特发性快速眼动睡眠行为障碍的病例对照家系研究。

A case-control-family study of idiopathic rapid eye movement sleep behavior disorder.

机构信息

Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China.

Sleep Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Ann Neurol. 2019 Apr;85(4):582-592. doi: 10.1002/ana.25435. Epub 2019 Mar 19.

DOI:10.1002/ana.25435

PMID:30761606

Abstract

OBJECTIVE

To determine the familial aggregation of idiopathic rapid eye movement sleep behavior disorder (iRBD), neurodegenerative diseases, and related biomarkers.

METHODS

A total of 404 and 387 first-degree relatives of 102 patients with iRBD and of 89 controls were recruited, respectively. Among them, 204 and 208 relatives of patients and controls underwent face-to-face clinical assessment, whereas 97 and 75 relatives underwent further video-polysomnographic assessment, respectively.

RESULTS

Compared with relatives of controls, relatives of patients demonstrated higher levels of RBD features, including chin tonic electromyography activity (mean = 1.5 ± 7.5 vs 0.3 ± 1.0, p = 0.04) and behavioral events (n [weighted %] = 12 [11.3] vs 2 [1.9], adjusted hazard ratio [aHR] = 7.69, 95% confidence interval [CI] = 1.54-33.33, p = 0.009) during rapid eye movement sleep, probable diagnosis (n [%] = 57 [14.9] vs 20 [4.9], aHR = 3.45, 95% CI = 1.96-6.25, p < 0.001), and definite diagnosis (n [weighted %] = 10 [8.4] vs 2 [1.4], aHR = 5.56, 95% CI = 1.16-25.00, p = 0.03). They also had higher risks of Parkinson disease (3.1% vs 0.5%, aHR = 5.88, 95% CI = 1.37-25.00, p = 0.02), dementia (6.9% vs 2.6%, aHR = 2.44, 95% CI = 1.15-5.26, p = 0.02), constipation (8.3% vs 2.4%, adjusted odds ratio = 4.21, 95% CI = 1.34-13.17, p = 0.01), and motor dysfunction (Movement Disorders Society Unified Parkinson's Disease Rating Scale part III motor score, mean = 1.9 ± 3.2 vs 0.9 ± 2.3, p = 0.002). The unaffected relatives of patients demonstrated a higher likelihood ratio of prodromal Parkinson disease (median [interquartile range] = 0.27 [1.19] vs 0.22 [0.51], p = 0.03).

INTERPRETATION

iRBD is familially aggregated from isolated features to full-blown sleep disorder. Relatives of patients carry a higher risk of alpha-synucleinopathy in terms of neurodegenerative diseases and prodromal markers, suggesting a familial aggregation and staging pathology of alpha-synucleinopathy. Ann Neurol 2019;85:582-592.

摘要

目的

确定特发性快速眼动睡眠行为障碍（iRBD）、神经退行性疾病及其相关生物标志物的家族聚集性。

方法

共招募了 102 例 iRBD 患者的 404 名一级亲属和 89 名对照者的 387 名一级亲属。其中，204 名和 208 名患者和对照者的亲属接受了面对面的临床评估，而 97 名和 75 名亲属分别接受了进一步的视频多导睡眠图评估。

结果

与对照者亲属相比，患者亲属表现出更高水平的 RBD 特征，包括颏肌肌电图活动（平均值=1.5±7.5 与 0.3±1.0，p=0.04）和行为事件（n [加权%] =12 [11.3] 与 2 [1.9]，调整后的危险比[aHR] =7.69，95%置信区间[CI] =1.54-33.33，p=0.009）、可能诊断（n [%] =57 [14.9] 与 20 [4.9]，aHR=3.45，95%CI=1.96-6.25，p<0.001）和明确诊断（n [加权%] =10 [8.4] 与 2 [1.4]，aHR=5.56，95%CI=1.16-25.00，p=0.03）。他们还具有更高的帕金森病（3.1%与 0.5%，aHR=5.88，95%CI=1.37-25.00，p=0.02）、痴呆（6.9%与 2.6%，aHR=2.44，95%CI=1.15-5.26，p=0.02）、便秘（8.3%与 2.4%，调整后的优势比[aOR]=4.21，95%CI=1.34-13.17，p=0.01）和运动功能障碍（运动障碍协会统一帕金森病评定量表第三部分运动评分，平均值=1.9±3.2 与 0.9±2.3，p=0.002）的风险。患者的未受影响亲属具有更高的前驱性帕金森病可能性比值（中位数[四分位距] =0.27 [1.19] 与 0.22 [0.51]，p=0.03）。