Clinical Core

临床核心寻求建立在自1948年以来获得的、横跨 弗雷明翰心脏研究的六个队列。重要的是，就科学前提而言，有那么多 血管/新陈代谢、生活方式、血浆和遗传指标已纵向收集了近7年 包括早年到中年时期的几十年，可以用来识别新的和扩展已知的 阿尔茨海默病(AD)的风险因素和生物标记物以及认知恢复能力，其中一些将被追踪 通过这份U19申请中提出的三个项目。FHS认知的广度和深度 衰老和痴呆症数据提供了一个表型存储库，与来自 神经病理核心可通过数据核心共享，并可被更广泛的研究进一步利用 社区为检测和预防战略提供信息，这些战略将降低几十年后AD的风险。目标1将 通过开展临床研究，持续监测和诊断痴呆事件的所有队列 对那些被标记为痴呆症/阿尔茨海默病风险人群的检查(神经心理学、神经病学)，保持每周 共识诊断会议，以确定新的痴呆症病例和主要亚型(例如，阿尔茨海默病、血管 痴呆、额-颞叶痴呆、路易体)和MCI亚型(遗忘性单域、遗忘性多领域 领域、非遗忘单一领域、非遗忘多领域)，并确定所有人的最终认知状态 FHS参与者在死亡后，包括没有记录的痴呆症证据(例如，死亡时认知完好无损 从而潜在地满足认知复原力的标准)。目标2将扩展纵向表征 通过重复使用FHS队列中所有幸存成员的认知 自1999年起实施神经心理学(NP)测试方案。NP评估还将包括 管理2005年增加的NP测试以及更深层次的NP表型，包括编码 从要捕获的数字语音和数字笔录音中获取的错误/无关响应和新的派生措施 分别是口头和书面答复。目标3将扩展对大脑结构的纵向表征 通过重复获取使用1999年开始实施的MRI方案的脑MRI扫描，包括 2008年增加了扩散张量成像协议的采集。测量下丘脑和白质的新方法 除了与AD相关的传统皮质和皮质下感兴趣区外，还将获得物质完整性。 AIM 4将继续维持FHS的脑捐赠计划操作，包括临终临床 对所有进行尸检的病例进行评估和死后诊断评估，并召集 临床病理会议，以协调临床和神经病理诊断。

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.