ATOMOXETINE FOR ATTENTION DEFICITS IN ADULTS WITH MILD HD

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目前还没有研究过改善亨廷顿病患者注意力和执行功能的药物，尽管有证据表明，这些认知领域可能是异常的，甚至在运动症状出现之前。由于认知症状与功能残疾高度相关，旨在改善认知功能的治疗将对疾病早期的患者产生重大好处。托莫西汀是此类试验的理想选择。它已被证明对患有ADHD的成年人有效，它选择性地将去甲肾上腺素和多巴胺靶向前额叶皮质，而不是皮质下区域。这种选择性对HD患者来说是一个优势，因为与使用精神刺激剂相比，运动副作用更不容易发生。本研究是一项可行性研究，我们建议对20名早期HD患者给予80 mg托莫西汀或安慰剂治疗4周，这些患者也有轻度认知症状。然后，这两组人将交叉进入另一种情况(托莫西汀或安慰剂)。参与者将接受ADHD症状和一系列敏感的神经心理测试的评估。基于ADHD和HD的共同神经回路，以及托莫西汀对成人ADHD注意力的有效性已被证明，在托莫西汀治疗阶段，注意力和执行功能的认知测试以及受试者报告的ADHD症状的表现有望得到改善。在研究期间，没有预测到运动状态的变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. No medications have been investigated to improve attention and executive functions in patients with Huntington's disease despite the evidence that these cognitive domains can be abnormal, even before motor symptom onset. Because cognitive symptoms are highly associated with functional disability, treatments aimed at improving cognitive function would be of significant benefit to patients in the early stages of the disease. Atomoxetine is the ideal choice for such a trial. It has proven efficacy in adults with ADHD and it selectively targets norepinephrine and dopamine in the prefrontal cortex rather than in subcortical areas. This selectivity is an advantage for patients with HD because motor side effects are less likely to be facilitated than with a psychostimulant. The present study is a feasibility study in which we propose to administer either 80 mg atomoxetine for 4 weeks or placebo to 20 patients with early HD and who also complain of mild cognitive symptoms. The groups will then crossover to the other condition (atomoxetine or placebo). Participants will be assessed on measures of ADHD symptoms and a sensitive battery of neuropsychological tests. Based on the shared neural circuitry in ADHD and HD, and the demonstrated effectiveness of atomoxetine on attention in adults with ADHD, improved performance on cognitive tests of attention and executive functions and on subjects' report of ADHD symptoms are expected in the atomoxetine treatment phase. No changes in motor status are predicted during the study.