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Severe sleep apnoea associated with white matter hyperintensities

Presented by
Dr Diego Carvalho, Mayo Clinic, MN, USA
AAN 2023

Reduced slow-wave sleep (SWS) and severe obstructive sleep apnoea (OSA) were associated with a higher burden of white matter hyperintensities (WMH) in a study in predominantly cognitively unimpaired, older adults. Sleep apnoea and sleep, in general, may be a target to prevent vascular contributions to cognitive impairment and dementia (VCID).

WMH are a known marker of vascular contributions to VCID in the elderly. OSA is highly prevalent among the elderly (15–65% in the community) and has been associated with mild cognitive impairment, dementia, stroke, and an increase in WMH. “There is still uncertainty about the sleep characteristics associated with WMH and associated cerebrovascular disease," said the study presenter, Dr Diego Carvalho (Mayo Clinic, MN, USA). His clinic has been conducting the population-based Mayo Clinic Study of Aging (MCSA) since 2004. The MCSA is a large-scale prospective population-based study examining the incidence, prevalence, and risk factors of mild cognitive impairment and dementia. Dr Carvalo and his group selected 140 participants without dementia who underwent at least 1 brain MRI and polysomnography (PSG) as part of their clinical care. The study aimed to determine whether PSG parameters are associated with neuroimaging biomarkers of cerebrovascular disease related to white matter integrity in older adults with OSA [1].

The 140 participants had WMH from fluid-attenuated inversion recovery (FLAIR)-MRI; 103 had fraction anisotropy (FA) of the genu of the corpus callosum (genu FA) from diffusion MRI. The mean age was 73 years and the median interval between MRI imaging and PSG was 1.74 (0.9–3.2) years. For every 10-point decrease in N3%, there was a 0.058 increase in the log of WMH (95% CI 0.006–0.111; P=0.030) and 0.006 decrease in the log of genu FA (95% CI -0.012 to -0.0002; P=0.042). “The effect size is about the same as that of 2.5 to 3 years of ageing,” commented Dr Carvalo. In a posthoc analysis, participants with severe OSA had a higher WMH burden than those with mild sleep apnoea after matching for age, sex, and N3%, with a median WMH of 0.0073 versus 0.0067 (P=0.039), respectively.

Dr Carvalo stressed that no causation could be inferred from the presented cross-sectional data, but he did speculate on mechanisms of action. He suggested that lowering slow-wave sleep caused by OSA may induce axonal injury, dysmyelination, and perhaps accumulation of metabolic waste, thus contributing to WMH. He concluded that this study supports for the link between sleep depth/fragmentation, intermittent hypoxia, and vascular contributions to cognitive impairment and dementia.

  1. Carvalho D, et al. Reduced Slow-Wave Sleep and Severe Sleep Apnea are Associated with Neuroimaging Biomarkers of Cerebrovascular Disease. S6.004, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.

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