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Sex Differences in the Associations of Obesity with Tau, Amyloid PET, and Cognitive Outcomes in Preclinical Alzheimer's Disease: Cross-Sectional A4 Study
Wang X, Sundermann EE, Buckley RF, Reas ET, McEvoy LK, Banks SJ, A4 Study Team.. Journal of Alzheimer's disease : JAD, 2023-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background The association between obesity and Alzheimer's disease (AD) is complex. Recent studies indicated the relationships between obesity and AD may differ by sex, and women may benefit from being overweight in terms of AD risk. Objective We investigated whether sex modifies the associations of obesity with tau positron emission tomography (PET), amyloid PET, and cognition in preclinical AD. Methods We included 387 cognitively-unimpaired amyloid-positive participants (221 women, 166 men, 87.6% non-Hispanic White) with available 18F-flortaucipir PET, 18F-florbetapir PET, and completed the Preclinical Alzheimer Cognitive Composite (PACC) tests from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. Participants were categorized based on body mass index (BMI: kg/m2): normal-weight (BMI: 18.5-25), overweight (BMI: 25-30), and obese (BMI≥30). Results Significant sex by BMI category interactions on PACC and its components: Mini-Mental State Examination (MMSE) and Reminding Test-Free+Total Recall (FCSRT96) revealed that overweight and obese women outperformed normal-weight women on FCSRT96, while obese men showed poorer MMSE performance than normal-weight men. These interactions were independent of APOE4. There were no significant interactions of sex by BMI category on tau and amyloid PET. However, sex-stratified analyses observed obesity was associated with less regional tau and mean cortical amyloid in women, not in men. Conclusion This study found that in preclinical AD, overweight and obesity were associated with better verbal memory in women, whereas obesity was associated with worse global cognition among men. Future studies focusing on the mechanism for this relationship may inform sex-specific interventions for AD prevention.
Key findings
- Results Significant sex by BMI category interactions on PACC and its components: Mini-Mental State Examination (MMSE) and Reminding Test-Free+Total Recall (FCSRT96) revealed that overweight and obese women outperformed normal-weight women on FCSRT96, while obese men showed poorer MMSE performance than normal-weight men.
- There were no significant interactions of sex by BMI category on tau and amyloid PET.
- However, sex-stratified analyses observed obesity was associated with less regional tau and mean cortical amyloid in women, not in men.
- Conclusion This study found that in preclinical AD, overweight and obesity were associated with better verbal memory in women, whereas obesity was associated with worse global cognition among men.
Why it matters
In 387 cognitively unimpaired amyloid-positive participants, sex modified how obesity related to cognition, but there were no significant sex-by-BMI interactions on tau or amyloid PET. This is a cross-sectional observational study and does not test any treatment, cure or prevention.
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Study details
- Participants387
- Effect size87.6%
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (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 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 387 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 11 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.2 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 2 / 6 | Cited 2.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Sarah Jane Banks: h-index 28 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37574737) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
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Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Wang, X., Sundermann, E. E., Buckley, R. F., Reas, E. T., McEvoy, L. K., Banks, S. J., et al. (2023). Sex Differences in the Associations of Obesity with Tau, Amyloid PET, and Cognitive Outcomes in Preclinical Alzheimer's Disease: Cross-Sectional A4 Study. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-230466
Vancouver
Wang X, Sundermann EE, Buckley RF, Reas ET, McEvoy LK, Banks SJ, et al. Sex Differences in the Associations of Obesity with Tau, Amyloid PET, and Cognitive Outcomes in Preclinical Alzheimer's Disease: Cross-Sectional A4 Study. Journal of Alzheimer's disease : JAD. 2023. doi:10.3233/jad-230466. PMID: 37574737.
BibTeX
@article{wang2023-37574737,
author = {Wang, X. and Sundermann, E. E. and Buckley, R. F. and Reas, E. T. and McEvoy, L. K. and Banks, S. J. and {A4 Study Team}},
title = {{Sex Differences in the Associations of Obesity with Tau, Amyloid PET, and Cognitive Outcomes in Preclinical Alzheimer's Disease: Cross-Sectional A4 Study}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2023},
doi = {10.3233/jad-230466},
pmid = {37574737},
url = {https://doi.org/10.3233/jad-230466}
}
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