Introduction: Stark disparities exist in the prevalence of Alzheimer’s disease (AD) and related dementias (ADRD) by social determinants of health (SDoH). Limited research is available on associations of SDoH with AD/ADRD biomarkers. This study aims to assess the impact of SDoH measures on ADRD-associated neuroimaging and plasma biomarkers. Hypothesis: SDoH measures of area deprivation index (ADI), social vulnerability index (SVI), and environmental justice index (EJI) will be positively associated with poorer ADRD-associated neuroimaging and plasma biomarkers, and cardiometabolic health will partially account for this association. Methods: This study includes participant data from the Wake Forest Alzheimer’s Disease Research Center from baseline visits. Independent SDoH variables include ADI, SVI, and EJI. Dependent variables include cortical thickness and white matter hyperintensity (WMH) volume, adjusted for intracranial volume, from MRI, and plasma glial fibrillary acidic protein (GFAP) and pTau-181. We conducted bivariate and hierarchical multivariable linear regressions, with demographics (age, sex, education,&cognitive diagnosis) [Model 1], additional adjustment for cardiometabolic health with cardiometabolic index (CMI) [Model 2], and estimated glomerular filtration rate (eGFR) [Model 3; for plasma biomarkers] as covariates. Results: In bivariate analyses, a significant negative association was observed between ADI and cortical thickness (β=-0.08, p=0.047). No other significant associations were observed. In multivariable analyses (Table 1) , EJI was negatively associated with cortical thickness (β=-0.04, p=0.04), and both ADI and SVI were negatively associated with GFAP (β=-0.36, p<0.01&β=-0.52, p<0.01, respectively), in Model 1. Additionally adjusting for CMI in Model 2, the negative associations of ADI and SVI with GFAP were preserved (β=-0.33, p=0.02&β=-0.50, p<0.01, respectively). In Model 3, further adjusting for eGFR, ADI remained negatively associated with GFAP (β=-0.37, p=0.03). Conclusions: Place-based environmental injustice was associated with lower cortical thickness, while neighborhood disadvantage and social vulnerability were associated with higher GFAP levels in adjusted models, suggesting place-based SDoH may be associated with structural brain changes and neuroinflammation. The impact of place-based SDoH needs to be further studied in association with ADRD biomarkers to better understand how we may tackle SDoH among older adults.

Social determinants of health (SDoH) are important environmental factors in cardiometabolic risk and cognitive aging. Area Deprivation Index (ADI) is a measure of neighborhood-level socioeconomic disadvantage and has been studied in normal cognition (NC), but relatively less is known about impact in those with mild cognitive impairment (MCI). This study explores, in participants with NC and MCI enrolled in the Wake Forest ADRC Clinical Core, baseline measures of metabolic risk (Oral Glucose Tolerance Testing of blood glucose 120-minute post-challenge; OGTT-120), cognition (Preclinical Alzheimer’s Cognitive Composite; PACC), demographics (age, education, diagnosis, race, sex), and participant national ADI rank (using baseline home address). Consensus diagnosis of NC and MCI was adjudicated by a panel of experts. Demographics of community-dwelling adults enrolled as a convenience sample in the Wake Forest ADRC with metabolic and cognitive measures by cognitive status is listed in Table 1. MCI participants, compared with CN, were older, more likely male and white, with lower education and PACC, and higher ADI (higher = more disadvantaged). Significant differences in ADI were observed when participants were stratified by race (Figure 1); post-hoc tests indicate significantly higher ADI in Black compared to white participants, and to some degree, by higher ADI among Black participants compared with Asian participants. OGTT-120 in participants with NC (n = 265) and MCI (n = 156) was not significantly associated with ADI national rank (Figure 2A); when controlling for age, sex, education, and diagnosis, there was still no association between OGTT-120 and ADI. Higher ADI was significantly associated with lower PACC scores in individuals with NC (p = 0.044), but not MCI (Figure 2B); this association remained significant (p = 0.004) independent of age, sex, education, and diagnosis (all covariates p<0.001). Among community-dwelling older adults, ADI national rank differs by participant race. OGTT-120 does not correlate with ADI in participants with NC or MCI. PACC scores correlate negatively with ADI national rank in participants with NC, but not MCI; this relationship remained when controlling for covariates. Further analyses are necessary to examine the association between cardiometabolic risk and ADI.

