Carvalho, D Z

ABSTRACT 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.

Abstract Introduction Sleepiness has been associated with functional and cognitive decline, and may present with excessive daytime sleepiness (EDS) and/or increased sleep duration. We investigated whether sleepiness and changes in sleep patterns are associated with FDG-PET levels in wake-promoting regions. Methods From the Mayo Clinic Study of Aging cohort, we identified 373 cognitively-unimpaired middle-aged and older adults (mean +/- s.d. 66.1 +/- 13.2 yo) who underwent FDG-PET. EDS was defined as ESS score &gt;=10. Changes in sleep patterns (sleeping more, less, or no change) were assessed using question #16 of the Beck Depression Inventory-2. We used probabilistic maps to create regions of interest (ROIs): the locus coeruleus (LC), posterior lateral hypothalamus (PLH), and the basal forebrain divided in 1) medial septum/diagonal band of Broca (MS/DB) and 2) nucleus basalis of Meynert (nbM). FDG-PET levels were referenced to the pons (SUVR). In this cross-sectional analysis, we fit linear models to assess the association between EDS and changes in sleeping patterns with FDG SUVR in in each ROI, while controlling for age, sex, education, BMI, witnessed apneas, and cardiovascular risk factors. Results 10.5% had EDS, 15% reported sleeping more and 21% reported sleeping less than usual. 30.7% of participants with EDS reported sleeping more, 25.6% less, and 43.5% the same. EDS was associated with an elevation in FDG-PET SUVR in the MS/DB region (.035 [95% CI .008; .063], p=.012), while sleeping more was associated with a decrease in FDG-PET SUVR in the same region (-.027 [95%CI -.052; -.002], p=.036). Sleeping less was associated with an increase in FDG-PET SUVR in the PLH (.021 [95% CI .005; .03], p=.019). No associations were found in other ROIs. Conclusion Our results suggest that sleepiness and changes in sleep patterns in cognitively-unimpaired middle-aged and older adults were associated with measurable metabolic changes in areas of the brain involved in sleep and wakefulness. Further research should clarify whether these findings could represent different phenotypes of sleepiness with potential diagnostic and prognostic implications. Support NIA/NIH