Clinical Core

临床核心

• 批准号: 10256770
• 负责人: Rhoda Au
• 金额: $ 253.88万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10256770
• 关键词: Alzheimer' s Disease; Alzheimer' s disease diagnostic; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Attenuated; Autopsy; Blood Vessels; Brain; Cessation of life; Charge; Clinic; Clinical; Clinical assessments; Code; Cognition; Cognitive; Cognitive aging; Cohort Studies; Collection; Communities; Consensus; Data; Databases; Dementia; Derivation procedure; Detection; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease Resistance; Enrollment; Evaluation; Framingham Heart Study; Frontotemporal Dementia; Generations; Genetic; Genetic Markers; Home; Hypothalamic structure; Impaired cognition; Lewy Bodies; Lewy Body Dementia; Life Style; MRI Scans; Magnetic Resonance Imaging; Measures; Metabolic; Monitor; Neurologist; Neurology; Neuropsychological Tests; Neuropsychology; Nursing Homes; Parents; Participant; Phenotype; Plasma; Predictive Factor; Prevention strategy; Process; Protocols documentation; Research; Resistance; Retrieval; Risk Factors; Spouses; Structure; Time; Update; Vascular Dementia; Voice; adjudication; clinical examination; cognitive change; cohort; data resource; dementia risk; digital; interest; meetings; member; middle age; mild cognitive impairment; multi-ethnic; neuropathology; novel; offspring; operation; programs; protective factors; recruit; repository; research clinical testing; resilience; response; white matter

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.

临床核心旨在建立自 1948 年以来在各个领域获得的非凡数据资源的基础上 弗雷明汉心脏研究的六个队列。重要的是，就科学前提而言，许多 已纵向收集了近 7 年的血管/代谢、生活方式、血浆和遗传测量数据 包括早年到中年时期的几十年，可以用来识别新事物并扩展已知的 阿尔茨海默病（AD）和认知弹性的风险因素和生物标志物，其中一些将被研究 通过本 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存储库，与尸检数据相结合 神经病理学核心可以通过数据核心共享，并可以通过更广泛的研究进一步利用 社区提供检测和预防策略的信息，以降低几十年后 AD 的风险。目标1将 通过进行临床研究，继续对所有队列的痴呆症事件进行监测和诊断 对那些被标记为有痴呆/AD 风险的人进行检查（神经心理学、神经病学），维持每周一次 共识诊断会议，以确定新的痴呆症病例和主要亚型（例如 AD、血管性痴呆） 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证据（例如，死亡时认知完好且 从而可能满足认知弹性的标准）。目标 2 将扩展纵向特征 通过重复施用相同的药物，FHS 队列中所有幸存成员的认知能力 自 1999 年起实施的神经心理学 (NP) 测试方案。NP 评估还将包括 2005 年添加的 NP 测试管理以及更深入的 NP 表型分析，包括编码 错误/无关响应以及从数字语音和数字笔录音中捕获的新颖的衍生测量 分别进行口头和书面答复。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 协议重复采集脑部 MRI 扫描，包括 2008 年添加了弥散张量成像协议的获取。下丘脑和白细胞的新测量 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 的脑捐赠计划运营，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估，并召开 临床病理学会议以协调临床与神经病理学诊断。