Objective: We investigated the impacts of apolipoprotein E (APOE) genotype and glucocerebrosidase gene (GBA) heterozygote mutations on dementia or psychosis in Parkinson’s disease (PD).

Background: GBA heterozygote mutations, one of the most prominent genetic risks in PD, are associated with the development of dementia and psychosis in PD. The relationship between these symptoms and APOE genotype in PD is not clear, though pathological studies have revealed the co-existence of Lewy bodies and Alzheimer pathologies to various degrees.

Methods: 213 PD patients (age 66.8 [10.8], mean [SD]) were examined. We performed the full sequence of GBA and determined APOE genotype using restriction fragment length polymorphism analysis. Odds ratios (ORs) of GBA mutations and APOE alleles for dementia and psychosis history were calculated using logistic regression analysis (adjusted for sex, age, PD duration, and Hoehn & Yahr stage).

Results: We identified GBA mutations in 19 subjects (8.8%). APOE4 and E2 alleles were found in 45 (21.1%) and 24 subjects (11.3%), respectively. Forty-three subjects (21.2%) were diagnosed with dementia and 76 (35.7%) had a history of psychosis. GBA mutations showed a significant impact on dementia (OR 8.7, 95% CI 2.3-33.1, p=0.002); by contrast, APOE4 allele did not. Psychosis history was significantly associated with GBA mutations and APOE4 allele (3.5, 1.1-11.7, p=0.038 and 2.4, 1.1-5.1, p=0.028, respectively). APOE2 allele did not show any significant impact on these symptoms.

Conclusions: Not only GBA mutations but also the APOE4 allele were significantly related to the development of psychosis in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-risk-factors-of-dementia-and-psychosis-in-parkinsons-disease/