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Original Contribution
May 2003

Depression as a Risk Factor for Alzheimer Disease: The MIRAGE Study

Author Affiliations

From the Departments of Neurology and Medicine (Genetics Program), Boston University School of Medicine, Boston, Mass (Drs Green, Auerbach, and Farrer); Departments of Epidemiology (Drs Green and Farrer) and Biostatistics (Drs Cupples and Farrer), Boston University School of Public Health; Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany (Dr Kurz); Department of Epidemiology, University of Alabama at Birmingham, School of Public Health, Birmingham (Dr Go); Department of Medical Genetics and Medicine (Neurology), University of British Columbia, Vancouver (Dr Sadovnick); The Wein Center, Mt Sinai Medical Center and the University of Miami School of Medicine, Miami, Fla (Dr Duara); Department of Epidemiology, School of Public Health, University of Washington, Seattle (Dr Kukull); Rancho Los Amigos Rehabilitation Center and Department of Neurology, University of Southern California, Los Angeles (Dr Chui); Department of Medicine, Sections of Clinical Pharmacology (Dr Edeki) and Neurology (Dr Griffith), Morehouse School of Medicine, Atlanta, Ga; Department of Neurology, Case Western Reserve University, Cleveland, Ohio (Dr Friedland); and Department of Psychiatry, Medical University of South Carolina, Charleston (Dr Bachman).

Arch Neurol. 2003;60(5):753-759. doi:10.1001/archneur.60.5.753

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.