Browsing by Author "Cushman, Mary"
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Item ABO blood type, factor VIII, and incident cognitive impairment in the REGARDS cohort(American Academy of Neurology, 2014-09-30) Alexander, Kristine S.; Zakai, Neil A.; Gillett, Sarah; McClure, Leslie A.; Wadley, Virginia; Unverzagt, Fred; Cushman, Mary; Department of Medicine, IU School of MedicineOBJECTIVE: To assess the relationships among ABO group, factor VIII (FVIII), and incident cognitive impairment in a large, prospective cohort study of black and white adults in the United States using a nested case-control design. METHODS: Incident cognitive impairment was defined using cognitive domain tests over a mean follow-up of 3.4 years. ABO blood group was measured by genotyping in a nested case-control sample of 495 cases with cognitive impairment and 587 controls. RESULTS: Those with blood group AB and those with higher FVIII had an increased risk of cognitive impairment, adjusting for age, race, region, and sex (respective odds ratios 1.82, 95% confidence interval [CI] 1.15-2.90; and 1.24, 95% CI 1.10-1.38 for 40 IU/dL higher FVIII). Mean FVIII was higher in those with blood type AB (142 IU/dL; 95% CI 119-165) compared with O (104 IU/dL; 95% CI 101-107), and FVIII mediated 18% of the association between AB group and incident cognitive impairment (95% CI for mediation -30% to 68%). CONCLUSIONS: Blood group AB and higher FVIII were associated with increased incidence of cognitive impairment in this prospective study. The association of blood group AB with incident cognitive impairment was not significantly mediated by FVIII levels.Item The American Heart Association Life's Simple 7 and incident cognitive impairment: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study(Ovid Technologies Wolters Kluwer -American Heart Association, 2014-06) Thacker, Evan L.; Gillett, Sarah R.; Wadley, Virginia G.; Unverzagt, Frederick W.; Judd, Suzanne E.; McClure, Leslie A.; Howard, Virginia J.; Cushman, Mary; Department of Psychiatry, IU School of MedicineBACKGROUND: Life's Simple 7 is a new metric based on modifiable health behaviors and factors that the American Heart Association uses to promote improvements to cardiovascular health (CVH). We hypothesized that better Life's Simple 7 scores are associated with lower incidence of cognitive impairment. METHODS AND RESULTS: For this prospective cohort study, we included REasons for Geographic And Racial Differences in Stroke (REGARDS) participants aged 45+ who had normal global cognitive status at baseline and no history of stroke (N=17 761). We calculated baseline Life's Simple 7 score (range, 0 to 14) based on smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. We identified incident cognitive impairment using a 3-test measure of verbal learning, memory, and fluency obtained a mean of 4 years after baseline. Relative to the lowest tertile of Life's Simple 7 score (0 to 6 points), odds ratios of incident cognitive impairment were 0.65 (0.52, 0.81) in the middle tertile (7 to 8 points) and 0.63 (0.51, 0.79) in the highest tertile (9 to 14 points). The association was similar in blacks and whites, as well as outside and within the Southeastern stroke belt region of the United States. CONCLUSIONS: Compared with low CVH, intermediate and high CVH were both associated with substantially lower incidence of cognitive impairment. We did not observe a dose-response pattern; people with intermediate and high levels of CVH had similar incidence of cognitive impairment. This suggests that even when high CVH is not achieved, intermediate levels of CVH are preferable to low CVH.Item Blood Pressure and Cognitive Decline Over 8 Years in Middle-Aged and Older Black and White Americans(American Heart Association, 2019-02) Levine, Deborah A.; Galecki, Andrzej T.; Langa, Kenneth M.; Unverzagt, Frederick W.; Kabeto, Mohammed U.; Giordani, Bruno; Cushman, Mary; McClure, Leslie A.; Safford, Monika M.; Wadley, Virginia G.; Psychiatry, School of MedicineAlthough the association between high blood pressure (BP), particularly in midlife, and late-life dementia is known, less is known about variations by