Aims: Understanding how risk factors affect the timing of dementia onset can support prevention efforts and care planning. We hypothesised that frailty brings symptoms forward, leading to a younger age at dementia diagnosis.
Methods: Longitudinal data were drawn from community-dwelling participants in the Rush Memory and Aging Project in Northeastern Illinois. Baseline information included age, education level, sex and APOE ε4 status. Frailty was assessed with a 41-item frailty index; neuropathologic burden was measured post-mortem using a 10-item index. We used accelerated failure time models to evaluate the relationships between frailty (frailty index scores ≥ 0.25) and age at dementia diagnosis.
Results: Among 1,614 participants (mean age 79.6 years; 75% women) followed for up to 23.9 years, frailty was associated with a 3.6% younger age at dementia diagnosis (TR 0.96, 95% CI 0.95–0.98), equivalent to a diagnosis occurring roughly 2–3 years earlier. This association was stronger in men than in women, yet evident across all sex, education and APOE ε4 subgroups. In the autopsy subset (N = 906), frailty was linked to a 9.8% younger age at dementia diagnosis among those who died with low neuropathologic burden (TR 0.90, 95% CI 0.85–0.96), equivalent to a diagnosis approximately 5–6 years earlier, but showed no measurable association in individuals with intermediate or high neuropathologic burden.
Conclusions: Frailty might independently accelerate the onset of dementia, especially in people with comparatively low levels of neuropathologic change. Incorporating routine frailty assessment into clinical practice could be advantageous.