| Title: | Re-evaluating sleep difficulty as a risk factor for dementia in the UK Biobank cohort: addressing survival bias using a semi-competing risks approach |
| Journal: | Age and Ageing |
| Published: | 1 Aug 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40833209/ |
| DOI: | https://doi.org/10.1093/ageing/afaf235 |
Publication 16063
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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.</p>
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.</p>
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.</p>
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.</p>
16 Keywords
- Adult
- Age Factors
- Aged
- Biological Specimen Banks
- Dementia
- Female
- Humans
- Incidence
- Male
- Middle Aged
- Proportional Hazards Models
- Risk Assessment
- Risk Factors
- Sleep Wake Disorders
- UK Biobank
- United Kingdom
3 Authors
- Tao Sun
- Xinyu Jiang
- Xiaojun Wang
1 Application
| Application ID | Title |
|---|---|
| 127327 | Novel Statistical Methods for Complex Survival Data with Applications to Disability Development in the Elderly |
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