Healthy Aging and Senile Dementia

描述（由申请人提供）：本申请的首要目的是确定表征从认知正常进展到阿尔茨海默病（AD）引起的认知障碍的最早阶段的指标。AD领域正在向预防策略的目标转变，但这些努力不仅取决于治疗的发展，还取决于对症状性AD高风险个体的详细了解，以便将其用于临床试验，疾病修饰疗法，并监测治疗成功。 本续期申请的总体具体目标是： 1.跟踪HASD中的当前参与者并添加新的入组者，以将样本量保持在约250例。 2.每年从HASD参与者中获得临床和心理测量指标的纵向数据，并以3年为间隔进行以下测量： a.注意力控制和神经网络完整性的新措施（项目1） B. [18F] florbetapir淀粉样蛋白成像（成像核心） C. CSF分析物的测定（项目2） D.结构MRI和静息状态功能连接MRI（成像核心） e.睡眠效率（Project 2） F.预测进展速度的SNP（项目3） G.在尸检时，将A和tau负荷、突触完整性和神经元损失的测量与项目1和2以及成像核心的变量相关联 3.表征认知、成像、分子生物标志物和遗传因素，这些因素区分认知正常的老年人、有和没有临床前AD以及有症状的AD个体。 4.分析来自所有核心和项目（生物统计核心）的所有疾病标志物变化率之间的关联。

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).