title: Midlife type 2 diabetes and poor glycaemic control as risk factors for cognitive decline in early old age: a post-hoc analysis of the Whitehall II cohort study.
abstract: BACKGROUND
  Type 2 diabetes increases the risk for dementia, but whether it affects cognition before old age is unclear. We investigated whether duration of diabetes in late midlife and poor glycaemic control were associated with accelerated cognitive decline.
  
  
  METHODS
  5653 participants from the Whitehall II cohort study (median age 54.4 years [IQR 50.3-60.3] at first cognitive assessment), were classified into four groups: normoglycaemia, prediabetes, newly diagnosed diabetes, and known diabetes. Tests of memory, reasoning, phonemic and semantic fluency, and a global score that combined all cognitive tests, were assessed three times over 10 years (1997-99, 2002-04, and 2007-09). Mean HbA1c was used to assess glycaemic control during follow-up. Analyses were adjusted for sociodemographic characteristics, health-related behaviours, and chronic diseases.
  
  
  RESULTS
  Compared with normoglycaemic participants, those with known diabetes had a 45% faster decline in memory (10 year difference in decline -0.13 SD, 95% CI -0.26 to -0.00; p=0.046), a 29% faster decline in reasoning (-0.10 SD, -0.19 to -0.01; p=0.026), and a 24% faster decline in the global cognitive score (-0.11 SD, -0.21 to -0.02; p=0.014). Participants with prediabetes or newly diagnosed diabetes had similar rates of decline to those with normoglycaemia. Poorer glycaemic control in participants with known diabetes was associated with a significantly faster decline in memory (-0.12 [-0.22 to -0.01]; p=0.034) and a decline in reasoning that approached significance (-0.07 [-0.15 to 0.00]; p=0.052).
  
  
  CONCLUSIONS
  The risk of accelerated cognitive decline in middle-aged patients with type 2 diabetes is dependent on both disease duration and glycaemic control.
  
  
  BACKGROUND
  US National Institutes of Health, UK Medical Research Council.
authors.affiliation: INSERM U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif, France; Université Paris Sud 11, Paris, France.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Tuligenga
authors.affiliation: INSERM U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif, France; Université de Versailles St-Quentin-en-Yvelines, Versailles, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Dugravot
authors.affiliation: Departments of Epidemiology and Public Health, University College London, London, UK; First Department of Medicine, Semmelweis University Faculty of Medicine, Budapest, Hungary.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Tabák
authors.affiliation: INSERM U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Elbaz
authors.affiliation: Departments of Epidemiology and Public Health, University College London, London, UK.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Brunner
authors.affiliation: Departments of Epidemiology and Public Health, University College London, London, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimäki
authors.affiliation: INSERM U1018, Centre for Research in Epidemiology and Population Health, Hôpital Paul Brousse, Villejuif, France; Departments of Epidemiology and Public Health, University College London, London, UK; Centre de Gérontologie, Hôpital Ste Périne, AP-HP, Paris, France; Université de Versailles St-Quentin-en-Yvelines, Versailles, France. Electronic address: archana.singh-manoux@inserm.fr.
authors.forename: Archana
authors.initials: A
authors.lastname: Singh-Manoux
mesh_terms: D015331:Cohort Studies; D003704:Dementia / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors