When it comes to dementia, women bear much more of the burden than men. Two-thirds of adults living with Alzheimer’s disease in America are female, according to the Alzheimer’s Association 2019 Alzheimer’s Disease Facts and Figure report.
“We used to believe the differences in prevalence were related to longevity, in terms of women living longer than men,” says Rebecca Edelmayer, PhD, director of scientific engagement at the Alzheimer’s Association. “We now think that there’s likely more biological reasons for these differences and prevalence.”
Research presented at the July 2019 Alzheimer’s Association International Conference (AAIC) may help to elucidate those reasons.
According to a statement released by Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer, “The research reported at AAIC gets us one step closer to answering that question, by identifying specific biological and social reasons why Alzheimer’s is different in men and women.”
Do Men’s and Women’s Brains Function Differently?
Two studies presented at this year’s AAIC focused on brain function differences between men and women.
“We’ve seen research showing that women tend to perform better on verbal memory tests than men in early stages of the disease,” says Dr. Edelmayer. “In some ways, this may actually mask the disease in women, because women are experiencing the same amount of Alzheimer’s-related brain changes as men.”
An investigation led by Erin Sundermann, PhD, a neuropsychologist at University of California in San Diego School of Medicine, may shed light on this phenomenon. She and her colleagues followed 453 women and 569 men who were participating in the Alzheimer’s Disease Neuroimaging Initiative. Using brain scans, she and her collaborators measured amyloid plaques, which are a hallmark of Alzheimer’s.
The scientists observed that the women scored higher than men on a verbal memory test when amyloid plaque accumulation appeared to be minimal to moderate, indicating early-stage Alzheimer’s. When the amyloid accumulation was more extreme, women and men performed equally on the verbal test.
As part of their analysis, Dr. Sundermann and her team also measured the participants’ brain glucose metabolism. They observed that this processing of glucose was significantly higher for women when they were displaying minimal to moderate amyloid accumulation.
“It’s possible women have better verbal memory recall early on in the disease because they have better networks and more connected networks operating in the brain,” says Edelmayer.
In a similar vein, Sepideh (Sepi) Shokouhi, PhD, assistant professor of psychiatry and behavioral sciences at Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues used positron emission tomography (PET) to examine the structure of the brain and how tau builds up and spreads.
In patients with dementia, the protein tau accumulates and forms tangles that kill brain cells.
The investigators scanned a group of healthy adults (123 men and 178 women) and a group of individuals with mild cognitive impairment (101 men and 60 women). The images revealed that women with mild cognitive impairment had very different structural and functional connections that appeared to speed the spread of tau.
“Women may have better connections in the brain, but they also have a higher tau burden because it’s able to spread through the brain more quickly,” says Edelmayer. “This may be somewhat of a double-edged sword.”
How Might Genes Play a Role in Alzheimer’s Sex Differences?
In other research, Brian Kunkle, PhD, a genetic epidemiologist and associate scientist at the University of Miami Miller School of Medicine in Florida, and colleagues analyzed genetic risk differences between men and women.
The scientist analyzed two large datasets of genetic information: one of 5,522 dementia patients (just over one-half female) and 4,919 controls (about 60 percent female), and a separate group of 9,135 dementia patients (60 percent female) and 9,677 controls (also 60 percent female).
They identified 11 different genes connected to the development of Alzheimer’s that were distinct between men and women. For example, the genes MCOLN3 and CHMP2B (involved in endocytosis, a process connected to the development of Alzheimer’s, according to an article published in May 2019 in AlzForum) were related to risk only in men, while the CD1E and PTPRC genes (related to immunity) were linked to risk only in women.
Does Paid Employment Preserve Brain Function?
A fourth study evaluated how employment may influence the progression and development of Alzheimer’s in women. Elizabeth Rose Mayeda, PhD, an assistant professor of epidemiology at UCLA Fielding School of Public Health in Los Angeles, and collaborators reviewed data on 6,386 women born between 1935 and 1956.
Over an average follow-up of about 14 years, they compared rates of memory decline between those who worked for wages and those who did not. The researchers discovered that women who did not engage paid employment had faster rates of memory decline.
For example, married women with children who never earned wages experienced a 61 percent faster drop in average memory performance between ages 60 and 70 years. Women who had a prolonged period of single motherhood without waged employment demonstrated an 83 percent faster decline in memory in that same age range.
Dr. Mayeda and her team concluded that participation in the paid labor force may help prevent late-life memory decline among women, possibly because of the mental stimulation, financial benefits, and social benefits of working outside the home.
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