Age at Menopause and Brain Atrophy Among Older Women
An erratum to this article was published (JAMA Netw Open, 1 Oct 2026 ↗)
Authors' conclusion
In this cohort study of older women, earlier menopause was associated with less favorable functional and structural neurological outcomes, with associations persisting and intensifying decades after the menopausal transition.
Study context
- Population
- Older women in the Religious Orders Study and Rush Memory and Aging Project; mean age at enrollment 78.30 (SD 7.85) years; 6.6% Black or African American, 92.2% White non-Hispanic774 with serial 3T MRI
- Participants
- 2,603 women
- Exposure
- Earlier vs later age at menopause, overall and by menopause type
- Outcome
- Global and domain-specific cognitive decline, time to AD diagnosis, AD neuropathologic change at autopsy, and brain volume trajectories incl. total brain volume and white matter hyperintensity volume
Methodological detailsprespecified 3-family Benjamini-Hochberg correction, up to 18 years of follow-up
- Prespecified 3-family Benjamini-Hochberg correction
- Up to 18 years of follow-up
Main finding
As reported in the abstract
Age at menopause and cognitive decline, AD diagnosis and white matter hyperintensity volume
- Global cognitive decline: β per year earlier menopause age (SD), SE = 0.0004, FDR-corrected P = .04
- −0.0009
- Episodic memory decline: β, SE = 0.0005, FDR-corrected P = .03
- −0.0014
- Time to Alzheimer disease (AD) diagnosis, full cohort: time ratio
- 0.998 (95% CI, 0.997-0.999; FDR-corrected P = .02)
- Time to AD diagnosis, surgical menopause: time ratio
- 1.000 (95% CI, 0.998-1.000; P = .008)
- White matter hyperintensity volume accumulation, spontaneous menopause: f2 (FDR-corrected P < .001)
- 0.30
Observational data: associations, not effects.
Original publication
Age at Menopause and Brain Atrophy Among Older Women. JAMA Netw Open. Published 3 August 2026. doi:10.
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