21 November 2022
The menopause transition (MT) is a neuro-endocrine process that impacts the aging trajectories of multiple organ and systems including the brain. The MT occurs over time and is characterized by clinically defined stages with specific neurological symptoms. However, the way this process impacts the human brain remains unclear. Recently Mosconi et al.  reported a multi-modality neuroimaging study that indicates substantial differences in brain structure, connectivity, and energy metabolism across MT stages (pre-, peri- and post-menopause). These effects involved brain regions sub-serving 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 during postmenopause, 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 in the postmenopausal stage, suggesting adaptive compensatory processes. In parallel to the adaptive process, amyloid-β deposition was more pronounced in peri- and postmenopausal women carrying the apolipoprotein E-4 (APOE-4) genotype, the major genetic risk factor for late-onset Alzheimer’s disease (AD), relative to genotype-matched males.