Abstract Background: African American (AA) men are, on average, diagnosed with prostate cancer at younger ages and more advanced stages than white men and therefore may be at greater risk of having cancer treatment negatively impact their work ability and job opportunities. This longitudinal, observational study aims to better identify whether race, household income (< or ≥ 300% the U.S. poverty line), or work-related factors may place some men with prostate cancer at greater risk for experiencing negative employment impacts from cancer treatment and its side effects. Here we report on individual and employment-related factors by race and income prior to treatment initiation. Methods: AA and white men who were expected to undergo primary curative treatment (prostatectomy or radiation therapy) in the near future for prostate cancer were recruited through the Wake Forest NCORP Research Base (UG1CA189824, NCT03963739) between 2019 and 2023. Participants were AA or white, recently employed, expecting to be working in 6 months, and willing to disclose income status. Participants answered questions prior to treatment initiation related to employment and working conditions, work ability, and demographic characteristics. Differences in outcomes by race and income were analyzed with Fisher's exact test or t-test. Results: The baseline questionnaire was completed by 244 men; 48% AA/52% white and 64% higher/36% lower Income. Most planned treatments included radiation therapy (60%) and/or prostatectomy (41%), with no statistical differences by income or race. Higher income men were significantly more likely than lower income men to be married, have attained higher education, have a management or professional job, work full-time, be a permanent employee, salaried, eligible to retain their job under FMLA, work in an office/home, have a psychologically demanding job, and less likely to hold a physically demanding job. AA men were significantly less likely than white men to be married, have attained higher education, have a management or professional job, or work in an office/home. AA men were more continuously hopeful about the future (69%) compared to white men (52%; p=0.0079). There were no significant differences across categories in age, perceived current work ability in relation to physical (69% very good) or mental (71% very good) demands, or number of jobs held. Prior to treatment, participants reported almost optimal current work ability (mean 9.0, SD 1.2) with a range of 0 to 10 with 10 as best possible work ability. Conclusion: In this study, income category is a greater predictor than race of job characteristics that may impact employment following definitive prostate cancer treatment. Citation Format: Joanne C. Sandberg, Emily V. Dressler, Louis S. Krane, Karen M. Winkfield, Lingyi Lu, Andrew M. Mayfield, Drew C. Monitto, J. Daniel Pennington, Deimante M. Tamkus, Glenn J. Lesser. Employment characteristics and work ability differences by race and income before undergoing curative treatment for prostate cancer (PCW WF-1802) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 805.

Machine learning models are increasingly being used to estimate “brain age” from neuroimaging data. The gap between chronological age and the estimated brain age gap (BAG) is potentially a measure of accelerated and resilient brain aging. Brain age calculated in this fashion has been shown to be associated with mortality, measures of physical function, health, and disease. Here, we estimate the BAG using a voxel-based elastic net regression approach, and then, we investigate its associations with mortality, cognitive status, and measures of health and disease in participants from Atherosclerosis Risk in Communities (ARIC) study who had a brain MRI at visit 5 of the study. Finally, we used the SOMAscan assay containing 4877 proteins to examine the proteomic associations with the MRI-defined BAG. Among N = 1849 participants (age, 76.4 (SD 5.6)), we found that increased values of BAG were strongly associated with increased mortality and increased severity of the cognitive status. Strong associations with mortality persisted when the analyses were performed in cognitively normal participants. In addition, it was strongly associated with BMI, diabetes, measures of physical function, hypertension, prevalent heart disease, and stroke. Finally, we found 33 proteins associated with BAG after a correction for multiple comparisons. The top proteins with positive associations to brain age were growth/differentiation factor 15 (GDF-15), Sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SEVP 1), matrilysin (MMP7), ADAMTS-like protein 2 (ADAMTS), and heat shock 70 kDa protein 1B (HSPA1B) while EGF-receptor (EGFR), mast/stem-cell-growth-factor-receptor (KIT), coagulation-factor-VII, and cGMP-dependent-protein-kinase-1 (PRKG1) were negatively associated to brain age. Several of these proteins were previously associated with dementia in ARIC. These results suggest that circulating proteins implicated in biological aging, cellular senescence, angiogenesis, and coagulation are associated with a neuroimaging measure of brain aging.

