帕金森病患者不同睡眠障碍主诉与脑灰质体积的相关性研究

Grey matter alterations in patients with Parkinson′s disease with different sleep disorders

目的探讨伴与不伴睡眠障碍的帕金森病患者脑灰质体积的改变特征及不同睡眠障碍主诉与患者临床情况及脑灰质体积之间的相关性。方法收集2018年1月至2021年12月在北京医院神经内科就诊的帕金森病患者46例及体检中心招募的健康对照者38名。根据帕金森病睡眠量表(PDSS)评分(PDSS总分≤82分或任何一项评分<5分被认为存在睡眠障碍)将帕金森病患者分为伴睡眠障碍(PD-S,n=26)和不伴睡眠障碍(PD-nS,n=20)两组。运用简易精神状态检查量表(MMSE)、统一帕金森病评定量表第三部分(UPDRS-Ⅲ)、汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、非运动症状问卷(NMSQ)、帕金森病生活质量问卷(PDQ-39)对患者的认知、运动、焦虑抑郁、非运动症状及生活质量进行评定。通过基于体素的形态学分析方法对所有受试者的灰质体积进行分析,并采用多元线性回归分析检验其与帕金森病患者夜间睡眠质量之间的相关性。结果PD-nS组较对照组双侧边缘叶、海马旁回、杏仁核、扣带回、海马、右侧小脑、双侧额颞叶、双侧枕叶及左侧顶叶灰质体积萎缩;PD-S组较对照组双侧边缘叶、海马旁回、杏仁核、右侧小脑、双侧额颞叶及双侧顶枕叶灰质体积萎缩。PD-S组较PD-nS组的焦虑抑郁[(HAMA评分:(12.04±5.32)分与(7.25±4.68)分,t=-3.18,P=0.003;HAMD评分:(12.19±5.59)分与(6.95±3.19)分,t=-4.01,P<0.001]及非运动症状评分[NMSQ评分:(12.92±5.18)分与(9.90±4.10)分,t=-2.14,P=0.038]更高,生活质量更差[PDQ-39评分:(35.31±22.01)分与(22.40±9.00)分,t=-2.71,P=0.010],左侧岛叶及左侧额顶叶灰质体积减小(P<0.001,未校正,体素>100)。帕金森病患者夜间睡眠质量与右侧颞中回(β=0.006,95%CI 0.002~0.010,P=0.003)、左侧额中回(β=0.006,95%CI 0.002~0.010,P=0.002)、右侧小脑(β=0.014,95%CI 0.005~0.023,P=0.003)和右侧枕中回(β=0.017,95%CI 0.011~0.024,P<0.001)灰质体积具有相关性。帕金森病患者夜间不宁状态与左侧边缘叶、双侧枕叶、右侧小脑及顶叶灰质体积减小有关(β=0.008,95%CI 0.006~0.010,P<0.001),夜尿症状与双侧边缘叶、右侧顶下回、双侧额叶体积减小有关(β=0.010,95%CI 0.008~0.013,P<0.001),白天过度嗜睡与右侧枕叶、左侧颞叶体积减少有关(β=0.014,95%CI 0.010~0.019,P<0.001),部分脑区(双侧额叶、左侧边缘叶及扣带回)代偿性增大(P<0.001,未校正,体素>60)。结论睡眠障碍是帕金森病患者常见的非运动症状,与其焦虑抑郁状态、非运动症状及生活质量相关。伴有睡眠障碍的帕金森病患者存在多个脑区的灰质体积改变,可能与其睡眠质量、夜间不宁状态、夜尿及白天过度嗜睡症状相关。

Objective To investigate the grey matter alterations of Parkinson′s disease(PD)patients with and without sleep disorders,and to explore the relationship between different sleep-related problems and clinical variables as well as grey matter volume(GMV)in PD.Methods Forty-six PD patients and 38 healthy controls(HCs)were recruited from January 2018 to December 2021 in the Department of Neurology,Beijing Hospital.PD patients were divided into PD with sleep disorders(PD-S,n=26)and PD without sleep disorders(PD-nS,n=20)subgroups(cutoff points of 82 for Parkinson′s Disease Sleep Scale or less than 5 for each item was considered as an indicator of substantial sleep disorder).The Mini-Mental State Examination(MMSE),the third part of the Unified Parkinson′s Disease Rating Scale(UPDRS-Ⅲ),Hamilton Rating Scale for Anxiety(HAMA),Hamilton Rating Scale for Depression(HAMD),Non-Motor Symptoms Questionnaire(NMSQ),and Parkinson′s Disease Questionnaire-39(PDQ-39)were used to evaluate cognitive function,motor symptoms,anxious and depressive symptoms,non-motor symptoms,and the quality of life of the patients.Optimized voxel-based morphometry was applied to the magnetic resonance imaging brain images in all participants,and multiple linear regression analysis was used to test the correlation between GMV and sleep quality in patients with PD.Results Compared with the HCs,PD-nS patients showed decreased GMV in bilateral limbic lobe,parahippocampal gyrus,amygdala,cingulate gyrus,hippocampus,right cerebellum,bilateral frontotemporal lobe,bilateral occipital lobe and the left parietal lobe.PD-S group exhibited reduced GMV in bilateral limbic lobe,parahippocampal gyrus,amygdala,right cerebellum,bilateral frontotemporal lobe and bilateral parietal-occipital lobe,compared to the HCs.Compared with PD-nS,PD-S patients revealed higher depressive(HAMD score:12.19±5.59 vs 6.95±3.19,t=-4.01,P<0.001),anxious(HAMA score:12.04±5.32 vs 7.25±4.68,t=-3.18,P=0.003),and non-motor symptoms scores(NMSQ score:12.92±5.18 vs 9.90±4.10,t=-2.14,P=0.038),poorer quality of life(PDQ-39 score:35.31±22.01 vs 22.40±9.00,t=-2.71,P=0.010),and reduced GMV in the left insula,frontal,and parietal lobe(P<0.001,uncorrected,cluster>100).There was a marked relationship between sleep quality and the reduced GMV of the right medial temporal gyrus(β=0.006,95%CI 0.002-0.010,P=0.003),left middle frontal gyrus(β=0.006,95%CI 0.002-0.010,P=0.002),the right cerebellum(β=0.014,95%CI 0.005-0.023,P=0.003),and the right medial occipital gyrus(β=0.017,95%CI 0.011-0.024,P<0.001).Significant grey matter changes were associated with nocturnal restlessness,mainly within the left limbic lobe,bilateral occipital lobe,the right cerebellum,and parietal lobe(β=0.008,95%CI 0.006-0.010,P<0.001).Furthermore,nocturia in PD was related to certain grey matter atrophy,including bilateral limbic lobe,the right inferior parietal gyrus,and bilateral frontal lobe(β=0.010,95%CI 0.008-0.013,P<0.001).The symptom of daytime dozing was correlated with GMV reduction in the right occipital lobe,the left temporal lobe(β=0.014,95%CI 0.010-0.019,P<0.001).There were also several compensatory brain regions,including bilateral frontal lobe,the left limbic lobe and cingulate(P<0.001,uncorrected,cluster>60).Conclusions Sleep disturbance is common in PD,which is related to the anxious and depressive symptoms,non-motor symptoms,and the quality of life.PD patients with different sleep disorders show grey matter alterations in severeal brain regions,which are associated with sleep quality,nocturnal restlessness,psychosis,and daytime dozing.