Alzheimer's Dementia Pathologies Differ by Race

Nancy A. Melville

July 15, 2015

Brain autopsies of African Americans who died with Alzheimer's disease (AD) show significantly higher rates of mixed pathologies compared with whites, suggesting more complex underlying causes of the dementia and the potential need for different therapeutic strategies, new research shows.

"Almost everything we know about Alzheimer's disease has been learned on predominantly white populations," lead author Lisa L. Barnes, PhD, from Rush University Medical Center in Chicago, Illinois, told Medscape Medical News.

"This study underscores the dangers in generalizing results from one population to another."

The findings were published online July 15 in Neurology.

Largest Study of Minorities

The study, which represents the largest to date of minority populations with Alzheimer's dementia, involved brain autopsies of 41 African Americans and 81 European Americans with a clinical diagnosis of AD, which were matched with the same level of disease severity, as well as for age, sex, and education level.

While AD pathology was confirmed in most of the samples — in 93% of black as well as white descendants — only 19.5% of blacks had AD as a single-dementia pathology as the cause of their dementia, compared with 42% of whites.

Blacks were more likely than whites to have AD mixed with other pathologies (70.7% vs 50.6%), including Lewy bodies, which are associated with hallucinations and sleep disorders (31.7% in blacks vs 24.7% in whites), and Alzheimer's plus Lewy bodies as well as infarcts (26.8% vs 2.5%).

In looking at any pathology, blacks were more likely than whites to have Lewy bodies (58.5% vs 27.2%) and infarct (43.9% vs 27.2%).

Levels of severe arteriolar sclerosis and atherosclerosis were also higher in blacks, prompting the researchers to hypothesize that black patients would be more likely to have Alzheimer's pathology combined with infarcts.

But the higher levels of mixed pathologies with Lewy bodies were unexpected.

"It was not surprising to see that both African Americans and whites had mixed pathologies," said Dr Barnes.

"What was surprising was the patterns of mixed pathology that we observed [specifically that] African Americans were more likely to have all three of the common pathologies."

The researchers speculated that the finding may represent a selection bias related to the types of patients who present to a memory clinic with dementia, Dr Barnes added.

"It may be the case that African Americans are more likely to seek treatment for behavioral problems than for memory problems."

The findings are particularly important in light of the fact that current Alzheimer's treatments are designed to target specific Alzheimer's pathologies — on the basis of research consisting mainly of white populations.

"Most available treatments focus primarily on amyloid," Dr Barnes said. "It will be important for the field to develop new treatments that target other common pathologies."

"Prevention strategies for Alzheimer's dementia should target risk factors for these other pathologies, in addition to risk factors for plaques and tangles."

The higher rates of atherosclerosis and arteriolar sclerosis are also important factors in Alzheimer's disease in blacks, in terms of disease severity as well as treatment, Dr Barnes noted.

"There is research suggesting that both large- and small-vessel disease can contribute to cognitive impairment, and thus it may worsen the Alzheimer's disease in African Americans," she said.

"Treatment of the risk factors for vessel disease, such as diabetes, hypertension, diet, obesity, et cetera," she continued, "therefore may possibly help with delaying onset and progression of the dementia."

Complex Disease

The findings underscore the complicated nature of the causes of dementia with AD, neurologist Richard B. Lipton, MD, told Medscape Medical News.

"Though Alzheimer's disease is the most common cause of dementia in older adults, this study shows, as others have, that Alzheimer's disease as the sole pathology is uncommon," said Dr Lipton, the Edwin S. Lowe Professor and Vice Chair of Neurology and director of the Division of Cognitive Aging and Dementia at Albert Einstein College of Medicine in New York.

With the benefits of therapies for Alzheimer's possibly diminished in the presence of other pathologies, the study has important clinical implications particularly in the treatment of black patients, Dr Lipton added.

"In a person with clinical Alzheimer's disease, the index of diagnostic suspicion should be high for Lewy body dementia and vascular disease, even more so in blacks than whites," he said.

"If treatment appears less successful in blacks than whites, one explanation may be the presence of untreated concomitant pathology. [Meanwhile], because Lewy body disease is so common in blacks, developing treatments for Lewy body disease should be a priority."

Racial differences in terms of prevalence of Alzheimer's disease have been previously reported, including in a report from the Alzheimer's Association showing rates of the disease to be more than two times higher in blacks than whites, according to Heather M. Snyder, PhD, director of Medical and Scientific Operations for the Alzheimer's Association.

"We know there's an increased prevalence of Alzheimer's disease among African Americans, but we don't completely understand why," she told Medscape Medical News.

"I think what's interesting about this study is it suggests perhaps changes in the brain could play a role," she said.

"While there is nothing currently available to stop progression of the disease, understanding differences in populations is going to be important as we get to that point of being able to stop or slow progression so that we can better tailor treatments to individuals."

The study received support from the National Institutes of Health and the Illinois Department of Public Health. The authors, Dr Lipton, and Dr Snyder have disclosed no relevant financial relationships.

Neurology. Published online July 15, 2015. Abstract


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