Frailty May Be a Risk Factor for Dementia

Frailty measurements may be predictive of high-risk populations suitable for enrollment in clinical trials for dementia prevention and treatment, according to study findings published in JAMA Neurology.

Researchers retrospectively analyzed data from 4 large prospective cohort studies (English Longitudinal Study of Ageing, Health and Retirement Study, Rush Memory and Aging Project, National Alzheimer Coordinating Center) to determine when the degree of frailty accelerates before dementia and explore how frailty is associated with the risk for dementia.

Individuals aged 60 and older without cognitive impairment at baseline and at least 1 follow-up assessment were eligible for inclusion.

The primary outcome was incident all-cause dementia, which was ascertained via physician-derived diagnoses, self- and informant-report, and a battery of cognitive tests. Bayesian generalized linear mixed regression and Cox proportional hazards models were used in statistical analysis.  

A total of 29,849 participants (mean age, 71.6; women, 62%; White, 85%) contributed 257,963 person-years of follow-up, during which 3154 cases of incident dementia occurred. 

Researchers identified an acceleration in frailty trajectories between 4 and 9 years prior to dementia onset.

Among individuals who developed dementia, adjusted expected frailty index scores were higher in women vs men in 3 of the 4 studies by a range of 16.2% to 20.9%.

Overall, frailty was strongly associated with the risk for dementia (range, adjusted hazard ratio [aHR], 1.18; 95% CI, 1.13-1.24 to aHR, 1.73; 95% CI, 1.57-1.92). This association was maintained among participants whose time between measured frailty and incident dementia exceeded the defined acceleration window (range, aHR, 1.18; 95% CI, 1.12-1.23 to aHR, 1.43; 95% CI, 1.14-1.80).

These results were retained in sensitivity analyses.

Study limitations include the likelihood of reverse causality and the exclusion of several markers of social deprivation that may be associated with dementia.

“These findings suggest that frailty measurements can be used to identify high-risk population groups for preferential enrollment into clinical trials for dementia prevention and treatment, and that frailty itself may represent a useful upstream target for behavioral and societal approaches to dementia prevention,” the researchers concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.