UC San Diego

Background

We sought to examine whether frailty is associated with dementia, Alzheimer's disease (AD), and non-AD dementia risk.

Methods

This is a prospective population-based cohort derived from an integrated health maintenance organization. The sample consisted of 2,619 participants aged 65 and older without dementia at baseline followed from 1994 to 2010. Frailty was defined as having at least 3 of the following criteria: weakness (grip strength), slowness (walking speed), weight loss, low physical activity, and self-reported exhaustion. Follow-up occurred every 2 years to identify incident dementia, possible or probable AD, and non-AD dementia using standard research criteria. Covariates came from self-report and study measures. We used adjusted Cox proportional hazards models to examine the association between frailty and each outcome.

Results

Over a mean follow-up of 6.5 years, 521 participants developed dementia (of which 448 developed AD). In the model adjusted for age, sex, education, and race, the hazard ratio for frailty was 1.78 (95% confidence interval [CI] 1.32-2.40). In the fully adjusted models, the hazard ratio for frailty was 1.20 for all-cause dementia (95% CI 0.85-1.69), 1.08 for AD (95% CI 0.74-1.57), and 2.57 for non-AD dementia (95% CI 1.08-6.11). For all-cause dementia, we found an interaction between baseline cognitive score and frailty (p = .02); hazard ratio for frailty was 1.78 for those with higher global cognition (95% CI 1.14-2.78) and 0.79 for those with lower global cognition (95% CI 0.50-1.26).

Conclusion

Frailty was associated with dementia when adjusting only for demographic variables but not in the fully adjusted model. Frailty was associated with higher risk of developing non-AD dementia but not AD. Although frailty was not associated with all-cause dementia in the entire sample, an association did exist in participants with higher cognitive scores. Mechanisms underlying these associations remain to be elucidated.