{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:47:02Z","timestamp":1789667222674,"version":"4.0.1"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["341007"],"award-info":[{"award-number":["341007"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HUS Diagnostic Center and Helsinki University Hospital competitive","award":["TYH2020231"],"award-info":[{"award-number":["TYH2020231"]}]},{"name":"HUS Diagnostic Center and Helsinki University Hospital competitive","award":["TYH2022316"],"award-info":[{"award-number":["TYH2022316"]}]},{"name":"Medicinska Underst\u00f6dsf\u00f6reningen Liv och H\u00e4lsa rf, Finska L\u00e4kares\u00e4llskapet, \u00c5ke, Sara och Christel L\u00f6nnqvist\u2019s fund"},{"DOI":"10.13039\/501100003125","name":"Finnish Cultural Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004012","name":"Jane and Aatos Erkko Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Population-based cohort studies are essential for understanding the pathological basis of dementia in older populations. Previous studies have shown that limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) increases with age, but there have been only a few studies, which have investigated this entity in a population-based setting. Here we studied the frequency of LATE-NC and its associations with other brain pathologies and cognition in a population aged \u2265 85\u2005years.<\/jats:p>\n               <jats:p>The population-based Vantaa 85+ study cohort includes all 601 individuals aged \u226585\u2005years who were living in Vantaa, Finland in 1991. A neuropathological examination was performed on 304 subjects (50.5%) and LATE-NC staging was possible in 295 of those. Dementia status and Mini-Mental State Examination (MMSE) scores were defined in the baseline study and three follow-ups (1994\u201399). The LATE-NC stages were determined based on TDP-43 immunohistochemistry, according to recently updated recommendations. Arteriolosclerosis was digitally assessed by calculating the average sclerotic index of five random small arterioles in amygdala and hippocampal regions, and frontal white matter. The association of LATE-NC with arteriolosclerosis and previously determined neuropathological variables including Alzheimer\u2019s disease neuropathologic change (ADNC), Lewy-related pathology (LRP), hippocampal sclerosis (HS) and cerebral amyloid angiopathy (CAA), and cognitive variables were analysed by Fisher\u2019s exact test, linear and logistic regression (univariate and multivariate) models.<\/jats:p>\n               <jats:p>LATE-NC was found in 189 of 295 subjects (64.1%). Stage 2 was the most common (28.5%) and stage 3 the second most common (12.9%), whereas stages 1a, 1b and 1c were less common (9.5%, 5.1% and 8.1%, respectively). Stages 1a (P &amp;lt; 0.01), 2 (P &amp;lt; 0.001) and 3 (P &amp;lt; 0.001) were significantly associated with dementia and lower MMSE scores. LATE-NC was associated with ADNC (P &amp;lt; 0.001), HS (P &amp;lt; 0.001), diffuse neocortical LRP (P &amp;lt; 0.002), and arteriolosclerosis in amygdala (P &amp;lt; 0.02). In most cases LATE-NC occurred in combination alongside other neuropathological changes. There were only six subjects with dementia who had LATE-NC without high levels of ADNC or LRP (2% of the cohort, 3% of the cases with dementia), and five of these had HS. In all multivariate models, LATE-NC was among the strongest independent predictors of dementia. When LATE-NC and ADNC were assessed in a multivariate model without other dementia-associated pathologies, the attributable risk was higher for LATE-NC than ADNC (24.2% versus 18.6%).<\/jats:p>\n               <jats:p>This population-based study provides evidence that LATE-NC is very common and one of the most significant determinants of dementia in the general late-life aged population.<\/jats:p>","DOI":"10.1093\/brain\/awae212","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T08:13:49Z","timestamp":1719562429000},"page":"154-167","source":"Crossref","is-referenced-by-count":30,"title":["Limbic-predominant age-related TDP-43 encephalopathy in the oldest old: a population-based study"],"prefix":"10.1093","volume":"148","author":[{"given":"Elizaveta","family":"Mikhailenko","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kia","family":"Colangelo","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarno","family":"Tuimala","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Kero","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]},{"name":"Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Savola","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]},{"name":"Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Raunio","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]},{"name":"Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloise H","family":"Kok","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarit","family":"Tanskanen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"M\u00e4kel\u00e4","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Puttonen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]},{"name":"Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko I","family":"M\u00e4yr\u00e4np\u00e4\u00e4","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]},{"name":"Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darshan","family":"Kumar","sequence":"additional","affiliation":[{"name":"Aiforia Technologies Plc. , 00150 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karri","family":"Kaivola","sequence":"additional","affiliation":[{"name":"Translational Immunology, Research Programs Unit, University of Helsinki , Helsinki , 00014","place":["Finland"]},{"name":"Department of Neurology, University of Helsinki and Helsinki University Hospital , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Paetau","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]},{"name":"Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pentti J","family":"Tienari","sequence":"additional","affiliation":[{"name":"Translational Immunology, Research Programs Unit, University of Helsinki , Helsinki , 00014","place":["Finland"]},{"name":"Department of Neurology, University of Helsinki and Helsinki University Hospital , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomo","family":"Polvikoski","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University , Newcastle upon Tyne NE1 7RU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-5466","authenticated-orcid":false,"given":"Liisa","family":"Myllykangas","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki , 00014 Helsinki ,","place":["Finland"]},{"name":"Department of 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