Background: Psychosis is one of the most serious complications of advanced parkinsonism, but many patients are spared. The genetic factors predisposing to psychosis are unclear.
Objectives: To assess the association between apolipoprotein E (APOE) polymorphism and the development of psychosis in patients with Parkinson's disease (PD).
Methods: Eighty-seven patients with advanced PD were assessed. Psychosis was diagnosed in 50 patients who manifested paranoid delusions, hallucinations without insight, or disorders of perception. Time of onset of psychosis was retrieved from the medical records and caregivers' recall. APOE genotype was determined by restriction enzyme digests of amplified alleles. Cox models of logistic regression and Kaplan-Meier survival curves were used to assess factors determining early development of psychosis.
Results: APOE epsilon3/epsilon4 allele was carried by 20 patients (14 with psychosis), epsilon2/epsilon3 by 11 patients (10 with psychosis), epsilon3/epsilon3 by 55 patients (25 with psychosis) and epsilon2/epsilon4 by one patient who had psychosis. The mean age of onset of PD symptoms was 60.0 +/- 12.5 years. The mean duration of motor symptoms at the onset of psychosis was 7.3 +/- 4.3 years for the 15 patients harboring an APOE epsilon4 allele and 10.1 +/- 6.2 years among those who did not carry APOE epsilon4 (n = 35). The APOE epsilon4 allele was significantly associated with earlier onset of psychosis (P < 0.05) when the age of onset of motor symptoms and presence of dementia were included in the Cox regression model. Carrying the APOE epsilon4 allele was a significant risk factor for earlier appearance of psychosis with a hazard ratio of 3.24 (95% CI 1.62-6.46) while dementia by itself did not increase the risk.
Conclusion: Parkinson's disease patients who carry the APOE epsilon4 allele develop psychosis earlier.