托莫西汀治疗帕金森病轻度认知障碍的随机临床试验。
A Randomized Clinical Trial of Atomoxetine for Mild Cognitive Impairment in Parkinson's Disease.
作者信息
Hinson Vanessa K, Delambo Amy, Elm Jordan, Turner Travis
机构信息
Department of Neurology Medical University of South Carolina Charleston South Carolina USA.
Division of Biostatistics and Epidemiology Medical University of South Carolina Charleston South Carolina USA.
出版信息
Mov Disord Clin Pract. 2016 Nov 17;4(3):416-423. doi: 10.1002/mdc3.12455. eCollection 2017 May-Jun.
BACKGROUND
Mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with diminished norepinephrine from the locus coeruleus to the prefrontal cortex. Atomoxetine is a specific norepinephrine reuptake inhibitor that has been approved by the US Food and Drug Administration to treat attention deficit hyperactivity disorder in adults. The authors hypothesized that atomoxetine would improve attention and executive functioning in patients with PD-MCI.
METHODS
Thirty participants who met Movement Disorder Society Task Force Level I criteria for PD-MCI were enrolled in a randomized controlled trial of atomoxetine. Cognitive evaluations were performed at baseline and after 10 weeks of treatment or placebo. A safety visit was performed at Week 12. A global statistical test was used to examine treatment effects on standardized tests of attention, working memory, processing speed, and set shifting (primary outcome measure). Secondary outcomes included cognitive measures hypothesized to be insensitive to atomoxetine, the Conners Adult Attention Deficit Hyperactivity Disorder Rating Scale, and safety measures.
RESULTS
Fifteen participants were randomized to each arm. Groups were similar on medical and demographic variables and baseline cognition. Three serious adverse events occurred; 2 on atomoxetine (syncope, isolated episode of atrial fibrillation) and 1 on placebo (atrial fibrillation). The global statistical test of primary outcome measures did not reveal a significant difference between groups. However, significant improvements were observed for atomoxetine but not placebo on subjective measures of attention and impulsivity (Conners Adult Attention Deficit Hyperactivity Disorder Rating Scale).
CONCLUSIONS
Atomoxetine treatment produced subjective, but not objective, improvements in PD-MCI. Failure to detect objective differences may be due to insensitivity of cognitive tests or severity of cognitive deficits in the study participants.
背景
帕金森病轻度认知障碍（PD-MCI）与蓝斑核到前额叶皮质的去甲肾上腺素减少有关。托莫西汀是一种特异性去甲肾上腺素再摄取抑制剂，已被美国食品药品监督管理局批准用于治疗成人注意力缺陷多动障碍。作者推测托莫西汀可改善PD-MCI患者的注意力和执行功能。
方法
30名符合帕金森病运动障碍协会工作组I级标准的PD-MCI患者参加了托莫西汀的随机对照试验。在基线以及治疗10周或服用安慰剂后进行认知评估。在第12周进行安全性访视。采用整体统计检验来检查治疗对注意力、工作记忆、处理速度和定势转换标准化测试（主要结局指标）的效果。次要结局包括假设对托莫西汀不敏感的认知指标、康纳斯成人注意力缺陷多动障碍评定量表以及安全性指标。
结果
每组随机分配15名参与者。两组在医学和人口统计学变量以及基线认知方面相似。发生了3起严重不良事件；2起发生在服用托莫西汀的患者中（晕厥、孤立性房颤发作），1起发生在服用安慰剂的患者中（房颤）。主要结局指标的整体统计检验未显示两组之间存在显著差异。然而，在注意力和冲动性的主观指标（康纳斯成人注意力缺陷多动障碍评定量表）方面，托莫西汀组有显著改善，而安慰剂组没有。
结论
托莫西汀治疗使PD-MCI患者在主观方面而非客观方面得到改善。未能检测到客观差异可能是由于认知测试不敏感或研究参与者认知缺陷的严重程度所致。
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