title: Albuminuria and cognitive decline in people with diabetes and normal renal function.
abstract: OBJECTIVE
  Diabetes mellitus is associated with increased risk of cognitive impairment. This study examines whether microvascular disease, as measured by albuminuria and decline in estimated GFR (eGFR), is associated with cognitive decline during 3.3 years of follow-up in individuals with diabetes with a normal baseline eGFR (approximately 90 ml/min per 1.73 m(2)).
  
  
  METHODS
  Participants were from the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes study (N=2977; mean age 62.5 ± 5.8 years; recruitment from August 2003 to December 2005, followed through June 2009), which examined the association of intensive versus standard glucose control on cognitive function. Participants underwent three neuropsychologic tests at baseline, 20 months, and 40 months. Tests included information processing speed, verbal memory, and executive function. Mixed-effects models were used to assess the association of albuminuria and eGFR on the percentage decline in each test.
  
  
  RESULTS
  Participants with albuminuria at baseline and follow-up (persistent albuminuria) (-5.8% [95% confidence interval (CI), -7.3 to -4.2]) and participants with albuminuria at follow-up but none at baseline (progressive albuminuria) (-4.1% [95% CI, -5.6 to -2.7]) had greater percentage declines on information processing speed than participants without albuminuria at baseline and at follow-up (no albuminuria) (-2.6% [95% CI, -3.4 to -1.9]) (P=0.001 and P=0.10, respectively). There were borderline percentage changes in the test of verbal memory (4.8% [95% CI, 2.4 to 7.1] and 4.7% [95% CI, 2.5 to 7.0] versus 7.1% [95% CI, 6.0 to 8.3]; P=0.11 and P=0.08, respectively). On logistic regression analysis, persistent albuminuria (odds ratio, 1.37 [95% CI, 1.09 to 1.72]) and progressive albuminuria (odds ratio, 1.25 [95% CI, 1.02 to 1.56]) were associated with a ≥ 5% decline in information processing speed scores but not with verbal memory or executive function performance. A 1 ml/min per 1.73 m(2) per year eGFR decline had a borderline association with decline in tests of cognitive function.
  
  
  CONCLUSIONS
  Persistent albuminuria and progressive albuminuria are associated with a decline in cognitive function in relatively young individuals with diabetes with unimpaired eGFR. These findings do not rule out the possibility of other processes causing cognitive decline.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Barzilay
authors.forename: James F
authors.initials: JF
authors.lastname: Lovato
authors.forename: Anne M
authors.initials: AM
authors.lastname: Murray
authors.forename: Jeff
authors.initials: J
authors.lastname: Williamson
authors.forename: Faramaz
authors.initials: F
authors.lastname: Ismail-Beigi
authors.forename: Diane
authors.initials: D
authors.lastname: Karl
authors.forename: Vasilios
authors.initials: V
authors.lastname: Papademetriou
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D003071:Cognition; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D018450:Disease Progression; D056344:Executive Function; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D016015:Logistic Models; D008297:Male; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors