NEW research has shown that earlier menopause may be associated with faster cognitive decline, earlier Alzheimer disease (AD) onset, and greater accumulation of white matter hyperintensities in older women, with structural associations particularly evident following spontaneous menopause.
This study has examined whether age at menopause is associated with cognitive decline, AD onset and structural brain changes decades after the menopausal transition, including whether associations have differed between spontaneous and surgical menopause.
The researchers used data from the Religious Orders Study and Rush Memory and Aging Project, with up to 18 years of follow-up. Analyses included 2,603 women with cognitive data, 1,287 with neuropathology available at autopsy and 774 with serial 3T magnetic resonance imaging.
Mean age at enrolment was 78.3 years (SD, 7.85), with 172 women (6.6%) identifying as Black or African American and 2400 (92.2%) as White non-Hispanic. Investigators assessed age at menopause overall and by menopause type.
Earlier menopause was associated with faster global cognitive decline (β = −0.0009 SD per year earlier menopause age; SE = 0.0004; FDR-corrected P = .04) and episodic memory decline (β = −0.0014; SE = 0.0005; FDR-corrected P = .03). Earlier menopause was also associated with earlier AD diagnosis (time ratio = 0.998; 95% CI, 0.997–0.999; FDR-corrected P = .02).
In women with spontaneous menopause, earlier menopause was associated with faster white matter hyperintensity volume accumulation (f² = 0.30; FDR-corrected P < .001), with the association increasing with age and absent following surgical menopause. A menopause occurring 5 years earlier was associated with approximately 15% greater white matter hyperintensity volume accumulation over 10 years.
The findings suggest that menopause age remains associated with functional and structural brain ageing decades after the menopausal transition. The strongest structural association was observed for white matter hyperintensity accumulation following spontaneous menopause, while associations with total brain volume loss were modest.
The authors have proposed menopause age as a midlife-identifiable marker that could support dementia risk stratification and targeted prevention before cognitive or structural changes become apparent.
Reference
Campagna MP et al. Age at menopause and brain atrophy among older women. JAMA Netw Open. 2026;9(8):e2630973.
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