Ram A Sharma1, Andrew W Varga2, Omonigho M Bubu3, Elizabeth Pirraglia1, Korey Kam2, Ankit Parekh4, Margaret Wohlleber1, Margo D Miller1, Andreia Andrade1, Clifton Lewis1, Samuel Tweardy1, Maja Buj1, Po L Yau1, Reem Sadda5, Lisa Mosconi1, Yi Li1, Tracy Butler1, Lidia Glodzik1, Els Fieremans6, James S Babb6, Kaj Blennow7,8, Henrik Zetterberg7,8,9, Shou E Lu10, Sandra G Badia11,12,13, Sergio Romero14,15, Ivana Rosenzweig16,17, Nadia Gosselin18,19, Girardin Jean-Louis20, David M Rapoport2, Mony J de Leon1, Indu Ayappa2, Ricardo S Osorio1. 1. 1 Center for Brain Health, Department of Psychiatry, and. 2. 2 Division of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. 3. 3 Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, Florida. 4. 4 College of Engineering, The University of Iowa, Iowa City, Iowa. 5. 5 Harlem Hospital-Columbia University Medical Center, New York, New York. 6. 6 Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, New York. 7. 7 Institute of Neuroscience and Psychiatry, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 8. 8 Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 9. 9 Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, United Kingdom. 10. 10 Department of Biostatistics, Rutgers School of Public Health, Piscataway, New Jersey. 11. 11 Sleep Unit, Respiratory Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 12. 12 Institute for Biomedical Research Sant Pau, CIBERSAM, Barcelona, Spain. 13. 13 Department of Clinical Psychology and Psychobiology, University of Barcelona, Barcelona, Spain. 14. 14 Biomedical Engineering Research Centre, Department of Automatic Control, Universitat Politècnica de Catalunya, Barcelona, Spain. 15. 15 CIBER de Bioingeniería, Biomateriales y Nanomedicina, Barcelona, Spain. 16. 16 Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. 17. 17 Sleep Disorders Centre, Guy's and St. Thomas' Hospital, GSTT NHS Trust, London, United Kingdom. 18. 18 Center for Advanced Research in Sleep Medicine, Hospital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada; and. 19. 19 Department of Psychology, Universite de Montreal, Montreal, Quebec, Canada. 20. 20 Center for Healthful Behavior Change, Division of Health and Behavior, Department of Population Health, New York University Langone Medical Center, New York, New York.
Abstract
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 [F1,88 = 4.26; P < 0.05] and AHI4% [F1,87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in ADPiB-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 (F1,28 = 2.96, P = 0.09; and F1,28 = 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.
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 [F1,88 = 4.26; P < 0.05] and AHI4% [F1,87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in ADPiB-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 (F1,28 = 2.96, P = 0.09; and F1,28 = 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.
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