Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study. American journal of respiratory and critical care medicine RATIONALE:Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. OBJECTIVES:To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. METHODS:Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid β was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. MEASUREMENTS AND MAIN RESULTS:We found that severity of OSA indices (AHIall [F = 4.26; P < 0.05] and AHI4% [F = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in AD-mask (Alzheimer's disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F = 2.96, P = 0.09; and F = 2.32, not significant, respectively). CONCLUSIONS:In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly. 10.1164/rccm.201704-0704OC

Obstructive sleep apnea may induce orexinergic system and cerebral β-amyloid metabolism dysregulation: is it a further proof for Alzheimer's disease risk? Liguori Claudio,Mercuri Nicola Biagio,Nuccetelli Marzia,Izzi Francesca,Cordella Alberto,Bernardini Sergio,Placidi Fabio Sleep medicine BACKGROUND:Obstructive Sleep Apnea (OSA) is associated with pathological changes of cerebral β-amyloid dynamics. Orexin has been demonstrated interfering with β-amyloid metabolism in Alzheimer's Disease (AD) pathology. The present study investigated cerebrospinal-fluid (CSF) β-amyloid (Aβ), β-amyloid (Aβ) and orexin levels in OSA patients compared to AD patients and controls. METHODS:OSA and AD patients were included in this study and compared to a group of controls. Patients and controls underwent lumbar puncture for the assessment of CSF Aβ, Aβ, tau proteins, orexin levels, and polysomnography to measure nocturnal sleep architecture. RESULTS:20 OSA patients, 20 AD patients, and 15 controls were included in our study. OSA patients showed higher CSF orexin levels than AD patients and controls, and AD patients showed higher CSF orexin levels than controls. Moreover, CSF Aβ and Aβ were lower in OSA patients than controls, but higher in OSA patients compared to AD patients. However, AD patients showed lower CSF Aβ levels but comparable CSF Aβ levels than controls. Sleep macrostructure was similarly altered in OSA and AD patients compared to controls. Finally, the apnea-hypopnea index (AHI) was related to the ratio Aβ/Aβ and CSF orexin levels in OSA patients. CONCLUSION:This study proved the alteration of CSF orexin levels and β-amyloid isoforms 40 and 42 in OSA patients. We suppose that sleep disruption and intermittent hypoxia, the two core features of OSA, may induce orexinergic system and cerebral β-amyloid metabolism dysregulation. This evidence further supports the current hypothesis that OSA may possibly start AD neuropathological processes. 10.1016/j.sleep.2019.01.003