Research suggests earlier menopause and poor synaptic health together contribute to increased risk of Alzheimer’s disease

Two-thirds of people diagnosed with Alzheimer’s disease dementia are women, but the causes of this sex disparity remain largely unknown. Relative to men, women show greater burdens of Alzheimer’s proteins in the brain and experience faster cognitive decline particularly at the onset of symptoms.

A new study led by researchers at Sunnybrook Health Sciences Centre and the University of Toronto suggests that earlier menopause may contribute to women’s increased risk of Alzheimer’s. The research was published today in a special women’s health edition of Science Advances.

Menopause is a major biological transition that may influence women’s late-life brain health. Earlier estrogen depletion — via earlier menopause — has been associated with an increased risk for dementia, including Alzheimer’s dementia. Synaptic dysfunction, a disruption of the function or structure between brain neurons, also incites and exacerbates Alzheimer’s progression.

The study examined how the timing of menopause and synaptic health together influence Alzheimer’s-related brain changes and cognitive decline.

“Despite the known role of estrogens in maintaining the health of the brain’s connections, there remains a notable lack of research investigating how women’s endocrine health factors interact with synaptic functioning to influence Alzheimer’s pathology and cognitive decline,” explains the study's first author, Madeline Wood Alexander, who is a graduate student in the Harquail Centre for Neuromodulation at Sunnybrook Research Institute and at the Rehabilitation Sciences Institute in U of T’s Temerty Faculty of Medicine.

“These findings highlight the importance of both hormonal factors and synaptic health in influencing AD risk in women.”

With data from 268 women in the Rush Memory and Aging Project, the study found that women who experienced earlier menopause showed stronger links between poorer synaptic health with greater buildup of harmful tau tangles and faster cognitive decline.

In exploratory analyses, these relationships were less pronounced in women who had taken menopausal hormone therapy, suggesting that hormone treatment may play a protective role in brain aging.

“There is a critical need for more research focused on women’s health, which has long been undervalued, understudied, and underfunded,” adds Jennifer Rabin, scientist in the Hurvitz Brain Sciences Research Program, assistant professor in Temerty Medicine’s department of medicine and senior author of the study.

“By prioritizing research that includes women, we not only address critical gaps in knowledge but also uncover interventions that could help all brains stay healthier for longer.”