Biomarkers of dementia in obstructive sleep apnea

Abstract

Epidemiologic and mechanistic evidence is increasingly supporting the notion that obstructive sleep apnea is a risk factor for dementia. Hence, the identification of patients at risk of cognitive decline due to obstructive sleep apnea may significantly improve preventive strategies and treatment decision-making. Cerebrospinal fluid and blood biomarkers obtained through genomic, proteomic and metabolomic approaches are improving the ability to predict incident dementia. Therefore, fluid biomarkers have the potential to predict vulnerability to neurodegeneration in individuals with obstructive sleep apnea, as well as deepen our understanding of pathophysiological processes linking obstructive sleep apnea and dementia. Many fluid biomarkers linked to Alzheimer's disease and vascular dementia show abnormal levels in individuals with obstructive sleep apnea, suggesting that these conditions share common underlying mechanisms, including amyloid and tau protein neuropathology, inflammation, oxidative stress, and metabolic disturbances. Markers of these processes include amyloid-β, tau proteins, inflammatory cytokines, acute-phase proteins, antioxydants and oxidized products, homocysteine and clusterin (apolipoprotein J). Thus, these biomarkers may have the ability to identify adults with obstructive sleep apnea at high risk of dementia and provide an opportunity for therapeutic intervention. Large cohort studies are necessary to establish a specific fluid biomarker panel linking obstructive sleep apnea to dementia risk.

Keywords: Alzheimer's disease; Cerebrospinal fluid; Genomics; Inflammation; Metabolomics; Mild cognitive impairment; Oxidative stress; Proteomics; Sleep-disordered breathing; Vascular dementia.

Fig. 1.. Potential mechanisms linking obstructive sleep apnea (OSA) to the development of dementia.

Recent evidence suggests that the hallmarks of OSA, i.e., hypoxia and disturbed sleep, may directly contribute to the development of the neuropathology of Alzheimer’s disease (AD) in the brain. Secondly, OSA may indirectly be involved in the incidence of dementia via its role in the development of other risk factors. Of note, OSA is a risk factor for stroke and cerebrovascular events, which in turn are a core pathophysiological component of vascular dementia. Moreover, OSA may also indirectly contribute to the development of dementia via secondary pathological mechanisms involved in neurodegeneration, such as oxidative stress. These mechanisms may also interact with concomitant AD neuropathology or other risk factors. Dotted arrows represent potential bidirectional relationships. The presence of amyloid-β (Aβ) deposition in the brain has been associated with sleep impairments as well as pathological mechanisms such as inflammation. Other risk factors, such as obesity, are associated with the development of OSA and other pathological mechanisms, such as inflammation.