Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition

Lisa Mosconi, Valentina Berti, Jonathan Dyke, Eva Schelbaum, Steven Jett, Lacey Loughlin, Grace Jang, Aneela Rahman, Hollie Hristov, Silky Pahlajani, Randolph Andrews, Dawn Matthews, Orli Etingin, Christine Ganzer, Mony de Leon, Richard Isaacson, Roberta Diaz Brinton

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


All women undergo the menopause transition (MT), a neuro-endocrinological process that impacts aging trajectories of multiple organ systems including brain. The MT occurs over time and is characterized by clinically defined stages with specific neurological symptoms. Yet, little is known of how this process impacts the human brain. This multi-modality neuroimaging study indicates substantial differences in brain structure, connectivity, and energy metabolism across MT stages (pre-menopause, peri-menopause, and post-menopause). These effects involved brain regions subserving higher-order cognitive processes and were specific to menopausal endocrine aging rather than chronological aging, as determined by comparison to age-matched males. Brain biomarkers largely stabilized post-menopause, and gray matter volume (GMV) recovered in key brain regions for cognitive aging. Notably, GMV recovery and in vivo brain mitochondria ATP production correlated with preservation of cognitive performance post-menopause, suggesting adaptive compensatory processes. In parallel to the adaptive process, amyloid-β deposition was more pronounced in peri-menopausal and post-menopausal women carrying apolipoprotein E-4 (APOE-4) genotype, the major genetic risk factor for late-onset Alzheimer’s disease, relative to genotype-matched males. These data show that human menopause is a dynamic neurological transition that significantly impacts brain structure, connectivity, and metabolic profile during midlife endocrine aging of the female brain.

Original languageEnglish (US)
Article number10867
JournalScientific reports
Issue number1
StatePublished - Dec 2021

ASJC Scopus subject areas

  • General


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