scholarly journals Association of Sickle Cell Trait with Measures of Cognitive Function and Dementia in African Americans

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1099-1099
Author(s):  
Chen Nemin ◽  
Christina Caruso ◽  
Alvaro Alonso ◽  
Vimal K. Derebail ◽  
Abhijit V Kshirsagar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Cognitive Function ◽  
African Americans ◽  
Cognitive Decline ◽  
Cognitive Dysfunction ◽  
Sickle Cell ◽  
Risk Allele ◽  
Sickle Cell Trait ◽  
Z Score

Abstract Background: The prevalence of cerebral small vessel disease (CSVD) and its associated complication of cognitive decline is significantly higher amongst African Americans than non-Hispanic Whites. Sickle cell anemia or sickle cell disease has been associated with a 30-45% increased prevalence of CSVD which presents as silent cerebral infarcts and impaired cognitive function. However, the association between sickle cell trait (heterozygosity for the sickle cell mutation) and cognitive decline or dementia has not been reported. Hypothesis: African Americans with SCT will have a significantly higher incidence and prevalence of cognitive impairment and dementia compared to those without SCT. Methods: We studied African Americans participants enrolled in the community-based prospective Atherosclerosis Risk in Communities (ARIC) study. SCT genotype status was determined using Taqman® genotyping from blood samples collected at baseline. Data from cognitive assessments at visits 2, 4 and 5, and an MRI performed at visit 5 were used for analysis. Using linear regression models for visit 2 cognitive measures and visit 5 brain MRI outcomes, a generalized estimating equation (GEE) for cognitive change, and Cox models for the incidence of dementia, we determined whether SCT was associated with a higher risk for cognitive dysfunction, global and regional brain volumes, and dementia. Results: Distribution of traditional risk factors for cognitive decline were not significantly different between participants with SCT (N = 176) and those without SCT (N = 2,532). In multivariable, cross-sectional analyses of 2,708 participants, those participants with SCT compared to those without SCT did not show a statistically significant difference in the global or domain-specific cognitive function scores at baseline. Participants with SCT did not experience a faster 20-year cognitive decline compared to participants without SCT. Also, participants with SCT had larger parietal cortical volume (100.5 cm3 vs. 97.9 cm3, diff. = 2.67 (0.24, 5.11) cm3, p = 0.03), and lower incidence of dementia (HR = 0.63 95% CI = 0.38, 1.05) compared to those without SCT. Participants with a co-inheritance of the apolipoprotein E (APOE) ε4 risk allele and SCT (N = 63) had worse scores on the digit symbol substitution test (DSST) at baseline (z-score = -0.08 (-0.26, 0.09), Pinteraction = 0.05) and over time (z-score = -0.12 (-0.38, 0.14), Pinteraction = 0.04), compared to those with the APOE ε4 risk allele who do not have SCT (N = 113). SCT was associated with 2-fold increased risk of dementia among participants with diabetes mellitus and a 55% reduction in risk of dementia among those without diabetes mellitus (Pinteraction = 0.01). Conclusions: SCT was not an independent risk factor for prevalent or incident cognitive decline, but it could potentially interact with and modify other risk factors for dementia and cognitive dysfunction. Disclosures Key: UniQure BV: Research Funding.

Association of Sickle Cell Trait with Risk of Coronary Heart Disease in African Americans

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 11-11 ◽  
Author(s):  
Hyacinth I Hyacinth ◽  
Carty L Cara ◽  
Samantha R Seals ◽  
Marguerite R. Irvin ◽  
Rakhi P. Naik ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
African Americans ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Crude Incidence Rate ◽  
Crude Incidence

