Stout Julie C, Queller Sarah, Baker Kalyca N, Cowlishaw Sean, Sampaio Cristina, Fitzer-Attas Cheryl, Borowsky Beth
School of Psychological Sciences, Monash University, Clayton, VIC, Australia.
Mov Disord. 2014 Sep;29(10):1281-8. doi: 10.1002/mds.25964. Epub 2014 Jul 7.
Cognitive dysfunction is central to Huntington's disease (HD) and undermines quality of life. Clinical trials are now targeting cognitive outcomes in HD; however, no cognitive battery has been optimized for HD clinical trials. We evaluated 16 cognitive tests in a 20-site, five-country, observational study designed to mimic aspects of a clinical trial (e.g., data collection managed by a contract research organization, repeated testing, prespecified statistical analyses). Fifty-five early HD, 103 premanifest HD (pre-HD), and 105 controls were tested at visit 1, visit 2 (1-3 days later), and visit 3 (5-7 weeks after visit 1). For inclusion in a recommended battery, tests were evaluated for sensitivity, practice effects, reliability, domain coverage, feasibility, and tolerability. Most tests differentiated controls from pre-HD and early HD and showed excellent psychometric properties. We selected six tests to constitute the Huntington's Disease Cognitive Assessment Battery (HD-CAB): Symbol Digit Modalities Test, Paced Tapping, One Touch Stockings of Cambridge (abbreviated), Emotion Recognition, Trail Making B, and the Hopkins Verbal Learning Test. These tests demonstrated sensitivity to disease status (Cohen's d effect sizes: early HD= -1.38 to -1.90 and pre-HD= -0.41 to -0.78), and acceptable reliability (r's 0.73-0.93). A composite score yielded large effect sizes (early HD = -2.44 and pre-HD = -0.87) and high reliability (r = 0.95). HD-CAB is the first cognitive battery designed specifically for use in late premanifest and early HD clinical trials. Adoption of the HD-CAB will facilitate evaluation of treatments to improve cognition in HD.
认知功能障碍是亨廷顿舞蹈症（HD）的核心问题，会损害生活质量。目前临床试验的目标是改善HD患者的认知结果；然而，尚无专门针对HD临床试验优化的认知测试组合。我们在一项涉及20个研究点、5个国家的观察性研究中评估了16项认知测试，该研究旨在模拟临床试验的各个方面（例如，由合同研究组织管理数据收集、重复测试、预先指定的统计分析）。55名早期HD患者、103名症状前HD（pre-HD）患者和105名对照者在第1次访视、第2次访视（1 - 3天后）和第3次访视（第1次访视后5 - 7周）接受测试。为了纳入推荐的测试组合，我们对各项测试的敏感性、练习效应、可靠性、领域覆盖范围、可行性和耐受性进行了评估。大多数测试能够区分对照组与pre-HD组和早期HD组，并且显示出优异的心理测量学特性。我们选择了六项测试组成亨廷顿舞蹈症认知评估组合（HD-CAB）：符号数字模式测试、节奏敲击测试、简化版剑桥单触长袜测试、情绪识别测试、连线测验B以及霍普金斯词语学习测试。这些测试显示出对疾病状态的敏感性（科恩d效应量：早期HD = -1.38至-1.90，pre-HD = -0.41至-0.78），以及可接受的可靠性（r值为0.73 - 0.93）。综合评分产生了较大的效应量（早期HD = -2.44，pre-HD = -0.87）和较高的可靠性（r = 0.95）。HD-CAB是首个专门为症状前晚期和早期HD临床试验设计的认知测试组合。采用HD-CAB将有助于评估改善HD患者认知功能的治疗方法。
