Sleep disruption and Alzheimer's disease risk: Inferences from men with benign prostatic hyperplasia

BACKGROUND: Sleep disturbances may increase risks of Alzheimer's disease (AD) and other dementias. Benign prostatic hyperplasia (BPH) is usually associated with lower urinary tract symptoms, including nocturia, and thereby disturbed sleep. We examined if men with BPH are at increased risk of AD and all-cause dementia. METHODS: In a Danish nationwide cohort (1996–2016), we identified 297,026 men with BPH, defined by inpatient or outpatient hospital diagnosis or by BPH-related surgical or medical treatment, and 1,107,176 men from the general population matched by birth year. We computed rates, cumulative incidences, and adjusted hazard ratios (HRs) of AD and all-cause dementia. Follow-up started 1 year after BPH diagnosis date/index date. FINDINGS: Median follow-up was 6·9 years (Interquartile range (IQR), 3·6 – 11·6 years] in the BPH cohort and 6·4 years (IQR: 3·4 – 10·8 years) in the comparison cohort. The cumulative 1–10 year risk of AD was 1·15% [95% confidence interval (CI), 1·11–1·20], in the BPH cohort and 1·00% (95% CI, 0·98 – 1·02) in the comparison cohort. The adjusted 1–10–year hazard ratios were 1·16 (95% CI: 1·10–1·21) for AD and 1·21 (95% CI: 1·17–1·25) for all-cause dementia. From >10 years up to 21 years of follow-up, BPH remained associated with 10%- 20% increased risk of AD and all-cause dementia. INTERPRETATION: During up to 21 years of follow-up, men with BPH had persistently higher risk of AD and all-cause dementia compared with men in the general population. Our results identify BPH as a common, potentially remediable disorder associated with dementia risk. FUNDING: Lundbeckfonden, Aarhus University Research Foundation, and the National Institutes of Health.