【作者】 王晓彤；

【导师】 谭兰；

【作者基本信息】 青岛大学 ， 神经病学， 2021， 硕士

【摘要】 研究目的:在中老年人群中,睡眠紊乱是一种非常常见的症状,而且在神经退行性病变中扮演着重要的角色,特别是突触核蛋白病。睡眠紊乱是突触核蛋白病的临床前表现之一。突触核蛋白病是由脑内α-突触核蛋白(alpha-synuclein,α-syn)的异常沉积导致的,脑内的过度沉积的α-syn又可反映在脑脊液(cerebrospinal fluid,CSF)中总的α-syn下降上。然而截至目前,睡眠异常和CSF中α-syn之间的是否存在关联还没有相关研究和讨论,本研究便着眼于此。研究方法:本研究从“中国人阿尔茨海默病生物标记和生活方式研究”(the Chinese Alzheimer’s Biomarker and Lifestyl E study,CABLE)这个数据库中纳入了536名认知正常的个体(人群的年龄在40到90岁之间)。纳入的人群均有CSF的生物标本和专门的睡眠评估数据。利用匹兹堡睡眠质量指数(Pittsburgh Sleep Quality Index,PSQI)评估纳入人群近一个月的睡眠行为,用酶联免疫吸附法(enzyme-linked immune-sorbent assay,ELISA)检测他们CSF中总α-syn的浓度,采用多元线性回归模型和多元非线性回归模型进行数据的分析和研究。结果:CSF中总的α-syn的含量与睡眠时间点和持续时间呈非线性关系。太早或太晚上床睡觉或是睡着的人的CSF中总α-syn水平较低。经过分析可知,个体上床睡觉及睡着最合适的时间点应该在晚上10点半左右(上床睡觉最适合的时间点是晚上10点26分,睡着的最合适的时间点是晚上10点40分)。除了睡眠时刻外,在该项研究中,夜间睡眠持续时间的长短也和CSF中α-syn的浓度呈现非线性关系。在睡眠持续时间过长或睡眠时间不足的个体中,我们发现受试者CSF中总α-syn含量较低。通过数据分析,得出的一个人最合适的睡眠时长是七个半小时左右(7.24小时)。除了以上倒U型关系之外,睡眠特征和CSF中α-syn是否存在着线性关联也被纳入了研究范畴。经过分析发现,通过PSQI量表评定的睡眠特征中(有序变量),整体睡眠质量较差(β=0.0621;P=0.0242)的个体、睡眠潜伏期(躺到床上到睡着的这段时间)延长(β=0.0415;P=0.0174)的个体以及睡眠效率较低(β=-0.0479;P=0.0033)的个体CSF中总α-syn含量也都会降低。然而在数据分析时并没有发现CSF中总α-syn含量与睡眠紊乱和日间功能障碍有明显的相关性。除此之外,本研究还分析了PSQI量表中原始数据(连续变量)和CSF中α-syn的线性关系,并且发现PSQI量表总分(β=-0.0122;P=0.0147)和具体的睡眠效率(β=0.0036;P=0.0017)都与CSF中α-syn浓度有关。睡眠总分越高的个体,睡眠质量越差,睡眠质量差和睡眠效率低的个体,他们的CSF中α-syn浓度都是降低的。结论及意义:在认知正常的健康的老年人中,较差的睡眠质量(例如较长的睡眠潜伏期,较低的睡眠效率,睡眠时间的过长和过短或是不合适的睡眠时间点)都会导致个体CSF中总α-syn水平降低。睡眠的监测和科学合理的安排睡眠或许可以为诊断和预防突触核蛋白病提供新的切入点和启发。更多还原

【Abstract】 Background: Sleep disorders as a preclinical symptom of synucleinopathies become more prevalent in older adults.Synucleinopathies might be caused by abnormal aggregation of alpha-synuclein in the brain,which were indicated by alpha-synuclein levels in cerebrospinal fluid.We aimed to investigate the association of sleep characteristics with alpha-synuclein in cerebrospinal fluid in older adults.Methods: Our study recruited 536 cognitively intact individuals(aged between 40 to90 years old)from the Chinese Alzheimer’s Biomarker and Lifestyl E study.Sleep behaviors were assessed by Pittsburgh Sleep Quality Index and total alpha-synuclein in cerebrospinal fluid was measured by enzyme-linked immune-sorbent assay.We used multiple linear and non-linear regression models for research.Results: Significant non-linear associations of alpha-synuclein in cerebrospinal fluid with sleep time and duration were revealed.According to the analysis,individuals who went to bed and fell asleep too early or late tended to have lower cerebrospinal fluid alpha-synuclein concentrations(reflection point for time to bed and fall asleep were 10:26p.m.and 10:40 p.m.).In addition to the sleep time,there was a nonlinear relationship between sleep duration and α-syn concentrations in cerebrospinal fluid.Lower alpha-synuclein in cerebrospinal fluid was also observed in individuals with either excessive or insufficient sleep duration(reflection point: 7.24 hours).Except for the nonlinear relationships,we also explored whether there were certain linear relationships between sleep characteristics and α-syn levels in cerebrospinal fluid.In the sleep characteristics(ordered variables)assessed by Pittsburgh Sleep Quality Index scale,overall poor sleep quality(β =-0.0621;P = 0.0242),long sleep latency(β =-0.0415;P =0.0174)and lower sleep efficiency(β =-0.0479;P = 0.0033)showed linear associations with lower cerebrospinal fluid alpha-synuclein levels,while other sleep characteristics showed non-significant associations with cerebrospinal fluid alpha-synuclein levels.Furthermore,we explored linear relationships between the original data(continuous variables)in Pittsburgh Sleep Quality Index scale and α-syn levels in cerebrospinal fluid.We found that the total score of Pittsburgh Sleep Quality Index(β =-0.0122;P = 0.0147)and specific sleep efficiency(β = 0.0036;P = 0.0017)were related to α-syn concentration in cerebrospinal fluid.The higher the total score of Pittsburgh Sleep Quality Index,the worse the sleep quality.The lower the sleep quality and sleep efficiency,the lower theα-syn concentration in cerebrospinal fluid.Conclusions: Poor sleep activities,such as longer sleep latency,lower sleep efficiency and excessive or insufficient sleep durations,were all associated with lower levels of alpha-synuclein in cerebrospinal fluid in older adults,which may provide a new insight into prevention of synucleinopathies.更多还原