Biological Basis for the 'Female Advantage' in Alzheimer's

Megan Brooks

July 17, 2019

LOS ANGELES — Women may be better able than men to "compensate" for Alzheimer disease (AD) pathology because their brains can maintain metabolic function.

Investigators found that women have higher brain glucose metabolism than men, which may explain the "female advantage" when it comes to maintaining verbal memory in early AD.

However, Erin Sundermann, PhD, neuropsychologist, University of California, San Diego, School of Medicine, said the female advantage may be a double-edged sword because it may mask early signs of AD and delay diagnosis, which can lead to "missed opportunity for early intervention when currently available treatments are most effective," she noted.

The study was presented here at a press briefing at the Alzheimer's Association International Conference (AAIC) 2019.

Better Brain Efficiency

Research has shown that women typically outperform men on tests of verbal memory throughout life, even during the early stages of AD, despite the fact that men and women show a similar degree of AD-related pathology in the brain. The neural mechanisms for the female advantage in verbal memory are unclear.

Sundermann and her colleagues tested the hypothesis that higher brain efficiency in women compared to men partially accounts for the female advantage in verbal memory. They defined efficiency as the ability of the brain to metabolize glucose, the chief energy source. Low metabolism reflects low brain efficiency and dysfunction.

The researchers studied 1044 older adults (44% women) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). All participants completed the Rey Auditory Verbal Learning Test and were assessed with respect to regional glucose metabolism (measured with 18-fluorodeoxyglucose positron-emission tomography), cortical amyloid-β burden, and/or cerebrospinal fluid phosphorylated-tau levels at baseline.

Replicating earlier findings, women outperformed men on verbal memory tests when amyloid-β plaque burden was minimal to moderate. Women also had higher levels of glucose metabolism than men in the presence of moderate amyloid-β burden. This partially accounted for their better verbal memory scores at this stage of dementia, Sundermann reported.

However, the edge women have in metabolic brain function and verbal memory disappeared at later stages of AD, when amyloid deposition was severe.

Alzheimer's Not the Same in Men and Women

"I think these findings really challenge the possibly erroneous assumption that Alzheimer's operates in the same way in men and women and according to the same temporal pattern," Sundermann told the briefing.

A better understanding of sex differences in AD may lead to "improved diagnostic precision and measurement of Alzheimer's disease risk and better design of clinical trials," she added.

Susanne Craft, PhD, who is on the Alzheimer's Association Medical and Scientific Council and who chaired the briefing, noted that understanding sex differences in dementia is "very important in our understanding of Alzheimer's disease.

"Women are at the epicenter of the Alzheimer's epidemic. They are much more likely to develop Alzheimer's as well as serve as caregivers to those living with the disease. It's imperative that we understand what the basis for this disproportionate risk is," said Craft.

This study and related studies reported here at AAIC 2019 "suggest that there may be biological underpinnings that contribute to that risk," said Craft.

Funding for the study was provided by the National Institutes of Health and the Alzheimer's Disease Neuroimaging Initiative. Sundermann and Craft have disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2019: Abstract P3-475. Presented July 16, 2019.

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