β-Blocker Use and Delayed Onset and Progression of Huntington Disease

IF 20.4 1区医学 Q1 CLINICAL NEUROLOGY

JAMA neurology Pub Date : 2024-12-02 DOI:10.1001/jamaneurol.2024.4108

Jordan L. Schultz, Amy C. Ogilvie, Lyndsay A. Harshman, Peg C. Nopoulos

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引用次数: 0

Abstract

ImportanceHuntington disease (HD) is characterized by motor, cognitive, and psychiatric decline. β-Blockers may play a therapeutic role by decreasing enhanced sympathetic tone in HD.ObjectiveTo evaluate the impact of β-blockers on the timing of motor diagnosis onset and progression of HD symptoms.Design, Setting, and ParticipantsThis observational, longitudinal multicenter study used the Enroll-HD platform database (initiated September 2011 to present), including propensity score–matched cohorts of patients with premanifest HD (preHD) and early motor-manifest HD (mmHD) who were either users or nonusers of β-blockers. Participants included patients with genetically confirmed preHD (n = 4683 eligible participants) or mmHD (n = 3024 eligible participants) who were taking a β-blocker and were matched to similar non–β-blocker users.ExposureUninterrupted use of a β-blocker for more than 1 year.Main Outcomes and MeasuresFor PreHD: risk of receiving a motor diagnosis of HD over time. For mmHD: progression rate of total motor score, total functional capacity score, and the symbol digit modalities test. Post hoc analyses were performed to test additional clarifying hypotheses after the primary analyses were completed.ResultsThis study included 174 preHD β-blocker users (59 males; 115 females) with a mean age of 46.4 (SD, 13.1) years and a mean cytosine-adenine guanine repeat length of 41.1 (SD, 2.4) who were well matched to 174 preHD non–β-blocker users. The preHD β-blocker users showed a statistically significant reduction in the annualized hazard of receiving a motor diagnosis compared with nonusers (n = 174) (hazard ratio, 0.66; 95% CI, 0.46-0.94; P = .02). There were 149 mmHD β-blocker users (86 males; 60 females) with a mean age of 58.9 (SD, 11.3) years and a mean cytosine-adenine guanine repeat length of 42.0 (SD, 2.3) matched to 149 mmHD non–β-blocker users. The β-blocker users had a slower mean annualized worsening in total motor score (mean difference [MD], −0.45; 95% CI, −0.85 to −0.06; q = 0.025), total functional capacity score (MD, 0.10; 95% CI, 0.02-0.18; q = 0.025), and symbol digit modalities test (MD, 0.33; 95% CI, 0.10-0.56; q = 0.017) compared with matched nonusers.Conclusions and RelevanceIn this study, β-blocker use was associated with delayed motor onset in preHD and reduced the rate of worsening of symptoms in mmHD. These findings demonstrated that β-blockers may have a therapeutic role in HD but further studies are required.

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β受体阻滞剂的使用与亨廷顿病的延迟发病和进展

亨廷顿病（HD）的特征是运动、认知和精神衰退。β受体阻滞剂可能通过降低HD患者交感神经张力增强而发挥治疗作用。目的评价β受体阻滞剂对HD患者运动诊断、发病及进展时间的影响。设计、环境和参与者：这项观察性、纵向多中心研究使用了注册HD平台数据库（从2011年9月开始至今），包括倾向评分匹配的前期HD （preHD）和早期运动表现HD （mmHD）患者队列，这些患者要么使用β受体阻滞剂，要么不使用。参与者包括遗传确诊的preHD患者（n = 4683名符合条件的参与者）或mmHD患者（n = 3024名符合条件的参与者），这些患者正在服用β受体阻滞剂，并与类似的非β受体阻滞剂使用者相匹配。不间断使用β受体阻滞剂超过1年。预HD的主要结局和措施：随着时间的推移，接受HD运动诊断的风险。mmHD：总运动评分、总功能容量评分和符号数字模态测试的进展率。在初步分析完成后，进行事后分析以检验额外的澄清假设。结果本研究纳入174例hd前期β受体阻滞剂使用者(男性59例；115名女性)，平均年龄为46.4 （SD, 13.1）岁，平均胞嘧啶-腺嘌呤-鸟嘌呤重复长度为41.1 (SD, 2.4)，与174名hd前非β受体阻滞剂使用者匹配良好。preHD β受体阻滞剂使用者与未使用者相比，接受运动诊断的年化风险有统计学意义的降低（n = 174）(风险比，0.66；95% ci, 0.46-0.94；P = .02)。共有149名mmHD β受体阻滞剂使用者(86名男性；60名女性)，平均年龄58.9 （SD, 11.3）岁，平均胞嘧啶-腺嘌呤-鸟嘌呤重复长度为42.0 (SD, 2.3)，与149 mmHD非β受体阻滞剂使用者相匹配。β受体阻滞剂使用者的总运动评分平均年化恶化速度较慢(平均差值[MD]， - 0.45；95% CI,−0.85 ~−0.06；q = 0.025)，总功能容量评分(MD, 0.10；95% ci, 0.02-0.18；q = 0.025)，符号数字模态检验(MD, 0.33；95% ci, 0.10-0.56；Q = 0.017)。结论和相关性在这项研究中，β受体阻滞剂的使用与hd前期的延迟运动发作相关，并降低了mmHD症状恶化的比率。这些发现表明β受体阻滞剂可能在HD中具有治疗作用，但需要进一步的研究。

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来源期刊

JAMA neurology CLINICAL NEUROLOGY-

CiteScore

41.90

自引率

1.70%

发文量

250

期刊介绍： JAMA Neurology is an international peer-reviewed journal for physicians caring for people with neurologic disorders and those interested in the structure and function of the normal and diseased nervous system. The Archives of Neurology & Psychiatry began publication in 1919 and, in 1959, became 2 separate journals: Archives of Neurology and Archives of General Psychiatry. In 2013, their names changed to JAMA Neurology and JAMA Psychiatry, respectively. JAMA Neurology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications.