Association between chronic fatigue and common cerebrovascular and neurodegenerative diseases: a prospective cohort study

Background Chronic fatigue (CF) is increasingly prevalent, yet its role as an independent risk factor for cerebrovascular and neurodegenerative diseases remains underexplored.Objective This study aimed to prospectively assess the association between CF and the risks of Parkinson's disease (PD), Alzheimer's disease (AD), cerebral infarction (CI), and all-cause mortality (ACM).Methods We utilized data from 167,098 UK Biobank participants (aged 40–69) with baseline information on CF (≥6 months). Cox proportional hazards models with three tiers of covariate adjustment (demographics, lifestyle, comorbidities) were used to examine associations with incident PD, AD, CI, and ACM. Fine-Gray competing risk models accounting for death were also employed for PD, AD, and CI.Results CF was independently associated with significantly increased risks of PD (fully-adjusted HR = 3.02, 95% CI = 2.42–3.76, p < 0.0001), AD (HR = 1.68, 1.21–2.34, p = 0.002), CI (HR = 1.19, 1.02–1.39, p = 0.027), and ACM (HR = 1.86, 1.73–2.00, p < 0.0001). Competing risk analyses confirmed robustness (e.g. for PD: sHR = 2.97, p < 0.0001).Conclusions Chronic fatigue is an independent risk factor for developing PD, AD, CI, and for ACM. Assessment of CF may help identify high-risk populations for targeted prevention.