More than 5.5 million Americans are living with Alzheimer's disease, of whom two-thirds are women. Women also account for 60 percent of caregivers of those afflicted with Alzheimer's disease. The Society for Women's Health Research Interdisciplinary Network convened an expert panel of scientists and clinicians to review what is currently known in regard to sex differences in Alzheimer's disease and highlighted knowledge gaps as well as priority research areas in the field. These findings were recently published in the journal Alzheimer's & Dementia .
Here are a few notable differences between women and men.
Age is the major risk factor for Alzheimer's disease, and women on average live longer than men. However, longevity alone does not fully explain why two-thirds of Alzheimer's patients are women. Even after taking into account the difference in longevity, some studies have suggested that women are still at a higher risk . Results varied though based on when and where the studies were carried out, and gender differences in educational and occupational opportunities may also have contributed to these mixed results . Less education (e.g., none or primary school only) is associated with increased dementia risk, while higher levels of cognitive activity at mid- or late-life are linked to delayed onset of cognitive impairment . Interestingly, a recent analysis of numerous studies across the world did not find that the prevalence of Alzheimer's was significantly higher in women than in men after controlling for sex differences in longevity . Greater educational and occupational attainment for women in the past few decades may be closing the gap in dementia incidence between women and men . But unless sex differences in longevity diminish, women will continue to make up a large proportion of Alzheimer's patients.
Depression is linked to higher dementia risk  and women are two-fold more likely to have depression than men . Additionally, depression is associated with a smaller hippocampus, a brain region important for memory formation, in women, but this association was not observed in men . A history of depression is also associated with faster shrinkage of the hippocampus in women but not in men. The reasons for these sex differences, however, are currently unknown.
People who exercise are less likely to develop dementia, particularly Alzheimer's disease . A recent observational study reported that women who were at high fitness level were 88% less likely to develop dementia compared to those who were at medium fitness level . Despite numerous studies reporting benefits with exercise, women exercise less than men, which is only partly accounted for by gender differences in parenting roles . Interestingly, the magnitude of the benefit from exercise appears to vary in women depending on estrogen levels, with greater benefits observed when estrogen levels are high .
Women make up about 60% of all family caregivers for Alzheimer's patients. These rates are especially high for Hispanic and African-American caregivers . Women caregivers also have a two-fold higher caregiver burden than male caregivers and are more likely to leave their job to care for a family member. Some studies suggest that spousal caregivers may be at a higher risk of cognitive impairment or dementia than non-caregivers .
Apolipoprotein E, known as APOE, is a gene associated with varying risk of Alzheimer's. Of the three different APOE types (APOE2, APOE3, and APOE4), the APOE4 type is associated with an increased risk for Alzheimer's disease. Women with APOE4 are more likely to develop mild cognitive impairment or Alzheimer's disease than men with APOE4 . They are also more likely than men to have worse memory performance , greater brain atrophy, and lower brain metabolism . In APOE4 carriers with mild cognitive impairment, women have higher levels of biological markers associated with Alzheimer's than men.
A diagnosis of Alzheimer's disease involves tests of verbal memory, a function that women on average have an advantage for over men . The downside is women can perform well on these tests even in the presence of pathology, so diagnosis for mild cognitive impairment and Alzheimer's disease may be delayed. By the time women are diagnosed with these conditions, they already have a more severe disease burden and decline more rapidly compared to men. Alternative ways to improve early detection in women are warranted, such as using sex-specific cutoff scores or memory tests that do not show sex differences .
More research is needed to better understand how Alzheimer’s disease differs between women and men.
The expert panel identified these priority areas that merit further investigation:
More research in these areas will extend our understanding of how biological, societal, and cultural factors affect brain health and Alzheimer's risk, which in turn will lead to improved diagnosis, management, and individualized treatment options for both women and men.
Yuko Hara, PhD, is Director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery Foundation. Dr. Hara was previously an Assistant Professor in Neuroscience at the Icahn School of Medicine at Mount Sinai, where she remains an adjunct faculty member. Her research focused on brain aging, specifically how estrogens and reproductive aging influence the aging brain's synapses and mitochondria. She earned a doctorate in neurology and neuroscience at Weill Graduate School of Medical Sciences of Cornell University and a bachelor's degree in biology from Cornell University, with additional study at Keio University in Japan. Dr. Hara has authored numerous peer-reviewed publications, including articles in PNAS and Journal of Neuroscience.
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