Is There a Link Between Estrogen Exposure and Brain MRI Biomarkers of Dementia Risk?
BACKGROUND AND PURPOSE:
There is a higher prevalence of Alzheimer’s disease (AD) among women, and recent studies have sought to determine potential underlying mechanisms
However, studies investigating associations between reproductive lifespan and risk of dementia have found conflicting results
Schelbaum et al. (Neurology, 2021) examined the associations between a history of estrogen exposure (e.g., due to pregnancy or menopausal hormone therapy) and brain MRI biomarkers of AD in midlife
Cognitively normal women and men with reproductive history data, neuropsychological testing, and volumetric MRI scans
Reproductive history indicators such as
Age at menarche
Age at menopause
Number of children and pregnancies
Use of menopause hormonal therapy (HT) and/or hormonal contraceptives
Multiple regressions were used to examine associations between reproductive history indicators and primary outcomes, with adjustment for demographics and midlife health indicators
Voxel-wise gray matter volume (GMV)
Memory and global cognition scores
Women: 99 individuals | Men: 29 individuals
Mean (SD) age
Women: 52 (6) years
Men: 52 (7) years
All menopausal women exhibited lower GMV in AD-vulnerable regions as compared to men
Perimenopausal and postmenopausal women exhibited lower GMV in the temporal cortex vs premenopausal women
The following indicators of reproductive history were positively associated with GMV, chiefly in temporal cortex, frontal cortex, and precuneus (independent of age, APOE-4 status, and midlife health indicators)
Number of children and pregnancies
Use of HT and hormonal contraceptives
Reproductive history indicators were not directly associated with cognitive measures
However, GMV in temporal regions was positively associated with memory and global cognition scores
A history of increased estrogen exposure due to reproductive events such as pregnancy, longer reproductive span, and use of HT and hormonal contraceptives, were all associated with larger gray matter volume in midlife women
Although women may report poor memory and concentration during menopause transition, menopause itself is not associated with cognitive impairment | Protective reproductive factors may offset neurological effects
The authors state
These results are in line with preclinical work indicating neuroprotective effects of estrogen in women and provide neurophysiological correlates to epidemiological evidence of associations between indices of prolonged estrogen exposure and lower risk of dementia or cognitive decline
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