Healthy Aging and Senile Dementia

描述（由申请人提供）：本申请的总体目标是确定表征由阿尔茨海默病（AD）引起的认知障碍从认知正常到早期阶段进展的指标。阿尔茨海默病领域正朝着预防策略的目标转变，但这些努力不仅取决于治疗方法的发展，还取决于对症状性阿尔茨海默病高危人群的详细了解，以便针对他们进行临床试验，改善疾病的治疗，并监测治疗成功。

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).