Earlier menopause and poor synaptic health could raise Alzheimer's risk: Study

Early menopause may be linked to increased risk of Alzheimer’s disease among women, according to a study led by researchers at Sunnybrook Health Sciences Centre and the University of Toronto.

The researchers analyzed data from 268 women in the Rush University Memory and Aging Project and found strong links between poor synaptic health and faster cognitive decline among women who experienced earlier menopause.

The study, published in Science Advances, sheds new light on a potential cause of sex disparities in Alzheimer’s disease: Two-thirds of those diagnosed are women, with women showing greater burdens of Alzheimer’s proteins in the brain and experiencing faster cognitive decline – particularly at the onset of symptoms.

“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,” says the study’s first author Madeline Wood Alexander, a PhD student in Sunnybrook’s Harquail Centre for Neuromodulation and 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 [Alzheimer’s disease] risk in women.”

Menopause is a major biological transition that may influence women’s brain health later in life. Earlier depletion of estrogen – as a result of early menopause – has been associated with an increased risk of dementia and Alzheimer’s. Disruption of the function and structure of synapses linking brain neurons is also known to incite and exacerbate the progression of Alzheimer’s.

In the study’s exploratory analyses, these relationships were less pronounced among women who underwent menopausal hormone therapy – suggesting that hormone treatment could 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,” says the study’s senior author Jennifer Rabin, scientist in the Hurvitz Brain Sciences Research Program at Sunnybrook and assistant professor in Temerty Medicine’s department of medicine.

“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.”