Abstract Background The incidence of and mortality from coronary heart disease (CHD) is significantly higher among African Americans (AAs) compared to Whites, even after adjusting for traditional CHD risk factors. Studies suggests that the unexplained excess risk might be the result of genetic modifiers associated with African ancestry conferring a higher risk of CHD. One such gene variant is the sickle cell mutation. The heterozygous state, or sickle cell trait (SCT), with a prevalence of 8 - 12% among AAs, was previously deemed clinically benign; however, recent evidence indicates that SCT is associated with increased risk of chronic kidney disease venous thromboembolism and sudden death following exertion. Individuals with SCT have higher circulating levels of C-reactive protein, fibrinogen, prothrombin fragment 1.2 and D-dimer. We hypothesized that AAs with SCT have a higher risk for myocardial infarction (MI) and coronary heart disease (CHD) than AAs who are homozygous for wild-type hemoglobin. Methods We obtained genotype and phenotype data from the Women's Health Initiative (WHI) REasonsfor Geographic and Racial Differences in Stroke (REGARDS), Multi-Ethnic Study of Atherosclerosis (MESA), Jackson Heart Study (JHS) and Atherosclerosis Risk In Communities (ARIC) cohorts. The outcomes were incident MI or CHD. Incident MI was defined as adjudicated non-fatal or fatal MI, while incident CHD was defined as 1) adjudicated non-fatal MI, 2) fatal MI, 3) documented coronary revascularization procedures or 4) non-MI CHD death. SCT status was determined by either direct genotyping or imputation for rs334 using the 1000Genome reference panel. Homozygous individuals and those with a prior history of CHD were excluded. Individuals with incident “micro MI”, only defined in REGARDS, were also excluded from the analysis. Analysis was performed separately in each cohort using a Cox proportional hazard models to estimate the hazard ratio (HR) for incident MI or CHD comparing SCT carriers to non-carriers. Models in each cohort were adjusted for age, sex, study site or region of residence, hypertension or systolic blood pressure, diabetes, serum LDL or HDL or total cholesterol, and population stratification (using principal components of global ancestry). The results from each cohorts were then meta-analyzed using a random effect model due to significant heterogeneity between studies (I2 = 39.1%, p = 0.02 for MI meta-analysis and I2 = 56%, p = 0.01 for CHD meta-analysis). Results A total of 20,053 African American men and women were included in the combined sample; 1503 with SCT (7.5% prevalence). Average ages in years at baseline were: 65.0±6.0 in WHI (N = 2248), 62.0 ± 9.2 in REGARDS (N = 10573); 62.2±10.2 in MESA (N = 1556); 50.0 ± 11.9 in JHS (N = 2133); and 54.0 ± 6.0 in ARIC (N = 3543). There were no statistically significant differences in the distribution of traditional cardiovascular risk factors by SCT status within cohorts, except that atrial fibrillation was more prevalent among REGARDS participants with SCT compared to those without SCT (9.9% vs. 7.8%, p = 0.03). The crude incidence rate of MI per 1000 person years in those with SCT compared to those without SCT was: 4.0 vs. 5.2 in WHI; 5.7 vs. 5.0 in REGARDS; 5.8 vs 4.3 in MESA, 2.0 vs 2.1 in JHS; and 4.1 vs 5.9 in ARIC. For CHD, the crude incidence rate was: 5.8 vs. 7.2 in WHI, 8.9 vs. 7.4 in REGARDS; 15.4 vs. 6.4 in MESA; 3.4 vs. 3.4 in JHS; and 10.5 vs. 9.5 in ARIC. The HR (95% CI) for MI was: 0.96 (0.49 - 1.89) in WHI; 1.27 (0.8 - 2.0) in REGARDS; 1.84 (0.74 - 4.60) in MESA; 1.24 (0.28 - 5.44) in JHS; and 0.68 (0.42 - 1.10) in ARIC. And that for CHD was: 1.05 (0.63 - 1.74) in WHI; 1.49 (1.01 - 2.18) in REGARDS; 2.82 (1.48 - 5.38) in MESA; 1.45 (0.50 - 4.19) in JHS; and 1.10 (0.80 - 1.50) in ARIC. Meta-analysis showed that, while SCT status was not significantly associated with incident MI (1.10 [0.73 - 1.64]), it was significantly associated with incident CHD (1.42 [1.02 - 1.98] Figures 1a and 1b). Conclusions This study showed a significant association between SCT and incident CHD, but not MI. Our conclusion is limited by the significant heterogeneity that existed between studies. Since SCT status was not associated with MI, but was associated with CHD, further work is needed to confirm these findings, determine which CHD component(s) explain the observed association and elucidate the possible mechanism(s) involved. Disclosures No relevant conflicts of interest to declare.

scholarly journals Association among sickle cell trait, fitness, and cardiovascular risk factors in CARDIA

Blood ◽  
2017 ◽  
Vol 129 (6) ◽  
pp. 723-728 ◽  
Author(s):  
Robert I. Liem ◽  
Cheeling Chan ◽  
Thanh-Huyen T. Vu ◽  
Myriam Fornage ◽  
Alexis A. Thompson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
African Americans ◽  
Cardiovascular Risk Factors ◽  
Sickle Cell ◽  
Independent Risk Factor ◽  
Sickle Cell Trait ◽  
Key Points

