2023 Alzheimer's Association Research Fellowship (AARF)
Menopause, Hormone Therapy and Clinicopathology: An In-Vivo Perspective
How may hormone changes in women impact their risk for Alzheimer’s?
Gillian Coughlan, Ph.D.
Massachusetts General Hospital
Boston, MA - United States
Background
According to the 2023 Alzheimer’s Association Facts & Figures report, of the more than 6.5 million Americans aged 65 and older with Alzheimer’s, nearly two-thirds are women. Though the primary reason for this difference are unknown, research suggests sex hormones may be involved, specifically during menopause. In menopause, levels of certain hormones, including estrogen, drop in the body, and this drop may impact cognition (brain function) and dementia risk. Menopause may also be associated with vascular (blood vessel) damage, another potential risk factor for developing Alzheimer’s. In addition, other studies have found that women who undergo menopause at an earlier age (before age 40 or 45), as well as women who undergo hormone replacement therapy (in order to manage symptoms of menopause, such as hot flashes and fatigue), are at an even higher risk of cognitive decline and dementia. These findings reveal an urgent need for more research into biological mechanisms underlying the role of menopause and hormone therapy in Alzheimer’s risk.
Research Plan
Dr. Gillian Coughlan and colleagues will study menopause and Alzheimer’s using cognitive, brain scan and health data from older women and men in two large studies of aging. First, they will analyze this data to examine whether women accumulate brain levels of beta-amyloid and tau (two hallmark proteins associated with Alzheimer’s) faster than men, and whether these accumulations are even faster in women with early-onset menopause or a history of hormone therapy. The researchers will then assess how menopause and hormone therapy may impact (1) vascular-related brain changes (such as damage to white matter, the brain’s “wiring system”), (2) the role of tau and beta-amyloid in cognitive decline and (3) the role of a gene variation called APOE-e4 in promoting dementia risk.
Impact
Results from this project could refine our understanding of how hormone changes in women affect their brain health. They could also lead to novel strategies for preventing or treating dementia in post-menopausal women.