Both stroke and dementia are conditions associated with significant disability, mortality, caregiver burden, and health care costs. White matter hyperintensities (WMH) and small cerebral infarcts seen on brain MRI among older adults are common, seem to represent subcortical vascular disease, and are associated with cognitive and functional decline. Preventing infarcts and WMH progression through identification of modifiable risk factors (such as potentially vitamin D deficiency) could reduce disability among older adults. Low serum 25-hydroxyvitamin D [25(OH)D] levels are associated with cardiovascular disease and its risk factors such as hypertension and diabetes. Limited emerging data suggest that vitamin D may be important for cognitive functioning and protective against neurovascular injury. In addition, low 25(OH)D levels have been linked to neurodegenerative disorders such as Alzheimer's. No prior study has evaluated the association of vitamin D with subclinical cerebrovascular disease measured by brain MRI imaging in a prospective fashion thus minimizing the concerns of reverse causation plagued by cross-sectional studies. To date, there has been little research in the area of vitamin D and cognitive decline. This grant proposes to measure serum 25(OH)D levels in 1878 participants (60% women, 50% black race/ethnicity) of the Atherosclerosis Risk in Communities (ARIC) Brain MRI longitudinal study using from stored blood drawn at visit 3 (1993-1994) to address the following 3 aims: (1) To determine the prospective association of 25(OH)D levels with WMH progression and incident subclinical infarcts measured by repeat brain MRI performed 10 years later (2004- 2006) (2) To determine whether lower 25(OH)D levels will be associated with cognitive decline over 14 years of followup in 3 key cognitive domains (memory, language, word processing) (3) To determine whether 25(OH)D deficiency predicts incident clinical stroke/TIA over 10-15 years of followup. A subset will repeat cognitive testing and undergo a third Brain MRI in 2011-2013. Vitamin D deficiency is easy to screen for, although not yet widely accepted in clinical practice. Furthermore vitamin D deficiency is easy and affordable to treat with supplementation. Thus, if an association of 25(OH)D deficiency with stroke and cognitive decline is found and confirmed in subsequent clinical trials, this could have important implications for health policy and patient care with regard to screening and treatment for primary prevention of cerebrovascular disease.

Public Health Relevance

Vitamin D deficiency is common in the United States and has been associated with increased cardiovascular risk. Recent preliminary data suggests that adequate levels of vitamin D may be also important for preventing stroke, cognitive decline, and dementia, but this has been less well studied. We plan to measure vitamin D levels from stored blood from participants of the Atherosclerosis Risk In Communities (ARIC) Brain Magnetic Resonance Imaging (MRI) study who already completed 2 brain MRI scans taken 10 years apart and 4 sessions of comprehensive cognitive testing spanning 14 years to evaluate the role of vitamin D in brain aging.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Babcock, Debra J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
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
Tibuakuu, Martin; Zhao, Di; de Boer, Ian H et al. (2017) Relation of Serum Vitamin D to Risk of Mitral Annular and Aortic Valve Calcium (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol 120:473-478
Chin, Kathleen; Appel, Lawrence J; Michos, Erin D (2017) Vitamin D, Calcium, and Cardiovascular Disease: A""D""vantageous or ""D""etrimental? An Era of Uncertainty. Curr Atheroscler Rep 19:5
Chin, Kathleen; Zhao, Di; Tibuakuu, Martin et al. (2017) Physical Activity, Vitamin D, and Incident Atherosclerotic Cardiovascular Disease in Whites and Blacks: The ARIC Study. J Clin Endocrinol Metab 102:1227-1236
Kim, Samuel M; Lutsey, Pamela L; Michos, Erin D (2017) Vitamin D and Cardiovascular Disease: Can Novel Measures of Vitamin D Status Improve Risk Prediction and Address the Vitamin D Racial Paradox? Curr Cardiovasc Risk Rep 11:
Zhao, Di; Ouyang, Pamela; de Boer, Ian H et al. (2017) Serum vitamin D and sex hormones levels in men and women: The Multi-Ethnic Study of Atherosclerosis (MESA). Maturitas 96:95-102
Faridi, Kamil F; Zhao, Di; Martin, Seth S et al. (2017) Serum vitamin D and change in lipid levels over 5 y: The Atherosclerosis Risk in Communities study. Nutrition 38:85-93
Yao, Lu; Folsom, Aaron R; Pankow, James S et al. (2016) Parathyroid hormone and the risk of incident hypertension: the Atherosclerosis Risk in Communities study. J Hypertens 34:196-203
Lupton, Joshua R; Faridi, Kamil F; Martin, Seth S et al. (2016) Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study. J Clin Lipidol 10:72-81.e1
Michos, Erin D; Lutsey, Pamela L (2016) 25-hydroxyvitamin D Levels and Coronary Heart Disease Risk Reclassification in Hypertension--Is it worth the ""hype""? Atherosclerosis 245:237-9

Showing the most recent 10 out of 29 publications