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Association of Leucocyte Telomere Length With Stroke, Dementia, and Late-Life Depression:The Role of Modifiable Risk Factors

Title: Association of Leucocyte Telomere Length With Stroke, Dementia, and Late-Life Depression:The Role of Modifiable Risk Factors
Authors: Kimball,Tamara N.; Prapiadou,Savvina; Tack, Reinier W.P.; Yong-Qiang Tan,Benjamin; Senff, Jasper R.; Kourkoulis,Christina; Singh,Sanjula; Rosand,Jonathan; Anderson,Christopher D.; Projectafdeling CVZ
Publication Year: 2025
Subject Terms: Taverne; Clinical Neurology
Description: Background and ObjectivesStroke, dementia, and late-life depression (LLD) are age-related brain diseases that pose significant public health challenges and costs. Leucocyte telomere length (LTL) is a biological aging marker influenced by both genetic and lifestyle factors. The aim of our study was to determine the association between LTL and these diseases. We further investigated whether modifying risk factors of age-related brain disease, as measured using the Brain Care Score (BCS), mitigates LTL associations.MethodsWe analyzed participants from the UK Biobank with available LTL and risk factor information. We examined LTL's associations with stroke, dementia, and LLD, individually and as a composite outcome, using continuous measures and tertile stratification. Disease risks were evaluated through cumulative incidence curves, incidence rates per 1,000 person-years, and adjusted Cox models. Risk comparisons across LTL tertiles were stratified by risk factor profiles, with high BCS (≥15) indicating healthier lifestyle choices and low BCS (≤10) reflecting less optimal lifestyle choices. Mendelian randomization (MR) was used to test causal associations.ResultsThe study included 356,173 participants (median age 56 years; 53.69% female). Shorter LTL was consistently associated with higher incidence rates across all outcomes. Participants in the shortest LTL tertile had elevated risks of the composite outcome (hazard ratio [HR] 1.11; 95% CI 1.08-1.15), stroke (HR 1.08; 95% CI 1.02-1.15), dementia (HR 1.19; 95% CI 1.12-1.26), and LLD (HR 1.14; 95% CI 1.09-1.18). Individuals with both shorter LTL and lower BCS faced significantly increased risks of age-related brain diseases (HR 1.11; 95% CI 1.07-1.16) and individually for stroke (HR 1.10; 95% CI 1.02-1.19), dementia (HR 1.17; 95% CI 1.08-1.28), and LLD (HR 1.13; 95% CI 1.07-1.19). Conversely, individuals with higher BCS within the shortest LTL group did not show a significant increase in risk of any age-related brain diseases. MR analyses did not identify causal ...
Document Type: article in journal/newspaper
File Description: text/plain
Language: English
ISSN: 0028-3878
Relation: https://dspace.library.uu.nl/handle/1874/466654
Availability: https://dspace.library.uu.nl/handle/1874/466654
Rights: info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.EDF58AF0
Database: BASE