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Common neuropathologic change drivers of hippocampal sclerosis of ageing
Davis C. Woodworth, Jicheng Lou, William H. Yong, Elizabeth Head, María M. Corrada, Peter T. Nelson, S. Ahmad Sajjadi. Brain, 2025-05-05
Topic: Brain proteins, microglia and lab models
The aetiology of HS-A is heterogeneous, but HS-A is strongly associated with limbic-predominant age-related TDP-43 encephalopathy NC (LATE-NC). LATE-NC was strongly associated with HS-A (aOR = 3.7, 95% CI = 2.8, 5.0). While ADNC showed a modest association with HS-A in models where LATE-NC was not included as a predictor (aOR = 1.4, CI = 1.1, 1.8), this association was reduced when adjusting for LATE-NC (aOR = 1.11, CI = 0.9, 1.5); results were similar for the ADNC-related A/B/C scores and limbic LBs. However, several cerebrovascular NCs were similarly associated with HS-A both without adjusting for LATE-NC [atherosclerosis aOR = 1.4, arteriolosclerosis aOR = 1.6, white matter rarefaction (WMR) aOR = 1.4] and with adjusting for LATE-NC (atherosclerosis aOR = 1.4, arteriolosclerosis aOR = 1.5, WMR aOR = 1.3). In a combined model, LATE-NC was strongly associated with HS-A, but global cerebrovascular NCs, as well as APOE-ε4 (increased odds) and education (decreased odds), were also associated with HS-A. While ADNC seems to be associated with HS-A through its association with LATE-NC, the association of cerebrovascular NCs with HS-A independent of LATE-NC underlines the importance of vascular factors in the aetiology of HS-A.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Woodworth, D. C., Lou, J., Yong, W. H., Head, E., Corrada, M. M., Nelson, P. T., et al. (2025). Common neuropathologic change drivers of hippocampal sclerosis of ageing. Brain. https://doi.org/10.1093/brain/awaf158
Vancouver
Woodworth DC, Lou J, Yong WH, Head E, Corrada MM, Nelson PT, et al. Common neuropathologic change drivers of hippocampal sclerosis of ageing. Brain. 2025. doi:10.1093/brain/awaf158. PMID: 40323260.
BibTeX
@article{woodworth2025-40323260,
author = {Woodworth, Davis C. and Lou, Jicheng and Yong, William H. and Head, Elizabeth and Corrada, María M. and Nelson, Peter T. and Sajjadi, S. Ahmad},
title = {{Common neuropathologic change drivers of hippocampal sclerosis of ageing}},
journal = {Brain},
year = {2025},
doi = {10.1093/brain/awaf158},
pmid = {40323260},
url = {https://doi.org/10.1093/brain/awaf158}
}
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.
Key findings
- The aetiology of HS-A is heterogeneous, but HS-A is strongly associated with limbic-predominant age-related TDP-43 encephalopathy NC (LATE-NC).
- LATE-NC was strongly associated with HS-A (aOR = 3.7, 95% CI = 2.8, 5.0).
- While ADNC showed a modest association with HS-A in models where LATE-NC was not included as a predictor (aOR = 1.4, CI = 1.1, 1.8), this association was reduced when adjusting for LATE-NC (aOR = 1.11, CI = 0.9, 1.5); results were similar for the ADNC-related A/B/C scores and limbic LBs.
- However, several cerebrovascular NCs were similarly associated with HS-A both without adjusting for LATE-NC [atherosclerosis aOR = 1.4, arteriolosclerosis aOR = 1.6, white matter rarefaction (WMR) aOR = 1.4] and with adjusting for LATE-NC (atherosclerosis aOR = 1.4, arteriolosclerosis aOR = 1.5, WMR aOR = 1.3).
- In a combined model, LATE-NC was strongly associated with HS-A, but global cerebrovascular NCs, as well as APOE-ε4 (increased odds) and education (decreased odds), were also associated with HS-A.
Why it matters
In this neuropathology study, limbic-predominant age-related TDP-43 encephalopathy was strongly associated with hippocampal sclerosis of ageing, and cerebrovascular changes were also associated with it independently of LATE-NC. These are associations found in brain tissue and do not establish any treatment or prevention.
Study details
- Participants1,933
- Effect size51.3%; 14.4%; aOR = 3.7
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 1,933 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization 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 | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author S. Ahmad Sajjadi: h-index 24 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Irvine: institution h-index 1,195 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40323260) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
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