A cohort study of 29,849 participants aged ≥60 years across the U.S. and U.K. identified distinct frailty trajectories preceding dementia onset. Frailty, quantified by a frailty index score measuring cumulative health deficits across physical, mental, and social domains, accelerated significantly within a 4- to 9-year period before dementia diagnosis, suggesting it may serve as a valuable marker for identifying populations at elevated dementia risk.

Participants from four major cohort studies (English Longitudinal Study of Ageing, Health and Retirement Study, Rush Memory and Aging Project, and National Alzheimer Coordinating Center) had a mean age of 71.6 years at baseline, totaling 257,963 person-years of follow-up with 3,154 incident dementia cases. Bayesian generalized linear mixed models revealed that higher frailty levels correlated with increased dementia risk. Adjusted hazard ratios (aHRs) indicated that each 0.1 increase in frailty index score—reflecting roughly 4-5 additional health deficits—was linked to a significantly higher dementia risk, with aHRs varying by cohort, ranging from 1.18 (95% confidence interval [CI], 1.13-1.24) to 1.73 (95% CI, 1.57-1.92), strongest in NACC and weakest in HRS.

The analysis showed that frailty scores began diverging between participants who developed dementia and those who did not approximately 8-20 years before dementia onset, with accelerated increases in frailty occurring 4-9 years before diagnosis. Notably, females had higher frailty index scores than males (16.2%-20.9% on average) in the pre-dementia period.

Published in JAMA Neurology, these findings suggest frailty may function as an upstream marker for dementia risk, enabling earlier identification of at-risk populations for prevention trials. The authors suggest that frailty could be a modifiable target, with further research needed to clarify the impact of lifestyle interventions such as physical activity and nutritional support on dementia risk.

Full disclosures can be found in the published study.