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 Lipoprotein(a) and risk of cognitive impairment in Black and White Americans: the Reasons for Geographic and Racial Differences in Stroke cohort(Elsevier, 2023-08-08) Rentería, Miguel Arce; McClure, Leslie A.; Callas, Peter W.; LaBode-Richman, Vanessa M.; Kroll, Danielle S.; Manly, Jennifer J.; Kroll, Danielle S.; Manly, Jennifer J.; Zakai, Neil A.; Unverzagt, Frederick; Cushman, Mary; Psychiatry, School of MedicineBackground: Cognitive impairment has a substantial vascular etiology. Higher lipoprotein(a) [Lp(a)] is associated with cardiovascular disease risk, but its association with cognitive function is uncertain. We hypothesized that Lp(a) is a risk factor for cognitive impairment, a relationship that would be modified by race and sex. Objectives: To study the association of Lp(a) with cognitive impairment in a biracial cohort. Methods: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study recruited 30,239 Black and White Americans aged >45 years from 2003 to 2007. After 3.4 years, among participants with normal baseline cognition, baseline Lp(a) was measured in 434 cases of incident cognitive impairment and 557 controls. Cognitive impairment was defined as scores below the sixth percentile based on age, sex, race, and education norms on 2 or 3 components of a 3-test battery administered every 2 years. Results: Median Lp(a) was higher in Black than in White individuals. Among Black participants, the adjusted odds ratio (OR) of cognitive impairment per SD higher increment Lp(a) was 1.39 (95% CI: 1.05, 1.84). The OR in White participants was 1.03 (95% CI: 0.87, 1.21; P for race difference = .03). The relationship of Lp(a) with cognitive trajectory differed by sex and race. Elevated Lp(a) was associated with worse baseline memory in Black men and a steeper trajectory of verbal fluency decline in Black men than in White men and women. Conclusion: Higher Lp(a) was associated with increased risk of cognitive impairment in Black but not White individuals. Future studies should evaluate the biological and social mechanisms through which race and Lp(a) interact to increase risk of cognitive impairment.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 Nonalcoholic fatty liver disease and cognitive impairment: A prospective cohort study(Public Library of Science, 2023-04-14) Cushman, Mary; Callas, Peter W.; Alexander, Kristine S.; Wadley, Virginia; Zakai, Neil A.; Lidofsky, Steven D.; Unverzagt, Frederick W.; Judd, Suzanne E.; Psychiatry, School of MedicineBackground & aims: Nonalcoholic fatty liver disease (NAFLD) is prevalent and may affect cognitive function. We studied associations of NAFLD with risk of cognitive impairment. Secondarily we evaluated liver biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), their ratio, and gamma-glutamyl transpeptidase). Methods: In a prospective cohort study, the REasons for Geographic and Racial Differences in Stroke, among 30,239 black and white adults aged ≥45,495 cases of incident cognitive impairment were identified over 3.4 years follow up. Cognitive impairment was identified as new impairment in two of three cognitive tests administered every two years during follow up; word list learning and recall, and verbal fluency. 587 controls were selected from an age, race, sex-stratified sample of the cohort. The fatty liver index was used to define baseline NAFLD. Liver biomarkers were measured using baseline blood samples. Results: NAFLD at baseline was associated with a 2.01-fold increased risk of incident cognitive impairment in a minimally adjusted model (95% CI 1.42, 2.85). The association was largest in those aged 45-65 (p interaction by age = 0.03), with the risk 2.95-fold increased (95% CI 1.05, 8.34) adjusting for cardiovascular, stroke and metabolic risk factors. Liver biomarkers were not associated with cognitive impairment, except AST/ALT >2, with an adjusted OR 1.86 (95% CI 0.81, 4.25) that did not differ by age. Conclusions: A laboratory-based estimate of NAFLD was associated with development of cognitive impairment, particularly in mid-life, with a tripling in risk. Given its high prevalence, NAFLD may be a major reversible determinant of cognitive health.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 magnesium concentration and incident cognitive impairment: the reasons for geographic and racial differences in stroke study(Springer, 2021) Chen, Cheng; Xun, Pengcheng; Unverzagt, Frederick; McClure, Leslie A.; Ryan Irvin, Marguerite; Judd, Suzanne; Cushman, Mary; He, Ka; Psychiatry, School of MedicinePurpose: To examine the prospective association between serum Mg level and the incidence of cognitive impairment. Methods: A random sub-cohort (n = 2063) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was included in this study. Baseline serum Mg concentration was measured using inductively coupled plasma mass spectrometry. According to the current reference interval of serum magnesium (0.75-0.95 mmol/L), we classified participants below the interval as Level 1 and used it as the referent. The rest of the study population were equally divided into three groups, named Level 2 to 4. Incident cognitive impairment was identified using the Six-Item Screener. Multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression models. Results: After adjustment for potential confounders, an inverse threshold association between serum Mg level and incident cognitive impairment was observed. Compared to those with hypomagnesemia (Level 1: < 0.75 mmol/L), the relative odds of incident cognitive impairment was reduced by 41% in the second level [OR (95% CI) = 0.59 (0.37, 0.94)]; higher serum Mg level did not provide further benefits [Level 3 and 4 versus Level 1: OR (95% CI) = 0.54 (0.34, 0.88) and 0.59 (0.36, 0.96), P for linear trend = 0.08]. Conclusions: Findings from this prospective study suggest that sufficient Mg status within the normal range may be beneficial to cognitive health in the US general population.