ARIC Neurocognitive Study (ARIC-NCS) Renewal 4 of 5

? DESCRIPTION (provided by applicant): ARIC Neurocognitive Study (ARIC-NCS) Renewal 1 of 5 Johns Hopkins Washington County Field Center Principal Investigator (Josef Coresh, MD, PhD). Rationale: Dementia and mild cognitive impairment (MCI) pose a large and increasing health and societal burden on the aging US population and ARIC is uniquely suited to contribute critical information on the vascular, and potentially preventable, contributions to dementia and MCI incidence. Progress: ARIC NCS (Visit 5: 2011-13) measured a battery of cognitive tests on ARIC participants aged 70- 89 and all study goals were met or exceeded, completing 6,538 exams, 2009 MRIs (520 in African-Americans) with a large number of dementia and Mild Cognitive Impairment (MCI) cases currently being adjudicated. Early papers were submitted within a month of completion of data collection and promising work is ongoing (~50 manuscript proposals). Collection of cognitive decline in late-life is needed and time sensitive since the cohort is experiencing ~5% annual mortality (mean age 78 years). Design: Follow-up cognitive testing (~30-year f/u, 2015-2018), at ages where cognitive decline begins to manifest across several domains or accelerates, thus providing many additional, diverse outcomes in the ARIC cohort (15,792 men and women ages 45-65 recruited in 1986-1989 and followed with detailed examinations). Outcomes: The late life cognitive outcomes targeted in the renewal differ from the one-time static measures of cognitive performance now available from the ARIC NCS baseline exam. A. Decline in global cognitive ability, executive function/processing speed, memory, and language - assessed during in ~4214, ~4 years after V5 (more comprehensive than possible in previous visits which had a more limited 3 test battery similar to older cardiovascular studies; 2nd visit in oldest subset). B. Incidence of MCI and dementia - detect ~1,521 dementia 1,134 MCI incident cases using procedures established after NCS V5 (2011-2013; expanded ARIC's semi-annual calls; response rate ~90%). C. Progression from MCI to dementia - following the 1,402 MCI cases identified at V5. Aims: We will study a wealth of modifiable vascular risk factors and measures of microvascular disease and atherosclerosis in midlife, many not available in other studies of cognition, for their contribution to late life cogntive decline and physical function. We will study the detailed 3T brain MRI imaging at visit 5 as a risk factor for cognitive decline at older age. We will determine if any of these associations are different in African- Americans, where longitudinal cognitive data are nearly non-existent and vascular burden is high, than in white ARIC participants. We will share these data all ARIC ancillaries (Appendix 4), including detailed genetic and biochemical studies across the lifespan. Summary: This NCS visit (V6: 2015-2018; V7: 2017-2018 in oldest subset) will advance knowledge about the potentially modifiable vascular contribution to cognitive decline in late life and provide the cornerstone for other synergistic ancillary studies by a large community of investigators which would not otherwise be possible.