Kristin Aaser Lunde1, Janete Chung2, Ingvild Dalen2, Kenn Freddy Pedersen3, Jan Linder4, Magdalena E Domellöf5, Eva Elgh6, Angus D Macleod7, Charalampos Tzoulis8, Jan Petter Larsen9, Ole-Bjørn Tysnes8, Lars Forsgren4, Carl E Counsell7, Guido Alves10, Jodi Maple-Grødem11. 1. The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Centre for Organelle Research, University of Stavanger, Stavanger, Norway. 2. The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway. 3. The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Department of Neurology, Stavanger University Hospital, Stavanger, Norway. 4. Department of Pharmacology and Clinical Neuroscience, Neurology, Umeå University, Umeå, Sweden. 5. Department of Pharmacology and Clinical Neuroscience, Neurology, Umeå University, Umeå, Sweden; Department of Psychology, Umeå University, Umeå, Sweden. 6. Department of Psychology, Umeå University, Umeå, Sweden. 7. Institute of Applied Health Sciences, Polwarth Building, University of Aberdeen, Aberdeen, UK. 8. Department of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway. 9. Network for Medical Sciences, University of Stavanger, Bergen, Norway. 10. The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Department of Neurology, Stavanger University Hospital, Stavanger, Norway; Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway. 11. The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Centre for Organelle Research, University of Stavanger, Stavanger, Norway. Electronic address: jodi.maple@uis.no.
Abstract
INTRODUCTION: Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease. METHODS: Four 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. RESULTS: A 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. 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 with other risk alleles.
INTRODUCTION: Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease. METHODS: Four 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. RESULTS: A 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. 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 with other risk alleles.
Authors: Jonas M den Heijer; Valerie C Cullen; Marialuisa Quadri; Arnoud Schmitz; Dana C Hilt; Peter Lansbury; Henk W Berendse; Wilma D J van de Berg; Rob M A de Bie; Jeffrey M Boertien; Agnita J W Boon; M Fiorella Contarino; Jacobus J van Hilten; Jorrit I Hoff; Tom van Mierlo; Alex G Munts; Anne A van der Plas; Mirthe M Ponsen; Frank Baas; Danielle Majoor-Krakauer; Vincenzo Bonifati; Teus van Laar; Geert J Groeneveld Journal: Mov Disord Date: 2020-07-02 Impact factor: 10.338
Authors: Thomas B Stoker; Marta Camacho; Sophie Winder-Rhodes; Ganqiang Liu; Clemens R Scherzer; Thomas Foltynie; Jonathan Evans; David P Breen; Roger A Barker; Caroline H Williams-Gray Journal: J Neurol Neurosurg Psychiatry Date: 2020-04-17 Impact factor: 10.154
Authors: Han-Joon Kim; Sarah Mason; Thomas Foltynie; Sophie Winder-Rhodes; Roger A Barker; Caroline H Williams-Gray Journal: Mov Disord Date: 2019-11-11 Impact factor: 10.338
Authors: Jodi Maple-Grødem; Kimberly C Paul; Ingvild Dalen; Kathie J Ngo; Darice Wong; Angus D Macleod; Carl E Counsell; David Bäckström; Lars Forsgren; Ole-Bjørn Tysnes; Cynthia D J Kusters; Brent L Fogel; Jeff M Bronstein; Beate Ritz; Guido Alves Journal: J Parkinsons Dis Date: 2021 Impact factor: 5.568