TBD Meeting (3102-18)

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid-beta oligomers, slowed cognitive decline by up to 47% while clearing brain amyloid in 81% of patients with mild cognitive impairment and very mild Alzheimer’s disease, a phase 2 study has shown.

At the Alzheimer’s Association International Conference, Eisai, which is developing the antibody along with Biogen, touted it the study results as an important step forward in a field desperate for success. But questions remain, especially about the unequal distribution of apolipoprotein E4 (APOE4)-positive patients across the six treatment groups: BAN2401 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, and 10 mg/kg biweekly, or placebo. This troubled some researchers, who said the mix could have biased cognitive results in the antibody’s favor. APOE4 carriers comprised about 70%-80% of every unsuccessful treatment arm in the trial, and 29% of the arm that conferred significant cognitive benefits.

“This is a big confound,” Keith Fargo, PhD, director of scientific programs and outreach at the Alzheimer’s Association, said when he saw the numbers. “An important point is that, according to the trial sponsors, for a period of time a regulatory body requested that people with the APOE4 Alzheimer’s risk gene not be included in the highest dose group, for safety reasons. Because of this, the people in the highest-dose group are different from people in the other groups on an important dimension; they were much less likely to have the APOE4 gene, which is known to be a major risk factor for cognitive decline. So it is plausible that the people on the highest dose declined differently due to genetic differences rather than due to being on the highest dose. A planned subgroup analysis will shed more light on this, and whether it reduces confidence in the overall findings. We eagerly await the results of this analysis.”

The decision to restructure the randomization was not Eisai’s, according to David Knopman, MD, chair of the Alzheimer’s Association Medical and Scientific Advisory Council.

“European regulators did not allow randomization of [some] APOE4 carriers to the highest dose,” he said in an interview. “I ultimately don’t know what it would do to the results, except make them even more difficult to justify as sufficient for registration. In general, in symptomatic Alzheimer’s dementia patients, APOE4 carriage has no substantial impact on rate of decline, but whether [APOE4] status interacted with the treatment is of course completely unknown. Bottom line: Just another feature that makes this a phase 2 study that needs to be followed by a phase 3 study with a simple design using the high dose.”

Alzheimer’s researcher Michael S. Wolfe, PhD, was more candid.

“Regardless of who made the decision and why, the data is what it is, and the question remains,” said Dr. Wolfe, the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “Given the numbers of E4-positive vs. E4-negative for each treatment group, the interpretation of the results is now seriously thrown into question. The one group that showed a clear slowing of cognitive decline versus placebo (10 mg/kg biweekly) also has far fewer E4-positive vs. E4-negative. This difference in proportion of E4-positive could be a major factor in the apparent reduced rate of cognitive decline and confounds the ability to tell if the 10-mg/kg biweekly dose is effective. In contrast, the 10-mg/kg monthly dose group has an E4-positive/-negative ratio more comparable to that of placebo, and the effect of the drug on cognitive decline under this dosing regimen is not clearly distinguishable from that seen with placebo.”

Additionally, BAN2401 failed to meet its 12-month prespecified primary cognitive endpoints, a conclusion determined by a complex Bayesian analysis that strove to predict an 80% probability of reaching at least a 25% cognitive benefit. In December, the company announced that the study hit just a 64% probability. But because Eisai felt the numbers were moving in the right direction, it continued with the additional 6 months of treatment, as allowed for in the study design, and then reanalyzed results with a simpler and more straightforward method. This analysis concluded that 10 mg/kg infused biweekly conferred a 30% slowing of decline on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, and a 47% slowing of decline on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog). It also cleared brain amyloid in 81% of subjects and sent cerebrospinal fluid (CSF) biomarkers in the right direction. CSF amyloid levels went up – to be expected if the antibody was clearing it from the brain – and CSF total tau went down, an indication of decreased neuronal injury.

Inquiries to Eisai to clarify these issues had not been returned at press time.

This is a developing story.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid-beta oligomers, slowed cognitive decline by up to 47% while clearing brain amyloid in 81% of patients with mild cognitive impairment and very mild Alzheimer’s disease, a phase 2 study has shown.

At the Alzheimer’s Association International Conference, Eisai, which is developing the antibody along with Biogen, touted it the study results as an important step forward in a field desperate for success. But questions remain, especially about the unequal distribution of apolipoprotein E4 (APOE4)-positive patients across the six treatment groups: BAN2401 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, and 10 mg/kg biweekly, or placebo. This troubled some researchers, who said the mix could have biased cognitive results in the antibody’s favor. APOE4 carriers comprised about 70%-80% of every unsuccessful treatment arm in the trial, and 29% of the arm that conferred significant cognitive benefits.

“This is a big confound,” Keith Fargo, PhD, director of scientific programs and outreach at the Alzheimer’s Association, said when he saw the numbers. “An important point is that, according to the trial sponsors, for a period of time a regulatory body requested that people with the APOE4 Alzheimer’s risk gene not be included in the highest dose group, for safety reasons. Because of this, the people in the highest-dose group are different from people in the other groups on an important dimension; they were much less likely to have the APOE4 gene, which is known to be a major risk factor for cognitive decline. So it is plausible that the people on the highest dose declined differently due to genetic differences rather than due to being on the highest dose. A planned subgroup analysis will shed more light on this, and whether it reduces confidence in the overall findings. We eagerly await the results of this analysis.”

The decision to restructure the randomization was not Eisai’s, according to David Knopman, MD, chair of the Alzheimer’s Association Medical and Scientific Advisory Council.

“European regulators did not allow randomization of [some] APOE4 carriers to the highest dose,” he said in an interview. “I ultimately don’t know what it would do to the results, except make them even more difficult to justify as sufficient for registration. In general, in symptomatic Alzheimer’s dementia patients, APOE4 carriage has no substantial impact on rate of decline, but whether [APOE4] status interacted with the treatment is of course completely unknown. Bottom line: Just another feature that makes this a phase 2 study that needs to be followed by a phase 3 study with a simple design using the high dose.”

Alzheimer’s researcher Michael S. Wolfe, PhD, was more candid.

“Regardless of who made the decision and why, the data is what it is, and the question remains,” said Dr. Wolfe, the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “Given the numbers of E4-positive vs. E4-negative for each treatment group, the interpretation of the results is now seriously thrown into question. The one group that showed a clear slowing of cognitive decline versus placebo (10 mg/kg biweekly) also has far fewer E4-positive vs. E4-negative. This difference in proportion of E4-positive could be a major factor in the apparent reduced rate of cognitive decline and confounds the ability to tell if the 10-mg/kg biweekly dose is effective. In contrast, the 10-mg/kg monthly dose group has an E4-positive/-negative ratio more comparable to that of placebo, and the effect of the drug on cognitive decline under this dosing regimen is not clearly distinguishable from that seen with placebo.”

