Prevalent Stroke, Fatigue, and Incident Dementia Risk in the UK Biobank.

BACKGROUND: Stroke is a major risk factor for dementia, and fatigue is common among stroke survivors. Whether self-reported fatigue is associated with dementia risk among individuals with prevalent stroke remains unclear. METHODS: We conducted a prospective cohort study of 484,749 UK Biobank participants without dementia at baseline. Participants were classified into four groups according to prevalent stroke and self-reported fatigue: neither exposure, fatigue only, prevalent stroke only, and prevalent stroke with fatigue. The primary outcome was incident all-cause dementia. Secondary outcomes were Alzheimer disease and vascular dementia. Cox proportional hazards models used age as the time scale and adjusted for demographic, socioeconomic, lifestyle, and cardiometabolic factors. Sensitivity analyses included landmark, competing-risk, extended-adjustment, stroke-subtype, and time-updated stroke analyses. RESULTS: Of 484,749 participants, 60,379 had fatigue only, 5,706 had prevalent stroke only, and 1,697 had both prevalent stroke and fatigue. Compared with participants with neither exposure, adjusted hazard ratios for all-cause dementia were 1.51 (95% CI, 1.42-1.60) for fatigue only, 1.94 (95% CI, 1.74-2.17) for prevalent stroke only, and 2.79 (95% CI, 2.32-3.35) for prevalent stroke with fatigue. For participants with both prevalent stroke and fatigue, hazard ratios were 1.86 (95% CI, 1.32-2.62) for Alzheimer disease and 4.33 (95% CI, 3.24-5.80) for vascular dementia. Among participants with prevalent stroke, fatigue was associated with all-cause dementia after adjustment for time from recorded stroke occurrence to baseline assessment (HR, 1.36; 95% CI, 1.10-1.70), whereas the associations with Alzheimer disease and vascular dementia were not statistically significant. CONCLUSIONS: Prevalent stroke with self-reported fatigue was associated with the highest risk of incident dementia compared with neither exposure. Among participants with prevalent stroke, fatigue was associated with all-cause dementia but not clearly with Alzheimer disease or vascular dementia.