Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study

• Published in: American journal of respiratory and critical care medicine Vol. 197; no. 7; pp. 933 - 943
• Main Authors: Sharma, Ram A, Varga, Andrew W, Bubu, Omonigho M, Pirraglia, Elizabeth, Kam, Korey, Parekh, Ankit, Wohlleber, Margaret, Miller, Margo D, Andrade, Andreia, Lewis, Clifton, Tweardy, Samuel, Buj, Maja, Yau, Po L, Sadda, Reem, Mosconi, Lisa, Li, Yi, Butler, Tracy, Glodzik, Lidia, Fieremans, Els, Babb, James S, Blennow, Kaj, Zetterberg, Henrik, Lu, Shou E, Badia, Sandra G, Romero, Sergio, Rosenzweig, Ivana, Gosselin, Nadia, Jean-Louis, Girardin, Rapoport, David M, de Leon, Mony J, Ayappa, Indu, Osorio, Ricardo S
• Format: Journal Article Publication
• Language: English
• Published: United States American Thoracic Society 01.04.2018
• Subjects: Aged; Aged, 80 and over; Alzheimer's disease; Alzheimer, Malaltia d; Amyloid beta-Peptides - cerebrospinal fluid; amyloid burden; Apnea; Apolipoproteins; Brain - metabolism; cerebrospinal fluid amyloid beta; Ciències de la salut; Cognitive ability; cognitive impairment; Dementia; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Hypertension; Hypoxia; Longitudinal Studies; Male; Medical imaging; Medicina; Middle age; Middle Aged; Mortality; Neurosciences; Neurovetenskaper; NMR; Nuclear magnetic resonance; obstructive sleep apnea; Older people; Original; Pathogenesis; Pittsburgh compound B positron emission tomography scan; Positron-Emission Tomography; Prospective Studies; Severity of Illness Index; Sleep apnea; Sleep apnea syndromes; Sleep Apnea, Obstructive - metabolism; Síndromes d'apnea del son; Àrees temàtiques de la UPC; United States > US; Pittsburgh Pennsylvania; obstructive sleep apnea; cerebrospinal fluid amyloid β; cognitive impairment; Pittsburgh compound B positron emission tomography scan; amyloid burden
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.201704-0704oc

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. To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. 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. 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). 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.