METHODS: 442 patients and 419 controls were followed for seven years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M and L444P. 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 carried a GBA variant, and nearly half (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.
DISCUSSION: GBA variants are of great clinical relevance for the development of dementia in Parkinson’s disease, especially due to the relatively higher frequency of these alleles compared to other risk alleles.
Bibliographical notePINE was supported by Parkinson’s UK (grant numbers G0502, G0914, G1302), Scottish Government Chief Scientist Office, BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, and RS MacDonald Trust. The Norwegian ParkWest study has been funded by the Research Council of Norway (grant number 177966), the Western Norway Regional Health Authority (grant number 911218), Stavanger University Hospital Research Funds (grant number 501611), and the Norwegian Parkinson’s Disease Association. Janete Chung and Kristin Aaser Lunde are supported by the Western Norway Regional Health Authority (grant numbers 911859 and 911830). The NYPUM study has been funded by the Swedish Medical Research Council, the Swedish Parkinson’s Disease Association, the Swedish Parkinson Foundation, Erling Persson Foundation, Kempe Foundation and the Västerbotten County Council.
The funding sources had no role in the design and conduct of the study: collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript: and decision to submit the manuscript for publication.
- Parkinson's disease
- Parkinson's disease with dementia
- genetic association
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- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Senior Lecturer (Clinical)
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Centre for Health Data Science
- School of Medicine, Medical Sciences & Nutrition, Grampian Data Safe Haven (DaSH)
- School of Medicine, Medical Sciences & Nutrition, Chronic Disease Research Group
Person: Clinical Academic