BACKGROUND Individuals with fragile X syndrome (FXS) typically demonstrate profound executive function (EF) deficits that interfere with learning, socialization, and emotion regulation. We completed the first large, non-pharmacological controlled trial for FXS, designed to evaluate the efficacy of Cogmed, a computer/tablet-based working memory (WM) training program. METHODS The study was a randomized, blinded, parallel two-arm controlled trial in 100 children and adolescents with FXS (63 male, 37 female; 15.28 ± 3.36 yrs.). Participants were randomized equally to adaptive (difficulty level adjusted to performance) or non-adaptive (control) Cogmed training. Participants were assessed at home using objective measures of WM (primary outcome) and EF at baseline, following 20-25 caregiver-supported sessions over 5-6 weeks, and at follow-up 3 months after cessation of training. Parents and teachers provided ratings of WM, attention, and EF. RESULTS The WM composite and selective domains of EF (distractibility, cognitive flexibility), as well as parent- and teacher-reported attention and EF, significantly improved across the full study sample, with many changes maintained at follow-up. However, comparisons of improvement between adaptive and non-adaptive control conditions did not differ, showing that progressively challenging the WM system by expanding span length did not provide added benefit overall. CONCLUSIONS Further experimental comparisons are needed before Cogmed working memory training can be considered empirically validated for children with FXS, forming the basis of treatment recommendation. However, given that prior studies show no significant changes on these measures in FXS without treatment, that improvements were maintained for 3 months, and that blinded teachers reported improvements in the classroom, the modest benefits seen in both adaptive and non-adaptive groups overall are unlikely to be attributable to placebo or practice effects alone. Future analyses examining inter-individual differences (e.g., baseline capacity, training efficiency, co-morbidity, training environment, characteristics of training aide) may help to link this intervention to outcomes and potential transfer effects. TRIAL REGISTRATION US National Institutes of Health (ClinicalTrials.gov), NCT02747394 .

中文翻译：

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患有脆性 X 综合征的儿童和青少年的认知训练：Cogmed 的一项随机对照试验。

背景技术患有脆性X综合征（FXS）的个体通常表现出严重的执行功能（EF）缺陷，这会干扰学习、社交和情绪调节。我们完成了 FXS 的第一个大型非药理学对照试验，旨在评估 Cogmed 的功效，Cogmed 是一种基于计算机/平板电脑的工作记忆 (WM) 训练计划。方法 该研究是一项随机、双盲、平行双臂对照试验，受试者为 100 名 FXS 儿童和青少年（63 名男性，37 名女性；15.28 ± 3.36 岁）。参与者被随机分配到适应性（根据表现调整难度水平）或非适应性（对照）Cogmed 训练。在 5-6 周内进行 20-25 次护理人员支持的课程后，以及在停止训练后 3 个月的随访中，参与者在家中使用 WM（主要结果）和 EF 的客观测量进行基线评估。家长和老师提供了 WM、注意力和 EF 的评分。结果 在整个研究样本中，WM 综合和 EF 的选择性领域（注意力分散、认知灵活性）以及家长和老师报告的注意力和 EF 均显着改善，并且在随访中仍保持许多变化。然而，自适应和非自适应控制条件之间的改进比较没有差异，这表明通过扩大跨度长度逐步挑战 WM 系统并没有带来总体上的额外好处。结论 在 Cogmed 工作记忆训练对 FXS 儿童进行实证验证之前，需要进行进一步的实验比较，形成治疗建议的基础。然而，考虑到之前的研究表明，在没有治疗的情况下，FXS 的这些指标没有显着变化，改善持续了 3 个月，而且盲法教师报告了课堂上的改善，适应性组和非适应性组总体上所看到的适度益处是不太可能单独归因于安慰剂或练习效果。未来分析检查个体间差异（例如，基线能力、培训效率、共病、培训环境、培训助手的特征）可能有助于将这种干预与结果和潜在的转移效应联系起来。试验注册美国国立卫生研究院 (ClinicalTrials.gov)，NCT02747394。