Frailty, trajectories of frailty, and cognitive impairment: evidence from five longitudinal cohort studies

Longitudinal studies examining the impacts of frailty and its transitions on cognitive impairment in older adults across multiple regions remain scarce. This study aimed to explore the associations of baseline frailty status and frailty trajectories with cognitive impairment in five large-scale cohort studies. Data were derived from five prospective cohorts conducted in the United States, England, Europe, China, and Korea. Univariate and multivariate Cox proportional hazards models were used to evaluate the relationship between baseline frailty and cognitive impairment. Meta-analyses were performed to synthesize the overall effect sizes across all cohorts. Trajectories of frailty were identified using latent class growth models. Univariate and multivariate logistic regression models were utilized to investigate the association between frailty trajectories and cognitive impairment. Among the 47,429 participants included in the analyses of baseline frailty status, 8,799 developed cognitive impairment over median follow-up periods of 4.09 to 10.00 years. Compared with robust participants, pre-frail participants exhibited a significantly increased risk of cognitive impairment (adjusted hazard ratio [HR] range: 1.17 [95% confidence interval [CI]: 1.02–1.34] to 1.35 [95% CI: 1.09–1.68], pooled HR: 1.25 [95% CI: 1.18–1.33]). Similarly, frail participants showed an elevated risk of cognitive impairment (adjusted HR range: 1.55 [95% CI: 1.25–1.92] to 2.16 [95% CI: 1.72–2.72], pooled HR: 1.69 [95% CI: 1.50–1.90]). A total of 22,310 participants were included in the analyses of frailty trajectory, among whom 4,717 developed cognitive impairment. Frailty trajectories were significantly associated with cognitive impairment: higher trajectory class was linked to an elevated risk of cognitive impairment (adjusted odds ratio [OR] range: 1.45 [95% CI: 1.09–1.93] to 4.37 [95% CI: 3.43–5.59]), whereas lower trajectory class was connected to a reduced risk (adjusted OR range: 0.46 [95% CI: 0.39–0.54] to 0.72 [95% CI: 0.59–0.88]). Baseline frailty status is associated with cognitive impairment in the broader aging populations, and frailty trajectories are linked to cognitive impairment among the surviving older adults. Early frailty screening and detection may facilitate risk stratification and improve the management of cognitive impairment in older populations.