Impaired glymphatic drainage underlying obstructive sleep apnea is associated with cognitive dysfunction

Abstract

Obstructive sleep apnea (OSA) is highly prevalent but easily undiagnosed and is an independent risk factor for cognitive impairment. However, it remains unclear how OSA is linked to cognitive impairment. In the present study, we found the correlation between morphological changes of perivascular spaces (PVSs) and cognitive impairment in OSA patients. Moreover, we developed a novel set of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) methods to evaluate the fluid dynamics of glymphatic drainage system. We found that the inflow and outflow parameters of the glymphatic drainage system in patients with OSA were obviously changed, indicating impairment of glymphatic drainage due to excessive perfusion accompanied with deficient drainage in OSA patients. Moreover, parameters of the outflow were associated with the degree of cognitive impairment, as well as the hypoxia level. In addition, continuous positive airway pressure (CPAP) enhances performance of the glymphatic drainage system after 1 month treatment in OSA patients. We proposed that ventilation improvement might be a new strategy to ameliorate the impaired drainage of glymphatic drainage system due to OSA-induced chronic intermittent hypoxia, and consequently improved the cognitive decline.

A Systematic Review and Meta-Analysis of Automated Methods for Quantifying Enlarged Perivascular Spaces in the Brain

“…The relationship between sleep and PVS burden was explored in eight studies (Berezuk et al, 2015; Lysen et al, 2022; Piantino et al, 2021; Aribisala et al, 2023; Hicks et al, 2023; Soitgu et al, 2023; Wang et al, 2023; Shih et al, 2023), with all except one (Hicks et al, 2023) identifying an association between at least one metric of sleep and PVS burden. Berezuk et al, (2015) and Lysen et al, (2022) reported a negative correlation between both sleep efficiency and PVS burden.…”

Treatment of hypertension and obstructive sleep apnea counteracts cognitive decline in common neurocognitive disorders in diagnosis-related patterns

“…New diffusion tensor imaging studies using analysis along perivascular space (APLS) as measure of glymphatic functioning link both AH 102 and OSA 103 to glymphatic impairment. A recent study employing dynamic contrast enhanced MRI in OSA patients revealed enlarged perivascular spaces, lateral ventricles and disturbed glymphatic flow as well as cognitive deficits measured by MMST and MoCA 104 . After 1 month of CPAP glymphatic function of OSA patients improved, thus emphasizing the need of treating OSA as a risk factor for dementia/NCD.…”

Positive airway pressure improves amnestic mild cognitive impairment in patients diagnosed with obstructive sleep apnoea hypopnoea syndrome. A review of the evidence

“…The importance of glymphatic drainage was demonstrated by Wang et al [40]. They found enlarged perivascular spaces in the bilateral frontal cortex and basal ganglia in OSAHS patients and even more prominently so in the severely hypoxic OSAHS patients.…”

“…Search term PubMed ("Mild cognitive impairment" OR "cognitive decline" OR "cognitive dysfunction" OR "mild cognitive deficit" OR "Alzheimer disease" OR AD OR amyloid OR "MCI" OR "amnestic mild cognitive impairment" OR "degenerative disease" OR "amyloid precursor protein A total of 45 studies were found. Of the 45, 15 studies discussed the hypothesised glymphatic system in relation to sleep [11,12,[23][24][25][26][27][28][29][30][31][32][33][34][35], 5 studies assessed the impact of PAP on brain fluid diffusivity in patients with OSAHS [36][37][38][39][40], 4 studies assessed the influence of PAP treatment on the level of AD biomarkers [29,31,41,42], 11 studies measured the impact of PAP treatment on cognitive function in OSAHS [1,4,14,[43][44][45][46][47][48][49][50] and 10 studies measured the impact of PAP treatment on cognitive function in OSAHS and aMCI/AD [7,8,17,20,21,[51][52][53][54]…”