Observational studyBrain and behavior2026
Leukocyte Telomere Length and Its Polygenic Risk Score in Post-Stroke Cognitive Impairment: Evidence From a Multicenter Cohort Study.
Observational study in Brain and behavior, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPost-stroke cognitive impairment (PSCI) is a frequent and disabling consequence of ischemic stroke. Leukocyte telomere length (LTL), a biomarker of systemic biological aging, has been implicated in cognitive outcomes, but evidence in stroke populations remains limited. We investigated whether baseline LTL and an LTL polygenic risk score (LTL-PRS) are associated with PSCI risk in a large Chinese stroke cohort.
methodsWe analyzed patients with ischemic stroke or transient ischemic attack (TIA) from the Third China National Stroke Registry-impairment of cognition and sleep (CNSR-III-ICONS) sub study. Baseline LTL was estimated from whole-genome sequencing (WGS) using TelSeq. An 18-SNP LTL-PRS (East-Asian weights) was z-standardized. Cognitive status at 12 months was assessed using the Montreal Cognitive Assessment (MoCA); PSCI was defined as an age-, sex-, education-adjusted norm-referenced threshold (z score ≤ -1.5). Fifty-one participants missing education required for the adjusted PSCI definition were excluded, leaving 923 for analysis. Multivariable logistic regression tested associations of LTL and LTL-PRS with PSCI, with exploratory interaction and stratified analyses by age, sex, and stroke subtype.
resultsPSCI occurred in 191 of 923 patients (20.7%). Neither continuous LTL nor LTL-PRS was associated with PSCI overall. Exploratory analyses provided nominal evidence of heterogeneity by age (p-interaction = 0.038) and stroke subtype (p-interaction = 0.01), whereas evidence for sex interaction was inconclusive (p-interaction = 0.07). Associations with the MoCA executive function domain were weak and sensitive to covariate adjustment.
conclusionsBaseline telomere metrics showed, at most, modest and context-dependent associations with PSCI. Neither LTL nor this limited-variant LTL-PRS demonstrated overall prognostic utility, highlighting the need for integrated, longitudinal multi-omic approaches for individualized cognitive risk prediction after stroke.
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