Sex differences in Alzheimer risk: Brain imaging of endocrine vs chronologic aging.
Level 4 - case-series / case-control
Cross-sectional observational neuroimaging study comparing biomarker endophenotypes across endocrine stages and male controls.
PubMed 28855400 · doi:10.1212/WNL.0000000000004425
What was done
This observational multimodality brain imaging study evaluated 42 cognitively normal women aged 40 to 60 (15 asymptomatic premenopausal controls [CNT], 13 perimenopausal [PERI], and 14 postmenopausal [MENO]) and 18 age- and education-matched men. Participants underwent volumetric MRI to assess gray and white matter volumes, 18F-FDG-PET for cerebral glucose metabolism, and Pittsburgh compound B (PiB)-PET for beta-amyloid deposition. Differences in neuroimaging markers were analyzed across groups while adjusting for chronological age.
What was found
After controlling for age, PERI and MENO women showed significant increases in Alzheimer disease endophenotypes—specifically hypometabolism, elevated beta-amyloid deposition, and reduced gray and white matter volumes in AD-vulnerable regions—compared to CNT women and men (p < 0.001). Biomarker abnormalities progressed stepwise: highest in MENO, intermediate in PERI, and lowest in CNT (p < 0.001). Amyloid deposition was notably exacerbated in APOE4-positive MENO women relative to all other groups (p < 0.001). Specific numerical values for metabolic rates or amyloid burden were not reported in the abstract.
Why it matters
These findings suggest that female Alzheimer risk emerges during the perimenopausal endocrine transition rather than from chronological aging alone, indicating an early midlife window of vulnerability for preventative interventions.
Limits
The study is limited by a small sample size (n = 60 total, with only 13–18 per subgroup) and a cross-sectional design that cannot establish longitudinal disease progression or direct causality. Detailed quantitative imaging values were omitted in the abstract, and participants were not followed to determine actual clinical conversion to Alzheimer disease.
Cited by
- supports Research by Lisa Mosconi shows that women begin developing cerebral glucose hypometabolism in perimenopause, preceding Alzheimer's disease diagnosis by over 25 years.
- context Approximately 20% of women in perimenopause show no cerebral metabolic decline on brain imaging, resembling men through the same period.