INTRODUCTION: Neighborhood disadvantage may be an important determinant of cardiometabolic health and cognitive aging. However, less is known about relationships among individuals with mild cognitive impairment (MCI). METHODS: The objective of this study is to investigate the relationship between neighborhood disadvantage measured by national Area Deprivation Index (ADI) rank with measures of cardiometabolic health and cognition among Wake Forest (WF) Alzheimer's Disease Research Center (ADRC) participants, with and without MCI. RESULTS: ADI was positively associated with blood pressure and cardiometabolic index (CMI), and negatively associated with global and Preclinical Alzheimer's Cognitive Composite (PACC5) scores, in cognitively unimpaired (CU) individuals. ADI was only positively associated with hemoglobin A1c (HbA1c) in MCI. DISCUSSION: Neighborhood disadvantage is associated more strongly with measures of cardiometabolic health and cognition among CU individuals rather than MCI. These findings demonstrate a need for structural solutions to address social determinants of health in an attempt to reduce cardiometabolic and cognitive risks.

Background: Adjuvant radiotherapy (RT) following surgery significantly improves breast cancer survival. However, some patients, particularly minorities, develop early adverse skin reactions (EASRs) or skin toxicities that negatively impact the quality of life (QOL). We assess RT-related EASRs and QOL using clinician-reported outcomes (CROs) and patient-reported outcomes (PROs) in a large multi-racial/ethnic breast cancer population. Methods: This prospective study recruited 1,000 breast cancer patients undergoing RT through the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base between 2011 and 2013. We used the Oncology Nursing Society (ONS) Skin Toxicity Criteria for CROs and Skindex-16 (SD-16) for PROs. Results: This study included 405 non-Hispanic whites (NHW), 277 black/African Americans (AA), 241 HW, 62 Asian/Pacific Islanders (ASPI), and 15 others. About 42% and 15% of patients developed RT-induced ONS grade 3+ and 4+ skin toxicities, respectively. RT-induced EASRs differed significantly by race/ethnicity at mid-RT, 1-month, and 2-month post-RT, but not at the end of RT. Total SD-16 scores differ by race/ethnicity at pre-RT, 1-month, and 6-month post-RT, but not at the end of RT. Overall, PROs have a moderate but significant correlation with CROs at the end of RT. Conclusion: RT-induced EASRs differed significantly by race/ethnicity. There was a moderate but significant correlation between PROs and CROs. However, PROs delineated a broader spectrum in capturing the impact of RT on patients’ QOL, which highlights the importance of integrating PROs in accessing RT-induced EASRs, particularly in minorities with worse RT-induced EASRs. Trial Registration: NCT01407770 (09/02/2011) Citation Format: James J. Urbanic, Edward G. Shaw, Cristiane Takita, Jean L. Wright, Edward H. Ip, Lingyi Lu, Luis Baez-Diaz, Doris R. Brown, Jon Strasser, Kathy Baglan, Mark Palmer, Anu Thakrar, Amarinthia E. Curtis, Glenn Lesser, Jennifer J. Hu. Radiotherapy-induced early adverse skin reactions: Comparative analysis of clinician- and patient-reported outcomes in a multi-racial/ethnic breast cancer population (WF-97609) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1900.

There is an increasing interest in using machine learning and artificial intelligence to estimate chronological age using neuroimaging data. The gap between chronological age and estimated brain age (brain age gap, BAG) is used as a measure of accelerated/resilient brain aging. Previously, BAG has been associated with cognitive status. However, whether the BAG varies across sex and cognitive status have been less explored. The present study examines these associations and validates a voxel-based machine learning approach based on the elastic net regression (ENR) for BAG calculation. Using data from the Atherosclerosis Risk in Communities Study (ARIC) study, the Wake Forest School of Medicine Alzheimer’s Disease Research Center (WFSM-ADRC) clinical cohort and Alzheimer’s Disease Neuroimaging Initiative (ADNI), we examined associations of BAG across cognitive status and sex. We used structural MRI scans from 1853 ARIC participants (ages 67-90, 60% females), 508 from the WFSM-ADRC (55-95 yo., 66% females) and 584 ADNI cognitively normal (CN) participants (55-90 yo., 57% females). All images were aligned into a common template and the derived gray matter (GM) probability maps from ADNI MRIs were used as input to train the machine learning algorithm. Once the model was fitted the ARIC and WFSM-ADRC GM probability maps were provided as input to the algorithm to estimate the BAG values. Finally, an age bias correction was applied. Linear regression methods were used to investigate differences between groups. Age, race, education, sex, and cognitive status were included in the model. We found in both ARIC and WFSM-ADRC participants that differences in BAG values between CN-MCI and MCI-Dementia participants were highly significant. In addition, when we examined differences in BAG values across sex per cognitive status, we found again in both cohorts that differences were only significant for CN individuals. See Table 1 for details. Our analyses show that our approach to estimate chronological age using high-dimensional ENR, produces BAG values which are strongly associated with cognitive status. The increased severity of cognitive impairment is related to accelerated brain aging. Differences in BAG between men and women were significant for CN individuals only.

BACKGROUND:Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.METHODS:We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.RESULTS:We replicated 2 loci (rs9369640 and rs9349379 near PHACTR1 and rs10757278 near CDKN2B) for CAC and one locus for cIMT (rs7412 and rs445925 near APOE-APOC1) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near CSNK1A1L/LINC00547/POSTN at 13q13.3) at P=2.0×10-8 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints POSTN, encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (P<3.1×10-4) for 3 previously reported coronary artery disease loci for these subclinical atherosclerotic phenotypes (rs2891168 near CDKN2B-AS1 and rs11170820 near FLJ12825 for CAC, and rs7412 near APOE for cIMT).CONCLUSIONS:Our results provide potential biological mechanisms that could link CAC and cIMT to increased cardiovascular disease risk in individuals with T2D.

Relative to European Americans, African Americans have lower 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (VDBP) concentrations, higher 1,25-dihydroxyvitamin D (1,25(OH)2D3) concentrations and bone mineral density (BMD), and paradoxically reduced burdens of calcified atherosclerotic plaque (subclinical atherosclerosis). To identify genetic factors contributing to vitamin D and BMD measures, association analysis of >14M variants was conducted in a maximum of 697 African American-Diabetes Heart Study participants with type 2 diabetes (T2D). The most significant association signals were detected for VDBP on chromosome 4; variants rs7041 (β = 0.44, SE = 0.019, P = 9.4x10-86) and rs4588 (β = 0.17, SE = 0.021, P = 3.5x10-08) in the group-specific component (vitamin D binding protein) gene (GC). These variants were found to be independently associated. In addition, rs7041 was also associated with bioavailable vitamin D (BAVD; β = 0.16, SE = 0.02, P = 3.3x10-19). Six rare variants were significantly associated with 25OHD, including a non-synonymous variant in HSPG2 (rs116788687; β = -1.07, SE = 0.17, P = 2.2x10-10) and an intronic variant in TNIK (rs143555701; β = -1.01, SE = 0.18, P = 9.0x10-10), both biologically related to bone development. Variants associated with 25OHD failed to replicate in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of vitamin D metabolism and bone mineral density phenotypes in an African American population enriched for T2D could provide insight into ethnic specific differences in vitamin D metabolism and bone mineral density.

Background To determine if individuals with food insecurity (FI) were less likely to have seen a mental health professional (MHP) within the past year than individuals without FI. Methods This is a cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) conducted in the United States between 2007 and 2014. All participants 20 years of age or older were eligible for this study. We excluded participants who were pregnant, missing FI data, or missing data from the Patient Health Questionnaire (PHQ-9). The primary outcome was self-reported contact with a MHP in the past 12 months. We used multivariable logistic regression models to test the association between FI and contact with a MHP, controlling for all demographic and clinical covariates. Results Of the 19,789 participants, 13.9% were food insecure and 8.1% had major depressive disorder (MDD). In bivariate analysis, participants with FI were significantly more likely to have MDD (5.3% vs 2.8%, p < 0.0001) and to have been seen by a MHP in the preceding 12 months (14.0% vs 6.9%, p < 0.0001). In multivariable models, adults with FI had higher odds of having seen a MHP (OR = 1.32, CI: 1.07, 1.64). Conclusions This study demonstrates that individuals with FI were significantly more likely to have seen a MHP in the preceding 12 months compared to individuals without FI. Given the growing interest in addressing unmet social needs in healthcare settings, this data suggests that visits with MHPs may be a valuable opportunity to screen for and intervene on FI.

BACKGROUND:Patients with stage 1 systolic hypertension have increased risk of cardiovascular disease (CVD) events.METHODS:Using Cox models, we assess the effect of targeting an intensive SBP goal of less than 120 mmHg compared with standard SBP goal of less than 140 mmHg on the risk of CVD events in adults with stage 1 systolic hypertension with diabetes mellitus enrolled in Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) (n = 1901) and without diabetes mellitus enrolled in Systolic Blood Pressure Intervention Trial (SPRINT) (n = 3484) that used identical SBP goal interventions.OUTCOMES:In ACCORD BP, the primary composite CVD outcome was the first occurrence of myocardial infarction, stroke, or CVD mortality. In SPRINT, the primary composite CVD outcome was the first occurrence of myocardial infarction, other acute coronary syndrome, stroke, heart failure, or CVD mortality.RESULTS:In SPRINT, targeting an intensive SBP goal significantly reduced the risk of the primary CVD outcome [hazard ratio 0.75 (95% confidence interval, 0.58-0.98); events 1.78 vs. 2.37%/year]. In ACCORD BP, the relationships of SBP goal with the primary CVD outcome was modified by the glycemia goal intervention (interaction P = 0.039). In the standard glycemia subgroup (A1c target 7-7.9%), intensive SBP goal significantly reduced the risk of the primary CVD outcome [hazard ratio 0.61 (0.40-0.94); events 1.63 vs. 2.56%/year]. In the intensive glycemia subgroup (A1c target <6%), the risk of the primary CVD outcome was not significantly different between groups [hazard ratio 1.20 (0.76-1.89); events 1.91 vs. 1.60%/year].CONCLUSION:Targeting an intensive SBP goal significantly reduced the risk of CVD events in patients with stage 1 systolic hypertension without diabetes and with diabetes on standard glycemia goal.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10−8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein–deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification. Genome-wide analyses identify variants near HDAC9 associated with abdominal aortic calcification and other cardiovascular phenotypes. Functional work shows that HDAC9 promotes an osteogenic vascular smooth muscle cell phenotype, enhancing calcification and reducing contractility.

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4 . LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Introduction: Approximately 17.3 million adults have systolic blood pressure (SBP) between 130 and 139 mmHg in the USA, and they have increased risk of cardiovascular disease (CVD). Hypothesis: In ...

