Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Child Study Center, Yale School of Medicine, New Haven, CT, USA.
Psychol Med. 2021 Jul;51(9):1524-1535. doi: 10.1017/S0033291720000288. Epub 2020 Feb 24.
This study integrated an experimental medicine approach and a randomized cross-over clinical trial design following CONSORT recommendations to evaluate a cognitive training (CT) intervention for attention deficit hyperactivity disorder (ADHD). The experimental medicine approach was adopted because of documented pathophysiological heterogeneity within the diagnosis of ADHD. The cross-over design was adopted to provide the intervention for all participants and make maximum use of data.
Children (n = 93, mean age 7.3 +/- 1.1 years) with or sub-threshold for ADHD were randomly assigned to CT exercises over 15 weeks, before or after 15 weeks of treatment-as-usual (TAU). Fifteen dropped out of the CT/TAU group and 12 out of the TAU/CT group, leaving 66 for cross-over analysis. Seven in the CT/TAU group completed CT before dropping out making 73 available for experimental medicine analyses. Attention, response inhibition, and working memory were assessed before and after CT and TAU.
Children were more likely to improve with CT than TAU (27/66 v. 13/66, McNemar p = 0.02). Consistent with the experimental medicine hypotheses, responders improved on all tests of executive function (p = 0.009-0.01) while non-responders improved on none (p = 0.27-0.81). The degree of clinical improvement was predicted by baseline and change scores in focused attention and working memory (p = 0.008). The response rate was higher in inattentive and combined subtypes than hyperactive-impulsive subtype (p = 0.003).
Targeting cognitive dysfunction decreases clinical symptoms in proportion to improvement in cognition. Inattentive and combined subtypes were more likely to respond, consistent with targeted pathology and clinically relevant heterogeneity within ADHD.
本研究采用实验医学方法和随机交叉临床试验设计,遵循 CONSORT 建议,评估认知训练(CT)对注意缺陷多动障碍(ADHD)的干预效果。采用实验医学方法是因为 ADHD 诊断存在明确的病理生理学异质性。采用交叉设计是为了为所有参与者提供干预,并最大限度地利用数据。
患有或处于 ADHD 阈下的儿童(n = 93,平均年龄 7.3 +/- 1.1 岁)随机分为 CT 锻炼组,接受 15 周的 CT 锻炼,或治疗常规(TAU)组,接受 15 周的 TAU。15 名儿童退出 CT/TAU 组,12 名儿童退出 TAU/CT 组,66 名儿童完成交叉分析。CT/TAU 组中有 7 名儿童在退出前完成了 CT,因此有 73 名儿童可用于实验医学分析。在 CT 和 TAU 之前和之后评估注意力、反应抑制和工作记忆。
与 TAU 相比,儿童更有可能通过 CT 改善(27/66 v. 13/66,McNemar p = 0.02)。与实验医学假说一致,反应者在所有执行功能测试中都有所改善(p = 0.009-0.01),而非反应者则没有改善(p = 0.27-0.81)。临床改善程度可由专注注意力和工作记忆的基线和变化分数预测(p = 0.008)。在注意力不集中和混合型亚型中,反应率高于多动冲动型亚型(p = 0.003)。
针对认知功能障碍进行靶向治疗可使临床症状与认知改善成正比。注意力不集中和混合型亚型更有可能反应,这与靶向病理和 ADHD 内的临床相关异质性一致。