Association of Reproductive History With Brain MRI Biomarkers of Dementia Risk in Midlife
Schelbaum E, Loughlin L, Jett S, Zhang C, Jang G, Malviya N, Hristov H, Pahlajani S et al.. Neurology, 2021-11-03
Topic: Risk, prevention and care in population studies
Background and objectives To examine associations between indicators of estrogen exposure from women's reproductive history and brain MRI biomarkers of Alzheimer disease (AD) in midlife. Methods We evaluated 99 cognitively normal women 52 ± 6 years of age and 29 men 52 ± 7 years of age with reproductive history data, neuropsychological testing, and volumetric MRI scans. We used multiple regressions to examine associations among reproductive history indicators, voxel-wise gray matter volume (GMV), and memory and global cognition scores, adjusting for demographics and midlife health indicators. Exposure variables were menopause status, age at menarche, age at menopause, reproductive span, hysterectomy status, number of children and pregnancies, and use of menopause hormonal therapy (HT) and hormonal contraceptives (HC). Results All menopausal groups exhibited lower GMV in AD-vulnerable regions compared to men, with perimenopausal and postmenopausal groups also exhibiting lower GMV in temporal cortex compared to the premenopausal group. Reproductive span, number of children and pregnancies, and use of HT and HC were positively associated with GMV, chiefly in temporal cortex, frontal cortex, and precuneus, independent of age, APOE ε4 status, and midlife health indicators. Although reproductive history indicators were not directly associated with cognitive measures, GMV in temporal regions was positively associated with memory and global cognition scores. Discussion Reproductive history events signaling more estrogen exposure such as premenopausal status, longer reproductive span, higher number of children, and use of HT and HC were associated with larger GMV in women in midlife. Further studies are needed to elucidate sex-specific biological pathways through which reproductive history influences cognitive aging and AD risk.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Schelbaum, E., Loughlin, L., Jett, S., Zhang, C., Jang, G., Malviya, N., et al. (2021). Association of Reproductive History With Brain MRI Biomarkers of Dementia Risk in Midlife. Neurology. https://doi.org/10.1212/wnl.0000000000012941
Vancouver
Schelbaum E, Loughlin L, Jett S, Zhang C, Jang G, Malviya N, et al. Association of Reproductive History With Brain MRI Biomarkers of Dementia Risk in Midlife. Neurology. 2021. doi:10.1212/wnl.0000000000012941. PMID: 34732544.
BibTeX
@article{schelbaum2021-34732544,
author = {Schelbaum, E. and Loughlin, L. and Jett, S. and Zhang, C. and Jang, G. and Malviya, N. and Hristov, H. and Pahlajani, S. and others},
title = {{Association of Reproductive History With Brain MRI Biomarkers of Dementia Risk in Midlife}},
journal = {Neurology},
year = {2021},
doi = {10.1212/wnl.0000000000012941},
pmid = {34732544},
url = {https://doi.org/10.1212/wnl.0000000000012941}
}
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Key findings
- Results All menopausal groups exhibited lower GMV in AD-vulnerable regions compared to men, with perimenopausal and postmenopausal groups also exhibiting lower GMV in temporal cortex compared to the premenopausal group.
- Reproductive span, number of children and pregnancies, and use of HT and HC were positively associated with GMV, chiefly in temporal cortex, frontal cortex, and precuneus, independent of age, APOE ε4 status, and midlife health indicators.
- Although reproductive history indicators were not directly associated with cognitive measures, GMV in temporal regions was positively associated with memory and global cognition scores.
- Discussion Reproductive history events signaling more estrogen exposure such as premenopausal status, longer reproductive span, higher number of children, and use of HT and HC were associated with larger GMV in women in midlife.
Why it matters
In this study of midlife women and men, all menopausal groups had lower gray matter volume in Alzheimer-vulnerable brain regions than men, and several reproductive history factors were positively associated with gray matter volume. These indicators were not directly associated with cognitive measures, so the meaning for Alzheimer's risk is not yet clear.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 45 of the 96 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 85 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.1 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 8.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 3 / 4 | Cited 53 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | University of Arizona: institution h-index 1,336 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34732544) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 45 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 45 of the 96 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0000000000012941
- PubMed: 34732544
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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