For 34 years, the Clinical Core has recruited, assessed, and followed well-characterized adults 65 years and older, both those who are cognitively normal (CN) and those with symptomatic Alzheimer disease (AD), with clinical and cognitive assessments at entry and annually thereafter. This Core will continue to serve the needs of Healthy Aging and Senile Dementia Program Project research projects with well-established and effective protocols, procedures, and infrastructure. A particular strength of the Core is its expertise in clinically identifying the earliest symptomatic stages of AD in comparison with cognitively normal aging. In this renewal, the Clinical Core will focus on three experimental groups: (1) ?CN bio-neg? - Cognitively normal (CN), Clinical Dementia Rating (CDR) = 0), biomarker-negative participants; (2) ?Preclinical AD? - CN, CDR=0, biomarker- positive participants; and (3) ?Symptomatic AD? - Very mildly or mildly demented AD, CDR?0.5, biomarker- positive participants. There is additional emphasis on enrollment of African American participants. All participants return annually for clinical and psychometric assessments. Biomarker collection (CSF, blood, MRI, amyloid and tau PET, and sleep studies) will occur approximately every 3 years. Project 4 will utilize a smartphone application to test participants remotely in one-week bursts that occur every 6 months. In this renewal application, the Core's Specific Aims are to: 1. Maintain the current active cohort of participants, carefully characterized as to the presence or absence of symptomatic AD, to support longitudinal studies of the clinical, cognitive, behavioral, and biomedical correlates of symptomatic AD in comparison with normal aging and to mark the transition of CN participants with preclinical AD to cognitive impairment. 2. Annually enroll and assess new participants to enrich the Longitudinal Cohort for biomarker positivity and to replenish the Core's cohort in proportion to attritional losses. 3. Provide annual clinical and cognitive data to all Cores and Projects, by working closely with other Cores to coordinate data sharing and management and to integrate the Core's activities with the scientific goals of the program project. 4. Support Core D: Neuropathology through our voluntary autopsy consent program and obtain comprehensive information about cognitive status at time of death to support clinicopathological correlations. 5. Support Core D: Neuropathology, Core E: Imaging, and all Projects by referring, as appropriate, clinically well-characterized participants and/or their data.
Core B: Clinical Project Narrative The Clinical Core recruits, enrolls and maintains the registry of older research participants in the Healthy Aging and Senile Dementia PPG who undergo multiple complex and invasive procedures longitudinally. The objectives of this study are to identify the earliest brain changes of AD that correlate with the transition from cognitive normality to symptomatic AD.
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