Additionally, BAN2401 failed to meet its 12-month prespecified primary cognitive endpoints, a conclusion determined by a complex Bayesian analysis that strove to predict an 80% probability of reaching at least a 25% cognitive benefit. In December, the company announced that the study hit just a 64% probability. But because Eisai felt the numbers were moving in the right direction, it continued with the additional 6 months of treatment, as allowed for in the study design, and then reanalyzed results with a simpler and more straightforward method. This analysis concluded that 10 mg/kg infused biweekly conferred a 30% slowing of decline on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, and a 47% slowing of decline on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog). It also cleared brain amyloid in 81% of subjects and sent cerebrospinal fluid (CSF) biomarkers in the right direction. CSF amyloid levels went up – to be expected if the antibody was clearing it from the brain – and CSF total tau went down, an indication of decreased neuronal injury.

Inquiries to Eisai to clarify these issues had not been returned at press time.

This is a developing story.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid-beta oligomers, slowed cognitive decline by up to 47% while clearing brain amyloid in 81% of patients with mild cognitive impairment and very mild Alzheimer’s disease, a phase 2 study has shown.

At the Alzheimer’s Association International Conference, Eisai, which is developing the antibody along with Biogen, touted it the study results as an important step forward in a field desperate for success. But questions remain, especially about the unequal distribution of apolipoprotein E4 (APOE4)-positive patients across the six treatment groups: BAN2401 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, and 10 mg/kg biweekly, or placebo. This troubled some researchers, who said the mix could have biased cognitive results in the antibody’s favor. APOE4 carriers comprised about 70%-80% of every unsuccessful treatment arm in the trial, and 29% of the arm that conferred significant cognitive benefits.

“This is a big confound,” Keith Fargo, PhD, director of scientific programs and outreach at the Alzheimer’s Association, said when he saw the numbers. “An important point is that, according to the trial sponsors, for a period of time a regulatory body requested that people with the APOE4 Alzheimer’s risk gene not be included in the highest dose group, for safety reasons. Because of this, the people in the highest-dose group are different from people in the other groups on an important dimension; they were much less likely to have the APOE4 gene, which is known to be a major risk factor for cognitive decline. So it is plausible that the people on the highest dose declined differently due to genetic differences rather than due to being on the highest dose. A planned subgroup analysis will shed more light on this, and whether it reduces confidence in the overall findings. We eagerly await the results of this analysis.”

The decision to restructure the randomization was not Eisai’s, according to David Knopman, MD, chair of the Alzheimer’s Association Medical and Scientific Advisory Council.

“European regulators did not allow randomization of [some] APOE4 carriers to the highest dose,” he said in an interview. “I ultimately don’t know what it would do to the results, except make them even more difficult to justify as sufficient for registration. In general, in symptomatic Alzheimer’s dementia patients, APOE4 carriage has no substantial impact on rate of decline, but whether [APOE4] status interacted with the treatment is of course completely unknown. Bottom line: Just another feature that makes this a phase 2 study that needs to be followed by a phase 3 study with a simple design using the high dose.”

Alzheimer’s researcher Michael S. Wolfe, PhD, was more candid.

“Regardless of who made the decision and why, the data is what it is, and the question remains,” said Dr. Wolfe, the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, Lawrence. “Given the numbers of E4-positive vs. E4-negative for each treatment group, the interpretation of the results is now seriously thrown into question. The one group that showed a clear slowing of cognitive decline versus placebo (10 mg/kg biweekly) also has far fewer E4-positive vs. E4-negative. This difference in proportion of E4-positive could be a major factor in the apparent reduced rate of cognitive decline and confounds the ability to tell if the 10-mg/kg biweekly dose is effective. In contrast, the 10-mg/kg monthly dose group has an E4-positive/-negative ratio more comparable to that of placebo, and the effect of the drug on cognitive decline under this dosing regimen is not clearly distinguishable from that seen with placebo.”

Additionally, BAN2401 failed to meet its 12-month prespecified primary cognitive endpoints, a conclusion determined by a complex Bayesian analysis that strove to predict an 80% probability of reaching at least a 25% cognitive benefit. In December, the company announced that the study hit just a 64% probability. But because Eisai felt the numbers were moving in the right direction, it continued with the additional 6 months of treatment, as allowed for in the study design, and then reanalyzed results with a simpler and more straightforward method. This analysis concluded that 10 mg/kg infused biweekly conferred a 30% slowing of decline on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, and a 47% slowing of decline on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog). It also cleared brain amyloid in 81% of subjects and sent cerebrospinal fluid (CSF) biomarkers in the right direction. CSF amyloid levels went up – to be expected if the antibody was clearing it from the brain – and CSF total tau went down, an indication of decreased neuronal injury.

Inquiries to Eisai to clarify these issues had not been returned at press time.

This is a developing story.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid beta oligomers, slowed cognitive decline in patients with mild cognitive impairment or early Alzheimer’s dementia on two measures, while clearing brain amyloid in 81% of patients in a phase 2 study.

“The majority of subjects receiving the top dose [10 mg/kg intravenously, biweekly] went from being amyloid positive to amyloid negative,” by the end of the 18-month study, Lynn Kramer, MD, said at the Alzheimer’s Association International Conference.

Michele Sullivan?Mdedge News

At that dose, BAN2401 also slowed cognitive decline by 30% relative to placebo on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, which is codeveloping the drug with Biogen. The antibody also hit statistical significance on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), with a 47% slowing of decline. A third measure, the Clinical Dementia Rating Sum of Boxes (CDR-sb), showed a 26% reduction, but this was not statistically significant.

There were also significant changes in cerebrospinal fluid amyloid beta and total tau, said Dr. Kramer, chief medical officer of Eisai’s neurology division.

“In our opinion, we have fairly conclusive results,” he said at a press briefing. “We view this as robust enough to approach regulatory authorities [around the world] and discuss the next steps with them, and what we need to do to register this product.”

In addition to planning larger, longer phase 3 studies, Dr. Kramer said that Eisai might try to obtain FDA breakthrough therapy status.

BAN2401 selectively binds to amyloid-beta protofibrils – large, soluble amyloid-beta oligomers – and targets them for clearance. It was originally developed by Swedish biopharma company BioArctic; Eisai acquired the molecule in 2007 and entered a deal with Biogen in 2014.

This is a developing story. Please check back for details.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid beta oligomers, slowed cognitive decline in patients with mild cognitive impairment or early Alzheimer’s dementia on two measures, while clearing brain amyloid in 81% of patients in a phase 2 study.

