Reported rates of dementia differ by race although most studies have not focused on carefully measured outcomes confounding by education or other demographic factors nor have they studied other outcomes to dementia. of vascular risk factors explain at least some of these observed disparities by race but particular risk factors including diabetes may differentially affect the brain in African-American versus white participants. In addition we will review some of the disparities by race in studies focusing on the genetics of stroke small vessel disease and dementia. INTRODUCTION Disparities in stroke rates and stroke-related mortality are commonly reported in the so-called “stroke belt” 1 2 with higher rates among African-American individuals than among whites. Beyond clinical stroke African-Americans appear to be at increased risk for adverse subclinical brain changes and related sequelae including cognitive impairment and dementia.3 Possible explanations for the excess burden of unfavorable neurologic outcomes in African-Americans include: 1) higher prevalence of vascular risk factors including hypertension 4 diabetes 5 and smoking; 2) earlier onset of risk and greater severity or more poorly controlled6 risk factors; 3) greater Rabbit Polyclonal to CHST2. sensitivity to risk factors 3-O-(2-Aminoethyl)-25-hydroxyvitamin D3 (i.e. greater target organ damage at comparable levels of risk factor severity) or 4) differences in the social and environmental context. However the precise cause of excess risk in African-Americans remains to be determined. In this report we review findings from the Atherosclerosis Risk in Communities (ARIC) study with over 25 years of long-term follow-up on clinical and subclinical brain outcomes in a large cohort of African-American and white men and women. We will summarize findings related to stroke subclinical cerebrovascular disease (silent infarcts leukoaraiosis) brain atrophy cognitive decline and dementia with particular emphasis on disparities by race. We will provide evidence that observed disparities by race may be due to differences in risk factor presence severity and control. 3-O-(2-Aminoethyl)-25-hydroxyvitamin D3 In addition we will review genetic differences in or other 3-O-(2-Aminoethyl)-25-hydroxyvitamin D3 explanations for some of these observed associations by race and will discuss plans to evaluate unanswered questions regarding race-specific disparities in brain health. The ARIC study ARIC study participants were randomly recruited from four U.S. communities (Forsyth County NC (both African-American and white participants); Jackson MS (all African-American participants); Washington County MD (majority white participants); and suburbs of Minneapolis MN (majority white participants)) with an initial visit in 1987-1989 when participants were 45-64 years old.7 Participants have had four additional in-person visits in the field centers associated with each community: in 1990-1992 (visit 2) 1993 (visit 3) 1996 (visit 4) and most recently in 2011-2013 (visit 5; Table 1). All participants are 3-O-(2-Aminoethyl)-25-hydroxyvitamin D3 contacted via annual follow-up (AFU) calls and records for hospitalized events are obtained abstracted and reviewed via expert adjudication as well as an algorithmic diagnosis; stroke cases are therefore all identified by expert review. Dementia was not reviewed previously in ARIC and for the studies summarized in this paper when used as an outcome relied upon hospitalization codes.8 Whites and African-Americans all had the same standardized visit protocols (table 1) with the exception of the MRI visits at Visit 3 and the ARIC Brain MRI visit when recruitment was only at the Forsyth County NC and Jackson MS sites thus leading to a larger proportion of African-Americans than otherwise represented in the cohort. Table 1 Atherosclerosis Risk in Communities (ARIC) study visit timeline. The cohort underwent cognitive testing with the Delayed Word Recall Digit Symbol Substitution and the Word Fluency assessments at visits 2 4 5 and the Brain MRI ancillary visit with a more detailed neurocognitive battery also administered at the Brain MRI visit (to a subset; Table 1) and at visit 5. Stroke The ARIC study design allows evaluation not only of stroke prevalence but incidence which allows not only comparison of rates by race but also comparison of risk factors in association with incident cases. At the onset of the ARIC study prevalent stroke or transient ischemic attack (TIA) was estimated in 5.5% of African-Americans but in 6.3% of whites.9 At the Forsyth County NC site (the only site with both African-Americans and whites) rates for prevalent stroke or TIA were consistently higher for African-Americans than for whites.9 In addition over the course of the 25 years since.