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ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial.

ABSTRACT: AIMS/HYPOTHESIS:The 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. METHODS:Participants (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. RESULTS:Of 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/INTERPRETATION:The 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 REGISTRATION:ClinicalTrials.gov NCT00182910.

SUBMITTER: Murray AM

PROVIDER: S-EPMC5633725 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial.

Murray Anne M AM Hsu Fang-Chi FC Williamson Jeff D JD Bryan R Nick RN Gerstein Hertzel C HC Sullivan Mark D MD Miller Michael E ME Leng Iris I Lovato Laura L LL Launer Lenore J LJ

Diabetologia 20161020 1

<h4>Aims/hypothesis</h4>The 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. NCT0018 ...[more]

PMID: 27766347

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Project description:Depression 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.To determine whether comorbid depression in patients with type 2 diabetes accelerates cognitive decline.A 40-month cohort study of participants in the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) trial.Fifty-two clinics organized into 6 clinical networks across the United States and Canada.Two thousand nine hundred seventy-seven participants with type 2 diabetes at high risk for cardiovascular events.The 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.Mixed-effects statistical models were used to analyze cognitive test outcomes incorporating depression as a time-dependent covariate.Participants 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.Depression 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:BACKGROUND:People with type 2 diabetes are at risk of cognitive impairment and brain atrophy. We aimed to compare the effects on cognitive function and brain volume of intensive versus standard glycaemic control. METHODS:The Memory in Diabetes (MIND) study was done in 52 clinical sites in North America as part of Action to Control Cardiovascular Risk in Diabetes (ACCORD), a double two-by-two factorial parallel group randomised trial. Participants (aged 55-80 years) with type 2 diabetes, high glycated haemoglobin A(1c) (HbA(1c)) concentrations (>7·5%; >58 mmol/mol), and a high risk of cardiovascular events were randomly assigned to receive intensive glycaemic control targeting HbA(1c) to less than 6·0% (42 mmol/mol) or a standard strategy targeting HbA(1c) to 7·0-7·9% (53-63 mmol/mol). Randomisation was via a centralised web-based system and treatment allocation was not masked from clinic staff or participants. We assessed our cognitive primary outcome, the Digit Symbol Substitution Test (DSST) score, at baseline and at 20 and 40 months. We assessed total brain volume (TBV), our primary brain structure outcome, with MRI at baseline and 40 months in a subset of participants. We included all participants with follow-up data in our primary analyses. In February, 2008, raised mortality risk led to the end of the intensive treatment and transition of those participants to standard treatment. We tested our cognitive function hypotheses with a mixed-effects model that incorporated information from both the 20 and 40 month outcome measures. We tested our MRI hypotheses with an ANCOVA model that included intracranial volume and factors used to stratify randomisation. This study is registered with ClinicalTrials.gov, number NCT00182910. FINDINGS:We consecutively enrolled 2977 patients (mean age 62·5 years; SD 5·8) who had been randomly assigned to treatment groups in the ACCORD study. Our primary cognitive analysis was of patients with a 20-month or 40-month DSST score: 1378 assigned to receive intensive treatment and 1416 assigned to receive standard treatment. Of the 614 patients with a baseline MRI, we included 230 assigned to receive intensive treatment and 273 assigned to receive standard treatment in our primary MRI analysis at 40 months. There was no significant treatment difference in mean 40-month DSST score (difference in mean 0·32, 95% CI -0·28 to 0·91; p=0·2997). The intensive-treatment group had a greater mean TBV than the standard-treatment group (4·62, 2·0 to 7·3; p=0·0007). INTERPRETATION:Although significant differences in TBV favoured the intensive treatment, cognitive outcomes were not different. Combined with the non-significant effects on other ACCORD outcomes, and increased mortality in participants in the intensive treatment group, our findings do not support the use of intensive therapy to reduce the adverse effects of diabetes on the brain in patients with similar characteristics to those of our participants. FUNDING:US National Institute on Aging and US National Heart, Lung, and Blood Institute.

