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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
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Neurological, Aging and Musculoskeletal Epidemiology (NAME)
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Wright, Jacqueline
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Johns Hopkins University
Public Health & Prev Medicine
Schools of Public Health
United States
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Chen, Lin Y; Norby, Faye L; Gottesman, Rebecca F et al. (2018) Association of Atrial Fibrillation With Cognitive Decline and Dementia Over 20 Years: The ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). J Am Heart Assoc 7:
West, Nancy A; Tingle, Jonathan V; Simino, Jeannette et al. (2018) The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity. Alzheimer Dis Assoc Disord 32:131-136
Deal, Jennifer A; Sharrett, A Richey; Rawlings, Andreea M et al. (2018) Retinal signs and 20-year cognitive decline in the Atherosclerosis Risk in Communities Study. Neurology 90:e1158-e1166
Walker, Keenan A; Windham, B Gwen; Brown, Charles H et al. (2018) The Association of Mid- and Late-Life Systemic Inflammation with Brain Amyloid Deposition: The ARIC-PET Study. J Alzheimers Dis 66:1041-1052
Schneider, Andrea L C; Zhao, Di; Lutsey, Pamela L et al. (2018) Serum Vitamin D Concentrations and Cognitive Change Over 20 Years: The Atherosclerosis Risk in Communities Neurocognitive Study. Neuroepidemiology 51:131-137
Witt, Lucy S; Rotter, Jason; Stearns, Sally C et al. (2018) Heart Failure and Cognitive Impairment in the Atherosclerosis Risk in Communities (ARIC) Study. J Gen Intern Med 33:1721-1728
Walker, Keenan A; Windham, B Gwen; Power, Melinda C et al. (2018) The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study. Neurobiol Aging 68:26-33
Power, Melinda C; Rawlings, Andreea; Sharrett, A Richey et al. (2018) Association of midlife lipids with 20-year cognitive change: A cohort study. Alzheimers Dement 14:167-177
Lin, Frank R (2018) Time for a Top-Down Approach to Hearing Aid Affordability and Accessibility. Am J Public Health 108:166-168
Lee, Alexandra K; Rawlings, Andreea M; Lee, Clare J et al. (2018) Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) cohort study. Diabetologia 61:1956-1965

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