Increased Alzheimer's risk during the menopause transition: A 3-year longitudinal brain imaging study.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study comparing biomarker progression across cohorts
PubMed 30540774 · doi:10.1371/journal.pone.0207885
What was done
Fifty-nine cognitively normal participants aged 40–60 years (41 women: 15 premenopausal, 14 perimenopausal, 12 postmenopausal; and 18 men) were evaluated longitudinally at least 2 years apart over a 3-year study period. Investigators measured brain amyloid-beta (Aβ) load via 11C-PiB PET, glucose metabolism (CMRglc) via 18F-FDG PET, structural changes via MRI, and cognitive performance. Targeted minimum loss-based estimation was used to assess biomarker changes while adjusting for age, APOE4 status, and vascular risk.
What was found
Older age was associated with baseline Aβ and neurodegeneration but not with their rates of change. APOE4 status influenced Aβ accumulation rates but not neurodegenerative changes. Compared to men, perimenopausal and postmenopausal women demonstrated greater longitudinal declines in estrogen-dependent memory tests (p < .04) and higher rates of brain glucose metabolic (CMRglc) decline (p ≤ .015). Postmenopausal women had the highest rates of hippocampal volume loss (p ≤ .001) and higher rates of Aβ deposition than men (p < .01). CMRglc decline exceeded Aβ and atrophy changes across female groups compared to men.
Why it matters
These findings suggest that the endocrine transition during menopause coincides with early metabolic and neurodegenerative changes associated with Alzheimer's disease, pointing to midlife as a potential window for sex-specific prevention strategies.
Limits
The total sample size was small (N = 59), resulting in very small individual subgroups (12–18 per group). The follow-up duration (around 3 years) was relatively short for assessing long-term dementia risk, and clinical progression to mild cognitive impairment or dementia was not evaluated.
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.