EFFECT OF STATINS ON THE PATHOBIOLOGY OF ALZHEIMER'S DISEASE: THE ESPRIT TRIAL

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。[来自CRISP网站(编辑)]鉴于流行病学、动物和临床研究表明他汀类药物可能在阿尔茨海默病(AD)中具有预防作用，这项研究建议评估辛伐他汀对AD进展的脑脊液(CSF)和血浆标记物、中枢神经系统(CNS)胆固醇代谢和CNS炎症的影响。100名父母患有阿尔茨海默病的男性和女性将被招募参加这项为期9个月的随机对照试验，评估辛伐他汀每晚80毫克与安慰剂相比对以下生物标记物的影响：(1)脑脊液淀粉样β-42水平；(2)中枢神经系统胆固醇代谢的血浆标记物；(3)脑脊液和血浆炎症标记物；以及(4)核磁共振灌注。参与者将在基线和9个月的随访中抽出空腹实验室，收集脑脊液，进行认知测试，并进行核磁共振扫描(在50名受试者中)。在1个月、3个月和6个月的额外检查将评估副作用。认知测试也将在3个月的随访中重复进行。9个月时的结果测量将与基线进行比较。

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. [from CRISP website (edited)] Given the evidence from epidemiological, animal, and clinical research suggesting that statins may have a preventive role in Alzheimer's disease (AD), this study proposes to evaluate the effect of simvastatin on cerebrospinal fluid (CSF) and plasma markers of AD progression, central nervous system (CNS) cholesterol metabolism, and CNS inflammation in a population of middle-aged adults at increased risk for developing AD. One-hundred (100) men and women who have a parent with AD will be recruited for this 9-month randomized, controlled trial evaluating the effects of simvastatin 80 mg nightly vs. placebo on biomarkers of (1) CSF amyloid beta-42 levels; (2) plasma markers of CNS cholesterol metabolism; (3) CSF and plasma markers of inflammation; and (4) MRI perfusion. Participants will have fasting labs drawn, CSF collected, cognitive testing done, and MRI scans done (in 50 of the subjects) at baseline and 9-month follow-up. Additional visits at 1, 3, and 6 months will assess side effects. Cognitive testing will also be repeated at the 3-month follow-up. Outcome measures at 9 months will be compared to baseline.