Limbic-predominant age-related TDP-43 encephalopathy in the oldest old: a population-based study.

التفاصيل البيبلوغرافية
العنوان:	Limbic-predominant age-related TDP-43 encephalopathy in the oldest old: a population-based study.
المؤلفون:	Mikhailenko E; Department of Pathology, University of Helsinki, Helsinki, Finland., Colangelo K; Department of Pathology, University of Helsinki, Helsinki, Finland., Tuimala J; Department of Pathology, University of Helsinki, Helsinki, Finland., Kero M; Department of Pathology, University of Helsinki, Helsinki, Finland.; Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Savola S; Department of Pathology, University of Helsinki, Helsinki, Finland.; Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Raunio A; Department of Pathology, University of Helsinki, Helsinki, Finland.; Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Kok EH; Department of Pathology, University of Helsinki, Helsinki, Finland., Tanskanen M; Department of Pathology, University of Helsinki, Helsinki, Finland., Mäkelä M; Department of Pathology, University of Helsinki, Helsinki, Finland., Puttonen H; Department of Pathology, University of Helsinki, Helsinki, Finland.; Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Mäyränpää MI; Department of Pathology, University of Helsinki, Helsinki, Finland.; Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Kumar D; Aiforia Technologies Plc., Helsinki, Finland., Kaivola K; Translational Immunology, Research Programs Unit, University of Helsinki, Helsinki, Finland.; Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Paetau A; Department of Pathology, University of Helsinki, Helsinki, Finland.; Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Tienari PJ; Translational Immunology, Research Programs Unit, University of Helsinki, Helsinki, Finland.; Department of Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Polvikoski T; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., Myllykangas L; Department of Pathology, University of Helsinki, Helsinki, Finland.; Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland.
المصدر:	Brain : a journal of neurology [Brain] 2024 Jun 28. Date of Electronic Publication: 2024 Jun 28.
Publication Model:	Ahead of Print
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Oxford University Press Country of Publication: England NLM ID: 0372537 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2156 (Electronic) Linking ISSN: 00068950 NLM ISO Abbreviation: Brain Subsets: MEDLINE
أسماء مطبوعة:	Publication: Oxford : Oxford University Press Original Publication: London.
مستخلص:	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 neuropathological 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 ≥ 85 years. The population-based Vantaa 85+ study cohort includes all 601 individuals aged ≥ 85 years 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 3 follow-ups (1994-99). 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's disease neuropathological change (ADNC), Lewy-related pathology (LRP), hippocampal sclerosis (HS), and cerebral amyloid angiopathy (CAA), and cognitive variables were analysed by Fisher's exact test, linear and logistic regression (univariate and multivariate) models. 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 < 0.01), 2 (P < 0.001) and 3 (P < 0.001) were significantly associated with dementia and lower MMSE scores. LATE-NC was associated with ADNC (P < 0.001), HS (P < 0.001), diffuse neocortical LRP (P < 0.002), and arteriolosclerosis in amygdala (P < 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% vs. 18.6%). 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. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
فهرسة مساهمة:	Keywords: autopsy; mixed pathology; multivariate analysis; neurodegeneration; neuropathology; very old
تواريخ الأحداث:	Date Created: 20240628 Latest Revision: 20240628
رمز التحديث:	20240628
DOI:	10.1093/brain/awae212
PMID:	38938199
قاعدة البيانات:	MEDLINE

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تدمد:	1460-2156
DOI:	10.1093/brain/awae212