Investigation of Genetic Variants Associated with Alzheimer Disease in Parkinson Disease Cognition

• Published in: Journal of Parkinson's disease Vol. 6; no. 1; pp. 119 - 124
• Main Authors: Barrett, Matthew J., Koeppel, Alexander F., Flanigan, Joseph L., Turner, Stephen D., Worrall, Bradford B.
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2016
• Subjects: Aged; Alzheimer Disease - etiology; Alzheimer Disease - genetics; Cognition; Female; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Monomeric Clathrin Assembly Proteins - genetics; Parkinson Disease - complications; Parkinson Disease - genetics; Polymorphism, Single Nucleotide - genetics; Parkinson disease; dementia; mild cognitive impairment; genetics; Alzheimer disease
• ISSN: 1877-7171; 1877-718X
• DOI: 10.3233/JPD-150706

Background: Meta-analysis of genome-wide association studies have implicated multiple single nucleotide polymorphisms (SNPs) and associated genes with Alzheimer disease. The role of these SNPs in cognitive impairment in Parkinson disease (PD) remains incompletely evaluated. Objective: The objective of this study was to test alleles associated with risk of Alzheimer disease for association with cognitive impairment in Parkinson disease (PD). Methods: Two datasets with PD subjects accessed through the NIH database of Genotypes and Phenotypes contained both single nucleotide polymorphism (SNP) arrays and mini-mental state exam (MMSE) scores. Genetic data underwent rigorous quality control and we selected SNPs for genes associated with AD other than APOE. We constructed logistic regression and ordinal regression models, adjusted for sex, age at MMSE, and duration of PD, to assess the association between selected SNPs and MMSE score. Results: In one dataset, PICALM rs3851179 was associated with cognitive impairment (MMSE <  24) in PD subjects >  70 years old (OR = 2.3; adjusted p-value = 0.017; n = 250) but not in PD subjects≤70 years old. Conclusions: Our finding suggests that PICALM rs3851179 could contribute to cognitive impairment in older patients with PD. It is important that future studies consider the interaction of age and genetic risk factors in the development of cognitive impairment in PD.