Session Information
Date: Monday, October 8, 2018
Session Title: Parkinson's Disease: Genetics
Session Time: 1:15pm-2:45pm
Location: Hall 3FG
Objective: To study the effect of GBA variants on dementia in three deeply phenotyped population-based prospective cohorts of patients with incident Parkinson disease.
Background: Dementia is among the most common and severe non-motor symptoms of Parkinson disease (PD), affecting nearly 20% of all patients within the first 5 years of the disease, and the majority of patients if they survive for more than 10 years after diagnosis. Both polymorphisms and mutations in GBA may influence the development of dementia in patients with Parkinson’s disease, but few longitudinal studies have investigated the role of GBA variant subcategories in disease heterogeneity and progression.
Methods: Three Northern European population-based studies (the Swedish NYPUM study, the Norwegian ParkWest study and the Scottish PINE study) designed to determine the incidence, neurobiology and prognosis of Parkinson disease were analyzed for GBA genetic variants by SNP genotyping assays or whole exome sequencing. A total of 442 patients and 419 controls were followed for seven years and dementia was diagnosed using established criteria. GBA variant carriers were analyzed as one group, and subcategorized into “polymorphism” or “deleterious mutation” carriers. Associations between GBA carrier status and dementia were assessed with Cox survival analysis.
Results: A total of 12.0% of patients with Parkinson’s disease were carriers of a GBA variant, and nearly half of these (22/53) progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted HR 3.81, 95% CI 1.35 to 10.72; P = .011) or polymorphisms (adjusted HR 1.79; 95% CI 1.07 to 3.00; P = .028) progressed to dementia more rapidly than non-carriers.
Conclusions: GBA variants are of great clinical relevance for the development of dementia in Parkinson disease, especially due to the relatively higher frequency of these alleles in patients with Parkinson disease compared to other risk alleles.
To cite this abstract in AMA style:
K. Lunde, J. Chung, I. Dalen, K. Pedersen, J. Linder, M. Domellöf, E. Elgh, A. Macleod, C. Tzoulis, J. Larsen, O. Tysnes, L. Forsgren, C. Counsell, G. Alves, J. Maple-Grødem. Association of GBA polymorphisms and mutations with dementia in Parkinson disease: A 7-year study of three population-based incident cohorts [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/association-of-gba-polymorphisms-and-mutations-with-dementia-in-parkinson-disease-a-7-year-study-of-three-population-based-incident-cohorts/. Accessed June 14, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/association-of-gba-polymorphisms-and-mutations-with-dementia-in-parkinson-disease-a-7-year-study-of-three-population-based-incident-cohorts/