title: Depression and incident Alzheimer disease: the impact of disease severity.
abstract: OBJECTIVE
  To test the hypothesis that clinically significant depression (particularly severe depression) increases the risk of Alzheimer's disease (AD).
  
  
  METHODS
  A longitudinal, three-wave epidemiologic study was implemented in a sample of individuals aged 55 years and older (n = 4,803) followed up at 2.5 years and 4.5 years. This was a population-based cohort drawn from the Zaragoza Dementia and Depression (ZARADEMP) Project, in Zaragoza, Spain. Participants included individuals cognitively intact at baseline (n = 3,864). The main outcome measures were depression as assessed by using the diagnostic interview Geriatric Mental State- Automated Geriatric Examination for Computer Assisted Taxonomy package; and AD diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The Fine and Gray multivariate regression model was used in the analysis, accounting for mortality.
  
  
  RESULTS
  At baseline, clinically significant depression was diagnosed in 452 participants (11.7%); of these, 16.4% had severe depression. Seventy incident cases of AD were found at follow-up. Compared with nondepressed individuals, the incidence rate of AD was significantly higher in the severely depressed subjects (incidence rate ratio: 3.59 [95% confidence interval: 1.30-9.94]). A consistent, significant association was observed between severe depression at baseline and incident AD in the multivariate model (hazard ratio: 4.30 [95% CI: 1.39-13.33]). Untreated depression was associated with incident AD in the unadjusted model; however, in the final model, this association was attenuated and nonsignificant.
  
  
  CONCLUSIONS
  Severe depression increases the risk of AD, even after controlling for the competing risk of death.
authors.affiliation: Psychiatry Service, Hospital Clínico Universitario, Zaragoza, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gracia-García
authors.affiliation: Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain; Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain; Department of Preventive Medicine and Public Health, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: de-la-Cámara
authors.affiliation: Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain; Department of Psychology and Sociology, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Santabárbara
authors.affiliation: Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain; Psychiatry Service, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Lopez-Anton
authors.affiliation: Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Quintanilla
authors.affiliation: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain; Medical Records Service, Hospital Clínico Universitario, Zaragoza, Spain.
authors.forename: Tirso
authors.initials: T
authors.lastname: Ventura
authors.affiliation: Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain; Department of Psychology and Sociology, Universidad de Zaragoza, Zaragoza, Spain; Johns Hopkins University, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Marcos
authors.affiliation: Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain; Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain; Department of Preventive Medicine and Public Health, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Campayo
authors.affiliation: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain; Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Saz
authors.affiliation: Johns Hopkins University, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.
authors.forename: Constantine
authors.initials: C
authors.lastname: Lyketsos
authors.affiliation: Department of Medicine and Psychiatry, Universidad de Zaragoza, Zaragoza, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Ministry of Science and Innovation, Madrid, Spain; Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain; Department of Preventive Medicine and Public Health, Universidad de Zaragoza, Zaragoza, Spain. Electronic address: alobo@unizar.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lobo
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology*; D015897:Comorbidity; D003863:Depression / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
keywords: Alzheimer's disease; Risk factor; depression; incidence