Depression as a risk factor for Alzheimer disease: the MIRAGE Study.

Background: Depression symptoms may be associated with the development of Alzheimer disease (AD).
Objectives: To evaluate the association between depression symptoms and risk of AD, and to explore the temporal aspects of this association.
Setting: Academic institutions with specialized memory clinics.
Design: Cross-sectional, family-based, case-control study with standardized self- and proxy questionnaires to collect information on depression symptoms and other risk factors.
Participants: A total of 1953 subjects with AD and 2093 of their unaffected relatives enrolled in the Multi-institutional Research in Alzheimer's Genetic Epidemiology Study.
Main Outcome Measures: Odds ratios (ORs) of AD were estimated with and without depression symptoms, adjusted for age, sex, education, history of head trauma, and apolipoprotein E status.
Results: There was a significant association between depression symptoms and AD (adjusted OR, 2.13; 95% confidence interval [CI], 1.71-2.67). In families where depression symptoms first occurred within 1 year before the onset of AD, the association was higher (OR, 4.57; 95% CI, 2.87-7.31), while in the families where the depression symptoms first occurred more than 1 year before the onset of AD, the association was lower (OR, 1.38; 95% CI, 1.03-1.85). In families where depression symptoms first occurred more than 25 years before the onset of AD, there was still a modest association (OR, 1.71; 95% CI, 1.03-2.82).
Conclusions: Depression symptoms before the onset of AD are associated with the development of AD, even in families where first depression symptoms occurred more than 25 years before the onset of AD. These data suggest that depression symptoms are a risk factor for later development of AD.