The incidence rates of cerebral vascular disease (CBVD) and its associated cognitive impairment are rapidly increasing around the world. African Americans (AA) and patients with diabetes have higher rates of CBVD and associated cognitive dysfunction. However, the impact of race on the development of CBVD assessed by Magnetic Resonance Imaging (MRI) of the brain and cognitive testing remains poorly studied. Controversy exists regarding the severity of cerebral small blood vessel disease in AA, relative to European Americans (EA). Small blood vessel disease appears as """"""""white mater hyperintensities"""""""" (WMH) on brain MRI. Several studies have reported more WMH, and some less WMH, in AA relative to EA. Existing studies failed to account for the effects of potentially modifiable environmental risk factors that impact development of WMH, such as access to healthcare, socioeconomic status, blood pressure and blood sugar control. This application proposes to determine the environmental and genetic factors that underlie cerebral structural and functional changes in 600 AA with type 2 diabetes. We plan to re-evaluate 600 AA in the ongoing AA-Diabetes Heart Study (AA-DHS) with cerebral MRI and a battery of cognitive tests;these individuals have previously been tested for the presence of silent (sub-clinical) heart disease and all have DNA available for genetic testing. We plan to test for relationships between alterations in brain structure (including WMH) and brain function with cognitive performance in these AA subjects. To determine whether racial differences in the relationships between CBVD and cognitive performance are present, results in AA would be contrasted with similar data in EA who have T2D from the related Diabetes Heart Study (DHS-MIND). This proposal will attempt to detect the inherited and environmental factors that produce susceptibility to CBVD in AA. We expect that modifiable environmental risk factors may explain the higher rates of CBVD reported in existing studies of AA. Furthermore, attention to these modifiable risk factors may reduce the rates of CBVD and cognitive dysfunction in the high risk AA population.

Public Health Relevance

African Americans (AA) and individuals with diabetes have higher rates of cerebrovascular disease (CBVD) and associated impairment in cognitive function. This project proposes to evaluate CBVD using Magnetic Resonance Imaging (MRI) of the brain and performing a battery of cognitive tests in AA with type 2 diabetes. Results would be compared to existing MRI and cognitive data in a cohort of European Americans with type 2 diabetes to determine whether racial differences exist in the relationship between CBVD and cognitive performance and to identify the environmental and inherited causes of CBVD in the high risk and understudied AA community.

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
Corriveau, Roderick A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Wake Forest University Health Sciences
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Hughes, Timothy M; Sink, Kaycee M; Williamson, Jeff D et al. (2018) Relationships between cerebral structure and cognitive function in African Americans with type 2 diabetes. J Diabetes Complications 32:916-921
Freedman, Barry I; Sink, Kaycee M; Hugenschmidt, Christina E et al. (2017) Associations of Early Kidney Disease With Brain Magnetic Resonance Imaging and Cognitive Function in African Americans With Type 2 Diabetes Mellitus. Am J Kidney Dis 70:627-637
McLean, Nicholas O; Robinson, Todd W; Freedman, Barry I (2017) APOL1 Gene Kidney Risk Variants and Cardiovascular Disease: Getting to the Heart of the Matter. Am J Kidney Dis 70:281-289
Hughes, Timothy M; Sink, Kaycee M (2016) Hypertension and Its Role in Cognitive Function: Current Evidence and Challenges for the Future. Am J Hypertens 29:149-57
Raffield, Laura M; Cox, Amanda J; Freedman, Barry I et al. (2016) Analysis of the relationships between type 2 diabetes status, glycemic control, and neuroimaging measures in the Diabetes Heart Study Mind. Acta Diabetol 53:439-47
Palmer Allred, Nicholette D; Raffield, Laura M; Hardy, Joycelyn C et al. (2016) APOE Genotypes Associate With Cognitive Performance but Not Cerebral Structure: Diabetes Heart Study MIND. Diabetes Care 39:2225-2231
Freedman, Barry I; Gadegbeku, Crystal A; Bryan, R Nick et al. (2016) APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume. Kidney Int 90:440-449
Hsu, Fang-Chi; Yuan, Mingxia; Bowden, Donald W et al. (2016) Adiposity is inversely associated with hippocampal volume in African Americans and European Americans with diabetes. J Diabetes Complications 30:1506-1512
Maldjian, Joseph A; Shively, Carol A; Nader, Michael A et al. (2016) Multi-Atlas Library for Eliminating Normalization Failures in Non-Human Primates. Neuroinformatics 14:183-90
Raffield, Laura M; Brenes, Gretchen A; Cox, Amanda J et al. (2016) Associations between anxiety and depression symptoms and cognitive testing and neuroimaging in type 2 diabetes. J Diabetes Complications 30:143-9

Showing the most recent 10 out of 27 publications