Amyloid Burden in Obstructive Sleep Apnea

Article type: Research Article

Authors: Yun, Chang-Ho^{a; *} | Lee, Ho-Young^b | Lee, Seung Ku^c | Kim, Hyun^d | Seo, Hyung Suk^e | Bang, Seong Ae^b | Kim, Sang Eun^{b; f} | Greve, Douglas N.^g | Au, Rhoda^h | Shin, Chol^{c; i; 1} | Thomas, Robert J.^{j; 1}

Affiliations: [a] Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea | [b] Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea | [c] Institute of Human Genomic Study, Korea University Ansan Hospital, Ansan, Republic of Korea | [d] Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA | [e] Department of Radiology, Korea University Ansan Hospital, Ansan, Republic ofKorea | [f] Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, and Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon, Republic of Korea | [g] Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA | [h] Departments of Anatomy and Neurobiology, Neurology and Epidemiology, Schools of Medicine and Public Health, Boston University, Boston, MA, USA | [i] Department of Internal Medicine, Division of Pulmonary, Sleep and Critical Care Medicine, Korea University Ansan Hospital, Ansan, Republic ofKorea | [j] Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, USA

Correspondence: [*] Correspondence to: Chang-Ho Yun, MD, PhD, Department of Neurology, Bundang Clinical Neuroscience Institute, Seoul National University Bundang Hospital; 82 Gumi-ro 173 Beon-gil, Bundang, Seongnam, Gyeonggi 13620, Republic of Korea. Tel.: +82 31 787 7472; Fax: +82 31 787 4059; E-mail: ych333@gmail.com.

Note: [1] These authors contributed equally to this work as senior authors.

Abstract: To test the hypothesis that excessive amyloid deposition is a biological link between obstructive sleep apnea (OSA) and Alzheimer’s disease, we determined whether OSA increases cerebral amyloid burden, relative to controls, using Pittsburgh Compound B (PiB) PET imaging. The subjects were adult participants (age 50–65 years) from the Korean Genome and Epidemiology Study. Polysomnography, brain MRI including 3D images, and a detailed neuro-cognitive function test battery were done in 2011–2012. Nineteen OSA subjects (Apnea–Hypopnea Index [AHI] ≥15/h, 21.2±5.1/h; age 58.5±4.1 years; 9 male) and 19 controls (AHI 1.8±1.3/h; age 58.5±4.2 years; 9 male) underwent 60-min dynamic 11C-PiB PET. All subjects were right-handed with normal cognitive function and brain MRI. Controls were matched by age, gender, education, and APOE genotype. A voxel-wise comparison of PiB-PET images between the two groups was performed after spatial and count normalization with cerebellar gray matter as a reference. Covariates included the status of sleep duration, hypertension, diabetes, body mass index, exercise, depressive mood, smoking, and alcohol drinking. Cortical thickness on 3D MRI was also measured and compared between the two groups. The OSA group showed a higher PiB deposition in the right posterior cingulate gyrus and right temporal cortex (corrected p < 0.05). There was no area of higher uptake in the control compared with OSA. Regional differences in cortical thickness were not significant. The study suggests that OSA accelerates amyloid deposition and may contribute to the development or progression of Alzheimer’s disease.

Keywords: Alzheimer’s disease, cerebral cortex, dementia, positron-emission tomography, sleep

DOI: 10.3233/JAD-161047

Journal: Journal of Alzheimer's Disease, vol. 59, no. 1, pp. 21-29, 2017