Mitochondrial dysfunction is associated with cognitive impairment in adults with OSA without dementia

• Published in: Sleep medicine 2024-07, Vol.119, p.234-243
• Main Authors: Li, Mengfan, Shen, Tengqun, Yao, Ran, Sun, Hairong, Liu, Xiaoxiao, Li, Zhenguang, Zhang, Jinbiao
• Format: Article
• Language: English
• Subjects: Aged; Cognitive Dysfunction - etiology; Cognitive impairment; Female; Humans; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Mitochondria - metabolism; Mitochondrial dysfunction; Mitochondrial Proteins; Neuron-derived exosome; Neuropsychological Tests - statistics & numerical data; Obstructive sleep apnea; Polysomnography; Sleep Apnea, Obstructive - complications; Sleep Apnea, Obstructive - physiopathology
• ISSN: 1389-9457; 1878-5506
• DOI: 10.1016/j.sleep.2024.04.035

Increased reactive oxygen species associated with loss of mitochondrial function affect synaptic activity, which is an important mechanism underlying cognitive decline. This study assesses the role of mitochondrial proteins in neuron-derived exosomes (NDEs) on cognitive impairment in patients with obstructive sleep apnea (OSA) without dementia. Analyses were conducted in 268 study participants with complete polysomnography data, cognitive tests, and important clinical data available. NDEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of mitochondrial proteins, i.e., humanin and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), and synaptic protein, i.e., neurogranin (NRGN). A mediation analysis of the relationship between sleep parameters and cognition was performed using humanin, MOTS-c, and NRGN values as a mediating factor. Twenty-two patients with moderate to severe OSA who received CPAP therapy were followed up, and humanin, MOTS-c and NRGN levels were reassessed after 1 year of treatment. All participants were divided into the OSA + MCI group (n = 91), OSA-MCI group (n = 89), MCI group (MCI without OSA) (n = 38) and control group (normal cognitive state without OSA) (n = 50). The mean CD63-normalized NDE levels of humanin, MOTS-c, and NRGN in the OSA + MCI group were higher than those in the OSA-MCI and control groups. The NDE levels of humanin, MOTS-c, and NRGN in the MCI group were lower than those in controls. The odds of cognitive impairment in patients with OSA were higher with higher NDE levels of humanin, MOTS-c, and NRGN (odds ratio (OR): 2.100, 95 % confidence interval (CI): 1.646–2.679, P