Fatigue and cognitive function in UK biobank, CHARLS, and NHANES: A cross-sectional analysis

Fatigue is common but its association with cognitive function across populations using a simple, standardized assessment remains unclear.

Cross-sectional data from UK Biobank (UKB, n = 165,809), China Health and Retirement Longitudinal Study (CHARLS, n = 13,065), and NHANES (n = 2804). Fatigue was operationalized as self-reported central fatigue, defined as frequent tiredness/low energy (UKB, NHANES) or the proxy "everything was an effort" (CHARLS). Cognitive scores were standardized into z-scores. Linear and logistic regression adjusted for age, sex, education, lifestyle, and chronic diseases (β for linear models; OR for logistic models).

Fatigue prevalence: 12.1% (UKB), 16.7% (CHARLS), 17.3% (NHANES). Self-reported central fatigue was significantly associated with lower composite cognitive z-scores (UKB β= -0.190, CHARLS β= -0.235, NHANES β= -0.248, all p < 0.001) and increased odds of cognitive impairment (z<-1) (UKB OR=1.57, CHARLS OR=1.41, NHANES OR=2.29, all p < 0.001). Associations were broadly consistent across cognitive domains, particularly processing speed and executive function. After additional adjustment for depressive symptoms, the association remained significant in UKB and CHARLS but was attenuated and no longer significant in NHANES.

Despite differences in fatigue assessment, self-reported central fatigue was associated with poorer concurrent cognitive performance across the UK, China, and the US. However, the association was attenuated after depressive symptom adjustment and was no longer significant in NHANES. These cross-sectional findings are hypothesis-generating and do not support the use of single-item fatigue measures for clinical screening. Future longitudinal studies are needed.