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Mixed Pathologies and Cognitive Outcomes in Persons Considered for Anti-Amyloid Treatment Eligibility Assessment: A Community-Based Study
Kapasi A, James BD, Yu L, Sood A, Arvanitakis Z, Bennett DA, Boyle P, Schneider JA.. Neurology, 2025-08-18
Topic: Amyloid, tau and blood-test diagnosis
Results Among 428 older autopsied persons (mean age at death = 91 years, 70% women) considered for anti-amyloid treatment eligibility assessment, 58% had MCI and 42% had mild-stage Alzheimer dementia. In mixed-effects models, tangles and arteriolosclerosis were both associated with a faster rate of global cognitive decline. Separately, tangles and LATE-NC were associated with a faster decline in episodic memory, ADNC was associated with faster decline in semantic memory with Aβ being further associated with decline in working memory, and atherosclerosis was associated with a faster decline in perceptual speed. Infarcts and LBs were not associated with decline in global cognition or any cognitive domain. These findings suggest that, even among those eligible for anti-amyloid therapies, substantial cognitive decline may occur because of the presence of coexisting pathologies.
Key findings
- Results Among 428 older autopsied persons (mean age at death = 91 years, 70% women) considered for anti-amyloid treatment eligibility assessment, 58% had MCI and 42% had mild-stage Alzheimer dementia.
- In mixed-effects models, tangles and arteriolosclerosis were both associated with a faster rate of global cognitive decline.
- Separately, tangles and LATE-NC were associated with a faster decline in episodic memory, ADNC was associated with faster decline in semantic memory with Aβ being further associated with decline in working memory, and atherosclerosis was associated with a faster decline in perceptual speed.
- Infarcts and LBs were not associated with decline in global cognition or any cognitive domain.
- These findings suggest that, even among those eligible for anti-amyloid therapies, substantial cognitive decline may occur because of the presence of coexisting pathologies.
Why it matters
Among 428 autopsied older people considered for anti-amyloid treatment eligibility, several coexisting pathologies such as tangles and arteriolosclerosis were linked to faster cognitive decline. This suggests that even in people eligible for anti-amyloid therapies, other pathologies may still drive decline, but it does not test a treatment, cure or prevention.
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Study details
- Evidence strengthLow
How this study scored 46/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| 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 | 4 / 5 | 2025 — within 3 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 15 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 9.5× 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 | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Julie A. Schneider: h-index 151 (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 40825161) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000214004
- PubMed: 40825161
- 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. The record names 8 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
Kapasi, A., James, B. D., Yu, L., Sood, A., Arvanitakis, Z., Bennett, D. A., et al. (2025). Mixed Pathologies and Cognitive Outcomes in Persons Considered for Anti-Amyloid Treatment Eligibility Assessment: A Community-Based Study. Neurology. https://doi.org/10.1212/wnl.0000000000214004
Vancouver
Kapasi A, James BD, Yu L, Sood A, Arvanitakis Z, Bennett DA, et al. Mixed Pathologies and Cognitive Outcomes in Persons Considered for Anti-Amyloid Treatment Eligibility Assessment: A Community-Based Study. Neurology. 2025. doi:10.1212/wnl.0000000000214004. PMID: 40825161.
BibTeX
@article{kapasi2025-40825161,
author = {Kapasi, A. and James, B. D. and Yu, L. and Sood, A. and Arvanitakis, Z. and Bennett, D. A. and Boyle, P. and Schneider, J. A.},
title = {{Mixed Pathologies and Cognitive Outcomes in Persons Considered for Anti-Amyloid Treatment Eligibility Assessment: A Community-Based Study}},
journal = {Neurology},
year = {2025},
doi = {10.1212/wnl.0000000000214004},
pmid = {40825161},
url = {https://doi.org/10.1212/wnl.0000000000214004}
}
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