“The majority of subjects receiving the top dose [10 mg/kg intravenously, biweekly] went from being amyloid positive to amyloid negative,” by the end of the 18-month study, Lynn Kramer, MD, said at the Alzheimer’s Association International Conference.

Michele Sullivan?Mdedge News

At that dose, BAN2401 also slowed cognitive decline by 30% relative to placebo on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, which is codeveloping the drug with Biogen. The antibody also hit statistical significance on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), with a 47% slowing of decline. A third measure, the Clinical Dementia Rating Sum of Boxes (CDR-sb), showed a 26% reduction, but this was not statistically significant.

There were also significant changes in cerebrospinal fluid amyloid beta and total tau, said Dr. Kramer, chief medical officer of Eisai’s neurology division.

“In our opinion, we have fairly conclusive results,” he said at a press briefing. “We view this as robust enough to approach regulatory authorities [around the world] and discuss the next steps with them, and what we need to do to register this product.”

In addition to planning larger, longer phase 3 studies, Dr. Kramer said that Eisai might try to obtain FDA breakthrough therapy status.

BAN2401 selectively binds to amyloid-beta protofibrils – large, soluble amyloid-beta oligomers – and targets them for clearance. It was originally developed by Swedish biopharma company BioArctic; Eisai acquired the molecule in 2007 and entered a deal with Biogen in 2014.

This is a developing story. Please check back for details.

[email protected]

CHICAGO – BAN2401, a monoclonal antibody that targets soluble amyloid beta oligomers, slowed cognitive decline in patients with mild cognitive impairment or early Alzheimer’s dementia on two measures, while clearing brain amyloid in 81% of patients in a phase 2 study.

“The majority of subjects receiving the top dose [10 mg/kg intravenously, biweekly] went from being amyloid positive to amyloid negative,” by the end of the 18-month study, Lynn Kramer, MD, said at the Alzheimer’s Association International Conference.

Michele Sullivan?Mdedge News

At that dose, BAN2401 also slowed cognitive decline by 30% relative to placebo on the Alzheimer’s Disease Composite Score (ADCOMS), a new tool developed and promoted by Eisai, which is codeveloping the drug with Biogen. The antibody also hit statistical significance on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), with a 47% slowing of decline. A third measure, the Clinical Dementia Rating Sum of Boxes (CDR-sb), showed a 26% reduction, but this was not statistically significant.

There were also significant changes in cerebrospinal fluid amyloid beta and total tau, said Dr. Kramer, chief medical officer of Eisai’s neurology division.

“In our opinion, we have fairly conclusive results,” he said at a press briefing. “We view this as robust enough to approach regulatory authorities [around the world] and discuss the next steps with them, and what we need to do to register this product.”

In addition to planning larger, longer phase 3 studies, Dr. Kramer said that Eisai might try to obtain FDA breakthrough therapy status.

BAN2401 selectively binds to amyloid-beta protofibrils – large, soluble amyloid-beta oligomers – and targets them for clearance. It was originally developed by Swedish biopharma company BioArctic; Eisai acquired the molecule in 2007 and entered a deal with Biogen in 2014.

This is a developing story. Please check back for details.

[email protected]

CHICAGO – Lowering systolic blood pressure to a target of 120 mm Hg or lower in people with cardiovascular risk factors reduced the risk of mild cognitive impairment by 19% and probable all-cause dementia by 17% relative to those who achieved a less intensive target of less than 140 mm Hg

Drug class didn’t matter. Cheap generics were just as effective as expensive name brands. It equally benefited men and women, whites, blacks, and Hispanics. And keeping systolic blood pressure at 120 mm Hg or lower prevented MCI just as well in those older than 75 as it did for younger subjects.

The stunning announcement came during a press briefing at the Alzheimer’s Association International Conference, as Jeff D. Williamson, MD, unveiled the results of the 4-year SPRINT MIND study. Strict blood pressure control for 3.2 years, with a systolic target of 120 mm Hg or lower, reduced the incidence of mild cognitive impairment by a magnitude of benefit that no amyloid-targeting investigational drug has ever approached.

“I think we can say this is the first disease-modifying strategy to reduce the risk of MCI,” Dr. Williamson said during at the briefing. And although the primary endpoint – the 17% relative risk reduction for probable all-cause dementia – didn’t meet statistical significance, “It’s comforting to see that the benefit went in the same direction and was of the same magnitude. Three years of treatment and 3.2 years of follow-up absolutely reduced the risk.”

Brain imaging underscored the clinical importance of this finding and showed its physiologic pathway. People in the strict BP arm had 18% fewer white matter hyperintensities after 4 years of follow-up.

The news is an incredible step forward for the field that has stumbled repeatedly, clinicians agreed. Generic antihypertensives can be very inexpensive. They are almost globally available, and confer a host of other benefits, not only on cardiovascular health but on kidney health as well, said Dr. Williamson, chief of geriatric medicine at Wake Forest University, Winston-Salem, N.C.

“Hypertension is a highly prevalent condition, with 60%-70% having it. The 19% overall risk reduction for MCI will have a huge impact,” he said.

Maria Carrillo, PhD, chief scientific officer of the Alzheimer’s Association, was somewhat more guarded, but still very enthusiastic.

“I think the most we can say right now is we are able to reduce risk,” she said in an interview. “But the reality is that reducing the risk of MCI by 19% will have a huge impact on dementia overall. And slowing down the disease progress is a disease modification, versus developing symptoms. So, if that is the definition we are using, the I would say yes, it is disease modifying,” for dementias arising from cerebrovascular pathology.

SPRINT MIND was a substudy of the Hypertension Systolic Blood Pressure Intervention Trial (SPRINT). It compared two strategies for managing hypertension in older adults. The intensive strategy had a target of less than 120 mm Hg, and standard care, a target of less than 140 mm Hg. SPRINT showed that more intensive blood pressure control produced a 30% reduction in the composite primary composite endpoint of cardiovascular events, stroke, and cardiovascular death. The intensive arm was so successful that SPRINT helped inform the 2017 American Heart Association and American College of Cardiology high blood pressure clinical guidelines.

The SPRINT MIND substudy looked at whether intensive management had any effect on probable all-cause dementia or MCI, as well as imaging evidence of changes in white matter lesions and brain volume.

It comprised 9,361 SPRINT subjects who were 50 years or older (mean 68; 28% at least 75) and had at least one cardiovascular risk factor. Nearly a third (30%) were black, and 10% Hispanic. The primary outcome was incident probable dementia. Secondary outcomes were MCI and a composite of MCI and/or probable dementia.

In SPRINT, physicians could choose any appropriate antihypertensive regimen, but they were encouraged to use drugs with the strongest evidence of cardiovascular benefit: thiazide-type diuretics encouraged as first-line, and then loop diuretics and beta-adrenergic blockers. About 90% of the drugs used during the study were generics.

