Women are twice as likely to develop late-onset Alzheimer’s disease (AD) as men, often attributed to women’s longevity. Recent evidence has emerged suggesting that gender-specific risk factors may drive this difference in addition to a longer lifespan. Attention has now shifted towards identifying the factors that put women at higher risk of late-onset AD. Once identified, these factors can be evaluated for potential modification through lifestyle changes or early medical intervention, or both. If modifiable, the time for prevention would likely be prior to the start of symptoms, possibly during midlife.

In a recent study, with support from Cure Alzheimer’s Fund, Dr. Lisa Mosconi of Weill Cornell Medicine and her team examined the late-onset risk factors associated most strongly with Alzheimer’s-related changes in the brains of cognitively normal middle-aged men and women. The results of the study appeared in the July 14, 2020 issue of the journal Neurology, a publication of the American Academy of Neurology.

The findings suggest that among a wide range of risk factors for late-onset AD, including depression, smoking, and AD family history, menopause status was second to female sex as most strongly associated with brain changes related to AD. Other strong associations were hormone therapy, thyroid disease, and hysterectomy status. The study included 85 women and 36 men between the ages of 40 and 65. The two gender groups did not differ by APOE4 status or family history of AD.

The researchers identified brain changes via amyloid PET scan detecting amyloid-beta levels, as well as FDG PET scan and structural MRI for detecting overall brain neurodegeneration. Results from the female and male groups that were matched for age (since age is the biggest risk factor of late-onset AD) showed that on average the women had 30% higher amyloid levels on the amyloid PET scans, 22% lower glucose metabolism on the FDG PET, and 11% lower grey and white matter volume detected by the MRI. The male group did not have any of the brain changes that were being examined, pointing to the fact that these were indeed female-specific.

Since the study participants had normal cognition, and the study was not designed to assess those that later experienced cognitive decline, more research would be needed to generalize the results. Dr. Mosconi is actively investigating why the menopause transition—both whether a woman has begun it and where she is along its spectrum—correlates with an increased risk of AD-related brain changes. 

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NEUROLOGY: https://n.neurology.org/content/95/2/e166