Summary: Longer and greater lifetime exposure to estrogen was linked with larger gray matter volume in middle-aged women.
Source: Alzheimer’s Research UK
Researchers based in the United States report a relationship between markers of extended estrogen exposure and reduced brain shrinkage in women during midlife.
These results were published in the peer-reviewed journal Neurology.
Past studies on estrogen’s impact on brain health have produced mixed outcomes. Some research suggests that the decline in estrogen after menopause may contribute to accelerated brain aging and increase the long-term risk of Alzheimer’s disease.
The study included 128 volunteers (99 women and 29 men) aged 40–65, all of whom carried risk factors for Alzheimer’s disease such as the APOE4 gene variant or a family history of dementia.
Participants provided detailed reproductive histories through questionnaires and interviews. The reproductive factors examined included:
- Whether the participant had undergone menopause or a hysterectomy
- Age at first menstruation (menarche)
- Age at menopause
- Length of reproductive span (time between menarche and menopause)
- Number of pregnancies and number of children
- Use of menopausal hormone therapy (HT) and hormonal contraceptives (HC)
Researchers performed brain MRI scans to measure gray matter volume in regions known to be vulnerable in Alzheimer’s disease. Lower gray matter volumes in these regions have been associated with higher dementia risk and poorer cognitive health. All participants also completed neuropsychological tests to evaluate memory, language and overall cognitive function.
Overall, indicators of greater lifetime estrogen exposure—being pre-menopausal, having more children, a longer reproductive span, and use of HT or HC—were associated with larger gray matter volumes in women during midlife.
The study did not find a direct link between reproductive history and performance on cognitive tests. However, individuals with better memory and global cognition scores did tend to have greater gray matter volume, particularly in temporal brain regions.
Dr. Sara Imarisio, head of research at Alzheimer’s Research UK, commented: “Two thirds of people with dementia are women. While part of that difference is explained by women’s longer lifespans, hormones such as estrogen have also been implicated. Events like the onset of menstruation, childbirth and menopause are major biological milestones, and it is important to understand how these changes might influence long-term brain health and dementia risk.”
“This study found that greater exposure to estrogen was linked to reduced brain shrinkage in midlife—a pattern that can indicate lower dementia risk—yet it is a relatively small study and does not establish why this association exists. The scans were not specific to Alzheimer’s disease, so we cannot draw firm conclusions about future Alzheimer’s risk from these findings alone. The next step is to investigate the biological mechanisms by which reproductive history could affect cognitive aging and dementia risk.”
“Alzheimer’s disease arises from a complex interplay of age, genetics and lifestyle. Some factors are modifiable and others are not. Current evidence supports lifestyle measures that may help maintain brain health, including avoiding smoking, drinking within recommended limits, staying mentally and physically active, eating a balanced diet, and managing blood pressure and cholesterol.”
About this brain aging research news
Author: Press Office
Source: Alzheimer’s Research UK
Contact: Press Office – Alzheimer’s Research UK
Image: The image is in the public domain
Original Research: Closed access.
“Association of Reproductive History With Brain MRI Biomarkers of Dementia Risk in Midlife” by Eva Schelbaum et al. Neurology
Abstract
Association of Reproductive History With Brain MRI Biomarkers of Dementia Risk in Midlife
Objective.
To investigate links between reproductive history indicators that reflect lifetime estrogen exposure and brain MRI markers associated with Alzheimer’s disease risk in midlife.
Methods.
The study evaluated 99 cognitively normal women (average age 52.6 years) and 29 men (average age 52.7 years) who provided reproductive histories, completed neuropsychological testing, and underwent volumetric MRI. Multiple regression analyses examined associations between reproductive variables and voxel-wise gray matter volume (GMV), memory and global cognition scores, adjusting for demographic factors and midlife health. Exposure variables included menopause status, ages at menarche and menopause, reproductive span, hysterectomy status, number of children and pregnancies, and use of menopausal hormone therapy and hormonal contraceptives.
Results.
Compared with men, all menopausal groups showed lower gray matter volume in regions vulnerable to Alzheimer’s disease. Peri-menopausal and post-menopausal women also showed reduced GMV in temporal cortex relative to pre-menopausal women. Longer reproductive span, greater number of children and pregnancies, and use of HT and HC were independently associated with larger GMV, particularly in temporal and frontal cortices and the precuneus, even after adjusting for age, APOE-4 status and midlife health factors. While reproductive history measures were not directly linked to cognitive scores, greater GMV in temporal regions correlated with better memory and global cognition.
Conclusions.
Reproductive history markers that suggest higher lifetime estrogen exposure—such as being pre-menopausal, having a longer reproductive span, having more children, and using hormone therapies—were associated with larger gray matter volume in midlife women. Additional research is needed to clarify the sex-specific biological pathways through which reproductive history may influence cognitive aging and Alzheimer’s disease risk.