Key Points SCT status is not significantly associated with longitudinal changes in fitness among African Americans. SCT status is not an independent risk factor for hypertension, diabetes, or metabolic syndrome among African Americans.

scholarly journals Association of sickle cell trait with measures of cognitive function and dementia in African Americans

2019 ◽  
Vol 16 ◽  
pp. 100201 ◽  
Author(s):  
Nemin Chen ◽  
Christina Caruso ◽  
Alvaro Alonso ◽  
Vimal K. Derebail ◽  
Abhijit V. Kshirsagar ◽  
...  
Keyword(s):  
Cognitive Function ◽  
African Americans ◽  
Sickle Cell ◽  
Sickle Cell Trait

scholarly journals Corrigendum to ‘Association of sickle cell trait with measures of cognitive function and dementia in African Americans’ eNeurologicalSci, Vol. 16 (2019), 100,201

2020 ◽  
Vol 21 ◽  
pp. 100281
Author(s):  
Nemin Chen ◽  
Christina Caruso ◽  
Alvaro Alonso ◽  
Vimal K. Derebail ◽  
Abhijit V. Kshirsagar ◽  
...  
Keyword(s):  
Cognitive Function ◽  
African Americans ◽  
Sickle Cell ◽  
Sickle Cell Trait

scholarly journals MON-636 The Relationship Between Glucose Control & Cognitive Function in People with Diabetes After a Lacunar Stroke

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Tali Cukierman-Yaffe ◽  
Leslie McClure ◽  
Thomas Risoli ◽  
Jackie Bosch ◽  
Hertzel C Gerstein ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Function ◽  
Cognitive Dysfunction ◽  
Glucose Control ◽  
High Risk Population ◽  
Z Score ◽  
Lacunar Stroke ◽  
The Relationship ◽  
Over Time

Abstract Background & Objective Both lacunar strokes and diabetes are risk factors for dementia and cognitive dysfunction. Thus, elucidating modifiable risk factors for cognitive dysfunction in people with type 2 diabetes who experienced a lacunar infarct has large public health implications. One such factor may be glycemic status, as measured by glycosylated hemoglobin (A1C). Thus, the aim of this study was to assess the relationship between A1C and cognitive function in people with diabetes after a lacunar stroke. Research Design & Methods The effect of baseline and follow-up A1C on the baseline and the change in Cognitive Assessment Screening Instrument (CASI) score over time among participants with a median of 2 cognitive assessments (range 1-5) was examined in of 942 individuals with diabetes and a lacunar stroke who participated in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (ClinicalTrials.gov number, NCT00059306). Results Every 1 % higher baseline A1C was associated with a 0.06 lower standardized CASI z-score (95% CI -0.101, -0.018). Higher baseline A1C values were associated with lower CASI z-score over time (p for interaction=0.037). A 1% increase in A1C over time, corresponded with a CASI score decrease of 0.021 (95% CI -0.0043, -0.038) during follow-up. All these remained statistically significant after adjustment for age, sex, education, race, depression, hypertension, hyperlipidemia, BMI, CVD, OSA, diabetic retinopathy, nephropathy insulin use and White Matter Abnormalities. Conclusion This analysis of 942 individuals with diabetes after a lacunar stroke demonstrates a relationship between A1C and change in cognitive scores over time. Intervention studies are needed in order to delineate if better glucose control could slow the rate of cognitive decline in this high risk population.

scholarly journals Sickle Cell Trait and Renal Function in Hispanics in the United States: the Northern Manhattan Study

2017 ◽  
Vol 27 (1) ◽  
pp. 11 ◽  
Author(s):  
Nicole D. Dueker ◽  
David Della-Morte ◽  
Tatjana Rundek ◽  
Ralph L. Sacco ◽  
Susan H. Blanton
Keyword(s):  
United States ◽  
Chronic Kidney Disease ◽  
African Americans ◽  
Kidney Disease ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
The United States ◽  
Genetic Mutation ◽  
Single Mutation ◽  
Increased Risk

