The transition to menopause is marked by a gradual decrease of estradiol. At the same time, the risk of dementia increases around menopause and it stands to reason that estradiol (or the lack thereof) plays a significant role for the development of dementia and other age-related neuropathologies. Here we investigated if there is a link between brain aging and estradiol-associated events, such as menarche and menopause. For this purpose, we applied a well-validated machine learning approach in a sample of 1,006 postmenopausal women who were scanned twice approximately two years apart. We observed less brain aging in women with an earlier menarche, a later menopause, and a longer reproductive span (i.e., the time interval between menarche and menopause). These effects were evident both cross-sectionally and longitudinally, which supports the notion that estradiol might contribute to brain preservation. However, more research is required as effects were small and no direct measures of estradiol were obtained in the current study.

The authors have declared no competing interest.

CB received funding from the South-Eastern Norway Regional Health Authority (2023037, 2022103). CG received support from Carl Zeiss Stiftung as a part of the IMPULS project (IMPULS P2019-01-006), the Federal Ministry of Science and Education (BMBF) under the frame of ERA PerMed (Pattern-Cog ERAPERMED2021-127) and the Marie Skłodowska-Curie Innovative Training Network (SmartAge 859890 H2020-MSCA-ITN2019).

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