Subjects were seen monthly for the first 3 months, during which medications were adjusted to achieve the target, and then every 3 months after that. Medications could be adjusted monthly to keep on target.

At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard treatment group. Treatment was stopped in August 2015 due to the observed cardiovascular disease benefit, after a median follow up of 3.26 years, but cognitive assessment continued until the end of June (N Engl J Med. 2015 Nov 26; 373:2103-16).

The SPRINT MIND study did not meet its primary endpoint. Adjudicated cases of probable all-cause dementia developed in 175 of the standard care group and 147 of the intensive treatment group; the 17% risk reduction was not statistically significant (P = .10).

However, it did hit both secondary endpoints. Adjudicated cases of MCI developed in 348 of the standard treatment groups and 285 of the intensive treatment group: a statistically significant 19% risk reduction (P = .01). The combined secondary endpoint of MCI and probable dementia was a significant 15% risk reduction (P = .02), with 463 cases in the standard care group and 398 in the intensive care group.

The imaging study comprised 454 subjects who had brain MRI at baseline and 4 years after randomization. There was no change in total brain volume, said Ilya Nasrallah, MD, of the University of Pennsylvania. But those in the intensively managed group had 18% lower white matter lesion load than those in the standard care group (P = .004).

White matter lesions often point to small vessel disease, which is conclusively linked to vascular dementia, and may also linked to Alzheimer’s disease. Most AD patients, in fact, have a mixed dementia that often includes a vascular component, Dr. Carillo said.

SPRINT MIND didn’t follow subjects past 4 years, and didn’t include any follow-up for amyloid or Alzheimer’s diagnosis. But preventing MCI is no trivial thing, according to David Knopman, MD, who moderated the session.

“There’s nothing that is benign about MCI,” said Dr. Knopman of the Mayo Clinic, Rochester, Minn. “it’s the first sign of overt cognitive dysfunction, and although the rate at which MCI progress to dementia is slow, the appearance of it is just as important as the appearance of more severe dementia. To be able to see an effect in 3.2 years is quite remarkable. I think is going to change clinical practice for people in primary care and the benefits at the population level are going to be substantial.”

Dr. Williamson drove this point home in a later interview, suggesting that physicians may want to think about how the SPRINT MIND results might apply to even younger patients with hypertension, and even if they don’t have other cardiovascular risk factors.

“I can’t say as a scientist that we have evidence to do that, yet. But as a physician, and for my own self and my own patients, I will adhere to the guidelines we have and keep blood pressure at less than 130 mm Hg, and certainly start treating people in their 50s, and probably in their 40s.”

***This article was updated 7/31/18.

[email protected]

SOURCE: Williamson et al. AAIC 2018 DT-0202 Nasrallah et al. AAIC 2018 DT-03-03

CHICAGO – Lowering systolic blood pressure to a target of 120 mm Hg or lower in people with cardiovascular risk factors reduced the risk of mild cognitive impairment by 19% and probable all-cause dementia by 17% relative to those who achieved a less intensive target of less than 140 mm Hg

Drug class didn’t matter. Cheap generics were just as effective as expensive name brands. It equally benefited men and women, whites, blacks, and Hispanics. And keeping systolic blood pressure at 120 mm Hg or lower prevented MCI just as well in those older than 75 as it did for younger subjects.

The stunning announcement came during a press briefing at the Alzheimer’s Association International Conference, as Jeff D. Williamson, MD, unveiled the results of the 4-year SPRINT MIND study. Strict blood pressure control for 3.2 years, with a systolic target of 120 mm Hg or lower, reduced the incidence of mild cognitive impairment by a magnitude of benefit that no amyloid-targeting investigational drug has ever approached.

“I think we can say this is the first disease-modifying strategy to reduce the risk of MCI,” Dr. Williamson said during at the briefing. And although the primary endpoint – the 17% relative risk reduction for probable all-cause dementia – didn’t meet statistical significance, “It’s comforting to see that the benefit went in the same direction and was of the same magnitude. Three years of treatment and 3.2 years of follow-up absolutely reduced the risk.”

Brain imaging underscored the clinical importance of this finding and showed its physiologic pathway. People in the strict BP arm had 18% fewer white matter hyperintensities after 4 years of follow-up.

The news is an incredible step forward for the field that has stumbled repeatedly, clinicians agreed. Generic antihypertensives can be very inexpensive. They are almost globally available, and confer a host of other benefits, not only on cardiovascular health but on kidney health as well, said Dr. Williamson, chief of geriatric medicine at Wake Forest University, Winston-Salem, N.C.

“Hypertension is a highly prevalent condition, with 60%-70% having it. The 19% overall risk reduction for MCI will have a huge impact,” he said.

Maria Carrillo, PhD, chief scientific officer of the Alzheimer’s Association, was somewhat more guarded, but still very enthusiastic.

“I think the most we can say right now is we are able to reduce risk,” she said in an interview. “But the reality is that reducing the risk of MCI by 19% will have a huge impact on dementia overall. And slowing down the disease progress is a disease modification, versus developing symptoms. So, if that is the definition we are using, the I would say yes, it is disease modifying,” for dementias arising from cerebrovascular pathology.

SPRINT MIND was a substudy of the Hypertension Systolic Blood Pressure Intervention Trial (SPRINT). It compared two strategies for managing hypertension in older adults. The intensive strategy had a target of less than 120 mm Hg, and standard care, a target of less than 140 mm Hg. SPRINT showed that more intensive blood pressure control produced a 30% reduction in the composite primary composite endpoint of cardiovascular events, stroke, and cardiovascular death. The intensive arm was so successful that SPRINT helped inform the 2017 American Heart Association and American College of Cardiology high blood pressure clinical guidelines.

The SPRINT MIND substudy looked at whether intensive management had any effect on probable all-cause dementia or MCI, as well as imaging evidence of changes in white matter lesions and brain volume.

It comprised 9,361 SPRINT subjects who were 50 years or older (mean 68; 28% at least 75) and had at least one cardiovascular risk factor. Nearly a third (30%) were black, and 10% Hispanic. The primary outcome was incident probable dementia. Secondary outcomes were MCI and a composite of MCI and/or probable dementia.

In SPRINT, physicians could choose any appropriate antihypertensive regimen, but they were encouraged to use drugs with the strongest evidence of cardiovascular benefit: thiazide-type diuretics encouraged as first-line, and then loop diuretics and beta-adrenergic blockers. About 90% of the drugs used during the study were generics.

Subjects were seen monthly for the first 3 months, during which medications were adjusted to achieve the target, and then every 3 months after that. Medications could be adjusted monthly to keep on target.