Abstract Introduction Aim is to evaluate validity, reliability, diagnostic precision, and user acceptability of computer simulations of cognitively demanding tasks when administered to older adults with and without cognitive impairment. Methods Five simulation modules were administered to 161 individuals aged ≥60 years with no cognitive impairment (N = 81), mild cognitive impairment (N = 52), or dementia (N = 28). Groups were compared on total accuracy and time to complete the tasks (seconds). Receiver operating characteristics were evaluated. Reliability was assessed over one month. Participants rated face validity and acceptability. Results Total accuracy (P < .0001) and time (P = .0015) differed between groups. Test‐retest correlations were excellent (0.79 and 0.88, respectively). Area under the curve ranged from good (0.77) to excellent (0.97). User ratings supported their face validity and acceptability. Discussion Brief computer simulations can be useful in assessing cognitive functional abilities of older adults and distinguishing varying degrees of impairment.

Context:Vitamin D inadequacy is common in the adult population of the United States. Although the genetic determinants underlying vitamin D inadequacy have been studied in people of European ancestry, less is known about populations with Hispanic or African ancestry.Objective:The Trans-Ethnic Evaluation of Vitamin D (TRANSCEN-D) genomewide association study (GWAS) consortium was assembled to replicate genetic associations with 25-hydroxyvitamin D [25(OH)D] concentrations from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) meta-analyses of European ancestry and to identify genetic variants related to vitamin D concentrations in African and Hispanic ancestries.Design:Ancestry-specific (Hispanic and African) and transethnic (Hispanic, African, and European) meta-analyses were performed with Meta-Analysis Helper software (METAL).Patients or Other Participants:In total, 8541 African American and 3485 Hispanic American (from North America) participants from 12 cohorts and 16,124 European participants from SUNLIGHT were included in the study.Main Outcome Measures:Blood concentrations of 25(OH)D were measured for all participants.Results:Ancestry-specific analyses in African and Hispanic Americans replicated single nucleotide polymorphisms (SNPs) in GC (2 and 4 SNPs, respectively). An SNP (rs79666294) near the KIF4B gene was identified in the African American cohort. Transethnic evaluation replicated GC and DHCR7 region SNPs. Additionally, the transethnic analyses revealed SNPs rs719700 and rs1410656 near the ANO6/ARID2 and HTR2A genes, respectively.Conclusions:Ancestry-specific and transethnic GWASs of 25(OH)D confirmed findings in GC and DHCR7 for African and Hispanic American samples and revealed findings near KIF4B, ANO6/ARID2, and HTR2A. The biological mechanisms that link these regions with 25(OH)D metabolism warrant further investigation.

To evaluate the validity, reliability and acceptability to users of five brief computer simulations of cognitively demanding, ecologically relevant activities when administered to older adults with no cognitive impairment, mild cognitive impairment and mild dementia. Five modules of the Simulation-Based Assessment of Cognition (SIMBAC) were developed for use on a computer tablet: recognizing faces, remembering names, filling a pillbox, using an automated teller machine (ATM), and a telephone renewal of a medication prescription. One hundred and sixty-one individuals >60 years of age were administered SIMBAC and separately given a clinical evaluation and classified as having no cognitive impairment (N=81), mild cognitive impairment (N=52) or mild dementia (N=28). Module scores for accuracy and time to complete (sec.) were calculated and summed for overall scores that were compared across groups; overall scores were also correlated with proxy-reported functional status questionnaires. Test-retest reliability was assessed over approximately one month. Participants rated the ecological relevance, face validity and user acceptability of each module. Clinical groups differed in both overall SIMBAC accuracy and time scores (p < 0.0001; p = 0.0015, respectively). Accuracy and time scores for the entire sample correlated with proxy-reported instrumental activities of daily living scores (rho = 0.68, -0.45, respectively; p<0.0001). SIMBAC demonstrated excellent ecological validity, face validity and user acceptability. Test-retest Intraclass correlation coefficients for total accuracy and total time scores were high (0.79 and 0.88, respectively).

Coronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European Americans. Genetic factors likely contribute to the observed ethnic differences. To identify genes associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association study (GWAS) was performed using the Illumina 5 M chip in 691 African American-Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart Study (JHS) participants with T2D. Genetic association tests were performed on the genotyped and 1000 Genomes-imputed markers separately for each study, and combined in a meta-analysis.