Older white women more likely to contract Alzheimer's

Older white women genetically predisposed to 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 — with one exception. From their mid-60s to mid-70s, women 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.

The study was published 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% of the 47 million cases of dementia worldwide.

Times — and data — have changed

The results contradict a seminal 20-year-old study that found women with one copy of ApoE4, a gene variant linked to Alzheimer’s, were diagnosed with the disease 50% more often than men with the same genetic profile.

The findings presented in the USC-led study expand the amount of participant data by ninefold and indicate the critical decade falls between 65 and 75, more than 10 years after the start of menopause. Previous studies in animals and humans have reported a relationship between ApoE4, menopause and cognitive decline.

“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.

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 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 oestrogen 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.”

Worry less, work out more

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 analysed. 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’s linked to obesity, which is associated with many chronic diseases.”

In the United States, Alzheimer’s disease is the fifth-leading cause of death for people 65 and older, but it may one day outpace the nation’s top two killers — heart disease and cancer. Alzheimer’s-related deaths increased by nearly 39% between 2000 and 2010, while heart disease-related deaths declined 31% and cancer deaths fell 32%, according to the Centers for Disease Control and Prevention.

Time to focus on women

Historically, women have not been adequately represented in clinical trials, especially in studies on heart disease. Women need to be represented equally to men — or even overrepresented, Pa said.

“The bottom line is women are not little men,” Pa said. “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.”

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