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Sex Differences in Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline
Madeline Wood Alexander, D. Luke Fischer, Lawren A. VandeVrede, Emma L. Nichols, Lei Yu, James Russell Pike, Walter Swardfager, Che‐Yuan Wu et al.. Annals of Neurology, 2025-07-11
Topic: Amyloid, tau and blood-test diagnosis
In the Rush dataset, we included 1,277 women and 579 men. In the National Alzheimer's Coordinating Center dataset, we included 3,283 women and 3,563 men. Across both datasets, men were more likely to have LBD, whereas women showed greater neuritic plaque and neurofibrillary tangle burdens. Sex modified the associations of LBD with neurofibrillary tangles (but not neuritic plaques), whereby LBD was more strongly associated with greater neurofibrillary tangle burden in women than men. Men showed faster LBD-related cognitive decline, whereas women showed faster neurofibrillary tangle-related decline, after adjusting for copathologies (neuritic plaques, neurofibrillary tangles, and LBD, as appropriate). In women, earlier age at menopause exacerbated the associations of LBD with neurofibrillary tangle burden and episodic memory decline. Sex may influence AD and LBD neuropathologies, highlighting the need for precision approaches to dementia prevention and intervention. ANN NEUROL 2025;98:1014-1026.
Key findings
- In the Rush dataset, we included 1,277 women and 579 men.
- In the National Alzheimer's Coordinating Center dataset, we included 3,283 women and 3,563 men.
- Across both datasets, men were more likely to have LBD, whereas women showed greater neuritic plaque and neurofibrillary tangle burdens.
- Sex modified the associations of LBD with neurofibrillary tangles (but not neuritic plaques), whereby LBD was more strongly associated with greater neurofibrillary tangle burden in women than men.
- Men showed faster LBD-related cognitive decline, whereas women showed faster neurofibrillary tangle-related decline, after adjusting for copathologies (neuritic plaques, neurofibrillary tangles, and LBD, as appropriate).
Why it matters
This study found sex differences in associations of Lewy body disease with Alzheimer's disease pathologies and cognitive decline, with men showing faster LBD-related decline and women faster neurofibrillary tangle-related decline. It highlights the need for precision approaches to dementia prevention and intervention, but no specific treatment is provided.
Study details
- Participants1,277
- Evidence strengthLow
How this study scored 53/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of Neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,277 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 9 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 5.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jennifer S. Rabin: h-index 34 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Toronto: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 14 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40646704) |
| Free to read | 2 / 2 | Free to read |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Alexander, M. W., Fischer, D. L., VandeVrede, L. A., Nichols, E. L., Yu, L., Pike, J. R., et al. (2025). Sex Differences in Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline. Annals of Neurology. https://doi.org/10.1002/ana.27308
Vancouver
Alexander MW, Fischer DL, VandeVrede LA, Nichols EL, Yu L, Pike JR, et al. Sex Differences in Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline. Annals of Neurology. 2025. doi:10.1002/ana.27308. PMID: 40646704.
BibTeX
@article{alexander2025-40646704,
author = {Alexander, Madeline Wood and Fischer, D. Luke and VandeVrede, Lawren A. and Nichols, Emma L. and Yu, Lei and Pike, James Russell and Swardfager, Walter and Wu, Che‐Yuan and others},
title = {{Sex Differences in Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline}},
journal = {Annals of Neurology},
year = {2025},
doi = {10.1002/ana.27308},
pmid = {40646704},
url = {https://doi.org/10.1002/ana.27308}
}
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