PMID- 30540774 OWN - NLM STAT- MEDLINE DCOM- 20190508 LR - 20240408 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 12 DP - 2018 TI - Increased Alzheimer's risk during the menopause transition: A 3-year longitudinal brain imaging study. PG - e0207885 LID - 10.1371/journal.pone.0207885 [doi] LID - e0207885 AB - Two thirds of all persons with late-onset Alzheimer's disease (AD) are women. Identification of sex-based molecular mechanisms underpinning the female-based prevalence of AD would advance development of therapeutic targets during the prodromal AD phase when prevention or delay in progression is most likely to be effective. This 3-year brain imaging study examines the impact of the menopausal transition on Alzheimer's disease (AD) biomarker changes [brain beta-amyloid load via 11C-PiB PET, and neurodegeneration via 18F-FDG PET and structural MRI] and cognitive performance in midlife. Fifty-nine 40-60 year-old cognitively normal participants with clinical, neuropsychological, and brain imaging exams at least 2 years apart were examined. These included 41 women [15 premenopausal controls (PRE), 14 perimenopausal (PERI), and 12 postmenopausal women (MENO)] and 18 men. We used targeted minimum loss-based estimation to evaluate AD biomarker and cognitive changes. Older age was associated with baseline Abeta and neurodegeneration markers, but not with rates of change in these biomarkers. APOE4 status influenced change in Abeta load, but not neurodegenerative changes. Longitudinally, MENO and PERI groups showed declines in estrogen-dependent memory tests as compared to men (p < .04). Adjusting for age, APOE4 status, and vascular risk confounds, the MENO and PERI groups exhibited higher rates of CMRglc decline as compared to males (p