Alzheimer’s Falls More Heavily on Women Than on Men

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 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.

This story is not unusual. Alzheimer’s dementia disproportionately affects women in a variety of ways.

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.

 

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. 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.

 

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 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.

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.

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.

Reference:  By Heather M. Snyder on December 28, 2016 (www.alz.org)