摘要： 目的 探讨血浆促食欲素A水平与路易体痴呆核心临床症状的相关性。方法 共纳入2019年1月至2021年12月首都医科大学附属北京天坛医院诊断与治疗的51例路易体痴呆患者以及性别、年龄、受教育程度相匹配的46例认知功能正常对照者，采用简易智能状态检查量表（MMSE）和蒙特利尔认知评价量表（MoCA）评估整体认知功能、临床痴呆评价量表（CDR）评估痴呆严重程度、日常生活活动能力量表（ADL）评估日常生活活动能力、汉密尔顿抑郁量表17项（HAMD-17）评估抑郁严重程度、神经精神科问卷（NPI）评估精神行为，测定血浆食欲素A水平；单因素和多因素Logistic回归分析筛查路易体痴呆影响因素，Pearson相关分析和偏相关分析探究血浆促食欲素A与路易体痴呆核心临床症状的相关性，多因素线性逐步回归分析探究血浆促食欲素A与神经心理学测验的线性相关关系。结果 路易体痴呆患者MMSE（Z=-8.387，P=0.000）和MoCA（Z=-8.479，P=0.000）评分均低于对照者，CDR（Z=-9.072，P=0.000）、ADL（Z=-8.692，P=0.000）、HAMD-17（Z=-7.568，P=0.000）、NPI（Z=-8.270，P=0.000）评分和血浆促食欲素A水平（Z=-2.688，P=0.007）均高于对照者；核心临床症状中有波动性认知功能障碍和有帕金森综合征患者血浆促食欲素A水平低于无波动性认知功能障碍（Z=-2.172，P=0.030）和无帕金森综合征（Z=-1.981，P=0.048）患者。Logistic回归分析显示，饮酒史是避免发生路易体痴呆的独立保护因素（OR=0.278，95% CI： 0.095~0.808； P=0.019）；血浆促食欲素A水平升高是路易体痴呆的独立危险因素（OR=6.878，95% CI： 1.241~38.137； P=0.027）。相关分析显示，血浆促食欲素A水平仅与核心临床症状中帕金森综合征呈负相关（r=-0.322，P=0.043）。多因素线性逐步回归分析显示，血浆促食欲素A与神经心理学测验评分无线性相关关系（均P>0.05）。结论 路易体痴呆患者血浆促食欲素A水平高于认知功能正常老年人，血浆促食欲素A水平升高更易罹患路易体痴呆，但可降低核心临床症状中帕金森综合征的发生率，促食欲素能系统功能失调可能是路易体痴呆的潜在发生机制。

关键词: Lewy体病, 食欲素, 危险因素, Logistic模型

Abstract: Objective To analyze the correlations between plasma orexin-A and clinical manifestations of dementia with Lewy bodies (DLB). Methods A total of 51 patients with DLB from Beijing Tiantan hospital, Capital Medical University, and 46 sex, age and education matched controls were conducted from January 2019 to December 2021. Overall cognitive function was assessed by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), dementia severity was assessed by Clinical Dementia Rating Scale (CDR), activities of daily living was assessed by Activities of Daily Living Scale (ADL), depression severity was assessed by Hamilton Depression Rating Scale 17 (HAMD-17), neuropsychiatric symptoms was assessed by Neuropsychiatric Inventory (NPI), and plasma orexin-A level was measured. The univariate and multivariate Logistic regression analyses were used to screen influencing factors for DLB. Pearson and partial correlation analyses were used to explore the correlation between plasma orexin-A and core clinical features of DLB. Multivariate linear stepwise regression analysis was used to analyze the linear correlation between plasma orexin-A level and neuropsychological tests. Results The scores of MMSE (Z=-8.387, P=0.000) and MoCA (Z=-8.479, P=0.000) in DLB group were significantly lower than those in control group, while the scores of CDR (Z=-9.072, P=0.000), ADL (Z=-8.692, P=0.000), HAMD-17 (Z=-7.568, P=0.000), NPI (Z=-8.270, P=0.000) and plasma orexin-A level (Z=-2.688, P=0.007) were significantly higher than those in control group. Plasma orexin-A level in DLB patients with fluctuating cognition (Z=-2.172, P=0.030) and with Parkinsonism (Z=-1.981, P=0.048) were lower than those without these symptoms, respectively. Logistic regression analysis showed drinking history was a potentially independent protective factor for DLB (OR=0.278, 95%CI:0.095-0.808; P=0.019), while increased plasma orexin-A level was an independent risk factor for DLB (OR=6.878, 95%CI:1.241-38.137; P=0.027). Correlation analysis showed that plasma orexin-A level was negatively correlated with the occurrence of Parkinsonism in patients with DLB (r=-0.322, P=0.043). Multivariate linear stepwise regression analysis showed no statistically significant relationship between the plasma orexin-A level and the scores of neuropsychological tests (P>0.05, for all). Conclusions The plasma orexin-A level in patients with DLB were higher than controls, and the elevated plasma orexin-A level could significantly increase the risk of DLB, while reduce the incidence of Parkinsonism. Dysfunction of orexin-A system might be a potential mechanism for the occurrence of DLB.

Key words: Lewy body disease, Orexins, Risk factors, Logistic models