Role of apolipoprotein E epsilon 4 (APOE*ε4) as an independent risk factor for incident depression over a 12-year period in cognitively intact adults across the lifespan

BACKGROUND: The apolipoprotein E ε4 allele (APOE*ε4) is indicated as a risk for Alzheimer's disease and other age-related diseases. The risk attributable to APOE*ε4 for depression is less clear and may be because of confounding of the relationship between dementia and depression. AIMS: We examined the risk of APOE* ε4 for incident depression and depressive symptomology over a 12-year period across the adult lifespan. METHOD: Participants were from the Personality and Total Health Through Life study, aged 20 to 24 (n = 1420), 40 to 44 (n = 1592) or 60–64 (n = 1768) at baseline, and interviewed every 4 years since 1999. Ethnicities other than White, those without genotyping and those with depression at baseline, or who reported strokes and scores on the Mini-Mental State Examination <27 at any observation, were excluded. RESULTS: Over the study period, there was no evidence that APOE*ε4+ was a risk factor for depression, including any depression (odds ratio (OR) = 0.94, 95% CI 0.77–1.16, P = 0.573), major depression (OR = 0.96, 95% CI 0.60–1.53, P = 0.860), minor depression (OR = 0.94, 95% CI 0.67–1.30, P = 0.695) or depressive symptomology (incidence rate ratio (IRR) = 1.02, 95% CI 0.97–1.08, P = 0.451). APOE*ε4 was unrelated to incident depression. Findings were consistent for all age cohorts. CONCLUSIONS: Among cognitively intact Australian adults who were free of depression at baseline, there was little evidence that APOE*ε4+ carriers are at increased risk for depression over a 12-year period among those who are cognitively intact.