White Matter Hyperintensity Burden and Short‐Interval Change Associated With Sleep Apnoea in the <scp>UK</scp> Biobank

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are a core neuroimaging marker of cerebral small vessel disease (CSVD). Sleep apnoea (SA) is a recognized vascular risk factor, but its associations with regional WMH burden, short-interval WMH change and cognitive performance in population-based cohorts remain incompletely defined. We examined these associations in the UK Biobank imaging cohort. METHODS: We conducted cross-sectional analyses with an exploratory longitudinal subset in propensity score-matched cohorts excluding major neurologic and cerebrovascular disease before imaging. SA was identified from hospital records and self-reports prior to brain magnetic resonance imaging (MRI). Head-size-normalized WMH volumes were analysed on the log1p scale using multivariable linear regression with robust standard errors. Total WMH was the primary outcome; periventricular WMH (PWMH), deep WMH (DWMH) and cognitive measures were secondary outcomes. Mediation analyses evaluated WMH as a mediator of SA-cognition associations. RESULTS: In cross-sectional analyses (N = 12,890; mean age, 67.4 years; 27.2% women), SA was associated with greater WMH burden. Total WMH volume was 10.7% higher among participants with SA (95% CI, 5.0%-16.6%; p < 0.001). PWMH and DWMH volumes were 10.0% (95% CI, 4.7%-15.7%; q < 0.001) and 15.7% (95% CI, 7.1%-25.1%; q < 0.001) higher, respectively. SA was associated with modestly worse cognitive performance, with effect estimates attenuated after adjustment for WMH burden and cardiometabolic conditions. Mediation analyses indicated that WMH burden, particularly PWMH, mediated associations between SA and cognitive performance. In the longitudinal subset (N = 698; median follow-up, 2.26 years), no significant between-group differences were observed in annualized WMH change. CONCLUSIONS: In this large population-based imaging cohort, SA was associated with higher WMH burden, a key neuroimaging marker of CSVD. Cognitive differences were modest, but WMH burden, particularly PWMH, consistently mediated associations between SA and cognitive performance. Longer term studies are needed to clarify temporal relationships and potential treatment effects.