This woman, Auguste Deter, was the first to be described by Alois Alzheimer with the disease that would one day bear his name. Credit: Image via Wikimedia Commons. Public Domain

Distinct biological and genetic factors may shape how it progresses in women—and understanding them could be crucial to prevention, diagnosis and treatment

For more than 25 years, Mary Read was a successful nurse in Lititz, Pennsylvania. But in 2010, at the age of 50, she started having trouble with her memory and thinking, making it difficult for her to complete routine tasks and follow instructions at work. The problems worsened, bringing her career to an abrupt end. In 2011, her doctor conducted a comprehensive evaluation, including a cognitive assessment, and found that she was in the early stages of younger-onset Alzheimer’s, which affects hundreds of thousands of people under 65.
A year earlier, Elizabeth Wolf faced another sort of upheaval. The 36-year-old community health program director was forced to abandon her own career, home and community in Vermont when both of her parents were diagnosed with Alzheimer’s three months apart. Wolf took the difficult decision to move back into her childhood home in Mount Laurel, New Jersey in order to become their primary caregiver.

These stories are not unusual. Alzheimer’s dementia disproportionately affects women in a variety of ways. Compared with men, 2.5 times as many women as men provide 24-hour care for an affected relative. Nearly 19 percent of these wives, sisters and daughters have had to quit work to do so. In addition, women make up nearly two-thirds of the more than 5 million Americans living with Alzheimer’s today. According to the Alzheimer’s Association 2016 Alzheimer’s Disease Facts and Figures, an estimated 3.3 million women aged 65 and older in the United States have the disease. To put that number in perspective, a woman in her sixties is now about twice as likely to develop Alzheimer’s as breast cancer within her lifetime.

Researchers are racing to figure out why. Women generally live longer than men, but mounting evidence suggests that longevity alone may not account for the unequal disease burden women face. It remains unclear whether women are truly at an increased risk for Alzheimer’s. But studies have revealed that there may be distinct biological and genetic factors shaping how the disease develops and progresses in women. Understanding these differences will be of key importance in devising new, more effective strategies for treating, preventing and diagnosing Alzheimer’s.

Consider the example of heart disease. The death rate dropped by nearly half as awareness that it was the leading cause of death in women rose dramatically during a 12-year period beginning in 1997. Now, research uncovering biological differences in heart disease is continuing to help doctors fine-tune diagnosis, prevention and treatment for women. For example, cardiologists are modifying how they identify potential risk factors, adjusting blood thinner dosages, and prescribing low-dose aspirin depending on a person’s sex, particularly for older women who have already had a heart attack. Tackling Alzheimer’s now requires a similar vision.

Mind the Gap

In May 2015, the Alzheimer’s Association hosted a think tank that brought together experts in biological sex differences and Alzheimer’s disease to develop a research agenda. This meeting, co-chaired by neuroscientist Roberta Diaz Brinton of the University of Arizona Health Services, neuropsychologist Suzanne Craft of Wake Forest University School of Medicine, and neurologist Kristine Yaffe of the University of California, San Francisco, identified three primary gaps in our knowledge. Specifically, they concluded that we need more research to understand the different roles that genetics, hormones and lifestyle factors play in Alzheimer’s in men and women.

In response, the Alzheimer’s Association launched a new funding initiative—the only one of its kind—investing $2.2 million across nine research projects. One, led by Brinton, focuses on the complex interplay between hormones and genes in Alzheimer’s disease. For more than two decades, Brinton has studied how major hormonal transitions, including puberty, pregnancy and menopause, can affect important connections in the brain. She and her colleagues are investigating whether the loss of estrogen in women in mid-life who carry a known risk gene for Alzheimer’s disease, APOEe4, leads to more significant brain cell damage, specifically in the brain’s white matter, compared to those who are not at this increased genetic risk. White matter acts as a relay station for communication between different areas of the brain. Brinton and colleagues suggest that these combined factors can increase a woman’s susceptibility to Alzheimer’s later in life.

Other projects are exploring potentially modifiable lifestyle factors, such as education, occupation, exercise, diet, stress and sleep—all of which may hold greater sway over women’s risk of developing Alzheimer’s. Take, for example, formal education, which strong evidence suggests may boost resilience to cognitive decline and dementia in both sexes. Data reported at the Alzheimer’s Association International Conference (AAIC) in 2015 showed that individuals who completed high school had a 28 percent lower risk of developing dementia compared to those with only an elementary school education. Although disparities in formal education between men and women are declining in the U.S. and other developed countries, significant differences still exist in current older populations.

Researchers are also learning that there may be differences in the brain’s response to stress between men and women. In a 38-year longitudinal study examining the link between stress and the risk for Alzheimer’s, women who had lived through more stressful events—such as divorce, widowhood, work problems or illness—had an increased likelihood of developing dementia. Another more recent 28-year-long study indicates that anxiety may play a role in increasing risk for dementia in women but not in men. Although these studies suggest a link, it is important to advance this research in larger and more diverse populations.

Looking Forward

Ultimately, the most effective approaches to preventing, treating and diagnosing Alzheimer’s and dementia may need to be tailored for each individual, taking into account multiple factors such as genetics, hormones and lifestyle. Investigating how sex differences contribute to Alzheimer’s may provide important clues to achieving this goal.

Advocacy can make a difference. Women must raise their voices about the importance of addressing the disproportionate impact Alzheimer’s has on us, and we need to convince others to do so too. One way to get involved is by joining the Alzheimer's Association’s My Brain movement. Launched in 2010, the initiative calls on a milllion women to use their amazing brains to help wipe out this disease. My Brain also provides knowledge and tools to help women advocate for a substantial increase in Alzheimer’s research funding.