race and sex. In a prospective national study of 22 164 blacks and whites ≥45 years without baseline cognitive impairment or stroke from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke), enrolled 2003 to 2007 and followed through September 2015, we measured changes in cognition associated with baseline systolic and diastolic BP (SBP and DBP), as well as pulse pressure (PP) and mean arterial pressure, and we tested whether age, race, and sex modified the effects. Outcomes were global cognition (Six-Item Screener; primary outcome), new learning (Word List Learning), verbal memory (Word List Delayed Recall), and executive function (Animal Fluency Test). Median follow-up was 8.1 years. Significantly faster declines in global cognition were associated with higher SBP, lower DBP, and higher PP with increasing age ( P<0.001 for age×SBP×follow-up-time, age×DBP×follow-up-time, and age×PP×follow-up-time interaction). Declines in global cognition were not associated with mean arterial pressure after adjusting for PP. Blacks, compared with whites, had faster declines in global cognition associated with SBP ( P=0.02) and mean arterial pressure ( P=0.04). Men, compared with women, had faster declines in new learning associated with SBP ( P=0.04). BP was not associated with decline of verbal memory and executive function, after controlling for the effect of age on cognitive trajectories. Significantly faster declines in global cognition over 8 years were associated with higher SBP, lower DBP, and higher PP with increasing age. SBP-related cognitive declines were greater in blacks and men.Item C-reactive protein and risk of cognitive decline: The REGARDS study(PLOS, 2020-12-31) Rentería, Miguel Arce; Gillett, Sarah R.; McClure, Leslie A.; Wadley, Virginia G.; Glasser, Stephen P.; Howard, Virginia J.; Kissela, Brett M.; Unverzagt, Frederick W.; Jenny, Nancy S.; Manly, Jennifer J.; Cushman, Mary; Psychiatry, School of MedicineMarkers of systemic inflammation are associated with increased risk of cognitive impairment, but it is unclear if they are associated with a faster rate of cognitive decline and whether this relationship differs by race. Our objective was to examine the association of baseline C-reaction protein (CRP) with cognitive decline among a large racially diverse cohort of older adults. Participants included 21,782 adults aged 45 and older (36% were Black, Mean age at baseline 64) from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. CRP was measured at baseline and used as a continuous variable or a dichotomous grouping based on race-specific 90th percentile cutoffs. Cognitive measures of memory and verbal fluency were administered every 2 years for up to 12 years. Latent growth curve models evaluated the association of CRP on cognitive trajectories, adjusting for relevant demographic and health factors. We found that higher CRP was associated with worse memory (B = -.039, 95% CI [-.065,-.014]) and verbal fluency at baseline (B = -.195, 95% CI [-.219,-.170]), but not with rate of cognitive decline. After covariate adjustment, the association of CRP on memory was attenuated (B = -.005, 95% CI [-.031,-.021]). The association with verbal fluency at baseline, but not over time, remained (B = -.042, 95% CI [-.067,-.017]). Race did not modify the association between CRP and cognition. Findings suggest that levels of CRP at age 45+, are a marker of cognitive impairment but may not be suitable for risk prediction for cognitive decline.Item N-terminal pro-B-type natriuretic peptide and risk of future cognitive impairment in the REGARDS cohort(IOS, 2016) Cushman, Mary; Callas, Peter W.; McClure, Leslie A.; Unverzagt, Frederick W.; Howard, Virginia J.; Gillett, Sarah R.; Thacker, Evan L.; Wadley, Virginia G.; Department of Psychiatry, IU School of MedicineBackground: Improved understanding of the etiology of cognitive impairment is needed to develop effective preventive interventions. Higher amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of cardiac dysfunction associated with risk of cardiovascular diseases and stroke in apparently healthy people. Objective: To study the association of NT-proBNP with risk of