Longitudinal dynamics in frailty and incident all-cause dementia: a multicohort study

Frailty changes over time, but how these changes relate to the risk of dementia remains uncertain.

To explore the temporal relationship between dynamic changes in frailty and incident all-cause dementia.

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.

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; I² = 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; I² = 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; I² = 0.0%). A higher cumulative frailty score was related to an increased dementia risk (HR: 1.26, 95% CI: 1.22-1.31; I² = 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; I² = 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; I² = 0.0% per score decrement).

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.