AD

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这是一项随机、安慰剂对照、双盲、多中心、为期2年的丙戊酸盐治疗试验，目标剂量为10-12 mg/kg/d，受试者为300例基线和自发病以来无激越和精神病的轻度至中度AD门诊患者。参与者将定期接受诊所就诊以及电话联系，以评估行为、认知、功能、安全性和耐受性。选择丙戊酸盐是因为其可能对AD患者的激越症状有效，在许多临床人群中的已知安全性特征，以及考虑到支持其在AD中的神经保护潜力的最新数据。主要假设是，对基线时无激越和精神病的AD受试者进行丙戊酸盐长期给药将延迟激越和/或精神病的出现。这种性质的影响可能会对公共卫生产生重大影响，例如，延迟机构化。 次要假设也将讨论。其中第一个是AD受试者的丙戊酸盐长期给药将减缓疾病的临床进展，测量结果为认知或功能下降的发生率降低。参与者将继续参加研究，并按照方案接受两年的随访，即使他们提前停止实验治疗，以检查对认知或功能下降进展的可能影响。此外，还将讨论慢性低剂量治疗的安全性和耐受性。

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. This is a randomized, placebo-controlled, double blind, multicenter, two-year trial of valproate therapy at a target dose of 10-12 mg/kg/d in 300 outpatients with mild to moderate AD who lack agitation and psychosis at baseline and since onset of illness. Participants will have regular clinic visits as well as telephone contacts for assessment of behaviour, cognition, function, safety and tolerability. Valproate was selected because of its possible symptomatic efficacy for agitation in AD, known safety profile in numerous clinical populations, and in view of recent data supporting its neuroprotective potential in AD. The primary hypothesis is that chronic valproate administration to participants with AD who lack agitation and psychosis at baseline will delay the emergence of agitation and/or psychosis. An effect of this nature may have significant public health implications, for instance, by delaying instutionalization. Secondary hypotheses will addressed as well. The first of these is that chronic valproate administration to participants with AD will attenuate clinical progression of illness measured by reduced rate of cognitive or functional decline. Participants will remain in the study and be followed per protocol for two years even if they discontinue experimental treatment prematurely, in order to examine possible effects on progression of cognitive or functional decline. In addition, the safety and tolerability of chronic low dose therapy will be addresed.