Genetic factors influencing the development and treatment of cognitive impairment and psychosis in Parkinson’s disease

Abstract

Abstract: Parkinson’s Disease (PD) is a neurodegenerative disease in which both genetic and environmental factors play significant roles. In addition to increasing the risk of developing PD, gene mutations might also influence the phenotypical characteristics of the disease, including the development of cognitive impairment and psychosis. For instance, mutations of the GBA gene, which encodes the enzyme γ-glucocerebrosidase, have been related to cognitive impairment or dementia and visual hallucinations. Interest in the APOE gene, which encodes the apolipoprotein E, stems from the finding of increased Alzheimer’s Disease risk in carriers of APOE ε4 alleles. In a cohort of 390 PD patients, APOE ε4 allele carriers showed significantly increased cognitive decline during the 2-year follow-up period. Mutations of the LRRK2 gene, which encodes the leucine-rich repeat kinase 2, have been related to a lower risk of cognitive impairment and dementia and lower scores for apathy and hallucinations. PD patients with mutations in the BDNF, COMT, PARP4 and MTCL1 genes showed increased risk cognitive impairment, dementia and visual hallucinations, but these results have not been replicated yet. Hallucinations have also been related to mutations in the cholecystokinin CCK gene. These findings suggest that gene mutations may be important determinants of cognitive impairment and psychosis in PD and highlight promising targets for new therapeutic approaches.