Women genetically predisposed to Alzheimer’s are more susceptible than men between ages 65 and 75, researchers discover.
White women whose genetic makeup puts them at higher risk for Alzheimer’s disease are more likely than white men to develop the disease during a critical 10–year span in their lives, according to a study headed by Keck School of Medicine of USC researchers.

The findings from one of the world’s largest big–data studies on Alzheimer’s counter long–held beliefs about who is at greatest risk for the disease and when, suggesting new avenues for clinical trials.

Study results show genetically vulnerable 55– to 85–year–old white men and women have the same odds of developing the memory–erasing disease. One exception: From their mid–60s to mid–70s, these women still face significantly higher risk. That may provide clues to disease causes and potential interventions among these women.

“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 — among the nation’s leaders in innovative scientific discovery.

The study was published Aug. 28 in the Journal of the American Medical Association Neurology. It included data from 57,979 North Americans and Europeans in the Global Alzheimer’s Association Interactive Network (GAAIN). This big–data project provides scientists around the world with shared data and sophisticated analysis tools to address a disease that makes up about 65 percent of the 47 million cases of dementia worldwide.

The new findings are significant because almost two–thirds of the more than 5 million Americans now living with Alzheimer’s disease are women, according to the Alzheimer’s Association.

Many attribute the imbalance in disease risk to the fact that women, on average, live longer than men. However, a growing body of evidence suggests other reasons also contribute to the difference. For instance, men have higher rates of heart disease and stroke. So, men who live longer may be healthier than women of the same age and may face less risk of developing Alzheimer’s, according to the USC–led study.

In the future, doctors who want to prevent Alzheimer’s may intervene at different ages for men and women, said Judy Pa, co–author of the study and an assistant professor of neurology at the USC Stevens Neuroimaging and Informatics Institute.

“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.” Only some women are at increased risk of developing Alzheimer’s in their mid–60s to mid–70s compared to men. To find out, women could have their DNA analyzed. However, Pa cautions that genetic testing for the ApoE4 variant is no crystal ball.

“There is controversy in terms of whether people should know their ApoE status because it is just a risk factor,” Pa said. “It doesn’t mean you’re going to get Alzheimer’s disease. Even if you carry two copies of ApoE4, your chances are greatly increased, but you could still live a long life and never have symptoms.”

Even if some women discover they are at heightened risk, they can improve their odds by making life changes. “Get more exercise. Work out your mind, especially in old age,” Pa said. “Pick up hobbies that are cognitively or physically challenging. Reduce processed sugar intake because it