Clinical Core

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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.