The Association Between Major Depression and Alzheimer's Disease Risk: Evidence from a 12-Year Longitudinal Study

Background: The relationship between depression, particularly major depression (MD), as a risk factor for Alzheimer's disease (AD) is well established; however, its precise role remains contested. Findings from the fourth wave of the ZARADEMP longitudinal study provide further insights into the association between MD and AD risk. Objectives: This study aimed to examine the association between MD and incident AD, controlling for established risk factors. Methods: The study analyzed 4803 participants, of whom 4057 were followed over a 12-year period as part of the ZARADEMP longitudinal study. Depression was assessed using the GMS-AGECAT, and dementia was diagnosed according to DSM-IV criteria. The association between MD and incident AD was evaluated using Cox proportional hazards regression models. Results: The incidence of AD was approximately twice as high in participants with MD compared to those without (relative risk = 2.07; 95% CI: 0.85-5.03; p = 0.123). This risk was nearly threefold higher in the fully adjusted model. Conclusions: These findings underscore a significant association between MD and an increased risk of AD, emphasizing the need for vigilant monitoring and potential early intervention among individuals diagnosed with MD.