中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (on line): 1-6.

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Alzheimer’s disease with sleep insufficiency: a cross-sectional study on correlations among clinical characteristics, orexinergic system and blood-brain barrier

  

  • 出版日期:2023-01-01 发布日期:2022-08-02

Peng Guo1 , Wen-Jing Zhang2 , Teng-Hong Lian1 , Wei-Jiao Zhang2 , Ming-Yue He2 , Ya-Nan Zhang3 , Yue Huang2, 4, 5, Du-Yu Ding2 , Hui-Ying Guan2 , Jing-Hui Li2 , Dan-Ning Li2 , Dong-Mei Luo2 , Wei-Jia Zhang2 , Hao Yue2 , Xiao-Min Wang6 , Wei Zhang1, 5, 7, 8, *   

  1. 1 Center for Cognitive Neurology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 2 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 3 Department of Blood Transfusion, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 4 Department of Pharmacology, School of Medical Sciences, Faculty of Medicine & Health, UNSW Sydney, Australia; 5 China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 6 Department of Physiology, Capital Medical University, Beijing, China; 7 Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, China; 8 Beijing Key Laboratory on Parkinson Disease, Beijing, China
  • Online:2023-01-01 Published:2022-08-02
  • Contact: Wei Zhang, MD, ttyyzw@163.com.
  • Supported by:
    This work was supported by The National Key Research and Development Program of China (2016YFC1306300, 2016YFC1306000); The National Key R&D Program of China-European Commission Horizon 2020 (2017YFE0118800-779238); The National Natural Science Foundation of China (81970992, 81571229, 81071015, 30770745); Capital’s Funds for Health Improvement and Research (CFH) (2022-2-2048); The Key Technology R&D Program of Beijing Municipal Education Commission (kz201610025030); The Natural Science Foundation of Beijing, China (7082032), The Key Project of Natural Science Foundation of Beijing, China (4161004); Capital Clinical Characteristic Application Research (Z121107001012161); Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing (JJ2018-48); High Level Technical Personnel Training Project of Beijing Health System, China (2009-3-26); Excellent Personnel Training Project of Beijing, China (20071D0300400076); Important National Science & Technology Specific Projects (2011ZX09102-003-01); Beijing Healthcare Research Project, China (JING-15-2); Basic-Clinical Research Cooperation Funding of Capital Medical University, China (2015-JL-PT-X04, 10JL49, 14JL15); Natural Science Foundation of Capital Medical University, Beijing, China (PYZ2018077) ; Youth Research Funding, Beijing Tiantan Hospital, Capital Medical University, China (2015-YQN-14, 2015-YQN-15, 2015-YQN-17).

摘要:

Abstract: Sleep disorders is common in AD patients. However, the correlations among clinical characteristics, orexinergic system and blood-brain barrier (BBB) in Alzheimer’s disease (AD) with sleep insufficiency (SI) patients remain unclear yet. Here, we enrolled a total of 50 AD patients. 19 cases with sleep duration ≤ 6 hours and 31 cases with sleep duration > 6 hours were divided into AD with SI (AD-SI) group and AD with no SI (AD-nSI) group, the ages of AD patients were 63.19 ± 10.09 and 61.58 ± 8.54 years old, as well as 18 males and 10 males of AD patients were recruited for AD-nSI and AD-SI groups, respectively. Demographic variables were collected, and clinical manifestations of cognitive function, neuropsychiatric symptoms and activities of daily livings were evaluated. The levels of orexinergic system and BBB factors in cerebrospinal fluid (CSF) from AD-SI and AD-nSI groups were measured. The correlations among above variables were analyzed. The results from this study SI is common in AD patients. The prolonged sleep latency and increased wakefulness are associated with SI. SI significantly impairs overall cognitive and multiple cognitive domains. The mechanisms underlying AD-SI include significant upregulation of orexinergic system indicated by the elevations of both orexin A and orexin B in CSF, and destruction of BBB reflected by the increase of MMP-3 in CSF, which precipitate each other and accelerate the progression of AD.

Key words: Alzheimer’s disease, sleep insufficiency, clinical characteristics, cognitive function, neuropsychiatric symptoms, orexinergic system, blood-brain barrier, matrix metalloproteinases, MMP-3, cerebrospinal fluid