title: Clinical and subclinical macrovascular disease as predictors of cognitive decline in older patients with type 2 diabetes: the Edinburgh Type 2 Diabetes Study.
abstract: OBJECTIVE
  Macrovascular disease may contribute to increased risk of accelerated cognitive decline in patients with type 2 diabetes. We aimed to determine associations of measures of macrovascular disease with cognitive change in a cognitively healthy older population with type 2 diabetes.
  
  
  METHODS
  Eight hundred thirty-one men and women (aged 60-75 years) attended two waves of the prospective Edinburgh Type 2 Diabetes Study (ET2DS). At baseline, clinical and subclinical macrovascular disease was measured, including cardiovascular event history, carotid intima-media thickness (cIMT), ankle brachial index (ABI), and serum N-terminal probrain natriuretic peptide (NT-proBNP). Seven neuropsychological tests were administered at baseline and after 4 years; scores were combined to a standardized general ability factor (g). Adjustment of follow-up g for baseline g assessed 4-year cognitive change. Adjustment for vocabulary (estimated premorbid ability) was used to estimate lifetime cognitive change.
  
  
  RESULTS
  Measures of cognitive decline were significantly associated with stroke, NT-proBNP, ABI, and cIMT, but not with nonstroke vascular events. The association of stroke with increased estimated lifetime cognitive decline (standardized β, -0.12) and of subclinical markers with actual 4-year decline (standardized β, -0.12, 0.12, and -0.15 for NT-proBNP, ABI, and cIMT, respectively) reached the Bonferroni-adjusted level of statistical significance (P < 0.006). Results altered only slightly on adjustment for vascular risk factors.
  
  
  CONCLUSIONS
  Stroke and subclinical markers of cardiac stress and generalized atherosclerosis are associated with cognitive decline in older patients with type 2 diabetes. Further investigation into the potential use of subclinical vascular disease markers in predicting cognitive decline is warranted.
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom. i.feinkohl@sms.ed.ac.uk
authors.forename: Insa
authors.initials: I
authors.lastname: Feinkohl
authors.forename: Marketa
authors.initials: M
authors.lastname: Keller
authors.forename: Christine M
authors.initials: CM
authors.lastname: Robertson
authors.forename: Joanne R
authors.initials: JR
authors.lastname: Morling
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Williamson
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Nee
authors.forename: Stela
authors.initials: S
authors.lastname: McLachlan
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Reynolds
authors.forename: Tom C
authors.initials: TC
authors.lastname: Russ
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.forename: Mark W J
authors.initials: MW
authors.lastname: Strachan
authors.forename: Jackie F
authors.initials: JF
authors.lastname: Price
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000150:complications / Q000378:metabolism / Q000503:physiopathology
chemical_list: D015415:Biomarkers