Growing older may be inevitable, but getting Alzheimer’s disease is not. Although we can’t stop the aging process, which is the biggest risk factor for Alzheimer’s, there are many other factors that can be modified to lower the risk of dementia.
Yet our ability to reduce Alzheimer’s risk and devise new strategies for prevention and treatment is impeded by a lack of knowledge about how and why the disease differs between women and men. There are tantalizing hints in the literature about factors that act differently between the sexes, including hormones and specific genes, and these differences could be important avenues of research. Unfortunately, in my experience, most studies of Alzheimer’s risk combine data for women and men.
For that reason, researchers at the Society for Women’s Health Research Interdisciplinary Network on Alzheimer’s Disease recently published a review paper in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association that calls for greater analysis of research data by sex to stimulate new approaches that will improve prevention, diagnosis and treatment of Alzheimer’s.
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We have some evidence, for example, that sex hormones such as estrogen influence the course of the disease, but we do not understand enough about why and how. Ovaries are the primary source of estrogen for premenopausal women, and surgical removal of a woman’s ovaries before menopause is associated with a higher risk of dementia. But using estrogen therapy after surgery until age 50 negates that risk. This fact suggests that estrogen may be protective in premenopausal women.
In men, there are conflicting studies as to whether androgen-deprivation therapy, which is used to treat prostate cancer, increases the risk for Alzheimer’s. Further investigation is needed into the role of sex hormones, the use of different hormonal treatments and the ways they each impact Alzheimer’s risk.
Among risk factors that affect both women and men, some are more common in one sex. For example, depression and sleep apnea are both risk factors for dementia, but depression is twice as common in women, and sleep apnea is much more common in men. Similarly, low education and poor job attainment are Alzheimer’s risk factors, but traditionally women have not had the same access to education and job opportunities as men, which puts them at increased risk.
The e4 allele of the APOE gene is the strongest and most common genetic risk factor for Alzheimer’s in both women and men, but it confers a greater risk in women. Women with APOE e4 are at increased risk of developing Alzheimer’s, compared with women without the allele and men with and without it.
Learning how sex impacts risk factors at various times across a life span is also critical. For example, in cardiovascular disease, taking aspirin helps to reduce heart attack and stroke risk in women aged 65 years and older. This effect is not seen in younger women. It is possible that certain Alzheimer’s risk factors may be strongest at certain points during our lives, and exploring this correlation is key for prevention and early intervention.
Risk factors are just one of the areas in which we need more research into the differences between the sexes in Alzheimer’s. Scientists have often overlooked sex differences in diagnosis, clinical trial design, treatment outcomes and caregiving. This bias has impeded progress in detection and care.
Approaches that incorporate sex differences into research have advanced innovation in respect to many diseases. We need to do the same in Alzheimer’s. Looking at these differences will greatly enhance our understanding of this thief of minds and improve health outlooks for all.
