Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery.
Level 4 - case-series / case-control
Cross-sectional observational study comparing biomarker levels across endocrine groups
PubMed 29016679 · doi:10.1371/journal.pone.0185926
What was done
A cross-sectional study evaluated 43 cognitively and clinically normal women aged 40–60 years stratified by endocrine status: premenopause (controls, n = 15), perimenopause (n = 14), and postmenopause (n = 14). Participants underwent clinical, laboratory, and neuropsychological testing, 18F-FDG-PET scans to measure cerebral metabolic rate of glucose (CMRglc), and assays of platelet mitochondrial cytochrome oxidase (COX) activity. Multiple regression and statistical parametric mapping were used to evaluate differences and biomarker associations across groups.
What was found
Postmenopausal women were older than perimenopausal and control participants, but groups were otherwise comparable for clinical measures and APOE4 distribution. Both perimenopausal and postmenopausal groups showed reductions in CMRglc in Alzheimer's disease-vulnerable brain regions and declined platelet mitochondrial COX activity compared to premenopausal controls (p < 0.001). Biomarker abnormalities followed a gradient: lowest in controls, intermediate in perimenopause, and highest in postmenopause (p < 0.001). These biomarkers correlated with immediate and delayed memory performance (Pearson's r = 0.26 to 0.32, p <= 0.05).
Why it matters
This study provides clinical evidence that brain hypometabolism and mitochondrial bioenergetic decline emerge during the perimenopausal transition, suggesting that endocrine transition stages may represent an early window for Alzheimer's disease risk mitigation.
Limits
The sample size is very small (n = 43 total, 14–15 per group). The cross-sectional design cannot establish within-individual progression or causality, and the postmenopausal group was significantly older than the other groups, introducing age as a potential confounder.
Cited by
- supports Estradiol specifically is critical for the brain's ability to utilize glucose for energy, and reductions in estradiol during perimenopause and menopause impair brain energy metabolism.