Alzheimer’s disease (AD) affects more women than men. In fact, 2/3 of American living AD victims are women. Historically, this has been attributed to the fact that women tend to live longer than men. In fact, after the diagnosis of AD is made, women survive longer. Recently, the prevailing belief is that there are other factors in this gender disparity, including biological and sociocultural ones.
Interestingly, while women generally seek medical care and use health services more often than men, the men in some of these AD studies were more likely to have neuroimaging services, hospitalization and hospice care for a neurodegenerative disorder than the women. In other words, even though men with AD have greater use of health services than women, they have a shorter survival. Some experts believe women get diagnosed later in disease progression because of the underdiagnosis caused by better performance on memory tests.
The presence of amyloid β plaques and clumps of the protein tau is one of the hallmarks of AD. Researchers have found that these neurofibrillary tangles of amyloid and tau do not look or behave the same in men and women. In women, cognitive testing prior to death correlated more closely with the amount of tangles present at autopsy. In people with normal cognition but high levels of amyloid β, accumulation of tau was accelerated in women. Further, in trials of lecanemab, an antiamyloid monoclonal antibody which helps clear amyloid from the brain, there was significantly less benefit on dementia scales in women. Finally, it has been shown on autopsy studies that the same amount of Alzheimer disease pathology causes greater cognitive decline in women than in men
Researchers have hypothesized that the drop of estrogen at menopause is in some way responsible for the gender disparity in the prevalence of AD. Estradiol is known to protect the brain by inhibiting inflammation and promoting new neuronal growth. Studies have shown earlier age of menopause was associated with poorer performance across the cognitive domains and that the number of children a woman had also may play a role. Further, some scientists believe estradiol replacement by patch or oral formulations was associated with higher memory performance, while others believe estradiol replacement increases the chance of dementia.
Women have two X chromosomes and men have one X and one Y chromosome. While the strongest genetic risk factor for AD, the apolipoprotein E ε4 (APOE4) variant, is not found on the X or Y chromosomes, having the APOE4 genetic variant appears to increase women’s risk of AD even more than it does men’s.
There are also medical and sociocultural risk factors that impact the risk of developing AD. Women have been shown to have more risk factors than men, including depression, diabetes, smoking, sleep disturbances, and educational level. Further, the impact on cognition by different risk factors was different in men and women.
What all agree on is that more study is needed to understand the gender differences in the risk of developing AD so the most effective interventions can be made. BeCare Neuro App can help by assessing your neurologic and cognitive health, guiding you on when to reach out for evaluation, and, if you are started on therapy, monitoring its benefit. Be empowered; become a driver in your own healthcare journey.