White women whose genes put them at risk of developing Alzheimer’s disease are more likely than white men with similar risk genes to be diagnosed between the ages of 65 and 75, a study drawing on patient data in North America and Europe reports.
Overall, between the ages of 55 and 85, Caucasian men and women with a genetic predisposition to Alzheimer’s had an equal risk of the disease. That risk, however, rose notably in women during that 10-year span of life, an outcome the study’s researchers thought deserving of close investigation in clinical trials.
The study, “Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis,” was published in the Journal of the American Medical Association Neurology. Researchers at the University of Southern California’s Keck School of Medicine led the study.
Data analyzed came from the Global Alzheimer’s Association Interactive Network (GAAIN), and included records of 57,979 North Americans and Europeans.
“Our discovery is important because it highlights how clinical trials could be weighted toward women — a susceptible part of the population — to help scientists more rapidly identify effective drug interventions to slow or cure Alzheimer’s,” Arthur Toga, director of the Stevens Neuroimaging and Informatics Institute at Keck, said in a press release.
Historically, women have been underrepresented in clinical trials. The study’s authors said women must be represented equally – if not overrepresented – given these findings, to address gender-specific traits in the disease.
“The bottom line is women are not little men,” said Judy Pa, a study co-author and an assistant professor at the university. “A lot more research needs to target women because gender-specific variations can be so subtle that scientists often miss them when they control for gender or use models to rule out gender differences. Most research today is ignoring a big part of the equation.”
This study builds on — and somewhat disagrees with — a seminal 1997 report. It found that women with one copy of ApoE4 — a gene variant linked to Alzheimer’s — were 50 percent more likely to be diagnosed than men with the same genetic profile. The new data analysis put the higher risk at ninefold.
“So much work has been dependent on one 1997 finding, but with tools like GAAIN, we now have the ability to reinvestigate with increased statistical power,” Toga said.
Among the possible reasons for the higher risk for Caucasian women in the 10 years after turning 65, researchers said, was menopause. Previous animal and human studies have reported a link between ApoE4, menopause and cognitive decline.
Women make up about two-thirds of the more than five million Americans with Alzheimer’s, the Alzheimer’s Association reports, an imbalance traditionally associated with most women living longer than men. The new study calls this assumption in to question, the researchers said.
“Menopause and plummeting estrogen levels, which on average begins at 51, may account for the difference,” Pa said. “However, scientists still don’t know what is responsible. Researchers need to study women 10, 15 or even 20 years before their most vulnerable period to see if there are any detectable signals to suggest increased risk for Alzheimer’s in 15 years.”
Researchers analyzed data from 27 studies assessing participants’ ApoE gene variation, sex, diagnosis status and age, as well as race and ethnicity. It focused on Caucasians only — a total of 31,340 people in North America and Europe diagnosed between the ages of 55 and 85 — because of poorer and insufficient data on minority groups. The team recommended that efforts be made to obtain data on minorities so a similar study could be done on them.
Pa also stressed that, while genetic testing for ApoE4 can provide hints of future health status, adapting a healthy lifestyle was more important.
“Get more exercise. Work out your mind, especially in old age,” she said. “Pick up hobbies that are cognitively or physically challenging. Reduce processed sugar intake because it’s linked to obesity, which is associated with many chronic diseases.”