Dataset Information

Association of the Haptoglobin Gene Polymorphism With Cognitive Function and Decline in Elderly African American Adults With Type 2 Diabetes: Findings From the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) Study.

ABSTRACT:

SUBMITTER: Beeri MS

PROVIDER: S-EPMC6324406 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Association of the Haptoglobin Gene Polymorphism With Cognitive Function and Decline in Elderly African American Adults With Type 2 Diabetes: Findings From the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) Study.

Beeri Michal S MS Lin Hung-Mo HM Sano Mary M Ravona-Springer Ramit R Liu Xiaoyu X Bendlin Barbara B BB Gleason Carey E CE Guerrero-Berroa Elizabeth E Soleimani Laili L Launer Lenore J LJ Ehrenberg Scott S Lache Orit O Seligman Yaakov K YK Levy Andrew P AP

JAMA network open 20181102 7

<h4>Importance</h4>African American individuals have higher dementia risk than individuals of white race/ethnicity. They also have higher rates of type 2 diabetes, which may contribute to this elevated risk. This study examined the association of the following 2 classes of alleles at the haptoglobin (Hp) locus that are associated with poor cognition, cardiovascular disease, and mortality: Hp 1-1 (associated with poor cognition and cerebrovascular disease) and Hp 2-1 and Hp 2-2 (associated with g ...[more]

PMID: 30646354

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Project description:ImportanceDepression has been identified as a risk factor for dementia among patients with type 2 diabetes mellitus but the cognitive domains and patient groups most affected have not been identified.ObjectiveTo determine whether comorbid depression in patients with type 2 diabetes accelerates cognitive decline.DesignA 40-month cohort study of participants in the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) trial.SettingFifty-two clinics organized into 6 clinical networks across the United States and Canada.ParticipantsTwo thousand nine hundred seventy-seven participants with type 2 diabetes at high risk for cardiovascular events.InterventionThe Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, and the modified Stroop test were used to assess cognition. The 9-item Patient Health Questionnaire was used to assess depression.Main outcomes and measuresMixed-effects statistical models were used to analyze cognitive test outcomes incorporating depression as a time-dependent covariate.ResultsParticipants with scores indicative of depression (9-item Patient Health Questionnaire, ≥10) showed greater cognitive decline during 40-month follow-up on all tests, with the following differences in estimated least squares means: Digit Symbol Substitution Test, 0.72 (95% CI, 0.25 to 1.19; P = .003), Rey Auditory Verbal Learning Test, 0.18 (95% CI, 0.07 to 0.29; P = .001), and Stroop interference, -1.06 (95% CI, -1.93 to -0.18; P = .02). This effect of depression on risk of cognitive decline did not differ according to previous cardiovascular disease; baseline cognition or age; or intensive vs standard glucose-lowering treatment, blood pressure treatment, lipid treatment, or insulin treatment. Addition of demographic and clinical covariates to models did not significantly change the cognitive decline associated with depression.Conclusions and relevanceDepression in patients with type 2 diabetes was associated with greater cognitive decline in all domains, across all treatment arms, and in all participant subgroups assessed. Future randomized trials will be necessary to determine if depression treatment can lower the risk of cognitive decline in patients with diabetes.

Project description:Aims/hypothesisThe Memory in Diabetes (MIND) substudy of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, a double 2x2 factorial parallel-group randomised clinical trial, tested whether intensive compared with standard management of hyperglycaemia, BP or lipid levels reduced cognitive decline and brain atrophy in 2977 people with type 2 diabetes. We describe the results of the observational extension study, ACCORDION MIND (ClinicalTrials.gov registration no. NCT00182910), which aimed to measure the long-term effects of the three ACCORD interventions on cognitive and brain structure outcomes approximately 4 years after the trial ended.MethodsParticipants (mean diabetes duration 10 years; mean age 62 years at baseline) received a fourth cognitive assessment and a third brain MRI, targeted at 80 months post-randomisation. Primary outcomes were performance on the Digit Symbol Substitution Test (DSST) and total brain volume (TBV). The contrast of primary interest compared glycaemic intervention groups at the ACCORDION visit; secondary contrasts were the BP and lipid interventions.ResultsOf the surviving ACCORD participants eligible for ACCORDION MIND, 1328 (68%) were re-examined at the ACCORDION follow-up visit, approximately 47 months after the intensive glycaemia intervention was stopped. The significant differences in therapeutic targets for each of the three interventions (glycaemic, BP and lipid) were not sustained. We found no significant difference in 80 month mean change from baseline in DSST scores or in TBV between the glycaemic intervention groups, or the BP and lipid interventions. Sensitivity analyses of the sites with ≥70% participation at 80 months revealed consistent results.Conclusions/interpretationThe ACCORD interventions did not result in long-term beneficial or adverse effects on cognitive or brain MRI outcomes at approximately 80 months follow-up. Loss of separation in therapeutic targets between treatment arms and loss to follow-up may have contributed to the lack of detectable long-term effects.Trial registrationClinicalTrials.gov NCT00182910.

Project description:BackgroundImpaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors.MethodsIncluded in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period (median eGFR/year = 1.9, IQR 1.7-3.2). The association between rapid kidney function decline (eGFR loss ≥ 5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI).ResultsOver 4 years of follow-up, 1,573 participants (20.9%) experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds (3.23, 95% CI, 2.51-4.16, p < 0.0001), independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring (3.74; 95% CI 2.63-5.31). Adding rapid kidney function decline during follow-up to other clinical predictors (WATCH-DM score, eGFR, and UACR at study entry and end of follow-up) improved HF risk classification (ROC AUC = + 0.02, p = 0.027; relative IDI = + 38%, p < 0.0001).ConclusionsIn patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D.

Dataset Information

Association of the Haptoglobin Gene Polymorphism With Cognitive Function and Decline in Elderly African American Adults With Type 2 Diabetes: Findings From the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) Study.

Publications

Association of the Haptoglobin Gene Polymorphism With Cognitive Function and Decline in Elderly African American Adults With Type 2 Diabetes: Findings From the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) Study.

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