Abstract
Women have a greater risk of developing Alzheimer's disease (AD) compared to men. This biological sex difference is primarily due to the greater longevity of women compared to men, but other factors also contribute to this difference, including a greater risk of AD among those with the apolipoprotein epsilon 4 (APOE4) genetic risk factor. Sex steroid hormones have myriad effects on the central nervous system, and other bodily systems that play an important role in brain health, including immune, metabolic and cardiovascular systems. Knowledge of the brain changes that occur in menopause is limited by the lack of large-scale longitudinal neuroimaging studies of women transitioning through the menopause, though such studies are currently underway. Initial evidence from cross-sectional studies and small longitudinal studies suggest that both brain structure and function may undergo changes, and that AD biomarkers may accumulate more rapidly during the menopause. Clearly the menopause is not a universal trigger for the development of AD, as all women who live into late life transition through the menopause and only a minority of women with develop AD. One of the factors that may make certain women more vulnerable to AD is vasomotor symptoms (VMS). Although a causal role of VMS is not established, correlational studies link objectively measured VMS with memory deficits, disruptions in brain function and the accumulation of white matter hyperintensities, small ischemic lesions that increase the risk of both vascular dementia and AD. Mood symptoms and sleep disruption also contribute to cognitive changes and alterations in brain health. Some evidence indicates that hormone therapy (HT) may be associated with lower levels of AD biomarkers, but more clinical trial data is needed, particularly in women with VMS. Medical societies reliably conclude based on the evidence to date that HT should not be used for the treatment of cognitive issues or the prevention of dementia. The use of HT for the treatment of VMS, however, is indicated and may help women to maintain more optimal brain health as they age.
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