Core B: Clinical Core

项目摘要/摘要 亚利桑那州ADCC的临床核心(CC)是由五个招聘网站组成的联盟，提供 全州由一名临床核心主任领导的标准化单位。因为它的 自成立以来，CC一直对临床前阿尔茨海默病(AD)的研究和 加速评估AD预防疗法。它包括一组认知未受损的人和每年 评估APOE e4纯合子(HMS)、杂合子和非携带者，并已导致我们纳入 独立资助的亚利桑那州载脂蛋白基因丰富队列的UDS纵向评估。抄送 资源用于判定他们进展为轻度认知障碍(MCI)和痴呆，从而导致 CC登记并同意登记参加我们的大脑和身体捐赠计划(BBDP)。消委会有 提供受试者、DNA、纵向认知数据和血样来描述临床前病程 以及在AD的三个遗传风险水平上未受损的人的认知衰退的轨迹；它有 支持我们确定与以下疾病相关的PET、MRI和脑脊液(CSF)变化的工作 临床前AD使用独立的NIA、国家和组织资金。它包括拉丁裔和美洲原住民 载脂蛋白E4携带者和非携带者，以澄清我们的进展与这些未被研究的人群的相关性。它 导致了其他有阿尔茨海默病遗传风险的群体的合作研究，包括儿童、年轻人APOE4 携带者，来自世界最大常染色体的哥伦比亚早老素1(PSEN1)E280A突变携带者 主要的AD(ADAD)队列和唐氏综合征患者。它已经提供了数据来帮助提供设计信息， 统计能力，并针对我们的阿尔茨海默病预防计划(API)和API的ADAD和 ApoE4 HM试验。CC维持在老龄化-痴呆症谱系的所有阶段有500名参与者的目标 包括350名正常对照组，50名MCI患者，100名AD和其他形式的退行性疾病患者 痴呆症。在这些诊断类别中嵌入了定义为拉丁裔和美洲原住民的队列。这个 CC利用我们的多机构诊断共识会议、集中化数据管理 计划，并与其他每个核心建立密切的工作关系。所有受试者都要接受标准化测试 诊断性测试：1)满足严格的入学标准；2)包括人口统计、历史、医学、 神经学、精神病学、神经心理学和遗传学测量；3)纳入NACC统一数据 SET(UDS)；以及4)采用对文化敏感的测试程序。符合登记条件的患者和 完成年度随访在两周一次的诊断共识会议上讨论。所有患者均接受APOE 在入境时进行基因分型，以及在所有地点进行年度标准化神经心理学测试。所有产品都提供 参加脑捐献计划，以确认临床诊断的神经病理学。有耐心的 对正在进行的研究项目的资格和参与情况进行跟踪和持续审查。

PROJECT SUMMARY/ABSTRACT The Clinical Core (CC) of the Arizona ADCC is a consortium of five recruitment sites providing catchment areas throughout the state that comprise a standardized unit under a single Clinical Core Director. Since its inception, the CC has had an over-arching interest in the study of preclinical Alzheimer's disease (AD) and the accelerated evaluation of AD prevention therapies. It includes a cohort of cognitively unimpaired and annually assessed APOE e4 homozygotes (HMs), heterozygotes, and non-carriers, and has led us to incorporate longitudinal UDS assessments in an independently funded genetically enriched Arizona APOE cohort. CC resources are used to adjudicate their progression to mild cognitive impairment (MCI) and dementia leading to CC enrollment and consent for enrollment into our Brain and Body Donation Program (BBDP). The CC has provided subjects, DNA, longitudinal cognitive data and blood samples to characterize the preclinical course and trajectories of cognitive decline in unimpaired persons at three levels of genetic risk for AD; it has supported our effort to characterize PET, MRI and cerebrospinal fluid (CSF) changes associated with preclinical AD using independent NIA, state and organizational funds. It includes Latino and Native American APOE4 carriers and non-carriers to clarify the relevance of our advances to these understudied populations. It has led to collaborative research in other groups at genetic risk for AD, including children, young adult APOE4 carriers, Colombian presenilin 1 (PSEN1) E280A mutation carriers from the world's largest autosomal dominant AD (ADAD) cohort, and Down syndrome patients. It has provided data to help inform the design, statistical power, and optimized endpoints for our Alzheimer's Prevention Initiative (API) and API's ADAD and APOE4 HM trials. The CC maintains a target of 500 participants at all stages of the aging-dementia spectrum including 350 normal controls, 50 patients with MCI, and 100 with AD and other forms of degenerative dementia. Embedded within these diagnostic categories are defined Latino and Native American cohorts. The CC capitalizes on our multi-institutional diagnostic consensus conference, centralized data management program, and close working relationships with each of the other Cores. All subjects undergo standardized diagnostic testing that: 1) fulfills strict entrance criteria; 2) includes demographic, historical, medical, neurological, psychiatric, neuropsychological, and genetic measures; 3) incorporates the NACC Uniform Data Set (UDS); and 4) employs culturally sensitive test procedures. Patients eligible for enrollment and those completing annual follow-up are discussed in a biweekly diagnostic consensus conference. All undergo APOE genotyping at entry, and an annual standardized neuropsychological battery of tests at all sites. All are offered enrollment in the Brain Donation Program for neuropathological confirmation of clinical diagnoses. Patient eligibility for and participation in ongoing research projects is tracked and reviewed on an ongoing basis.