Project description:Although brief cessation advice from healthcare professionals increases quit rates, smokers typically do not get this advice during hospitalisation, possibly due to resource issues, lack of training and professionals' own attitudes to providing such counselling. Medical students are a potentially untapped resource who could deliver cessation counselling, while upskilling themselves and changing their own attitudes to delivering such advice in the future; however, no studies have investigated this. We aimed to determine if brief student-led counselling could enhance motivation to quit and smoking cessation behaviours among hospitalised patients.A mixed-methods, 2-arm pilot feasibility randomised controlled trial with qualitative process evaluation enrolled 67 hospitalised adult smokers, who were recruited and randomized to receive a brief medical student-delivered cessation intervention (n?=?33) or usual care (n?=?34); 61 medical students received standardised cessation training and 33 were randomly assigned to provide a brief in-hospital consultation and follow-up support by phone or in-person one week post-discharge. Telephone follow-up at 3- and 6-months assessed scores on the Motivation to Stop Smoking Scale (MTSS; primary outcome) and several other outcomes, including 7-day point prevalent abstinence, quit attempts, use of cessation medication, and ratings of student's knowledge and efficacy. Data were analysed as intention to treat (ITT) using penalised imputation, per protocol, and random effects repeated measures. Focus group interviews were conducted with students post-intervention to elicit their views on the training and intervention process.Analyses for primary and most secondary outcomes favoured the intervention group, although results were not statistically significant. Point prevalence abstinence rates were significantly higher for the intervention group during follow-up for all analyses except 6-month ITT analysis. Fidelity was variable. Patients rated students as being "very" knowledgeable about quitting and "somewhat" helpful. Qualitative results showed students were glad to deliver the intervention; were critical of current cessation care; felt constrained by their inability to prescribe cessation medications and wanted to include cessation and other behavioural counselling in their normal history taking.It appears feasible for medical students to be smoking cessation interventionists during their training, although their fidelity to the intervention requires further investigation. A definitive trial is needed to determine if medical students are effective cessation counsellors and if student-led intervention could be tailored for other health behaviours.NCT02601599 (retrospectively registered 1 day after first participant recruited on November 3rd 2015).

Project description:Hyperglycaemia is associated with increased risk of cardiovascular complications in people with type 2 diabetes. We investigated whether reduction of blood glucose concentration decreases the rate of microvascular complications in people with type 2 diabetes.ACCORD was a parallel-group, randomised trial done in 77 clinical sites in North America. People with diabetes, high HbA(1c) concentrations (>7.5%), and cardiovascular disease (or >or=2 cardiovascular risk factors) were randomly assigned by central randomisation to intensive (target haemoglobin A(1c) [HbA(1c)] of <6.0%) or standard (7.0-7.9%) glycaemic therapy. In this analysis, the prespecified composite outcomes were: dialysis or renal transplantation, high serum creatinine (>291.7 micromol/L), or retinal photocoagulation or vitrectomy (first composite outcome); or peripheral neuropathy plus the first composite outcome (second composite outcome). 13 prespecified secondary measures of kidney, eye, and peripheral nerve function were also assessed. Investigators and participants were aware of treatment group assignment. Analysis was done for all patients who were assessed for microvascular outcomes, on the basis of treatment assignment, irrespective of treatments received or compliance to therapies. ACCORD is registered with ClinicalTrials.gov, number NCT00000620.10 251 patients were randomly assigned, 5128 to the intensive glycaemia control group and 5123 to standard group. Intensive therapy was stopped before study end because of higher mortality in that group, and patients were transitioned to standard therapy. At transition, the first composite outcome was recorded in 443 of 5107 patients in the intensive group versus 444 of 5108 in the standard group (HR 1.00, 95% CI 0.88-1.14; p=1.00), and the second composite outcome was noted in 1591 of 5107 versus 1659 of 5108 (0.96, 0.89-1.02; p=0.19). Results were similar at study end (first composite outcome 556 of 5119 vs 586 of 5115 [HR 0.95, 95% CI 0.85-1.07, p=0.42]; and second 1956 of 5119 vs 2046 of 5115, respectively [0.95, 0.89-1.01, p=0.12]). Intensive therapy did not reduce the risk of advanced measures of microvascular outcomes, but delayed the onset of albuminuria and some measures of eye complications and neuropathy. Seven secondary measures at study end favoured intensive therapy (p<0.05).Microvascular benefits of intensive therapy should be weighed against the increase in total and cardiovascular disease-related mortality, increased weight gain, and high risk for severe hypoglycaemia.US National Institutes of Health; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; and General Clinical Research Centers.

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ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial.

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ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial.

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