incident cognitive impairment. Methods: The Reasons for Geographic and Racial Differences in Stroke is a national cohort study of 30,239 black and white Americans age 45 and older at baseline, enrolled in 2003-7. Among participants without prebaseline stroke or cognitive impairment, baseline NT-proBNP was measured in 470 cases of incident cognitive impairment and 557 controls. Cases were participants scoring below the 6th percentile of demographically-adjusted means on at least 2 of 3 serially administered tests (word list learning, word list recall and semantic fluency) over 3.5 years follow-up. Results: Adjusting for age, gender, race, region of residence, education, and income, there was an increased odds ratio of incident cognitive impairment with increasing NT-proBNP; participants in the 4th versus 1st quartile (>127 versus ≤33 pg/ml) had a 1.69-fold increased odds (95% CI 1.11–2.58). Adjustment for cardiovascular risk factors and presence of an apolipoprotein E4 allele had no substantial impact on the odds ratio. Results did not differ by age, race, gender, or presence of an apolipoprotein E4 allele. Conclusion: Higher NT-pro-BNP was associated with incident cognitive impairment in this prospective study, independent of atherogenic and Alzheimer’s disease risk factors. Future work should clarify pathophysiologic connections of NT-proBNP and cognitive dysfunction.Item A PheWAS study of a large observational epidemiological cohort of African Americans from the REGARDS study(Biomed Central, 2019-01-31) Zhao, Xueyan; Geng, Xin; Srinivasasainagendra, Vinodh; Chaudhary, Ninad; Judd, Suzanne; Wadley, Virginia; Gutiérrez, Orlando M.; Wang, Henry; Lange, Ethan M.; Lange, Leslie A.; Woo, Daniel; Unverzagt, Frederick W.; Safford, Monika; Cushman, Mary; Limdi, Nita; Quarells, Rakale; Arnett, Donna K.; Irvin, Marguerite R.; Zhi, Degui; Psychiatry, School of MedicineBACKGROUND: Cardiovascular disease, diabetes, and kidney disease are among the leading causes of death and disability worldwide. However, knowledge of genetic determinants of those diseases in African Americans remains limited. RESULTS: In our study, associations between 4956 GWAS catalog reported SNPs and 67 traits were examined among 7726 African Americans from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which is focused on identifying factors that increase stroke risk. The prevalent and incident phenotypes studied included inflammation, kidney traits, cardiovascular traits and cognition. Our results validated 29 known associations, of which eight associations were reported for the first time in African Americans. CONCLUSION: Our cross-racial validation of GWAS findings provide additional evidence for the important roles of these loci in the disease process and may help identify genes especially important for future functional validation.Item Risk Factors for Poststroke Cognitive Decline: The REGARDS Study (Reasons for Geographic and Racial Differences in Stroke)(American Heart Association, 2018-04) Levine, Deborah A.; Wadley, Virginia G.; Langa, Kenneth M.; Unverzagt, Frederick W.; Kabeto, Mohammed U.; Giordani, Bruno; Howard, George; Howard, Virginia J.; Cushman, Mary; Judd, Suzanne; Galecki, Andrzej T.; Psychiatry, School of MedicineBackground and Purpose Poststroke cognitive decline (PSCD) causes disability. Risk factors for PSCD independent of survivors’ prestroke cognitive trajectories are uncertain. Methods Among 22,875 participants age ≥45 without baseline cognitive impairment from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, enrolled 2003–2007 and followed through September 2015, we measured the effect of incident stroke (n=694) on changes in cognitive functions and cognitive impairment (Six-Item Screener score <5) and tested whether patient factors modified the effect. Median follow-up was 8.2 years. Results Incident stroke was associated with acute declines in global cognition, new learning, verbal memory, and executive function. Acute declines in global cognition after stroke were greater in survivors who were black (P=0.04), male (P=0.04), had cardioembolic (P=0.001) or large artery stroke (P=0.001). Acute declines in executive