Abstract
INTRODUCTION: Sleep difficulty, a prevalent sleep disturbance in ageing populations, has shown paradoxical associations with dementia risk in prior epidemiological studies. Emerging evidence suggests that survival bias-where premature mortality in individuals with sleep difficulty obscures dementia risk-may explain these inconsistencies.
METHODS: We analysed data from 457,367 UK Biobank participants aged 40-69 years who were enrolled at baseline between 2006 and 2010 and followed until 2022. Sleep difficulty was assessed via self-reported questionnaires, and dementia was obtained from electronic health records. To address survival bias, we employed a semi-competing risks framework that jointly models dementia incidence and mortality, contrasting results with conventional Cox proportional hazard models.
RESULTS: Semi-competing risk analyses suggested that usual sleep difficulty modestly increased risks of vascular dementia (fully adjusted HR 1.14, 95% CI 1.02-1.28) and slightly increased all-cause dementia (HR 1.03, 95% CI 0.98-1.08) in the total sample. The association is particularly strong in younger adults (below 55 years old) and low APOE risk (APOE ε4 non-carriers) when adjusted for age, sex and education. Conversely, Cox models suggested a protective association between usual sleep difficulty and all-cause dementia in the total sample, aligning with prior UK Biobank studies. This discrepancy highlights how survival bias distorts risk estimates.
DISCUSSION: Our findings resolve conflicting evidence by demonstrating sleep difficulty’s direct dementia risk when accounting for competing mortality. The semi-competing risks approach provides a robust framework for ageing research, when survival bias is present. Clinically, these results underscore sleep difficulty management as a modifiable dementia prevention target in mid-to-late life.