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有限情感反应。冷漠是阿尔茨海默病（AD）最常见的神经精神症状之一，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住院治疗，这是AD直接成本的最大单一驱动因素。尽管在AD中冷漠的高患病率及其严重后果，但对于这种情况没有经过证实的治疗方法。非药物策略似乎对AD患者的情感淡漠作用有限，目前FDA批准的AD药物如胆碱酯酶抑制剂也是如此。最近，新的研究表明，多巴胺通路参与AD冷漠的生物学，以及多巴胺增强剂（如哌甲酯）治疗这种疾病的潜在价值。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，显示哌甲酯在治疗AD冷漠方面优于安慰剂，以及哌甲酯的潜在认知益处和有利的安全性/耐受性特征。[然而，这些研究没有回答与临床实践相关的一些关键问题。例如，在更大的样本中，治疗超过六周是否有效和安全？哌醋甲酯的潜在认知益处能否在该人群中重现并保持临床显著性？情感淡漠的减少和认知能力的改善能否转化为临床上显著的功能改变？AD患者情感淡漠的治疗是否会影响受试者的生活质量和药物经济学？我们建议通过进行一项多中心、平行、随机、双盲、安慰剂对照研究，在更大的样本中，在更长的时间内，采用针对冷漠AD患者优化的简明神经心理学测试，评估哌甲酯治疗AD患者冷漠的效果（哌甲酯痴呆冷漠试验II（ADMET II）），以解决这些问题。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，他们成功地合作执行了第一项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.]