The vascular contribution to cognitive impairment and dementia (VCID) is a critical area of research related to Alzheimer's Disease (AD) and the AD-related dementias (ADRD), particularly given its value in identifying areas for intervention and prevention. This proposal is a renewal application to the Atherosclerosis Risk in Communities (ARIC) Neurocognitive Study (ARIC-NCS), a community-based cohort from four U.S. communities, which, when first funded in 2011-2013, added detailed cognitive evaluation and adjudication of mild cognitive impairment (MCI and dementia, along with brain imaging and new vascular and cardiac markers, to 25 years of careful measurement and collection of cardiovascular risk factors, markers, and events through the parent ARIC study. Our previous studies have demonstrated the importance of midlife vascular risk factors in the development of later-life cognitive decline, dementia, and amyloid deposition, and, given the biracial structure of the cohort, have considered racial disparities in some of these risk factors and outcomes. In this renewal, we propose to not only study these cognitive impairments at older cohort ages with greater rates of MCI and dementia, in order to identify subsets which may offer potential avenues for late-life prevention of AD/ADRD's, but also to consider if similar midlife risk factors impact late-life physical function declines, as this may represent a parallel and possibly alternative pathway to prevention of both physical function impairment and AD/ADRD's. Furthermore, we will evaluate factors associated with maintenance of cognitive and physical function, as well as the concept of cognitive reserve: better-than-expected scores or less-than-expected decline for an observed level of brain pathology. To pursue these questions, we will perform annual visits of the ARIC cohort, for four total visits, with detailed neurocognitive testing and brain imaging with MRI and florbetapir PET in 1000 participants, to build upon the prior 30+ years' worth of detailed vascular risk factor and marker and lifestyle measurements, starting when participants were middle-aged. The size and diversity of our cohort allows us to conduct sex- and race-specific analyses. This renewal will provide valuable information about opportunities for prevention for AD/ADRD's, with direct relevance not only to the recent ADRD summit recommendations, but also the first goal of the National Alzheimer's Project Act (NAPA) to prevent and treat AD by 2025. Through our ongoing data sharing endeavors and collaborations with other studies, as well as the opportunities provided for ancillary studies building on the ARIC NCS study, the study will reach beyond the proposed aims described here.
One of the most promising avenues for prevention of Alzheimer's Disease and related dementias is through the prevention of vascular risk. This renewal application will build upon our prior studies, which demonstrated the importance of midlife vascular risk factors in the development of cognitive decline and dementia, by also considering factors associated with maintenance of both cognitive and physical function. Finally, this study will identify potential targets for prevention by evaluating a concept called cognitive reserve, which refers to maintenance of cognitive function despite abnormalities seen on brain imaging; this set of studies could contribute to prevention and reduction in the worldwide burden of Alzheimer's and other dementias.
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