HEALTHY AGING AND SENILE DEMENTIA

描述(由申请人提供)：本申请为健康老龄化和老年痴呆症(HASD)计划项目的5年续展申请，现已进入第25个年头。在这次更新中，继续关注阿尔茨海默型痴呆(DAT)的临床、心理测量和神经病理相关性，并与健康老龄化进行比较，新的研究重点针对临床前阿尔茨海默病。提出了五个互动和支持性核心：核心A：行政部门为所有组成部分提供行政支持，并确保在实现方案项目目标方面取得进展。核心B：临床招募、注册、心理测量和临床评估，每年评估受试者，以提供所有项目。核心C：生物统计监督数据管理，并向所有核心和项目提供统计信息。核心D：神经病理学为所有研究进行临床病理相关性的尸检，并根据需要为项目提供适当的组织和数据。核心E：神经成像收集我们队列中的结构成像数据，以可视化与认知衰退相关的解剖学变化。两个新项目取代了目前已经完成的项目1和4。新的项目1(“临床前AD预测中风后痴呆”JC Morris)研究了中风时大脑中淀粉样蛋白的存在(由PET PIB测量)与痴呆症后来发展之间的关系。新的项目4(“生物标记蛋白基因的序列变异和阿尔茨海默病的发病年龄”AM Goate)使用脑脊液蛋白质作为中间性状或内表型，以确定迟发性DAT的新的遗传风险因素。两个当前的项目将继续在这一申请中扩大他们的发现和探索新的倡议。项目2(“脑脊液和血浆中AD的前驱生物标记物”DM Holtzman)研究是否可以将脑脊液和血浆蛋白质组中的标记物结合起来，以更准确地确定认知正常的老年人患痴呆症的风险。项目3(“DAT的标记物：控制、变异性和个性”，D·巴洛塔)将开发认知标记物作为DAT的早期指标。总而言之，这些项目及其支持核心将侧重于临床前DAT与健康脑老化的比较，并解决检测临床前疾病的问题。

DESCRIPTION (provided by applicant): This application is for the 5-year renewal of the program project, Healthy Aging and Senile Dementia (HASD), now in its 25th year. In this renewal, there is a continued focus on the clinical, psychometric, and neuropathologic correlates of dementia of the Alzheimer type (DAT) in comparison with healthy aging with a new thrust addressing preclinical Alzheimer's disease. Five interactive and supportive Cores are proposed: Core A: Administration provides administrative support to all components and assures progress in accomplishing program project goals. Core B: Clinical recruits, enrolls, psychometrically and clinically assesses subjects annually to supply all projects. Core C: Biostatistics oversees data management and provides statistical input to all Cores and projects. Core D: Neuropathology performs postmortem examinations for clinicopathological correlation for all studies and provides appropriate tissue and data to Projects as needed. Core E: Neuroimaging collects structural imaging data on our cohort to visualize change in anatomy associated with cognitive decline. Two new projects replace the current Projects 1 and 4, which have been completed. The new Project 1 ("Preclinical AD predicts poststroke dementia" JC Morris) examines the relationship between the presence of amyloid in the brain (as measured by PET PIB) at time of stroke to the later development of dementia. The new Project 4 ("Sequence variation in genes for biomarker proteins and age at onset of Alzheimer's Disease" AM Goate) uses CSF proteins as intermediate traits, or endophenotypes, to identify novel genetic risk factors for late onset DAT. Two current projects will continue in this application to extend their findings and explore new initiatives. Project 2 ("Antecedent biomarkers of AD in CSF and plasma" DM Holtzman) examines whether markers in the CSF and plasma proteome can be combined to develop a more accurate determination of dementia risk in cognitively normal elderly individuals. Project 3 ("Markers for DAT: Control, Variability and Personality," D Balota) will develop cognitive markers as early indicators of DAT. Together, these projects and their supporting cores will focus on preclinical DAT in comparison with healthy brain aging and address the issue of detecting preclinical disease.