MD, Michael S. Okun, MD, and Adolfo Ramirez-Zamora, MD, are affiliated with the Fixel Center for Neurological Diseases in the department of neurology at the University of Florida in Gainesville. These comments summarize their editorial (JAMA Neurol. 2018 Oct 1 doi: 10.1001/jamaneurol.2018.2826).They reported no relevant conflicts of interest.
Describing the prescribing patterns of antidementia medication for patients with Parkinson’s disease is useful, particularly with regard to black and Hispanic patients, but the analysis by Sneha Mantri, MD, and her colleagues has methodological issues that limit its impact, wrote Christopher W. Hess, MD, Michael S. Okun, MD, and Adolfo Ramirez-Zamora, MD, wrote in an editorial.
While the researchers used the Anticholinergic Cognitive Burden (ACB) Scale and graded acetylcholinesterase inhibitor and high anticholinergic (ACH) activity medication combinations with the highest ACB score (3 on a scale of 0 to 3) and labeled them as a prescribing error, the ACB scale score alone should not be the sole determination of whether a prescription combination is deemed an error, the authors said.
“A problem, however, arises in defining the coadministration of an antidementia drug and a medication with high ACH activity as a prescribing error or a never event in all clinical circumstances,” the authors wrote. “Across the literature in this area, the most important principle repeatedly emphasized was that these resources are intended to identify potentially inappropriate medication (not inappropriate medications), and the recommendations and ratings provided cannot replace patient-specific clinical judgment.”
Further, medications such as clozapine and quetiapine fumarate are often prescribed for patients with Parkinson’s disease–related psychosis as a standard of care; those medications also have an ACB score of 3, which would label them as prescribing errors and never events under the study by Mantri et al., the authors continued.
“Variability in ACH activity scoring methods is an additional concern, as no criterion standard exists for ranking relative ACH activity and the scores for medications to treat Parkinson disease (such as quetiapine for Parkinson disease psychosis) can markedly differ between the scales commonly used (such as the ACB Scale),” they wrote.
Christopher W. Hess, MD, Michael S. Okun, MD, and Adolfo Ramirez-Zamora, MD, are affiliated with the Fixel Center for Neurological Diseases in the department of neurology at the University of Florida in Gainesville. These comments summarize their editorial (JAMA Neurol. 2018 Oct 1 doi: 10.1001/jamaneurol.2018.2826).They reported no relevant conflicts of interest.
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.
“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.
“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.
FROM JAMA NEUROLOGY
Key clinical point: Medicare beneficiaries with Parkinson’s disease often are concurrently prescribed a high-potency anticholinergic medication and an acetylcholinesterase inhibitor.
Major finding: More than 44% of patients experienced at least one never event, with higher rates of potential prescribing errors seen in Hispanic patients (adjusted OR, 1.11) and women (adjusted OR, 1.30).
Study details: An analysis of inpatient, outpatient, and prescription data for 268,407 Medicare beneficiaries with Parkinson’s disease over 12 months.
Disclosures: This study was funded by a grant from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health. The authors reported no relevant conflicts of interest.
Source: Mantri S et al. JAMA Neurol. 2018 Oct 1. doi: 10.1001/jamaneurol.2018.2820.
Cardiovascular Health and Cognitive Decline: What Is the Connection?
Maintaining cardiovascular health may reduce white matter hyperintensities and decrease the risk of dementia.
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.
“These two studies convey an immediately actionable message to clinicians, policy makers, and patients,” said Jeffrey L. Saver, MD, and Mary Cushman, MD, in an accompanying editorial. “Available evidence indicates that to achieve a lifetime of robust brain health free of dementia, it is never too early or too late to strive for attainment of ideal cardiovascular health.” Dr. Saver is a Professor of Neurology and Director of the Stroke Center at the University of California, Los Angeles. Dr. Cushman is a Professor of Medicine and Pathology at Larner College of Medicine at the University of Vermont in Burlington.
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.
The study included 6,626 people without a history of cardiovascular disease or dementia at baseline. Participants underwent in-person neuropsychologic testing between January 1999 and July 2016 and systematic detection of incident dementia. Participants had a mean age of 73.7, and 63.4% were women.
The investigators defined cardiovascular health using a seven-item tool from the American Heart Association (AHA). They determined the number of the AHA’s Life’s Simple Seven metrics that were at recommended levels (ie, nonsmoking, BMI < 25, regular physical activity, eating fish at least twice per week and fruits and vegetables at least three times per day, cholesterol < 200 mg/dL [untreated], fasting glucose < 100 mg/dL [untreated], and blood pressure < 120/80 mm Hg [untreated]).
Approximately 36.5% of the cohort had zero, one, or two optimal health metrics, 57.1% had three or four optimal health metrics, and 6.5% had five, six, or seven optimal health metrics.
During an average follow-up of 8.5 years, 745 participants developed dementia. Among participants with zero or one health metrics at optimal levels at baseline, the incidence rate of dementia was 1.76 per 100 person-years. Compared with this rate, the incidence rate per 100 person-years was 0.26 lower for participants with two optimal health metrics, 0.59 lower for participants with three optimal health metrics, 0.43 lower for participants with four optimal health metrics, 0.93 lower for participants with five optimal health metrics, and 0.96 lower for participants with six or seven optimal health metrics.
“In multivariable models, the hazard ratios for dementia were 0.90 per additional optimal metric,” the investigators said. “The study results support the recent recommendations of the AHA and the American Stroke Association for the promotion of the Life’s Simple Seven tool.”
Cerebrovascular Structure and Function in Young Adults
Wilby Williamson, BMBS
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.
