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Neuropathologic Profiles and Associated Cognitive Trajectories in Community-Living Older Adults
Yu L, Wang T, Du L, Bennett DA, Schneider JA, Boyle PA. JAMA Network Open, 2026-01-02
Topic: Risk, prevention and care in population studies
Latent neuropathologic profiles were identified using hierarchical clustering, and longitudinal cognitive trajectories associated with each profile were estimated using functional mixed-effects models. Results A total of 1633 older adults were included in the study. Hierarchical clustering revealed 5 distinct neuropathologic profiles: profile 1 (259 participants [15.9%]) was characterized by a high burden of infarcts and vessel diseases, profile 2 (201 participants [12.3%]) by high LATE-NC and hippocampal sclerosis, profile 3 (355 participants [21.7%]) by high Lewy bodies, profile 4 (159 participants [9.7%]) by high ADNC and amyloid angiopathy, and profile 5 (659 participants [40.4%]) by low pathology overall. Compared with vascular conditions, degenerative pathologies clustered into distinct profiles.
Key findings
- Latent neuropathologic profiles were identified using hierarchical clustering, and longitudinal cognitive trajectories associated with each profile were estimated using functional mixed-effects models.
- Results A total of 1633 older adults were included in the study.
- Hierarchical clustering revealed 5 distinct neuropathologic profiles: profile 1 (259 participants [15.9%]) was characterized by a high burden of infarcts and vessel diseases, profile 2 (201 participants [12.3%]) by high LATE-NC and hippocampal sclerosis, profile 3 (355 participants [21.7%]) by high Lewy bodies, profile 4 (159 participants [9.7%]) by high ADNC and amyloid angiopathy, and profile 5 (659 participants [40.4%]) by low pathology overall.
- Compared with vascular conditions, degenerative pathologies clustered into distinct profiles.
Why it matters
Among 1,633 community-living older adults, hierarchical clustering revealed five distinct neuropathologic profiles, including one characterized by high Alzheimer's disease neuropathologic change and amyloid angiopathy and another by high LATE-NC and hippocampal sclerosis, with different longitudinal cognitive trajectories. This describes how different brain pathologies group together and relate to cognition, and does not test any treatment, cure or prevention.
Study details
- Study designcohort
- Participants1,633
- Evidence strengthHigh
Limitations
The study focused on neuropathologic indices most commonly associated with cognitive impairment, with data on less common indices still being collected; not all pathologies were quantified with the same fidelity, as some were rated only present or absent; and the cohort was 97% White.
How this study scored 55/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 54 of the 98 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA Network Open) |
| Journal's citation record | 2 / 4 | JAMA Network Open: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,633 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 | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 14.1× 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 | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Patricia A. Boyle: h-index 18 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Rush University Medical Center: institution h-index 670 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41543852) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 54 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 54 of the 98 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamanetworkopen.2025.54354
- PubMed: 41543852
- 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).
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. Check the citation against the original before you use it.
APA 7th
Yu, L., Wang, T., Du, L., Bennett, D. A., Schneider, J. A., & Boyle, P. A. (2026). Neuropathologic Profiles and Associated Cognitive Trajectories in Community-Living Older Adults. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2025.54354
Vancouver
Yu L, Wang T, Du L, Bennett DA, Schneider JA, Boyle PA. Neuropathologic Profiles and Associated Cognitive Trajectories in Community-Living Older Adults. JAMA Network Open. 2026. doi:10.1001/jamanetworkopen.2025.54354. PMID: 41543852.
BibTeX
@article{yu2026-41543852,
author = {Yu, L. and Wang, T. and Du, L. and Bennett, D. A. and Schneider, J. A. and Boyle, P. A.},
title = {{Neuropathologic Profiles and Associated Cognitive Trajectories in Community-Living Older Adults}},
journal = {JAMA Network Open},
year = {2026},
doi = {10.1001/jamanetworkopen.2025.54354},
pmid = {41543852},
url = {https://doi.org/10.1001/jamanetworkopen.2025.54354}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.