Apathy in Alzheimer's Disease Methyphenidate Trial II (ADMET II)

描述（由申请人提供）：冷漠被定义为失去意志和主动性，对活动缺乏兴趣，缺乏生产力，以及对积极或消极因素的情感反应有限。冷漠是阿尔茨海默病（AD）最常见的神经精神症状（NPS）之一，影响约70%的AD患者，并对患者和护理人员造成严重的不良后果。冷漠的患者也更有可能需要制度化，这是AD直接成本的最大单一驱动因素。尽管阿尔茨海默病中冷漠的患病率很高，其后果也很严重，但目前还没有得到证实的治疗方法。非药物策略似乎对阿尔茨海默病的冷漠作用有限，正如目前fda批准的治疗阿尔茨海默病的药物，如胆碱酯酶抑制剂。最近，新的研究表明多巴胺通路参与阿尔茨海默病冷漠的生物学过程，以及多巴胺增强剂（如哌醋甲酯）在治疗阿尔茨海默病中的潜在价值。此外，我们最近报道了两项为期六周的随机对照试验的结果，显示哌醋甲酯在治疗AD患者的冷漠方面明显优于安慰剂，以及哌醋甲酯潜在的认知益处和良好的安全性/耐受性。然而，这些研究并没有回答一些与临床实践相关的关键问题。例如，在更大的样本中，治疗超过六周后是否有效和安全？哌甲酯的潜在认知益处能否在这一人群中重现并保持临床显著性？冷漠的减少和认知的改善是否可以转化为临床显著的功能改变？阿尔茨海默病患者的冷漠治疗对受试者的生活质量和药物经济学有影响吗？为了解决这些问题，我们建议开展一项多地点、平行、随机、双盲、安慰剂对照的研究，评估哌醋甲酯治疗阿尔茨海默病患者冷漠的效果（哌醋甲酯痴呆冷漠试验II (ADMET II)），在更大的样本中，在更长的时间内，采用一组简明的神经心理学测试，优化了对阿尔茨海默病患者的治疗效果。最终目标是收集足够有力的证据来支持临床实践的改变。这项试验将汇集一组研究人员，他们已经成功地合作执行了第一次ADMET研究，以及其他探索痴呆症神经精神症状治疗的临床试验。

DESCRIPTION (provided by applicant): Apathy is defined as a loss of will and initiative, lack of interest in activities, lack of productivity, as well as limited affective response to positive r negative elements . Apathy is one of the most common neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD), affecting approximately 70% of AD patients and resulting in serious adverse consequences for patients and caregivers. Apathetic patients are also more likely to require institutionalization, the largest single driver of direct costs in AD. Despite the high prevalence of apathy in AD and its serious consequences, there are no proven treatments for this condition. Nonpharmacologic strategies appear to have limited effects on apathy in AD, as do current FDA-approved medications for AD such as cholinesterase inhibitors. Recently, new research has suggested the involvement of dopamine pathways in the biology of apathy in AD and the potential value of dopamine enhancers, such as methylphenidate, for the treatment of this condition. Moreover, we have recently reported the results of two six- week randomized controlled trials showing a clear benefit of methylphenidate over placebo in treating apathy in AD, as well as potential cognitive benefits of methylphenidate and a favorable safety/tolerability profile. [However, a number of key questions relevant for clinical practice were not answered by these studies. For example, is the treatment effective and safe beyond six weeks in a larger sample? Can the potential cognitive benefit of methylphenidate be reproduced and remain clinically significant in this population? Can the combination of a decrease in apathy and an improvement in cognition be translated to clinically significant functional change? Does the treatment of apathy in AD have an impact on subject quality of life and pharmacoeconomics? We propose to address these questions by conducting a multi-site, parallel, randomized, double-blind, placebo-controlled study evaluating methylphenidate for the treatment of apathy in AD patients (Apathy in Dementia Methylphenidate Trial-II (ADMET II)) in a larger sample, over a more extensive period of time and employing a concise battery of neuropsychological tests optimized for apathetic AD patients. The ultimate goal is to collect evidence strong enough to support a change in clinical practice. This trial will bring together a team of investigators who have collaborated successfully in the execution of the first ADMET study as well as other clinical trials exploring treatments for neuropsychiatric symptoms of dementia.]