At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard treatment group. Treatment was stopped in August 2015 due to the observed cardiovascular disease benefit, after a median follow up of 3.26 years, but cognitive assessment continued until the end of June (N Engl J Med. 2015 Nov 26; 373:2103-16).

The SPRINT MIND study did not meet its primary endpoint. Adjudicated cases of probable all-cause dementia developed in 175 of the standard care group and 147 of the intensive treatment group; the 17% risk reduction was not statistically significant (P = .10).

However, it did hit both secondary endpoints. Adjudicated cases of MCI developed in 348 of the standard treatment groups and 285 of the intensive treatment group: a statistically significant 19% risk reduction (P = .01). The combined secondary endpoint of MCI and probable dementia was a significant 15% risk reduction (P = .02), with 463 cases in the standard care group and 398 in the intensive care group.

The imaging study comprised 454 subjects who had brain MRI at baseline and 4 years after randomization. There was no change in total brain volume, said Ilya Nasrallah, MD, of the University of Pennsylvania. But those in the intensively managed group had 18% lower white matter lesion load than those in the standard care group (P = .004).

White matter lesions often point to small vessel disease, which is conclusively linked to vascular dementia, and may also linked to Alzheimer’s disease. Most AD patients, in fact, have a mixed dementia that often includes a vascular component, Dr. Carillo said.

SPRINT MIND didn’t follow subjects past 4 years, and didn’t include any follow-up for amyloid or Alzheimer’s diagnosis. But preventing MCI is no trivial thing, according to David Knopman, MD, who moderated the session.

“There’s nothing that is benign about MCI,” said Dr. Knopman of the Mayo Clinic, Rochester, Minn. “it’s the first sign of overt cognitive dysfunction, and although the rate at which MCI progress to dementia is slow, the appearance of it is just as important as the appearance of more severe dementia. To be able to see an effect in 3.2 years is quite remarkable. I think is going to change clinical practice for people in primary care and the benefits at the population level are going to be substantial.”

Dr. Williamson drove this point home in a later interview, suggesting that physicians may want to think about how the SPRINT MIND results might apply to even younger patients with hypertension, and even if they don’t have other cardiovascular risk factors.

“I can’t say as a scientist that we have evidence to do that, yet. But as a physician, and for my own self and my own patients, I will adhere to the guidelines we have and keep blood pressure at less than 130 mm Hg, and certainly start treating people in their 50s, and probably in their 40s.”

***This article was updated 7/31/18.

[email protected]

SOURCE: Williamson et al. AAIC 2018 DT-0202 Nasrallah et al. AAIC 2018 DT-03-03

CHICAGO – Lowering systolic blood pressure to a target of 120 mm Hg or lower in people with cardiovascular risk factors reduced the risk of mild cognitive impairment by 19% and probable all-cause dementia by 17% relative to those who achieved a less intensive target of less than 140 mm Hg

Drug class didn’t matter. Cheap generics were just as effective as expensive name brands. It equally benefited men and women, whites, blacks, and Hispanics. And keeping systolic blood pressure at 120 mm Hg or lower prevented MCI just as well in those older than 75 as it did for younger subjects.

The stunning announcement came during a press briefing at the Alzheimer’s Association International Conference, as Jeff D. Williamson, MD, unveiled the results of the 4-year SPRINT MIND study. Strict blood pressure control for 3.2 years, with a systolic target of 120 mm Hg or lower, reduced the incidence of mild cognitive impairment by a magnitude of benefit that no amyloid-targeting investigational drug has ever approached.

“I think we can say this is the first disease-modifying strategy to reduce the risk of MCI,” Dr. Williamson said during at the briefing. And although the primary endpoint – the 17% relative risk reduction for probable all-cause dementia – didn’t meet statistical significance, “It’s comforting to see that the benefit went in the same direction and was of the same magnitude. Three years of treatment and 3.2 years of follow-up absolutely reduced the risk.”

Brain imaging underscored the clinical importance of this finding and showed its physiologic pathway. People in the strict BP arm had 18% fewer white matter hyperintensities after 4 years of follow-up.

The news is an incredible step forward for the field that has stumbled repeatedly, clinicians agreed. Generic antihypertensives can be very inexpensive. They are almost globally available, and confer a host of other benefits, not only on cardiovascular health but on kidney health as well, said Dr. Williamson, chief of geriatric medicine at Wake Forest University, Winston-Salem, N.C.

“Hypertension is a highly prevalent condition, with 60%-70% having it. The 19% overall risk reduction for MCI will have a huge impact,” he said.

Maria Carrillo, PhD, chief scientific officer of the Alzheimer’s Association, was somewhat more guarded, but still very enthusiastic.

“I think the most we can say right now is we are able to reduce risk,” she said in an interview. “But the reality is that reducing the risk of MCI by 19% will have a huge impact on dementia overall. And slowing down the disease progress is a disease modification, versus developing symptoms. So, if that is the definition we are using, the I would say yes, it is disease modifying,” for dementias arising from cerebrovascular pathology.

SPRINT MIND was a substudy of the Hypertension Systolic Blood Pressure Intervention Trial (SPRINT). It compared two strategies for managing hypertension in older adults. The intensive strategy had a target of less than 120 mm Hg, and standard care, a target of less than 140 mm Hg. SPRINT showed that more intensive blood pressure control produced a 30% reduction in the composite primary composite endpoint of cardiovascular events, stroke, and cardiovascular death. The intensive arm was so successful that SPRINT helped inform the 2017 American Heart Association and American College of Cardiology high blood pressure clinical guidelines.

The SPRINT MIND substudy looked at whether intensive management had any effect on probable all-cause dementia or MCI, as well as imaging evidence of changes in white matter lesions and brain volume.

It comprised 9,361 SPRINT subjects who were 50 years or older (mean 68; 28% at least 75) and had at least one cardiovascular risk factor. Nearly a third (30%) were black, and 10% Hispanic. The primary outcome was incident probable dementia. Secondary outcomes were MCI and a composite of MCI and/or probable dementia.

In SPRINT, physicians could choose any appropriate antihypertensive regimen, but they were encouraged to use drugs with the strongest evidence of cardiovascular benefit: thiazide-type diuretics encouraged as first-line, and then loop diuretics and beta-adrenergic blockers. About 90% of the drugs used during the study were generics.

Subjects were seen monthly for the first 3 months, during which medications were adjusted to achieve the target, and then every 3 months after that. Medications could be adjusted monthly to keep on target.

At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard treatment group. Treatment was stopped in August 2015 due to the observed cardiovascular disease benefit, after a median follow up of 3.26 years, but cognitive assessment continued until the end of June (N Engl J Med. 2015 Nov 26; 373:2103-16).

