Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease |
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| Authors: | Kristin Aaser Lunde Janete Chung Ingvild Dalen Kenn Freddy Pedersen Jan Linder Magdalena E Domellöf Eva Elgh Angus D Macleod Charalampos Tzoulis Jan Petter Larsen Ole-Bjørn Tysnes Lars Forsgren Carl E Counsell Guido Alves Jodi Maple-Grødem |
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| Institution: | 1. The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway;2. Centre for Organelle Research, University of Stavanger, Stavanger, Norway;3. Department of Neurology, Stavanger University Hospital, Stavanger, Norway;4. Department of Pharmacology and Clinical Neuroscience, Neurology, Umeå University, Umeå, Sweden;5. Department of Psychology, Umeå University, Umeå, Sweden;6. Institute of Applied Health Sciences, Polwarth Building, University of Aberdeen, Aberdeen, UK;7. Department of Neurology, Haukeland University Hospital, Bergen, Norway;8. Department of Clinical Medicine, University of Bergen, Bergen, Norway;9. Network for Medical Sciences, University of Stavanger, Bergen, Norway;10. Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway |
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| Abstract: | IntroductionBoth polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease.MethodsFour hundred forty-two patients and 419 controls were followed for 7 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.ResultsA total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers.DiscussionGBA 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 with other risk alleles. |
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| Keywords: | Parkinson's disease Parkinson's disease with dementia GBA Longitudinal Genetic association |
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