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
| Original language | English (US) |
|---|---|
| Pages (from-to) | 69-80 |
| Number of pages | 12 |
| Journal | Diabetologia |
| Volume | 60 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2017 |
Bibliographical note
Funding Information:The authors wish to thank M. Bartkoske, and S. Pederson, both at the Berman Center for Clinical Research, and N. Booth, at the Chronic Disease Research Group, all at the Minneapolis Medical Research Foundation, Hennepin County Medical Center, Minneapolis for their assistance in manuscript preparation. A list of Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) investigators is given in the electronic supplementary material (ESM). ACCORD was funded by the National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA#Y1-HC-9035 and IAA#Y1-HC-1010. ACCORDION MIND was funded through an intra-agency agreement between the National Institute on Aging (NIA) and NHLBI (AG-0008), NIA contract (HSN271201000023C) and the NIA Intramural Research Program. Other components of the National Institutes of Health, including the National Institute of Diabetes, and Digestive and Kidney Diseases and the National Eye Institute, contributed funding. The Centers for Disease Control and Prevention funded ACCORD substudies of cost-effectiveness and health-related quality of life. General Clinical Research Centers provided support at many sites. The following companies provided study medications, equipment or supplies: Abbott Laboratories (Abbott Park, IL, USA); Amylin Pharmaceutical (San Diego, CA, USA); AstraZeneca Pharmaceuticals LP (Wilmington, DE, USA); Bayer HealthCare LLC (Tarrytown, NY, USA); Closer Healthcare Inc. (Tequesta, FL, USA); GlaxoSmithKline Pharmaceuticals (Philadelphia, PA, USA); King Pharmaceuticals, Inc. (Bristol, TN, USA); Merck & Co., Inc. (Whitehouse Station, NJ, USA); Novartis Pharmaceuticals, Inc. (East Hanover, NJ, USA); Novo Nordisk, Inc. (Princeton, NJ, USA); Omron Healthcare, Inc. (Schaumburg, IL, USA); Sanofi U.S. (Bridgewater, NJ, USA); Schering-Plough Corporation (Kenilworth, NJ, USA). The donors of medications and devices had no role in the study design, data accrual and analysis, or manuscript preparation.
Funding Information:
ACCORD was funded by the National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA#Y1-HC-9035 and IAA#Y1-HC-1010. ACCORDION MIND was funded through an intra-agency agreement between the National Institute on Aging (NIA) and NHLBI (AG-0008), NIA contract (HSN271201000023C) and the NIA Intramural Research Program. Other components of the National Institutes of Health, including the National Institute of Diabetes, and Digestive and Kidney Diseases and the National Eye Institute, contributed funding. The Centers for Disease Control and Prevention funded ACCORD substudies of cost-effectiveness and health-related quality of life. General Clinical Research Centers provided support at many sites.
Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
Keywords
- Abnormal white matter volume
- Brain MRI
- Cognitive impairment
- Total brain volume
- Type 2 diabetes
