title: Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis.
abstract: BACKGROUND
  A history of depression may increase risk for developing Alzheimer disease (AD) later in life. Clarifying this relation might improve understanding of risk factors for and disease mechanisms in AD.
  
  
  OBJECTIVE
  To systematically review and complete a meta-analysis on the relation of depression and AD.
  
  
  METHODS
  We conducted electronic bibliographic searches of MEDLINE, PsychLit, EMBASE, and BIOSIS using search terms sensitive to studies of etiology combined with searches on terms related to depression and AD and reviewed reference lists of articles.
  
  
  METHODS
  Studies with data contrasting depressed vs nondepressed patients who did and did not later develop AD were included. Studies that related continuous measures of depression and cognitive status were excluded.
  
  
  METHODS
  Numerical data were independently extracted by 3 reviewers. They also rated studies on a scale that assessed quality indicators for observational studies. Data on the interval between observation of depression and the diagnosis of AD were collected when available.
  
  
  RESULTS
  Meta-analytic evaluation with random-effects models resulted in pooled odds ratios of 2.03 (95% confidence interval, 1.73-2.38) for case-control and of 1.90 (95% confidence interval, 1.55-2.33) for cohort studies. Findings of increased risk were robust to sensitivity analyses. Interval between diagnoses of depression and AD was positively related to increased risk of developing AD, suggesting that rather than a prodrome, depression may be a risk factor for AD.
  
  
  CONCLUSIONS
  A history of depression may confer an increased risk for later developing AD. This relation may reflect an independent risk factor for the disease.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Fla 33140, USA. rownby@med.miami.edu
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Ownby
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Crocco
authors.forename: Amarilis
authors.initials: A
authors.lastname: Acevedo
authors.forename: Vineeth
authors.initials: V
authors.lastname: John
authors.forename: David
authors.initials: D
authors.lastname: Loewenstein
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D015897:Comorbidity; D003431:Cross-Cultural Comparison; D003866:Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D015995:Prevalence; D017594:Publication Bias / Q000706:statistics & numerical data; D012044:Regression Analysis; D012307:Risk Factors