Depression and Incident Alzheimer Disease: The Impact of Disease Severity

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.