Interventions to Improve Memory in Patients with MS

描述（由申请人提供）：多发性硬化症（MS）是成年早期到中期最常见的致残原因之一。大约一半的多发性硬化症患者的认知障碍是导致这种疾病残疾的主要原因，它给患者及其家庭造成了巨大的社会经济和人际关系损失。PIs最近在NCMRR资助的一项小型临床试验中获得了令人兴奋的结果，该试验旨在治疗多发性硬化症的认知障碍，并寻求竞争更新。在之前的研究中，与安慰剂相比，乙酰胆碱酯酶抑制剂多奈哌齐在标准化主要结局上增强了受损MS患者的学习和记忆。患者和临床医生还注意到，与安慰剂组相比，多奈哌齐组的记忆力和认知能力有了显著改善。一些服用多奈哌齐的病人评论说，他们不再在开车时迷路了，他们更好地记住了按时支付账单，或者他们能够重返全职工作。由于先前对多发性硬化症患者认知功能障碍的康复努力收效甚微，因此确认多奈哌齐的疗效将为这一人群带来一种新的、改进的治疗标准。进一步的研究是至关重要的，因为这些阳性结果是在一个相对较小的样本中获得的。拟议的调查将在一个明确的临床试验中为这些结果提供跨多个中心的关键测试。如果多奈哌齐再次改善学习和记忆，并且效果对患者、其重要他人和临床医生都是明显的，它将改变治疗多发性硬化症认知障碍的实践指南，并改善患者的生活质量。为此，PIs建议在144名认知功能受损的MS患者中进行多奈哌齐多奈哌齐的多中心、双盲、随机、安慰剂对照、平行组临床试验，以证明该干预措施的有效性。特异性目的1：确定多奈哌齐治疗多发性硬化症患者认知功能障碍的疗效。据推测，多奈哌齐会增强言语记忆和自我报告的认知功能。具体目的2：检查治疗反应与基线受试者特征的关系，如基线神经心理表现和MS亚型。

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.