A new study finds that earlier menopause and reduced cardiac function may together worsen brain health, highlighting dementia risk factors.
Earlier age at menopause amplified the relationship between reduced cardiac function and markers of poorer brain health, including lower gray matter volume and higher white matter hyperintensity burden.
No significant associations were observed between age at menopause, cardiac function, and cognitive performance on standardized tests.
Findings highlight the need to consider sex-specific and menopausal factors in dementia risk research and prevention strategies.
Women face a higher risk than men for both cardiovascular disease and Alzheimer's disease, and evidence continues to link the 2. Research presented at The Menopause Society’s 2025 Annual Meeting in Orlando explored how age at menopause and cardiac function together influence brain structure and cognition in postmenopausal women.1,2
According to the investigators, reduced cardiac function can affect brain health by limiting the supply of oxygen and nutrients, potentially contributing to silent strokes and increasing dementia risk. Likewise, earlier menopause is associated with accelerated cognitive decline. The new analysis sought to determine whether these 2 factors have a compounding effect on brain outcomes.
The study, titled The Combined Influence of Earlier Menopause and Cardiac Function on Brain Health, included 701 postmenopausal women drawn from the Canadian Alliance for Healthy Hearts and Minds Study and the Ontario Health Study. Participants had a median age at menopause of 51 years (range, 25–61 years).
Cardiac function was measured via resting left ventricular ejection fraction (LVEF) on cardiac MRI. Brain MRI quantified gray matter volume (GMV) and white matter hyperintensity (WMH) burden—markers associated with cognitive aging and cerebrovascular injury. Cognitive performance was evaluated using the Montreal Cognitive Assessment (MoCA) and the Digit Symbol Substitution Test (DSST).
Statistical models adjusted for potential confounders, including age, ethnicity, years of education, menopausal hormone therapy, cause of menopause (spontaneous or surgical), visceral adipose tissue, systolic blood pressure, cardiac index, and intracranial volume.
The researchers found that age at menopause moderated the association between cardiac function and brain health. Specifically, women with an earlier menopause experienced a stronger link between lower LVEF and both reduced gray matter volume (β = –86.45; P = .0142) and higher white matter hyperintensity burden (β = 0.0012; P = .013).
Cognitive outcomes, however, were not significantly associated with these variables (MoCA: β = 0.0024; P = .251; DSST: β = –0.0046; P = .697).
“These findings suggest that earlier menopause and reduced cardiac function may have a compounding negative effect on brain health,” the authors concluded.
Lead author Tallinn Splinter, from the University of Toronto and the Sunnybrook Research Institute, emphasized the importance of understanding how menopause influences brain aging.
“We still don't fully understand how menopause, and especially earlier menopause, affects brain aging. By examining the intersection of heart and brain health, we were keen to shed light on this important but often overlooked area of research,” Splinter said.
Stephanie Faubion, MD, MBA, medical director for The Menopause Society, noted that the work contributes to a growing understanding of how sex-specific factors shape disease risk.
“These findings underscore the importance of integrating sex-specific factors, such as age at menopause, into research on dementia risk and informing targeted prevention and intervention strategies,” Faubion said.
The results highlight the intertwined nature of cardiovascular and neurological health among women. The authors propose that earlier menopause could amplify the effects of subclinical cardiac dysfunction on the brain, leading to greater vulnerability to neurodegeneration and cerebrovascular disease.
Further longitudinal studies are needed to clarify whether interventions that preserve cardiac health can mitigate brain aging in women who experience early menopause. As both cardiovascular disease and Alzheimer's disease remain leading causes of morbidity and mortality among women, the study underscores the potential of integrated preventive approaches targeting both heart and brain health.
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