The SPRINT MIND study did not meet its primary endpoint. Adjudicated cases of probable all-cause dementia developed in 175 of the standard care group and 147 of the intensive treatment group; the 17% risk reduction was not statistically significant (P = .10).

However, it did hit both secondary endpoints. Adjudicated cases of MCI developed in 348 of the standard treatment groups and 285 of the intensive treatment group: a statistically significant 19% risk reduction (P = .01). The combined secondary endpoint of MCI and probable dementia was a significant 15% risk reduction (P = .02), with 463 cases in the standard care group and 398 in the intensive care group.

The imaging study comprised 454 subjects who had brain MRI at baseline and 4 years after randomization. There was no change in total brain volume, said Ilya Nasrallah, MD, of the University of Pennsylvania. But those in the intensively managed group had 18% lower white matter lesion load than those in the standard care group (P = .004).

White matter lesions often point to small vessel disease, which is conclusively linked to vascular dementia, and may also linked to Alzheimer’s disease. Most AD patients, in fact, have a mixed dementia that often includes a vascular component, Dr. Carillo said.

SPRINT MIND didn’t follow subjects past 4 years, and didn’t include any follow-up for amyloid or Alzheimer’s diagnosis. But preventing MCI is no trivial thing, according to David Knopman, MD, who moderated the session.

“There’s nothing that is benign about MCI,” said Dr. Knopman of the Mayo Clinic, Rochester, Minn. “it’s the first sign of overt cognitive dysfunction, and although the rate at which MCI progress to dementia is slow, the appearance of it is just as important as the appearance of more severe dementia. To be able to see an effect in 3.2 years is quite remarkable. I think is going to change clinical practice for people in primary care and the benefits at the population level are going to be substantial.”

Dr. Williamson drove this point home in a later interview, suggesting that physicians may want to think about how the SPRINT MIND results might apply to even younger patients with hypertension, and even if they don’t have other cardiovascular risk factors.

“I can’t say as a scientist that we have evidence to do that, yet. But as a physician, and for my own self and my own patients, I will adhere to the guidelines we have and keep blood pressure at less than 130 mm Hg, and certainly start treating people in their 50s, and probably in their 40s.”

***This article was updated 7/31/18.

[email protected]

SOURCE: Williamson et al. AAIC 2018 DT-0202 Nasrallah et al. AAIC 2018 DT-03-03

CHICAGO – More pregnancies and a longer span of reproductive years appear to confer some level of protection against dementia, suggesting that lifetime estrogen exposure may be an important modulator of long-term cognitive health.

The study, presented at the Alzheimer’s Association International Conference, is the first to examine this question in a large cohort, comprising more than 14,500 women with up to 50 years of follow-up data. It is one of the first explorations in a renewed interest in the link between hormones and cognition, said Suzanne Craft, PhD, who moderated a press briefing on the topic.

“WHI [Women’s Heath Initiative] had a completely chilling effect on research into estrogen and cognition completely,” Dr. Craft of Wake Forest University, Winston-Salem, N.C., said in an interview. “Many well-regarded researchers simply couldn’t get funding and had to close their programs and move on to other areas. But now I think the pendulum is slowly moving back. It’s clear that something is going on, that there is a link. I’m glad we’re starting to explore this again.”

The investigation of women’s total reproductive experience affects dementia risk found several intriguing associations, said Paola Gilsanz, ScD, of Kaiser Permanente, Oakland, Calif. Earlier age of menarche, later menopause, and more completed pregnancies all independently reduced the risk of dementia in women.

Her study comprised 14,595 women, all members of the Kaiser Permanente health care database. All of them had completed a comprehensive health checkup sometime between 1964 and 1973, when they were 40-55 years old. They reported their number of miscarriages, number of children, ages at first and last menstrual period, and the total number of years in their reproductive period. Most of the group (68%) was white, but 16% were black, 6% Asian, and 5% Hispanic. Dr. Gilsanz looked at rates of dementia during 1996-2017, when the women were 62-86 years old.

A multivariate regression model controlled for age, race, education, midlife health issues (hypertension, smoking, and body mass index), hysterectomy, and late-life health issues (stroke, heart failure, and diabetes).

Half of the cohort (50%) had at least three children, and 75% had experienced at least one miscarriage. The average age at menarche was 13 years, and the average age at last natural menstrual period was 47 years. This equated to an average reproductive period of 34 years.

At the end of follow-up, 36% of the cohort had developed some type of dementia.

Women with at least three children were 12% less likely to develop dementia, compared with those with one child (hazard ratio, 0.88). The association remained significant even after researchers controlled for age, race, educational level, and hysterectomy.

Miscarriages also influenced the risk of dementia. Those who didn’t report one were 20% less likely to develop dementia than were those who had experienced at least one (HR, 0.81). The benefit of no miscarriage was even greater among women with at least three children, conferring a 28% reduced risk (HR, 0.72).

A shortened reproductive period increased the risk of dementia. Those who experienced menarche at 16 years or older had a 31% increased risk of dementia (HR, 1.31), and those who experienced their last period at age 45 or younger faced a 28% greater risk (HR, 1.28). Each additional year of reproductive capability was associated with a 2% decreased risk (HR, 0.98).

[email protected]

SOURCE: Gilsanz P et al. AAIC 2018, Abstract P3-587

CHICAGO – More pregnancies and a longer span of reproductive years appear to confer some level of protection against dementia, suggesting that lifetime estrogen exposure may be an important modulator of long-term cognitive health.

The study, presented at the Alzheimer’s Association International Conference, is the first to examine this question in a large cohort, comprising more than 14,500 women with up to 50 years of follow-up data. It is one of the first explorations in a renewed interest in the link between hormones and cognition, said Suzanne Craft, PhD, who moderated a press briefing on the topic.

“WHI [Women’s Heath Initiative] had a completely chilling effect on research into estrogen and cognition completely,” Dr. Craft of Wake Forest University, Winston-Salem, N.C., said in an interview. “Many well-regarded researchers simply couldn’t get funding and had to close their programs and move on to other areas. But now I think the pendulum is slowly moving back. It’s clear that something is going on, that there is a link. I’m glad we’re starting to explore this again.”

The investigation of women’s total reproductive experience affects dementia risk found several intriguing associations, said Paola Gilsanz, ScD, of Kaiser Permanente, Oakland, Calif. Earlier age of menarche, later menopause, and more completed pregnancies all independently reduced the risk of dementia in women.

Her study comprised 14,595 women, all members of the Kaiser Permanente health care database. All of them had completed a comprehensive health checkup sometime between 1964 and 1973, when they were 40-55 years old. They reported their number of miscarriages, number of children, ages at first and last menstrual period, and the total number of years in their reproductive period. Most of the group (68%) was white, but 16% were black, 6% Asian, and 5% Hispanic. Dr. Gilsanz looked at rates of dementia during 1996-2017, when the women were 62-86 years old.

