Interventions to Improve Memory in Patients with MS

描述（由申请人提供）：多发性硬化症（MS）是成年早期至中期残疾的最常见原因之一。 影响大约一半MS患者的认知障碍是这种疾病中残疾的主要原因，它对患者及其家人造成了巨大的社会经济和人际关系损失。PI最近在一项小型NCMRR资助的试点临床试验中获得了令人兴奋的结果，该试验旨在治疗MS中的认知障碍，并寻求与该提案进行竞争性更新。在先前的研究中，与安慰剂相比，乙酰胆碱酯酶抑制剂多奈哌齐增强了MS受损患者的标准化主要结局的学习和记忆。患者和临床医生还注意到多奈哌齐组与安慰剂组相比记忆和认知显著改善。一些服用多奈哌齐的患者评论说，他们在开车时不再迷路，他们更好地记得按时支付账单，或者他们能够重返全职工作。由于先前在MS中恢复认知障碍的努力几乎没有取得成功，因此确认多奈哌齐的疗效将为该人群带来新的和改进的护理标准。进一步的研究是至关重要的，因为这些阳性结果是在一个单一的网站在一个相对较小的样本。拟议的研究将在确定的临床试验中对多个中心的这些结果进行关键性测试。如果多奈哌齐再次改善学习和记忆，并且对患者，他们的重要他人和临床医生的影响是明显的，它将改变治疗MS认知障碍的实践指南，并改善受影响个体的生活质量。为此，PI建议在144名认知受损MS患者中进行多奈哌齐的多中心、双盲、随机、安慰剂对照、平行组临床试验，以证明这种干预的疗效。 具体目标1：确定多奈哌齐治疗MS患者认知障碍的疗效。据推测，多奈哌齐将增强言语记忆和自我报告的认知功能。 具体目标二：检查治疗应答与基线受试者特征（如基线神经心理学表现和MS亚型）的关系。

DESCRIPTION (provided by applicant): Multiple sclerosis (MS) represents one of the most frequent causes of disability in early to middle adulthood. The cognitive impairment affecting approximately half of MS patients is a primary reason for disability in this disorder, and it exacts a tremendous socioeconomic and interpersonal toll on patients and their families. The PIs recently obtained exciting results in a small NCMRR funded pilot clinical trial to treat cognitive impairment in MS and seek a competitive renewal with this proposal. In the previous study, the acetylcholinesterase inhibitor donepezil enhanced the learning and memory of impaired MS patients on a standardized primary outcome as compared to placebo. Patients and clinician also noted significantly improved memory and cognition in the donepezil versus placebo group. Some patients on donepezil commented that they no longer became lost while driving, that they better remembered to pay their bills on time, or that they were able to return to full time work. Since prior efforts to rehabilitate cognitive impairment in MS have met with little success, confirming the efficacy of donepezil would lead to a new and improved standard of care for this population. Further study is critical since these positive results were obtained in a relatively small sample at a single site. The proposed investigation will provide a crucial test of these results across multiple centers in a definitive clinical trial. If donepezil again improves learning and memory, and effects are evident to patients, their significant others, and clinicians, it will alter practice guidelines for treating cognitive impairment in MS, and improve the quality of life of affected individuals. To this end, the PIs propose a multicenter, double blind, randomized, placebo controlled, parallel group clinical trial of donepezil in 144 cognitively impaired MS patients to demonstrate the efficacy of this intervention. Specific Aim 1: To determine the efficacy of donepezil in the treatment of cognitive impairment in MS patients. It is hypothesized that donepezil will enhance verbal memory and self-reported cognitive function. Specific Aim 2: To examine the relationship of treatment response to baseline subject characteristics, such as baseline neuropsychological performance, and MS subtype.