title: The cross-sectional and longitudinal associations of diabetic retinopathy with cognitive function and brain MRI findings: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
abstract: OBJECTIVE
  Longitudinal evidence linking diabetic retinopathy with changes in brain structure and cognition is sparse. We used data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to determine whether diabetic retinopathy at baseline predicted changes in brain structure or cognition 40 months later.
  
  
  METHODS
  Participants from the ACCORD-MIND and ACCORD-Eye substudies were included in analyses of cognition (n = 1,862) and MRI-derived brain variables (n = 432). Retinopathy was categorized as none, mild nonproliferative, or moderate/severe. Tests of cognition included the Mini-Mental State Examination (MMSE), Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test, and Stroop test. Primary brain outcomes were gray matter and abnormal white matter volumes.
  
  
  RESULTS
  Baseline retinopathy was associated with lower gray matter volume (adjusted means of 470, 466, and 461 cm(3) for none, mild, and moderate/severe retinopathy, respectively; P = 0.03). Baseline retinopathy also predicted a greater change in MMSE and DSST scores at 40 months in each retinopathy category (MMSE: -0.20, -0.57, and -0.42, respectively [P = 0.04]; DSST: -1.30, -1.84, and -2.89, respectively [P = 0.01]).
  
  
  CONCLUSIONS
  Diabetic retinopathy is associated with future cognitive decline in people with type 2 diabetes. Although diabetic retinopathy is not a perfect proxy for diabetes-related brain and cognitive decline, patients with type 2 diabetes and retinopathy represent a subgroup at higher risk for future cognitive decline.
authors.affiliation: Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC chugensc@wakehealth.edu.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Hugenschmidt
authors.affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: James F
authors.initials: JF
authors.lastname: Lovato
authors.affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Walter T
authors.initials: WT
authors.lastname: Ambrosius
authors.affiliation: Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA.
authors.forename: R Nick
authors.initials: RN
authors.lastname: Bryan
authors.affiliation: Department of Medicine and Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH.
authors.forename: Karen R
authors.initials: KR
authors.lastname: Horowitz
authors.affiliation: National Institute on Aging, National Institutes of Health, Bethesda, MD.
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.affiliation: Departments of Neurology and Neurosurgery, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Lazar
authors.affiliation: Department of Medicine, Hennepin County Medical Center and University of Minnesota, Minneapolis, MN.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Murray
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Danis
authors.affiliation: Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Williamson
authors.affiliation: Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Miller
authors.affiliation: Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Ding
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000523:psychology; D003930:Diabetic Retinopathy / Q000150:complications* / Q000453:epidemiology / Q000523:psychology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011379:Prognosis; D012307:Risk Factors