Sleep mediates the association between homocysteine and oxidative status in mild cognitive impairment

• Published in: Scientific reports Vol. 7; no. 1; pp. 7719 - 9
• Main Authors: Sanchez-Espinosa, Mayely P., Atienza, Mercedes, Cantero, Jose L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.08.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1385/519; 631/378/2611; Aged; Alzheimer's disease; Amyloid; Antioxidants; Biomarkers; Brain Mapping; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Cognition; Cognitive ability; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - etiology; Cognitive Dysfunction - metabolism; Cognitive Dysfunction - psychology; Disease Susceptibility; Female; Homocysteine; Homocysteine - metabolism; Humanities and Social Sciences; Humans; Magnetic Resonance Imaging - methods; Male; Middle Aged; multidisciplinary; Neurodegenerative diseases; Oxidative Stress; Risk factors; Science; Science (multidisciplinary); Sleep; Therapeutic applications
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-08292-4

Tremendous progress has been made over the last few years in understanding how sleep and amyloid-β (Aβ) cooperate to speed up the progression of Alzheimer’s disease (AD). However, it remains unknown whether sleep deficits also interact with other risk factors that exacerbate the pathological cascade of AD. Based on evidence showing that higher levels of homocysteine (HCY) and sleep loss increase oxidative damage, we here investigate whether the relationship between HCY and total antioxidant capacity (TAC) is mediated by changes in objective sleep in healthy older (HO, N = 21) and mild cognitive impairment (MCI, N = 21) subjects. Results revealed that reduced TAC levels in MCI was significantly correlated with increased HCY, shorter sleep duration, lower sleep efficiency, and reduced volume of temporal regions. However, only the HCY-TAC association showed diagnostic value, and this relationship was mediated by poorer sleep quality in MCI patients. We further showed that HCY-related cerebral volume loss in MCI depended on the serial relationship between poorer sleep quality and lower TAC levels. These findings provide novel insights into how impaired sleep may contribute to maintain the relationship between HCY and oxidative stress in prodromal AD, and offer empirical foundations to design therapeutic interventions aimed to weaken this link.