Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease

Affiliations

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.

PMID: 29792872
DOI: 10.1016/j.jalz.2018.04.006

Multicenter Study

Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease

Kristin Aaser Lunde et al. Alzheimers Dement. 2018 Oct.

. 2018 Oct;14(10):1293-1301.

doi: 10.1016/j.jalz.2018.04.006. Epub 2018 May 21.

Authors

Affiliations

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.

PMID: 29792872
DOI: 10.1016/j.jalz.2018.04.006

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.

Keywords: GBA; Genetic association; Longitudinal; Parkinson's disease; Parkinson's disease with dementia.

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Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease

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Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease

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