Severe Obstructive Sleep Apnea and Increased Cortical Amyloid-β Deposition

Article type: Research Article

Authors: Ylä-Herttuala, Salla^{a; b} | Hakulinen, Mikko^{c; d} | Poutiainen, Pekka^e | Laitinen, Tiina M.^{c; d} | Koivisto, Anne M.^{f; g; h; i} | Remes, Anne M.^{j; k} | Hallikainen, Merja^g | Lehtola, Juha-Matti^{f; g} | Saari, Toni^{g; l} | Korhonen, Ville^{f; g} | Könönen, Mervi^{a; d; m} | Vanninen, Ritva^{m; n} | Mussalo, Hanna^{c; o} | Laitinen, Tomi^{c; o} | Mervaala, Esa^{a; b}

Affiliations: [a] Department of Clinical Neurophysiology, Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland | [b] Department of Clinical Neurophysiology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland | [c] Department of Clinical Physiology and Nuclear Medicine, Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland | [d] Department of Applied Physics, University of Eastern Finland, Kuopio, Finland | [e] Department of Cyclotron and Radiopharmacy, Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland | [f] Department of Neurology, Kuopio University Hospital, Kuopio, Finland | [g] Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland | [h] Department of Neurosciences, University of Helsinki, Helsinki, Finland | [i] Department of Geriatrics, Helsinki University Hospital, Helsinki, Finland | [j] Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland | [k] Medical Research Center, Oulu University Hospital, Oulu, Finland | [l] Department of Educational Sciences and Psychology, Philosophical Faculty, University of Eastern Finland, Joensuu, Finland | [m] Department of Radiology, Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, Finland | [n] Department of Radiology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland | [o] Department of Clinical Physiology and Nuclear Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland

Correspondence: [*] Correspondence to: Esa Mervaala, MD, PhD, Professor of Clinical Neurophysiology, Chief Physician, Imaging Center, Kuopio University Hospital and University of Eastern Finland, POB 100, 70029 KYS, Kuopio, Finland. Tel.: +358 44 7113245; Fax: +358 17 173244; E-mail: [email protected].

Abstract: Background:The suggested association between severe obstructive sleep apnea (OSA) and risk of Alzheimer’s disease (AD) needs further study. Only few recent reports exist on associations between brain amyloid-β (Aβ) burden and severe OSA in middle-aged patients. Objective:Examine the possible presence of cortical Aβ accumulation in middle-aged patients with severe OSA. Methods:We performed detailed multimodal neuroimaging in 19 cognitive intact patients (mean 44.2 years) with severe OSA (Apnea-Hypopnea Index >30 h–1). Known etiological factors for possible Aβ accumulation were used as exclusion criteria. Aβ uptake was studied with [11C]-PiB-PET, glucose metabolism with [18F]-FDG-PET, and structural imaging with 3.0T MRI. Results:When analyzed individually, in [11C]-PiB-PET a substantial number (∼32%) of the patients exhibited statistically significant evidence of increased cortical Aβ uptake based on elevated regional Z-score values, mostly seen bilaterally in the precuneus and posterior cingulum regions. Cortical glucose hypometabolism in [18F]-FDG-PET was seen in two patients. MRI did not show structural changes suggestive of AD-related pathology. Conclusion:Increased [11C]-PiB uptake was seen in middle-aged cognitively intact patients with severe OSA. These findings are similar to those described in cognitive unimpaired older OSA patients. The changes in cortical Aβ uptake suggest that severe OSA itself may predispose to alterations related to AD already in middle-age. Aβ clearance may be compromised without simultaneous evidence of metabolic or structural alterations. The results emphasize the importance of early diagnostics and proper treatment of severe OSA in cognitively intact middle-aged subjects, possibly diminishing the individual risk for later cognitive dysfunction.

Keywords: Alzheimer’s disease, amyloid, PET, sleep apnea

DOI: 10.3233/JAD-200736

Journal: Journal of Alzheimer's Disease, vol. 79, no. 1, pp. 153-161, 2021