Dementia and mild cognitive impairment (MCI) pose a large and increasing health and societal burden on the aging US population. New studies suggest that microvascular disease makes a substantial contribution to dementia and MCI. A few long-followed cohorts show strong associations of mid-life hypertension, diabetes, and smoking with dementia at older age in contrast to weak associations in studies of the elderly. An observational study relating dementia, MCI and cerebral changes observable on MRI to midlife vascular risk factors has the promise of suggesting dementia prevention strategies where none currently exist.
Aims : The proposed ARIC Neurocognitive study (ARIC-NCS) will focus on prediction of cognitive impairment from mid-life vascular risk factors and markers through a 5 center R01 ancillary study to the large, bi-ethnic prospective ARIC cohort study. Prediction is expected to be particularly strong in African-Americans and persons whose dementia or MCI is diagnosed as vascular or accompanied by MRI cerebrovascular signs.
Aims are to: 1) estimate the prevalence of dementia/MCI by race and sex in participants aged 70-89, 2) determine whether midlife vascular factors (risk factors and markers of macrovascular and microvascular disease) predict dementia, MCI and cognitive change, 3) determine whether the associations between midlife vascular factors and dementia/MCI differ by dementia/MCI subtype defined clinically or by MRI signs, 4) identify cerebral markers associated with cognitive change, including progression of MRI ischemic burden and atrophy across 3 MRI scans spanning 17 years, and 5) identify genomic regions containing susceptibility loci for cognitive decline, using 106 SNPs spanning the genome. Design/Methods: Prospective study of >7000 residents aged 70-89 in 4 US communities adding a 24-year follow-up evaluation with detailed neurocognitive assessment, retinal photography, lab assays and medical record review to 4 previous exams (1987-1999) which included midlife cognitive testing. Two thousand dementia and MCI cases and controls will undergo cerebral MRI with central measurement of cerebrovascular signs and brain volumes. ARIC is uniquely situated for this research since predictors already measured include macrovascular (carotid thickness, plaque and distensibility, peripheral artery disease) and microvascular markers (retinal arteriolar narrowing and nicking, retinal hemorrhage, exudates, and microaneurysms, microalbuminuria), cardiovascular events, hemostatic factors in 5 pathways, apoE, 106 SNPs across the genome, all major cardiovascular risk factors, and in many participants, one or two prior cerebral MRI exams. Implications: Longitudinal observational study of midlife vascular risk factors for cognitive and cerebral changes in the ARIC cohort will elucidate factors underlying ethnic disparities in dementia burden and provide the scientific basis for prevention strategies by identifying vascular therapeutic targets, optimal timing for interventions and useful intermediate outcomes.

Public Health Relevance

ARIC-NCS will provide the means for identifying groups at greater risk for dementia who might benefit from risk factor modification. Its public health relevance is evident given the growing magnitude of dementia and mild cognitive impairment, the realization of a strong association with vascular disease, and the reasonable assumption that the risk of dementia and mild cognitive impairment, like strokes, can be substantially reduced by risk factor modification.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-HOP-G (60))
Program Officer
Ni, Hanyu
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Public Health & Prev Medicine
Schools of Public Health
United States
Zip Code
Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer et al. (2014) Polygenic overlap between kidney function and large artery atherosclerotic stroke. Stroke 45:3508-13
Mayeda, Elizabeth R; Haan, Mary N; Neuhaus, John et al. (2014) Type 2 diabetes and cognitive decline over 14 years in middle-aged African Americans and whites: the ARIC Brain MRI Study. Neuroepidemiology 43:220-7
Gottesman, Rebecca F; Rawlings, Andreea M; Sharrett, A Richey et al. (2014) Impact of differential attrition on the association of education with cognitive change over 20 years of follow-up: the ARIC neurocognitive study. Am J Epidemiol 179:956-66
Koton, Silvia; Schneider, Andrea L C; Rosamond, Wayne D et al. (2014) Stroke incidence and mortality trends in US communities, 1987 to 2011. JAMA 312:259-68
Hanff, Thomas C; Sharrett, A Richey; Mosley, Thomas H et al. (2014) Retinal microvascular abnormalities predict progression of brain microvascular disease: an atherosclerosis risk in communities magnetic resonance imaging study. Stroke 45:1012-7
Gottesman, Rebecca F; Schneider, Andrea L C; Albert, Marilyn et al. (2014) Midlife hypertension and 20-year cognitive change: the atherosclerosis risk in communities neurocognitive study. JAMA Neurol 71:1218-27
Rost, Natalia S; Sadaghiani, Saloomeh; Biffi, Alessandro et al. (2014) Setting a gold standard for quantification of leukoaraiosis burden in patients with ischemic stroke: the Atherosclerosis Risk in Communities Study. J Neurosci Methods 221:196-201
Foroud, Tatiana; Lai, Dongbing; Koller, Daniel et al. (2014) Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7. Stroke 45:3194-9
Dadu, Razvan T; Fornage, Myriam; Virani, Salim S et al. (2013) Cardiovascular biomarkers and subclinical brain disease in the atherosclerosis risk in communities study. Stroke 44:1803-8
Yasar, Sevil; Xia, Jin; Yao, Wenliang et al. (2013) Antihypertensive drugs decrease risk of Alzheimer disease: Ginkgo Evaluation of Memory Study. Neurology 81:896-903

Showing the most recent 10 out of 13 publications