Association between the APOE genotype and psychopathologic symptoms in Alzheimer's disease

Abstract

Background: Psychiatric symptoms occur frequently in the course of AD, are a frequent contributor to institutionalization, predict cognitive decline and death, and often require treatment with psychotropic medications. Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results.

Objective: To determine whether APOE genotype predicts incident psychiatric symptomatology in patients with AD.

Methods: Eighty-seven patients with AD at early stages and no psychiatric history were followed semiannually for up to 9.3 years (mean 5.5 years) for development of delusions, illusions, hallucinations, behavioral symptoms, and depression. Cox proportional hazards models were used to examine the relative risk for incident psychiatric symptomatology (outcome) in relation to APOE genotype (predictor).

Results: The presence of one epsilon4 allele carried a 2.5-fold risk, whereas the presence of two epsilon4 alleles carried a 5.6-fold risk for development of delusions. The associations remained significant even when age, ethnicity, sex, education, duration of disease, and cognitive and functional performance were controlled for. The presence of two epsilon4 alleles was associated with reduced risk for developing hallucinations in the adjusted analysis only. No significant associations were detected between APOE genotype and the incidence of illusions, behavioral symptoms, or depression.

Conclusion: The presence of one or more epsilon4 alleles is a significant predictor for the incidence of delusions in the course of AD.

Figure

Cumulative hazard curves for developing delusions according to APOE genotype. The time axis is years from first evaluation until development of delusions (or last evaluation). Solid line = subjects with two ε4 alleles; long dashed line = subjects with one ε4 allele; short dashed line = subjects with no ε4 allele.