Abstract
ObjectivePrediabetes is a well-established risk factor for late-life dementia, and phenotypic age acceleration (PhenoAgeAccel) serves as a reliable biomarker reflecting cumulative biological aging burden. Few population-based cohorts have clarified their combined correlation with dementia-free survival among prediabetic adults. This study intended to explore the association between PhenoAgeAccel and dementia-free life expectancy in individuals with prediabetes.MethodsWe enrolled 45,608 prediabetic participants from UK Biobank with a median follow-up of 14.39 years. PhenoAgeAccel values were computed and categorized into three tertiles from low to high aging acceleration. Royston-Parmar parametric models were adopted to calculate dementia-free life expectancy at age 45 and 65. Competing risk analysis and five independent sensitivity analyses were performed to verify result stability.ResultsA total of 1,161 incident dementia events were documented during follow-up. Participants with lower PhenoAgeAccel presented significantly longer dementia-free survival at both baseline ages. At age 45, the lowest tertile gained an extra 1.99 dementia-free years (95%CI 0.95-3.03). Elevated PhenoAgeAccel predicted higher cumulative risks of dementia and all-cause mortality, with Gray's test P values of 0.008 and <0.001, respectively. All stratified and sensitivity analyses showed consistent findings.ConclusionsHigher biological aging is independently associated with prolonged dementia-free life expectancy in prediabetic populations. PhenoAgeAccel can facilitate dementia risk stratification and guide early preventive interventions for prediabetic groups.</p>