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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。[from鉴于流行病学、动物和临床研究的证据表明他汀类药物可能对阿尔茨海默病（AD）具有预防作用，本研究拟评估辛伐他汀对AD进展的脑脊液（CSF）和血浆标志物、中枢神经系统（CNS）胆固醇代谢、和中枢神经系统炎症的风险增加的中年人的人口发展为AD。将招募100名父母一方患有AD的男性和女性参与这项为期9个月的随机对照试验，评价辛伐他汀80 mg每晚与安慰剂相比对以下生物标志物的影响：（1）CSF淀粉样蛋白β-42水平;（2）CNS胆固醇代谢的血浆标志物;（3）CSF和炎症的血浆标志物;以及（4）MRI灌注。参与者将在基线和9个月随访时进行空腹实验室检查，收集CSF，进行认知测试，并进行MRI扫描（50例受试者）。第1、3和6个月的额外访视将评估副作用。还将在3个月随访时重复进行认知测试。将9个月时的结局指标与基线进行比较。

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.