Abstract / Summary
Introduction: Frailty changes over time, but how these changes relate to the risk of dementia remains uncertain. Objective: To explore the temporal relationship between dynamic changes in frailty and incident all-cause dementia. Methods: We included adults aged ≥ 60 years from four prospective cohorts in this pooled analysis. Frailty was assessed using a modified Fried phenotype at two separate time points, allowing the identification of longitudinal frailty transition patterns. The outcome was all-cause dementia, identified through active follow-up assessments or passive data collection. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived from Cox proportional hazards analyses. Results: Among 15,897 participants (51.3% female, mean age: 66.9 years), 1015 developed incident dementia over 131,621.3 person-years of follow-up. An increased risk of dementia was observed among robust participants who progressed to pre-frail/frail status, compared to those with stable robustness (pooled HR: 1.62, 95% CI: 1.06–2.47; I 2 = 66.8%). Similarly, pre-frail participants who progressed to frail status exhibited a higher dementia risk compared to those who remained pre-frail (pooled HR: 1.85, 95% CI: 1.47–2.34; I 2 = 0.0%). Conversely, participants who reverted from pre-frail to robust status experienced a reduced dementia risk (pooled HR: 0.59, 95% CI: 0.46–0.76; I 2 = 0.0%). A higher cumulative frailty score was related to an increased dementia risk (HR: 1.26, 95% CI: 1.22–1.31; I 2 = 0.0% per score increment). Participants whose frailty scores increased over time had a higher risk of dementia compared to those with stable scores (pooled HR: 1.33, 95% CI: 1.07–1.65; I 2 = 75.5% per score increment), while those with decreasing scores showed a mitigated dementia risk (pooled HR: 0.77, 95% CI: 0.65–0.91; I 2 = 0.0% per score decrement). Conclusions: Progression in frailty was associated with an increased risk of dementia, while reversal of pre-frailty reduced the risk. Our results highlight the importance of continuous monitoring and personalized interventions for managing frailty in older adults.