Associations of phenotypic aging with dementia-free life expectancy among 45,608 participants with prediabetes: a prospective cohort study.

OBJECTIVE

Prediabetes 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.

METHODS

We 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.

RESULTS

A 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.

CONCLUSIONS

Higher 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.