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Evolution and clustering of prodromal parkinsonian features in GBA1 carriers

Artikel i vetenskaplig tidskrift
Författare S. Mullin
M. Beavan
J. Bestwick
A. McNeill
C. Proukakis
T. Cox
D. Hughes
A. Mehta
Henrik Zetterberg
A. H. V. Schapira
Publicerad i Movement Disorders
Volym 34
Nummer/häfte 9
Sidor 1365-1373
ISSN 0885-3185
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 1365-1373
Språk en
Länkar dx.doi.org/10.1002/mds.27775
Ämnesord cognition, depression, Gaucher, glucocerebrosidase, olfaction, Parkinson's, prodromal
Ämneskategorier Neurovetenskaper

Sammanfattning

Background: Five to 25% of patients with PD carry glucocerebrosidase gene mutations, and 10% to 30% of glucocerebrosidase carriers will develop PD by age 80. Stratification of PD risk in glucocerebrosidase carriers provides an opportunity to target disease-modifying therapies. Objective: Cross-sectional and longitudinal survey of prodromal PD signs among glucocerebrosidase carriers. Design: Prospective assessment of 82 glucocerebrosidase mutation carriers and 35 controls over 4 to 5 years for prodromal clinical PD features. Results: At all time points, olfactory (measured using University of Pennsylvania Smell Identification Test) and cognitive (Montreal Cognitive Assessment) function and the International Parkinson and Movement Disorder Society UPDRS parts II and III scores were significantly worse amongst glucocerebrosidase mutation carriers. Progression to microsmia (odds ratio: 8.5; 95% confidence interval: 2.6–28.2; P < 0.05) and mild cognitive impairment (odds ratio: 4.2; 95% confidence interval: 1.1–16.6; P < 0.05) were more rapid compared to controls. Those with worse olfaction also had worse cognition (OR, 1.5; 95% CI: 0.0–2.8; P < 0.05) and depression (OR, 1.3; 95% CI: 0.6–2.8; P < 0.05). No participants reached the MDS prodromal PD diagnostic criteria before PD diagnosis. One participant developed PD. He did not fulfill the International Parkinson and Movement Disorder Society prodromal PD criteria before diagnosis. Conclusion: Assessment of individual and clustered PD prodromal features may serve as a useful tool to identify high-risk subjects for conversion to PD. As a result of the low conversion rate in our glucocerebrosidase mutation carriers to date, prospective validation is needed in larger cohorts to establish the profile of these features in PD convertors. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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