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Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
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2018 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, ISSN 1552-5260, Vol. 14, no 10, p. 1293-1301Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 14, no 10, p. 1293-1301
Keywords [en]
Parkinson's Disease
National Category
Neurology
Research subject
Genetics; Neurology
Identifiers
URN: urn:nbn:se:umu:diva-148814DOI: 10.1016/j.jalz.2018.04.006ISI: 000446086000006OAI: oai:DiVA.org:umu-148814DiVA, id: diva2:1216674
Projects
NYPUM projectParkWest studyPINE study
Funder
The Kempe FoundationsVästerbotten County CouncilThe Kempe FoundationsVästerbotten County CouncilAvailable from: 2018-06-12 Created: 2018-06-12 Last updated: 2019-05-07Bibliographically approved

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Linder, JanDomellöf, Magdalena E.Elgh, EvaForsgren, Lars

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Linder, JanDomellöf, Magdalena E.Elgh, EvaForsgren, Lars
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Clinical NeuroscienceDepartment of Pharmacology and Clinical NeuroscienceDepartment of Psychology
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Alzheimer's & Dementia
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