Healthy Aging and Senile Dementia

描述(申请人提供)：本申请的首要目标是确定表征由阿尔茨海默病(AD)引起的认知正常到认知损害早期阶段的指标。AD领域正在转向预防策略的目标，但这些努力不仅取决于治疗的发展，还取决于对哪些人具有高风险的症状性AD的详细了解，以便针对他们进行临床试验、疾病修改治疗，并监测治疗成功。 本次续签申请的总体具体目标是： 1.跟踪HASD的现有参与者，增加新的参与者，将样本量保持在~250。 2.每年从HASD参与者那里获得临床和心理测量的纵向数据，并每隔3年使用以下测量方法： A.注意力控制和神经网络完整性的新措施(项目1) B.用[18F]florbetapir(成像核心)进行淀粉样蛋白成像 C.脑脊液分析物的分析(项目2) D.结构核磁共振和静息状态功能连接核磁共振(成像核心) E.睡眠效率的衡量(项目2) F.预测进展速度的SNPs(项目3) G.在尸检时，将A？和tau负荷、突触完整性和神经元丢失的测量与项目1和2以及成像核心的变量相关联 3.确定认知、影像、分子生物标记物和遗传因素的特征，以区分认知正常的老年人、有无临床前AD的老年人和有症状的AD患者。 4.分析所有核心和项目的所有疾病标记物变化率之间的关系(生物统计核心)。

DESCRIPTION (provided by applicant): The overarching aim of this application is to determine the indicators that characterize the progression from cognitive normality to the earliest stages of cognitive impairment caused by Alzheimer disease (AD). The AD field is shifting toward the goal of prevention strategies, but these efforts depend not only on therapeutic development, but also on a detailed understanding of which individuals are at high risk for symptomatic AD in order to target them for clinical trials, disease-modifying therapies, and to monitor therapy success. The overall Specific Aims in this renewal application are to: 1. Follow current participants in HASD and add new enrollees to maintain the sample size at ~250. 2. Obtain longitudinal data from the HASD participants on an annual basis for clinical and psychometric measures and at 3 year intervals with the following measures: a. Novel measures of attentional control and neural network integrity (Project 1) b. Amyloid imaging with [18F] florbetapir (Imaging Core) c. Assays of CSF analytes (Project 2) d. Structural MRI and resting state functional connectivity MRI (Imaging Core) e. Measures of sleep efficiency (Project 2) f. SNPs that predict rate of progression (Project 3) g. At autopsy, correlate measures of A¿ and tau burden, synaptic integrity, and neuronal loss with variables from Projects 1 and 2 and from the Imaging Core 3. Characterize the cognitive, imaging, molecular biomarker, and genetic factors that distinguish cognitively normal older adults, with and without preclinical AD, and individuals with symptomatic AD. 4. Analyze associations among rates of change of all disease markers from all Cores and Projects (Biostatistics Core).