Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Genetics
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To evaluate the impact of genetic variants in the Glucocerebrosidase gene (GBA) on cognitive impairment in a large cohort of Parkinson’s disease (PD) patients with a detailed neuropsychological characterization.
Background: Cognitive decline is very common in patients with PD. Carriers of heterozygous pathogenic GBA mutations, which cause Gaucher disease (GD) in the homozygous state, have been shown to not only be more prone to develop PD, but also to be more likely to develop cognitive impairment and dementia rather early in the course of the disease. Besides the pathogenic coding variants in GBA, the influence of non-coding variants in possible gene-regulatory regions of the GBA gene on cognition is not known, yet.
Methods: A sample of 426 PD patients participating in the DEMPARK/LANDSCAPE study were included. These patients were classified as: PD without cognitive impairment (PD-noMCI), PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD) according to neuropsychological testing. All coding exons of the GBA gene were Sanger-sequenced in all patients including also exon-intron boundaries and adjacent UTR. All found GBA variants, coding and non-coding, were evaluated for their impact on outcome of neuropsychological testing. Cognitive test scores, were corrected for age, sex, and education.
Results: The frequency of GBA variants was significantly different among the three groups (p<0.001) with the highest frequency in PDD patients (37%) compared to PD-MCI (22.6%) and PD-noMCI (15.3%). This difference is not only caused by the known pathogenic variants, but also by other variants like the 3’UTR SNP rs708606. Correctional analysis revealed a significant association of the mutation status with the Brief Test of Attention (p=0.005). Remarkably, the strongest association with this test was found with the 3′ UTR SNP (p=0.0036).
Conclusions: Our results indicate that genetic variants of the GBA gene influence cognitive decline in patients with PD. To our knowledge, this is the first time that non-coding variants in GBA are found to have an impact on cognitive impairment. Further research is needed to validate these findings and its impact on longitudinal cognitive outcomes.
To cite this abstract in AMA style:
C. Schulte, I. Liepelt-Scarfone, C.E. Hagen, A.K. Hauser, K. Brockmann, T. Gasser, J.B. Schulz, K. Reetz, S. Gräber, B. Mollenhauer, C. Trenkwalder, K. Witt, N. Schmidt, R. Dodel, M. Balzer-Geldsetzer, U. Wüllner, T. Klockgether, A. Spottke, A. Storch, H.U. Wittchen, O. Riedel, S. Baudrexel, E. Kalbe, D. Berg, M.M. Mielke. Coding and non-coding glucocerebrosidase variants have an impact on cognitive decline in Parkinson’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/coding-and-non-coding-glucocerebrosidase-variants-have-an-impact-on-cognitive-decline-in-parkinsons-disease/. Accessed June 15, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/coding-and-non-coding-glucocerebrosidase-variants-have-an-impact-on-cognitive-decline-in-parkinsons-disease/