A multivariate regression model controlled for age, race, education, midlife health issues (hypertension, smoking, and body mass index), hysterectomy, and late-life health issues (stroke, heart failure, and diabetes).

Half of the cohort (50%) had at least three children, and 75% had experienced at least one miscarriage. The average age at menarche was 13 years, and the average age at last natural menstrual period was 47 years. This equated to an average reproductive period of 34 years.

At the end of follow-up, 36% of the cohort had developed some type of dementia.

Women with at least three children were 12% less likely to develop dementia, compared with those with one child (hazard ratio, 0.88). The association remained significant even after researchers controlled for age, race, educational level, and hysterectomy.

Miscarriages also influenced the risk of dementia. Those who didn’t report one were 20% less likely to develop dementia than were those who had experienced at least one (HR, 0.81). The benefit of no miscarriage was even greater among women with at least three children, conferring a 28% reduced risk (HR, 0.72).

A shortened reproductive period increased the risk of dementia. Those who experienced menarche at 16 years or older had a 31% increased risk of dementia (HR, 1.31), and those who experienced their last period at age 45 or younger faced a 28% greater risk (HR, 1.28). Each additional year of reproductive capability was associated with a 2% decreased risk (HR, 0.98).

[email protected]

SOURCE: Gilsanz P et al. AAIC 2018, Abstract P3-587

CHICAGO – More pregnancies and a longer span of reproductive years appear to confer some level of protection against dementia, suggesting that lifetime estrogen exposure may be an important modulator of long-term cognitive health.

The study, presented at the Alzheimer’s Association International Conference, is the first to examine this question in a large cohort, comprising more than 14,500 women with up to 50 years of follow-up data. It is one of the first explorations in a renewed interest in the link between hormones and cognition, said Suzanne Craft, PhD, who moderated a press briefing on the topic.

“WHI [Women’s Heath Initiative] had a completely chilling effect on research into estrogen and cognition completely,” Dr. Craft of Wake Forest University, Winston-Salem, N.C., said in an interview. “Many well-regarded researchers simply couldn’t get funding and had to close their programs and move on to other areas. But now I think the pendulum is slowly moving back. It’s clear that something is going on, that there is a link. I’m glad we’re starting to explore this again.”

The investigation of women’s total reproductive experience affects dementia risk found several intriguing associations, said Paola Gilsanz, ScD, of Kaiser Permanente, Oakland, Calif. Earlier age of menarche, later menopause, and more completed pregnancies all independently reduced the risk of dementia in women.

Her study comprised 14,595 women, all members of the Kaiser Permanente health care database. All of them had completed a comprehensive health checkup sometime between 1964 and 1973, when they were 40-55 years old. They reported their number of miscarriages, number of children, ages at first and last menstrual period, and the total number of years in their reproductive period. Most of the group (68%) was white, but 16% were black, 6% Asian, and 5% Hispanic. Dr. Gilsanz looked at rates of dementia during 1996-2017, when the women were 62-86 years old.

A multivariate regression model controlled for age, race, education, midlife health issues (hypertension, smoking, and body mass index), hysterectomy, and late-life health issues (stroke, heart failure, and diabetes).

Half of the cohort (50%) had at least three children, and 75% had experienced at least one miscarriage. The average age at menarche was 13 years, and the average age at last natural menstrual period was 47 years. This equated to an average reproductive period of 34 years.

At the end of follow-up, 36% of the cohort had developed some type of dementia.

Women with at least three children were 12% less likely to develop dementia, compared with those with one child (hazard ratio, 0.88). The association remained significant even after researchers controlled for age, race, educational level, and hysterectomy.

Miscarriages also influenced the risk of dementia. Those who didn’t report one were 20% less likely to develop dementia than were those who had experienced at least one (HR, 0.81). The benefit of no miscarriage was even greater among women with at least three children, conferring a 28% reduced risk (HR, 0.72).

A shortened reproductive period increased the risk of dementia. Those who experienced menarche at 16 years or older had a 31% increased risk of dementia (HR, 1.31), and those who experienced their last period at age 45 or younger faced a 28% greater risk (HR, 1.28). Each additional year of reproductive capability was associated with a 2% decreased risk (HR, 0.98).

[email protected]

SOURCE: Gilsanz P et al. AAIC 2018, Abstract P3-587

CHICAGO – The first comprehensive analysis of dementia prevalence among sexual minorities has found a rate of 8% in this population.

While only marginally lower than the 9% prevalence among a heterosexual comparator group, the disorder manifested at an earlier age and occurred more often among men, Jason Flatt, PhD, said at the Alzheimer’s Association International Conference. In addition, higher education didn’t exert the protective influence seen in general populations, said Dr. Flatt of the University of California, San Francisco.

The analysis of a large California health care database is the first step in learning more about dementia in this diverse population, he said. It’s an important quest because the age-risk curve is rising just as quickly among the LGB population as it is in the heterosexual population.

“We do know there are 2-3 million people who identify as LGB [lesbian, gay, or bisexual] in the U.S., and are 60 years old or older, and with the continued aging of our entire population, we expect this number to increase to about 6 million by 2040,” he said. “Given the gaps in collection of sexual orientation and gender identification, we haven’t been able to look at this issue before.”

Sexual minorities face unique dementia risks, Dr. Flatt noted. They are less likely to marry and have children than are heterosexuals, and twice as likely to live alone. “The often have little or no caregiver support, and are likely to have experienced stigma, discrimination, trauma, and high lifelong stress.”

These experiences make the LGB population less likely to seek out medical care, he said. “All of these things impact health over the life course.”

Michele Sullivan/MDedge News

Dr. Flatt and his colleagues drew their data from the Kaiser Permanente Research Program on Genes, Environment, and Health. The study examined dementia prevalence and comorbidities among 4,337 LGB subjects aged 60 years or older, compared with 195,264 age-matched heterosexual subjects. Dementia diagnoses occurred from 1996 to 2015, and the mean follow-up time was 9 years. A quarter of the sample identified as lesbian, 37% identified as gay men, and 38% as bisexual; among these, 48% were women. Depression was more common among the LGB group (35% vs. 28%), as was posttraumatic stress disorder (1.9% vs. 1%). Both are well documented risk factors for dementia.

However, there were no significant difference in other risk factors, including hypertension, stroke, and heart disease, Dr. Flatt noted. He and his associates did not examine midlife obesity, physical inactivity, or low educational attainment, but will do so in a future analysis.

