title: ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  ClinicalTrials.gov NCT00182910.
authors.affiliation: Division of Geriatrics, Department of Medicine, Hennepin County Medical Center and University of Minnesota, Minneapolis, MN, USA. amurray@bermancenter.org.|Berman Center for Clinical Research, Hennepin County Medical Center, 701 Park Avenue, Suite PPC4-440, Minneapolis, MN, 55415, USA. amurray@bermancenter.org.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Murray
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: Fang-Chi
authors.initials: FC
authors.lastname: Hsu
authors.affiliation: Geriatic Medicine, Department of Internal Medicine, J. Paul Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Williamson
authors.affiliation: Department of Radiology, University of Pennsylvania Health System, Philadelphia, PA, USA.
authors.forename: R Nick
authors.initials: RN
authors.lastname: Bryan
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.|Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada.
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.affiliation: Department of Psychiatry and Behavioural Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Sullivan
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Miller
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: Iris
authors.initials: I
authors.lastname: Leng
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Lovato
authors.affiliation: Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Bethesda, MD, USA.
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001921:Brain / Q000473:pathology / Q000502:physiology; D003071:Cognition / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents
keywords: Abnormal white matter volume; Brain MRI; Cognitive impairment; Total brain volume; Type 2 diabetes