function after stroke were greater in survivors who hadItem Serum mercury concentration and the risk of ischemic stroke: The REasons for Geographic and Racial Differences in Stroke Trace Element Study(Elsevier, 2018-08) Chen, Cheng; Xun, Pengcheng; McClure, Leslie A.; Brockman, John; MacDonald, Leslie; Cushman, Mary; Cai, Jianwen; Kamendulis, Lisa; Mackey, Jason; He, Ka; Neurology, School of MedicineBACKGROUND: Although biologically plausible, epidemiological evidence linking exposure to methylmercury with increased risk of ischemic stroke is limited. The effects of methylmercury may be modified by selenium, which is an anti-oxidant that often co-exists with mercury in fish. OBJECTIVES: To examine the association between serum mercury levels with the incidence of ischemic stroke and to explore the possible effect modifications by serum selenium levels and demographic and geographic factors. METHODS: A case-cohort study was designed nested in the REasons for Geographic and Racial Differences in Stroke cohort, including 662 adjudicated incident cases of ischemic stroke and 2494 participants in a randomly selected sub-cohort. Serum mercury was measured using samples collected at recruitment. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated using the Barlow-weighting method for the Cox proportional hazards regression model. RESULTS: No statistically significant association was observed between serum mercury concentration and the incidence of ischemic stroke (the highest vs. lowest quintile of mercury levels: HR = 0.82; 95% CI = 0.55-1.22; P for linear trend = 0.42). Sex (P for interaction = 0.06), but not serum selenium levels, modified the association; a more evident trend toward lower incidence of ischemic stroke with higher mercury levels was observed among women. CONCLUSION: This study does not support an association between mercury and the incidence of ischemic stroke within a population with low-to-moderate level of exposure. Further studies are needed to explore the possibility of mercury-induced ischemic stroke toxicity in other populations at higher exposure levels.Item Sickle cell trait and risk of cognitive impairment in African-Americans: The REGARDS cohort(Elsevier, 2019-05-24) Cahill, Christina R.; Leach, Justin M.; McClure, Leslie A.; Irvin, Marguerite Ryan; Zakai, Neil A.; Naik, Rakhi; Unverzagt, Frederick; Wadley, Virginia G.; Hyacinth, Hyacinth I.; Manly, Jennifer; Judd, Suzanne E.; Winkler, Cheryl; Cushman, Mary; Psychiatry, School of MedicineBackground: Sickle cell anemia may be associated with cognitive dysfunction, and some complications of sickle cell anemia might affect those with sickle cell trait (SCT), so we hypothesized that SCT is a risk factor for cognitive impairment. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled a national cohort of 30,239 white and black Americans from 2003 to 7, who are followed every 6 months. Baseline and annual global cognitive function testing used the Six-Item Screener (SIS), a validated instrument (scores range 0-6; ≤ 4 indicates cognitive impairment). Participants with baseline cognitive impairment and whites were excluded. Logistic regression was used to calculate the association of SCT with incident cognitive impairment, adjusted for risk factors. Linear mixed models assessed multivariable-adjusted change in test scores on a biennially administered 3-test battery measuring learning, memory, and semantic and phonemic fluency. Findings: Among 7743 participants followed for a median of 7·1 years, 85 of 583 participants with SCT (14·6%) developed incident cognitive impairment compared to 902 of 7160 (12·6%) without SCT. In univariate analysis, the odds ratio (OR) of incident cognitive impairment was 1·18 (95% CI: 0·93, 1·51) for those with SCT vs. those without. Adjustment did not impact the OR. There was no difference in change on 3-test battery scores by SCT status (all p > 0·11). Interpretation: In this prospective cohort study of black Americans, SCT was not associated with incident cognitive impairment or decline in test scores of learning, memory and executive function. Funding: National Institutes of Health, American Society of Hematology.