Abstract
OBJECTIVES: 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.