{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:12:15Z","timestamp":1790089935896,"version":"4.0.1"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012264","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023864","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG062706"],"award-info":[{"award-number":["R01AG062706"]}],"id":[{"id":"10.13039\/501100023864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hippocampal sclerosis of ageing (HS-A)\u2014severe cell loss and gliosis in the hippocampal formation\u2014is a neuropathologic change (NC) that affects up to 20% of elderly persons with dementia. The aetiology of HS-A is heterogeneous, but HS-A is strongly associated with limbic-predominant age-related TDP-43 encephalopathy NC (LATE-NC). Other NCs have also been implicated in relation to HS-A, but these associations have been inconsistent across previous studies. Also, because LATE-NC and HS-A are so strongly associated, it is important to adjust for LATE-NC when examining associations between other NCs and HS-A. The goal of this study was to examine associations of other common NCs with HS-A, both before and after adjusting for LATE-NC.<\/jats:p>\n               <jats:p>We analysed the National Alzheimer\u2019s Coordinating Center (NACC) neuropathology dataset and examined associations of Alzheimer\u2019s disease NC (ADNC), Lewy bodies (LB) and cerebrovascular NCs, with HS-A, adjusting for LATE-NC in multiple ways. We used Bayesian multilevel logistic regression models with monotonic modelling for ordinal predictors and report the odds ratios (OR) or average OR across levels (aOR), along with 95% credibility intervals (CI) as well as expected frequencies of HS-A for selected models and predictor levels.<\/jats:p>\n               <jats:p>Of n = 1933 autopsy participants included (average age at death of 83 years, 51.3% women), HS-A was present in 278 (14.4%). 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-\u03b54 (increased odds) and education (decreased odds), were also associated with HS-A. Predicted HS-A frequency for predictor levels of no LATE-NC or global cerebrovascular NCs was 1.5% (CI = 0.6%, 3.1%), while it was 94.5% (CI = 84%, 99.5%) for LATE-NC stage 3 and severe global cerebrovascular NC levels.<\/jats:p>\n               <jats:p>LATE-NC is likely the most important cause of 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.<\/jats:p>","DOI":"10.1093\/brain\/awaf158","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T14:22:46Z","timestamp":1746454966000},"page":"2400-2411","source":"Crossref","is-referenced-by-count":16,"title":["Common neuropathologic change drivers of hippocampal sclerosis of ageing"],"prefix":"10.1093","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6256-857X","authenticated-orcid":false,"given":"Davis C","family":"Woodworth","sequence":"first","affiliation":[{"name":"Department of Neurology, University of California , Irvine, CA 92697 ,","place":["USA"]},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California , Irvine, CA 92697 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,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-6396","authenticated-orcid":false,"given":"Elizabeth","family":"Head","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California , Irvine, CA 92697 ,","place":["USA"]},{"name":"Department of Pathology and Laboratory Medicine, University of California , Irvine, CA 92697 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda M","family":"Corrada","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California , Irvine, CA 92697 ,","place":["USA"]},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California , Irvine, CA 92697 ,","place":["USA"]},{"name":"Department of Epidemiology and Biostatistics, University of California , Irvine, CA 92697 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