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Men, Women and Alzheimer’s Risk

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Are men and women who carry a common gene that increases their risk of developing Alzheimer’s equally likely to get the disease in old age? A new analysis suggests they are, though women may develop symptoms at an earlier age.

The findings, from researchers at the Keck School of Medicine at the University of Southern California in Los Angeles, raise intriguing questions about when treatment for Alzheimer’s disease should be started in men and women. When effective methods to prevent the disease will be available, it is possible that women might have to begin treatment at earlier ages than men.

The study pooled data from 27 different studies that looked at nearly 58,000 men and women who ranged in age from 55 to 85. Most were non-Hispanic whites.

Participants were given gene tests to determine whether they carry the APOE-E4 gene, a common gene variant that increases the risk of developing Alzheimer’s. If you inherit a single copy of the gene from a parent, your risk of developing Alzheimer’s is increased, though many people who carry the gene never get Alzheimer’s. If you carry two copies, your risk is further increased.

Researchers also looked at who had been given a diagnosis of Alzheimer’s disease, and if so, at what age they got their diagnosis. They also looked at mild cognitive impairment, a serious form of memory loss that often precedes full-blown Alzheimer’s. The findings were published in JAMA Neurology.

The researchers found that among the overall age range of 55 to 85, men and women who carried the APOE-E4 gene were equally likely to develop Alzheimer’s.  Most cases of Alzheimer’s were diagnosed when people are in their 60s or 70s.

However, when the researchers looked at specific age groups, they found that women were more likely to develop Alzheimer’s between the ages of 65 to 75 compared to men aged 65 to 75. Between the ages of 55 to 70, women also appeared to be at increased risk of developing mild cognitive impairment compared men of those ages.

The authors suggest that women might be more likely to develop symptoms at younger ages because of estrogen loss and other changes that occur with menopause, which typically begins in a woman’s early 50s. “However, scientists still don’t know what is responsible,” said Dr. Judy Pa, a study co-author and assistant professor of neurology at USC. “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.”

“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,” said Arthur Toga, director of the USC Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine. Men tend to outnumber women in most clinical studies.

Researchers are hoping to discover new drugs and therapies that could prevent the onset of disease or delay its onset, since current approved drugs do not stop the relentless downward spiral of disease.

“If women are at increased risk for Alzheimer’s disease at younger ages, it is plausible that treatments for women may need to be initiated earlier, especially in those who carry an APOE-E4 allele,” the authors of the current study wrote.

More women than men currently live with Alzheimer’s disease. A main reason is that women tend to live longer than men, who tend to die at younger ages from heart disease and stroke. The longer you live, the greater your overall likelihood of developing Alzheimer’s or other forms of dementia. Men who survive heart disease to live to very old ages may also tend to have adopted various lifestyle factors that help keep Alzheimer’s at bay.

In an editorial accompanying the study, researchers at the University of California, San Francisco, posed the intriguing questions: “What if we could identify young women at high risk for Alzheimer’s disease decades before its onset, based on APOE-E4 status combined with other biomarkers, and offer a treatment derived from new-found, sex biology-based, APOE-E4 pathways? And what if the treatment worked in men, too?”

To develop such treatments, more research is critical for understanding not just any differences between men and women, but the underlying causes of Alzheimer’s as well.

In the meantime, “Get more exercise. Work out your mind, especially in old age,” Dr. Pa advised. “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.”

By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Sources: Scott C Neu, PhD; Judy Pa, PhD; Walter Kukull, PhD; et al: “Apoliprotein E Genotype and Sex Risk Factors for Alzheimer’s Disease: A Meta-Analysis.” Publihsed online Aug. 28, 2017.

Dena B. Duba, MD, PhD; Camile Rogine, BA: “Apolipoprotein E e$ and Risk Factors for Alzheimer Disease – Let’s Talk About Sex.” JAMA Neurology, published online Aug. 28, 2017.

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