Clinical Core

临床核心旨在建立在自1948年以来获得的非凡数据资源的基础上， 六个心脏病研究队列。重要的是，就科学前提而言， 血管/代谢、生活方式、血浆和遗传测量已经纵向收集了多达近7 几十年，包括早期到中年时期，可以用来确定新的和扩大已知的 阿尔茨海默病（AD）和认知弹性的风险因素和生物标志物，其中一些将被追求 通过U19申请中提出的三个项目。FHS认知的广度和深度 衰老和痴呆数据提供了一个表型库，结合来自 神经病理学核心可以通过数据核心共享，并可以进一步利用更广泛的研究 社区为检测和预防策略提供信息，这将在几十年后降低AD的风险。目标1将 通过开展临床研究，继续监测和诊断所有队列的痴呆症事件。 检查（神经心理学，神经学）为那些标记为痴呆/AD的风险，保持每周 共识诊断会议以确定痴呆和主要亚型的新病例（例如，AD，血管性 痴呆，额颞叶痴呆，路易体）和MCI亚型（遗忘单域，遗忘多域， 域、非遗忘单域、非遗忘多域），并确定所有人的最终认知状态 FHS参与者死亡后，包括没有记录的痴呆症证据（例如，死亡时认知完好， 从而潜在地满足认知弹性的标准）。目标2将扩展纵向表征 通过重复给予相同的药物， 神经心理学（NP）测试协议自1999年以来管理。NP评估还将包括 2005年增加的NP测试管理以及更深入的NP表型分析，包括编码 从数字语音和数字笔记录中获得的错误/无关响应和新的衍生测量， 口头和书面回答。目标3将扩展大脑结构的纵向表征 通过使用自1999年以来实施的MRI方案重复采集脑部MRI扫描，包括 2008年增加了弥散张量成像协议的采集。下丘脑和白色的新措施 除了传统的AD相关皮层和皮层下感兴趣区域之外，还将获得物质完整性。 目标4将继续维持FHS的大脑捐赠计划的运作，包括生前临床 对所有进行尸检的病例进行评估和尸检诊断评价， 临床病理会议，以协调临床与神经病理学诊断。

The Clinical Core seeks to build upon the extraordinary data resource that has been acquired since 1948 across the six Framingham Heart Study cohorts. Importantly, in terms of scientific premise, is that many vascular/metabolic, lifestyle, plasma and genetic measures have been collected longitudinally for up to nearly 7 decades that include the periods of early to mid-life and can be leveraged to identify new and expand on known risk factors and biomarkers of Alzheimer's disease (AD) and cognitive resiliency, some of which will be pursued through the three projects proposed within this U19 application. Both the breadth and depth of the FHS cognitive aging and dementia data provides a phenotypic repository, that in combination with autopsy data from the Neuropathology Core can be shared through the Data Core and can be further leveraged by the broader research community to inform detection and prevention strategies that will attenuate risk for AD decades later. Aim 1 will continue surveillance and diagnosis of all cohorts for incident dementia through the conduct of clinical examinations (neuropsychology, neurology) for those flagged as at risk for dementia/AD, maintain the weekly consensus diagnosis meetings to identify new cases of dementia and major subtypes (e.g., AD, vascular dementia, frontotemporal dementia, Lewy Body) and MCI subtypes (amnestic single domain, amnestic multi- domain, non-amnestic single domain, non-amnestic multi-domain) and determine final cognitive status for all FHS participants after death, including no documented evidence of dementia (e.g., died cognitively intact and thus potentially meeting criteria for cognitive resilience). Aim 2 will extend longitudinal characterization of cognition across all surviving members of FHS cohorts through repeat administration of the same neuropsychological (NP) test protocol administered since 1999. The NP assessments will also include administration of NP tests added in 2005 as well as deeper NP phenotyping that includes coding of error/extraneous responses and novel derived measures from digital voice and digital pen recordings to capture spoken and written responses, respectively. Aim 3 will extend longitudinal characterization of brain structure through repeat acquisition of brain MRI scans using the MRI protocol administered since 1999 and include acquisition of diffusion tensor imaging protocol added in 2008. Novel measures of the hypothalamus and white matter integrity will be acquired in addition to traditional AD-related cortical and subcortical regions of interests. Aim 4 will continue to maintain FHS' brain donation program operations, including antemortem clinical assessments and post-mortem diagnostic evaluations of all cases that come to autopsy and the convening of clinicopathological meetings to harmonize clinical versus neuropathological diagnoses.