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Abstract Details

RS4548513 (CTNNA3): A Genetic Risk Factor for Visual Construction Deficiency in Parkinson's disease
Aging, Dementia, and Behavioral Neurology
P1 - Poster Session 1 (5:30 PM-6:30 PM)
9-016
To detect genetic risk factors for cognitive decline in patients with Parkinson's disease (PD) using a genotyping array specific for neurodegenerative diseases.
The relevance of genetic influences on the cognitive capacity in PD patients is not fully understood.
A comprehensive neuropsychological test battery was applied in an initial sample of 114 PD patients (77 M, 37 F; mean age: 66 years; mean education: 14 years) and their results were correlated with 1233 markers linked to neurodegenerative diseases from the NeuroChip Assay. For the cognitive decline over three years, the Reliable Change Index (RCI) was calculated. Tests with less than 10% missing values were 20-fold imputed using the MICE package. We used the PLINK tool box and performed linear regression. Quality control was performed by applying a minimum allele frequency of 5% and removing markers outside the Hardy-Weinberg equilibrium. We only report significant genetic markers with a False Discovery Rate (FDR) corrected p-value. Markers found in this first step were checked for the influence of confounding variables (age, time since diagnosis, education and medication) by linear regression.
Among all neuropsychological tests, only the change in visual construction capacity (Rey Figure copy) showed a significant p-value on all imputation folds with one of the tested markers (rs4548513, mean FDR corrected p-value <.001). The post-hoc analysis using additional confounding variables showed no influence of confounders on the result.
SNP rs4548513 is known from literature as a suspected genetic risk factor for Alzheimer’s disease (AD). The present result supports the concept that cognitive decline in Alzheimers´s disease and PD share a underlying pathological mechanism. SNP rs4548513 is a candidate prognostic biomarker for visual cognitive deficits in PD and possibly also for PD dementia.
Authors/Disclosures

PRESENTER 		No disclosure on file
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Peter Fuhr, MD, FÂ鶹´«Ã½Ó³»­ The institution of Dr. Fuhr has received research support from Roche.
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