葡萄糖脑苷脂酶多态性和突变与帕金森病发病后痴呆的关联。

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

机构信息

The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway; Centre for Organelle Research, University of Stavanger, Stavanger, Norway.

The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.

出版信息

Alzheimers Dement. 2018 Oct;14(10):1293-1301. doi: 10.1016/j.jalz.2018.04.006. Epub 2018 May 21.

DOI:10.1016/j.jalz.2018.04.006

PMID:29792872

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.

摘要

简介

葡萄糖脑苷脂酶（GBA）的多态性和突变都可能影响帕金森病患者痴呆的发展。

方法

对 442 名患者和 419 名对照者进行了 7 年的随访。痴呆症的诊断采用了既定的标准。对参与者进行了 GBA 基因变异的分析，包括 E326K、T369M 和 L444P。使用 Cox 生存分析评估了 GBA 携带者状态与痴呆之间的关联。

结果

共有 12.0%的帕金森病患者携带 GBA 变异，其中近一半（22/53）在随访期间进展为痴呆。携带有害 GBA 突变（调整后的危险比 3.81，95%置信区间 1.35 至 10.72；P =.011）或多态性（调整后的危险比 1.79；95%置信区间 1.07 至 3.00；P =.028）的患者比非携带者更快进展为痴呆。