COMMENTARY

The Unique Gender Profiles of Alzheimer Disease

Richard S. Isaacson, MD

Disclosures

August 11, 2016

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Hi. My name is Richard Isaacson. I'm director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine at NewYork-Presbyterian. For decades, it's been thought that more women develop Alzheimer disease because they live longer than men, but new evidence suggests that it may not be that simple.

For example, women may be at higher risk than men due to genetics or hormones. Estrogen has been shown to reduce beta-amyloid in the brain, and a decline in estrogen over menopause may be a contributor. Hormone replacement therapy has shown mixed results, though. It may help if given earlier on, for example, but it may accelerate decline if given later. And more research is definitely needed to clarify this.

Women with Alzheimer disease have also been shown to cognitively decline faster than men with it, and also have more brain atrophy over time. But it's hard to say exactly why. Studies have also suggested that late-onset Alzheimer risk may be higher in women with one or more copies of the APOE ε4 gene, but this gene may have a comparatively lower impact on men. Gender differences apply not only to the pathogenesis of Alzheimer, but also to potential therapeutics. As one example, the latest research by Dr Roberta Brinton and colleagues[1] suggests that a woman's metabolic risk signature that includes, say, high blood pressure, high cholesterol, and high blood sugar, may be more likely to cognitively benefit from hormone replacement therapy.

When it comes to men, the most recent study published in Lancet Diabetes and Endocrinology[2] showed that prescribing testosterone for 3 years to healthy older men with low or low-to-normal testosterone levels did not improve cognitive function in any domain.

Overall, more research is needed, but it continues to become more and more clear that the future of Alzheimer prevention and treatment is not one-size-fits-all. And that's really the exact nature of clinical precision medicine and Alzheimer disease.

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