<p class="Pa7">Sickle cell anemia (SCA) is a common hematological disorder among individu­als of African descent in the United States; the disorder results in the production of abnormal hemoglobin. It is caused by homozygosity for a genetic mutation in HBB; rs334. While the presence of a single mutation (sickle cell trait, SCT) has long been considered a benign trait, recent research suggests that SCT is associated with renal dysfunction, including a decrease in estimated glomerular filtration rate (eGFR) and increased risk of chronic kidney disease (CKD) in African Americans. It is currently unknown whether similar associations are observed in Hispanics. Therefore, our study aimed to determine if SCT is associated with mean eGFR and CKD in a sample of 340 Dominican Hispanics from the Northern Manhattan Study. Using regression analyses, we tested rs334 for association with eGFR and CKD, adjusting for age and sex. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equa­tion and CKD was defined as eGFR &lt; 60 mL/min/1.73 m2. Within our sample, there were 16 individuals with SCT (SCT carriers). We found that SCT carriers had a mean eGFR that was 12.12 mL/min/1.73m2 lower than non-carriers (P=.002). Additionally, SCT carriers had 2.72 times higher odds of CKD compared with non-carriers (P=.09). Taken together, these novel results show that Hispanics with SCT, as found among African Americans with SCT, may also be at increased risk for kidney disease.</p><p class="Pa7"><em>Ethn Dis. </em>2017; 27(1)<strong>:</strong>11-14; doi:10.18865/ed.27.1.11.</p><p class="Pa7"> </p>

scholarly journals Sickle Cell Trait and Development of Microvascular Complications in Diabetes Mellitus

2010 ◽  
Vol 5 (6) ◽  
pp. 1015-1020 ◽  
Author(s):  
Anthony J. Bleyer ◽  
Sri V. Reddy ◽  
Leon Sujata ◽  
Gregory B. Russell ◽  
Damilola Akinnifesi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Microvascular Complications

Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis

Stroke ◽  
2021 ◽  
Author(s):  
Jessica W. Lo ◽  
John D. Crawford ◽  
David W. Desmond ◽  
Hee-Joon Bae ◽  
Jae-Sung Lim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Older Age ◽  
Individual Participant Data ◽  
Individual Participant ◽  
Global Cognition

Background and Purpose: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. Methods: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. Results: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th–75th percentile: 1.21–4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (−0.053 SD/year [95% CI, −0.073 to −0.033]; P <0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=−0.078 SD/year [95% CI, −0.11 to −0.045]; P <0.001 for global cognition in a subgroup analysis). Conclusions: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.

Abstract P053: Diabetes Risk Prediction and Sickle Cell Trait in African Americans From CARDIA and the Jackson Heart Study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Mary E Lacy ◽  
Gregory A Wellenius ◽  
Adolfo Correa ◽  
Mercedes R Carnethon ◽  
Robert I Leim ◽  
...  
Keyword(s):  
African Americans ◽  
Risk Prediction ◽  
Sickle Cell ◽  
Prediction Models ◽  
Sickle Cell Trait ◽  
Model Performance ◽  
Jackson Heart Study ◽  
Discriminative Ability ◽  
Heart Study

Introduction: Existing models to predict incident diabetes mellitus (DM) perform better in Whites than African Americans. In models that incorporate hemoglobin A1c (A1C) as a predictor of DM, the difference in model performance by race is more pronounced. In a recent study, we found that A1C was systematically underestimating glycemia in African Americans with sickle cell trait (SCT). Hypothesis: Given the poorer performance of DM prediction models in African Americans than Whites and the impact of SCT on the A1C-glycemia association, we hypothesized that incorporating sickle cell trait into DM prediction models would improve the ability of the model to predict future risk of DM. Methods: We pooled data collected from 2000-2012 on 3,122 African Americans (8.6% with SCT) from the Jackson Heart Study (JHS; n=2,065; mean age=54.71 years) and CARDIA (n=1,057; mean age=44.53). Over 5 years of follow-up in CARDIA and 10 years of follow-up in JHS, 85 CARDIA participants (8.1%) and 342 JHS participants (16.6%) developed DM. Using generalized estimating equations to account for correlation of repeated measures, we compared the discriminative ability and net reclassification improvement (NRI) resulting from the addition of SCT for a series of prediction models. Results: Overall, the addition of SCT to prediction models did not result in significant improvement in the discriminative ability. However, by the NRI index, the addition of SCT to measures of glycemia and to a fuller risk prediction model did improve prediction of DM. In the full model, adding SCT*A1C as a predictor resulted in 2% of events being reclassified as higher risk and 45% of non-events being reclassified as lower risk. Conclusion: Our results suggest that incorporating SCT into DM prediction for African Americans may result in modest improvement in model performance.

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