A dementia diagnosis occurred among 343 (8%) of the LGB group and 18,060 (9.2%) of the heterosexual group. The disorder manifested earlier in the LGB group (average 69 vs. 71 years). Self-identified men were overrepresented in the sample (63% vs. 44%) – a key difference, since women are generally found to have a significantly increased risk compared with men. However, Dr. Flatt noted, the study didn’t collect information that would show biological sex, so that number could be skewed.

Higher education didn’t seem to be as protective in the LGB population, with 62% having a college education, compared with 40% of the heterosexual sample.

In a regression analysis that adjusted for age and education, Dr. Flatt reported that 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 (OR, 2.5).

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

“We need to provide more LGB-affirming health care services, and this means training health care providers to meet these needs.” This 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.

[email protected]

SOURCE: Flatt J et al. AAIC 2018, Abstract P1-619.

CHICAGO – The first comprehensive analysis of dementia prevalence among sexual minorities has found a rate of 8% in this population.

While only marginally lower than the 9% prevalence among a heterosexual comparator group, the disorder manifested at an earlier age and occurred more often among men, Jason Flatt, PhD, said at the Alzheimer’s Association International Conference. In addition, higher education didn’t exert the protective influence seen in general populations, said Dr. Flatt of the University of California, San Francisco.

The analysis of a large California health care database is the first step in learning more about dementia in this diverse population, he said. It’s an important quest because the age-risk curve is rising just as quickly among the LGB population as it is in the heterosexual population.

“We do know there are 2-3 million people who identify as LGB [lesbian, gay, or bisexual] in the U.S., and are 60 years old or older, and with the continued aging of our entire population, we expect this number to increase to about 6 million by 2040,” he said. “Given the gaps in collection of sexual orientation and gender identification, we haven’t been able to look at this issue before.”

Sexual minorities face unique dementia risks, Dr. Flatt noted. They are less likely to marry and have children than are heterosexuals, and twice as likely to live alone. “The often have little or no caregiver support, and are likely to have experienced stigma, discrimination, trauma, and high lifelong stress.”

These experiences make the LGB population less likely to seek out medical care, he said. “All of these things impact health over the life course.”

Michele Sullivan/MDedge News

Dr. Flatt and his colleagues drew their data from the Kaiser Permanente Research Program on Genes, Environment, and Health. The study examined dementia prevalence and comorbidities among 4,337 LGB subjects aged 60 years or older, compared with 195,264 age-matched heterosexual subjects. Dementia diagnoses occurred from 1996 to 2015, and the mean follow-up time was 9 years. A quarter of the sample identified as lesbian, 37% identified as gay men, and 38% as bisexual; among these, 48% were women. Depression was more common among the LGB group (35% vs. 28%), as was posttraumatic stress disorder (1.9% vs. 1%). Both are well documented risk factors for dementia.

However, there were no significant difference in other risk factors, including hypertension, stroke, and heart disease, Dr. Flatt noted. He and his associates did not examine midlife obesity, physical inactivity, or low educational attainment, but will do so in a future analysis.

A dementia diagnosis occurred among 343 (8%) of the LGB group and 18,060 (9.2%) of the heterosexual group. The disorder manifested earlier in the LGB group (average 69 vs. 71 years). Self-identified men were overrepresented in the sample (63% vs. 44%) – a key difference, since women are generally found to have a significantly increased risk compared with men. However, Dr. Flatt noted, the study didn’t collect information that would show biological sex, so that number could be skewed.

Higher education didn’t seem to be as protective in the LGB population, with 62% having a college education, compared with 40% of the heterosexual sample.

In a regression analysis that adjusted for age and education, Dr. Flatt reported that 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 (OR, 2.5).

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

“We need to provide more LGB-affirming health care services, and this means training health care providers to meet these needs.” This 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.

[email protected]

SOURCE: Flatt J et al. AAIC 2018, Abstract P1-619.

CHICAGO – The first comprehensive analysis of dementia prevalence among sexual minorities has found a rate of 8% in this population.

While only marginally lower than the 9% prevalence among a heterosexual comparator group, the disorder manifested at an earlier age and occurred more often among men, Jason Flatt, PhD, said at the Alzheimer’s Association International Conference. In addition, higher education didn’t exert the protective influence seen in general populations, said Dr. Flatt of the University of California, San Francisco.

The analysis of a large California health care database is the first step in learning more about dementia in this diverse population, he said. It’s an important quest because the age-risk curve is rising just as quickly among the LGB population as it is in the heterosexual population.

“We do know there are 2-3 million people who identify as LGB [lesbian, gay, or bisexual] in the U.S., and are 60 years old or older, and with the continued aging of our entire population, we expect this number to increase to about 6 million by 2040,” he said. “Given the gaps in collection of sexual orientation and gender identification, we haven’t been able to look at this issue before.”

Sexual minorities face unique dementia risks, Dr. Flatt noted. They are less likely to marry and have children than are heterosexuals, and twice as likely to live alone. “The often have little or no caregiver support, and are likely to have experienced stigma, discrimination, trauma, and high lifelong stress.”

These experiences make the LGB population less likely to seek out medical care, he said. “All of these things impact health over the life course.”

Michele Sullivan/MDedge News

Dr. Flatt and his colleagues drew their data from the Kaiser Permanente Research Program on Genes, Environment, and Health. The study examined dementia prevalence and comorbidities among 4,337 LGB subjects aged 60 years or older, compared with 195,264 age-matched heterosexual subjects. Dementia diagnoses occurred from 1996 to 2015, and the mean follow-up time was 9 years. A quarter of the sample identified as lesbian, 37% identified as gay men, and 38% as bisexual; among these, 48% were women. Depression was more common among the LGB group (35% vs. 28%), as was posttraumatic stress disorder (1.9% vs. 1%). Both are well documented risk factors for dementia.

However, there were no significant difference in other risk factors, including hypertension, stroke, and heart disease, Dr. Flatt noted. He and his associates did not examine midlife obesity, physical inactivity, or low educational attainment, but will do so in a future analysis.

A dementia diagnosis occurred among 343 (8%) of the LGB group and 18,060 (9.2%) of the heterosexual group. The disorder manifested earlier in the LGB group (average 69 vs. 71 years). Self-identified men were overrepresented in the sample (63% vs. 44%) – a key difference, since women are generally found to have a significantly increased risk compared with men. However, Dr. Flatt noted, the study didn’t collect information that would show biological sex, so that number could be skewed.

Higher education didn’t seem to be as protective in the LGB population, with 62% having a college education, compared with 40% of the heterosexual sample.

In a regression analysis that adjusted for age and education, Dr. Flatt reported that 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 (OR, 2.5).

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

“We need to provide more LGB-affirming health care services, and this means training health care providers to meet these needs.” This 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.

[email protected]

SOURCE: Flatt J et al. AAIC 2018, Abstract P1-619.