Maintaining cardiovascular health may reduce white matter hyperintensities and decrease the risk of dementia.
Maintaining cardiovascular health may reduce white matter hyperintensities and decrease the risk of dementia.
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.
“These two studies convey an immediately actionable message to clinicians, policy makers, and patients,” said Jeffrey L. Saver, MD, and Mary Cushman, MD, in an accompanying editorial. “Available evidence indicates that to achieve a lifetime of robust brain health free of dementia, it is never too early or too late to strive for attainment of ideal cardiovascular health.” Dr. Saver is a Professor of Neurology and Director of the Stroke Center at the University of California, Los Angeles. Dr. Cushman is a Professor of Medicine and Pathology at Larner College of Medicine at the University of Vermont in Burlington.
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.
The study included 6,626 people without a history of cardiovascular disease or dementia at baseline. Participants underwent in-person neuropsychologic testing between January 1999 and July 2016 and systematic detection of incident dementia. Participants had a mean age of 73.7, and 63.4% were women.
The investigators defined cardiovascular health using a seven-item tool from the American Heart Association (AHA). They determined the number of the AHA’s Life’s Simple Seven metrics that were at recommended levels (ie, nonsmoking, BMI < 25, regular physical activity, eating fish at least twice per week and fruits and vegetables at least three times per day, cholesterol < 200 mg/dL [untreated], fasting glucose < 100 mg/dL [untreated], and blood pressure < 120/80 mm Hg [untreated]).
Approximately 36.5% of the cohort had zero, one, or two optimal health metrics, 57.1% had three or four optimal health metrics, and 6.5% had five, six, or seven optimal health metrics.
During an average follow-up of 8.5 years, 745 participants developed dementia. Among participants with zero or one health metrics at optimal levels at baseline, the incidence rate of dementia was 1.76 per 100 person-years. Compared with this rate, the incidence rate per 100 person-years was 0.26 lower for participants with two optimal health metrics, 0.59 lower for participants with three optimal health metrics, 0.43 lower for participants with four optimal health metrics, 0.93 lower for participants with five optimal health metrics, and 0.96 lower for participants with six or seven optimal health metrics.
“In multivariable models, the hazard ratios for dementia were 0.90 per additional optimal metric,” the investigators said. “The study results support the recent recommendations of the AHA and the American Stroke Association for the promotion of the Life’s Simple Seven tool.”
Cerebrovascular Structure and Function in Young Adults
Wilby Williamson, BMBS
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.
“These two studies convey an immediately actionable message to clinicians, policy makers, and patients,” said Jeffrey L. Saver, MD, and Mary Cushman, MD, in an accompanying editorial. “Available evidence indicates that to achieve a lifetime of robust brain health free of dementia, it is never too early or too late to strive for attainment of ideal cardiovascular health.” Dr. Saver is a Professor of Neurology and Director of the Stroke Center at the University of California, Los Angeles. Dr. Cushman is a Professor of Medicine and Pathology at Larner College of Medicine at the University of Vermont in Burlington.
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.
The study included 6,626 people without a history of cardiovascular disease or dementia at baseline. Participants underwent in-person neuropsychologic testing between January 1999 and July 2016 and systematic detection of incident dementia. Participants had a mean age of 73.7, and 63.4% were women.
The investigators defined cardiovascular health using a seven-item tool from the American Heart Association (AHA). They determined the number of the AHA’s Life’s Simple Seven metrics that were at recommended levels (ie, nonsmoking, BMI < 25, regular physical activity, eating fish at least twice per week and fruits and vegetables at least three times per day, cholesterol < 200 mg/dL [untreated], fasting glucose < 100 mg/dL [untreated], and blood pressure < 120/80 mm Hg [untreated]).
Approximately 36.5% of the cohort had zero, one, or two optimal health metrics, 57.1% had three or four optimal health metrics, and 6.5% had five, six, or seven optimal health metrics.
During an average follow-up of 8.5 years, 745 participants developed dementia. Among participants with zero or one health metrics at optimal levels at baseline, the incidence rate of dementia was 1.76 per 100 person-years. Compared with this rate, the incidence rate per 100 person-years was 0.26 lower for participants with two optimal health metrics, 0.59 lower for participants with three optimal health metrics, 0.43 lower for participants with four optimal health metrics, 0.93 lower for participants with five optimal health metrics, and 0.96 lower for participants with six or seven optimal health metrics.
“In multivariable models, the hazard ratios for dementia were 0.90 per additional optimal metric,” the investigators said. “The study results support the recent recommendations of the AHA and the American Stroke Association for the promotion of the Life’s Simple Seven tool.”
Cerebrovascular Structure and Function in Young Adults
Wilby Williamson, BMBS
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.
Study Examines Dementia Epidemiology in the LGB Population
Among older adults who are lesbian, gay, or bisexual, depression nearly triples the risk of dementia.
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.
The analysis of a large California health care database is the first step in learning more about dementia in this diverse population, said Dr. Flatt, Assistant Professor at the Institute for Health & Aging at the University of California, San Francisco.
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
Among older adults who are lesbian, gay, or bisexual, depression nearly triples the risk of dementia.
Among older adults who are lesbian, gay, or bisexual, depression nearly triples the risk of dementia.
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.
The analysis of a large California health care database is the first step in learning more about dementia in this diverse population, said Dr. Flatt, Assistant Professor at the Institute for Health & Aging at the University of California, San Francisco.
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.
The analysis of a large California health care database is the first step in learning more about dementia in this diverse population, said Dr. Flatt, Assistant Professor at the Institute for Health & Aging at the University of California, San Francisco.
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