Women are disproportionately affected by Alzheimer’s disease (AD) — nearly two-thirds of the 5 million Americans living with Alzheimer’s are women. The biological underpinnings for these sex-based differences have been somewhat of a mystery — until recently. New studies may have unraveled some of the biological mechanisms that make women so much more vulnerable to the debilitating disease.
It’s not just because women live longer
Alzheimer’s is the most common type of dementia. The symptoms of Alzheimer’s disease generally start off mild, which makes early diagnosis difficult, but they get worse over time and start to interfere with daily life more and more.
In the early stages, the damage is confined to the entorhinal cortex and hippocampus, two areas associated with memory, navigation, and perception of time. This sort of degeneration leads to memory loss and disorientation associated with the condition — though it has to be noted that Alzheimer’s starts damaging brain cells well before the first symptoms kick in.
Alzheimer’s disease is widely believed to be caused by the accumulation of beta-amyloid proteins which clump together to form plaques between neurons and disrupt cell function. Another physical characteristic of the Alzheimer’s diseased brain is the buildup of tau proteins, which tangle inside neurons, blocking their transport system.
Women live more than men in most countries around the globe, but that doesn’t explain the disproportionate amount of women affected by Alzheimer’s at any age. Previous studies have suggested that there are genetic and biologic factors that may raise the risk of developing the disease in women.
Scientists, for instance, have found associations between a gene called APOE-4 and a higher risk of Alzheimer’s for women than men in certain age groups. Also, women tend to do better on verbal tests than men, which can mask the symptoms of the disease in its early stages.
“Understanding these sex-specific differences may help us identify and apply customized prevention strategies for different populations against cognitive decline, Alzheimer’s disease and other dementias,” Maria Carrillo, chief science officer from the Alzheimer’s Association, said in a statement.
Researchers at Vanderbilt University scanned the brains of 301 people with no cognitive impairment and 161 individuals with mild impairments, mapping where tau proteins were deposited. These tau maps were overlaid onto nerve networks — highways that brain signals follow. The analysis revealed that tau deposits in women with mild impairment were more diffuse and spread out than in men, affecting more areas of the brain.
Elsewhere, at the University of California, San Diego, researchers analyzed more than 1,000 brain scans of older adults, which showed differences in how each gender uses sugar in the brain. Apparently, women metabolize sugar better, which may give them an edge in verbal skill tests that can compensate for some of the damage from dementia — at least initially in the disease’s early phases.
Finally, researchers at the University of Miami analyzed the genes of over 30,000 people, half with Alzheimer’s, half without it. They identified four genes that seem to be associated with sex-based differences in Alzheimer’s incidence. One of the genes confers risk in female and not males and three confer risk in males but not females. However, the research team still doesn’t know how exactly these genes affect risk.
“This research demonstrates that genetics may contribute to differences in risk and progression of Alzheimer’s disease between men and women,” says Brain Kunkle, a genetic epidemiologist from the University of Miami working on the study. “More research is needed to understand how much these genes contribute to Alzheimer’s risk, and whether they can be used to specifically identify men and women at risk for this disease.”