title: Effect of depression and diabetes mellitus on the risk for dementia: a national population-based cohort study.
abstract: OBJECTIVE
  Although depression and type 2 diabetes mellitus (DM) may independently increase the risk for dementia, no studies have examined whether the risk for dementia among people with comorbid depression and DM is higher than the sum of each exposure individually.
  
  
  OBJECTIVE
  To examine the risk for all-cause dementia among persons with depression, DM, or both compared with persons with neither exposure.
  
  
  METHODS
  We performed a national population-based cohort study of 2 454 532 adults, including 477 133 (19.4%) with depression, 223 174 (9.1%) with DM, and 95 691 (3.9%) with both. We included all living Danish citizens 50 years or older who were free of dementia from January 1, 2007, through December 31, 2013 (followed up through December 31, 2013). Dementia was ascertained by physician diagnosis from the Danish National Patient Register or the Danish Psychiatric Central Register and/or by prescription of a cholinesterase inhibitor or memantine hydrochloride from the Danish National Prescription Registry. Depression was ascertained by psychiatrist diagnosis from the Danish Psychiatric Central Research Register or by prescription of an antidepressant from the Danish National Prescription Registry. Diabetes mellitus was identified using the National Diabetes Register.
  
  
  METHODS
  We estimated the risk for all-cause dementia associated with DM, depression, or both using Cox proportional hazards regression models that adjusted for potential confounding factors (eg, demographics) and potential intermediates (eg, medical comorbidities).
  
  
  RESULTS
  During 13 834 645 person-years of follow-up, 59 663 participants (2.4%) developed dementia; of these, 6466 (10.8%) had DM, 15 729 (26.4%) had depression, and 4022 (6.7%) had both. The adjusted hazard ratio for developing all-cause dementia was 1.83 (95% CI, 1.80-1.87) for persons with depression, 1.20 (95% CI, 1.17-1.23) for persons with DM, and 2.17 (95% CI, 2.10-2.24) for those with both compared with persons who had neither exposure. The excess risk for all-cause dementia observed for individuals with comorbid depression and DM surpassed the summed risk associated with each exposure individually, especially for persons younger than 65 years (hazard ratio, 4.84 [95% CI, 4.21-5.55]). The corresponding attributable proportion due to the interaction of comorbid depression and DM was 0.25 (95% CI, 0.13-0.36; P < .001) for those younger than 65 years and 0.06 (95% CI, 0.02-0.10; P = .001) for those 65 years or older.
  
  
  CONCLUSIONS
  Depression and DM were independently associated with a greater risk for dementia, and the combined association of both exposures with the risk for all-cause dementia was stronger than the additive association.
authors: Division of Health Services Research and Psychiatric Epidemiology, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle.
authors: Wayne
authors: W
authors: Katon
authors: Department of Public Health, Research Unit for General Practice, Aarhus University, Aarhus, Denmark.
authors: Henrik Sondergaard
authors: HS
authors: Pedersen
authors: Department of Public Health, Research Unit for General Practice, Aarhus University, Aarhus, Denmark.
authors: Anette Riisgaard
authors: AR
authors: Ribe
authors: Department of Public Health, Research Unit for General Practice, Aarhus University, Aarhus, Denmark.
authors: Morten
authors: M
authors: Fenger-Grøn
authors: Division of Health Services Research and Psychiatric Epidemiology, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle.
authors: Dimitry
authors: D
authors: Davydow
authors: Department of Public Health, Research Unit for General Practice, Section of General Practice, University of Copenhagen, Copenhagen, Denmark.
authors: Frans Boch
authors: FB
authors: Waldorff
authors: Department of Public Health, Research Unit for General Practice, Aarhus University, Aarhus, Denmark.
authors: Mogens
authors: M
authors: Vestergaard
mesh_terms: D000368:Aged; D015331:Cohort Studies; D015897:Comorbidity; D003704:Dementia / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D003863:Depression / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors