Reproductive history events in midlife women may offer protection against brain aging

Reproductive history events indicating more estrogen correlated with larger gray matter volume in midlife women, according to a study published in Neurology.

“Reproductive history is a driver of brain aging in women, co-author Lisa Mosconi, PhD, associate professor of neuroscience in neurology and radiology and director of The Weill Cornell Women’s Brain Initiative, told Healio Neurology. “Our prior work showed that menopause is associated with reductions in the brain’s gray matter volume, which is a risk factor for Alzheimer’s [disease]. The present study shows that other factors related to women’s reproductive history appear to have a protective action instead, possibly offsetting the effects of menopause on brain aging. Protective factors identified in our study include a longer reproductive span, a higher number of children and use of hormonal therapy in midlife.”

Mosconi, who is also director of the Alzheimer’s Prevention Clinic, and colleagues assessed 99 cognitively normal women and 29 men around 52 years of age or older with reproductive history data, neuropsychological testing and volumetric MRI scans. Multiple regressions were used to assess correlations between reproductive history indicators, voxel-wise gray matter volume memory and global cognition scores. The findings were adjusted for participant demographics and midlife health indicators.

Menopause status, age at menarche, age at menopause, reproductive span, hysterectomy status, number of children and pregnancies, use of menopause hormonal therapy and hormonal contraceptives served as exposure variables.

Results showed all menopausal groups compared with men had lower gray matter volume in Alzheimer’s disease-vulnerable regions. In addition, gray matter volume in the temporal cortex was lower in the post-menopausal and peri-menopausal groups compared with the pre-menopausal group. Mosconi and colleagues found a correlation between reproductive span, number of children and pregnancies, use of hormonal therapy and hormonal contraceptives, and gray matter volume – primarily in the temporal cortex frontal cortex and precuneus – independent of age, APOE-4 status and midlife health indicators.

Reproductive history indicators were not directly correlated with cognitive measures; however, gray matter volume in temporal regions positively correlated with memory and global cognition scores.

“From a clinical perspective, these findings highlight the need for both OB/GYN and brain experts to support women throughout menopause and all stages of reproductive life,” Mosconi said.