Associations between risk of Alzheimer's disease and obstructive sleep apnea, intermittent hypoxia, and arousal responses: A pilot study

Cheng-Yu Tsai; Sheng-Ming Wu; Yi-Chun Kuan; Yin-Tzu Lin; Chia-Rung Hsu; Wen-Hua Hsu; Yi-Shin Liu; Arnab Majumdar; Marc Stettler; Chien-Ming Yang; Kang-Yun Lee; Dean Wu; Hsin-Chien Lee; Cheng-Jung Wu; Jiunn-Horng Kang; Wen-Te Liu

doi:10.3389/fneur.2022.1038735

Associations between risk of Alzheimer's disease and obstructive sleep apnea, intermittent hypoxia, and arousal responses: A pilot study

Front Neurol. 2022 Nov 30:13:1038735. doi: 10.3389/fneur.2022.1038735. eCollection 2022.

Authors

Cheng-Yu Tsai¹, Sheng-Ming Wu^{2

3}, Yi-Chun Kuan^{4

5

6

7

8}, Yin-Tzu Lin⁹, Chia-Rung Hsu⁵, Wen-Hua Hsu¹⁰, Yi-Shin Liu¹⁰, Arnab Majumdar¹, Marc Stettler¹, Chien-Ming Yang¹¹, Kang-Yun Lee^{2

3}, Dean Wu^{4

5

6

7

8}, Hsin-Chien Lee¹², Cheng-Jung Wu¹³, Jiunn-Horng Kang^{14

15

16}, Wen-Te Liu^{3

4

10

14}

Affiliations

¹ Department of Civil and Environmental Engineering, Imperial College London, London, United Kingdom.
² Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
⁴ Sleep Center, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
⁵ Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
⁶ Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁷ Taipei Neuroscience Institute, Taipei Medical University, Taipei, Taiwan.
⁸ Dementia Center, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
⁹ Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
¹⁰ School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
¹¹ Department of Psychology, National Chengchi University, Taipei, Taiwan.
¹² Department of Psychiatry, Taipei Medical University Hospital, Taipei, Taiwan.
¹³ Department of Otolaryngology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
¹⁴ Research Center of Artificial Intelligence in Medicine, Taipei Medical University, Taipei, Taiwan.
¹⁵ Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei, Taiwan.
¹⁶ Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.

Abstract

Objectives: Obstructive sleep apnea (OSA) may increase the risk of Alzheimer's disease (AD). However, potential associations among sleep-disordered breathing, hypoxia, and OSA-induced arousal responses should be investigated. This study determined differences in sleep parameters and investigated the relationship between such parameters and the risk of AD.

Methods: Patients with suspected OSA were recruited and underwent in-lab polysomnography (PSG). Subsequently, blood samples were collected from participants. Patients' plasma levels of total tau (T-Tau) and amyloid beta-peptide 42 (Aβ₄₂) were measured using an ultrasensitive immunomagnetic reduction assay. Next, the participants were categorized into low- and high-risk groups on the basis of the computed product (Aβ₄₂ × T-Tau, the cutoff for AD risk). PSG parameters were analyzed and compared.

Results: We included 36 patients in this study, of whom 18 and 18 were assigned to the low- and high-risk groups, respectively. The average apnea-hypopnea index (AHI), apnea, hypopnea index [during rapid eye movement (REM) and non-REM (NREM) sleep], and oxygen desaturation index (≥3%, ODI-3%) values of the high-risk group were significantly higher than those of the low-risk group. Similarly, the mean arousal index and respiratory arousal index (R-ArI) of the high-risk group were significantly higher than those of the low-risk group. Sleep-disordered breathing indices, oxygen desaturation, and arousal responses were significantly associated with an increased risk of AD. Positive associations were observed among the AHI, ODI-3%, R-ArI, and computed product.

Conclusions: Recurrent sleep-disordered breathing, intermittent hypoxia, and arousal responses, including those occurring during the NREM stage, were associated with AD risk. However, a longitudinal study should be conducted to investigate the causal relationships among these factors.

Keywords: Alzheimer's disease; amyloid beta-peptide 42; arousal response; obstructive sleep apnea; sleep-disordered breathing; total tau.