Early cognitive decline after bilateral subthalamic deep brain stimulation in Parkinson's disease patients with GBA mutations.
Aged
Cognitive Dysfunction
/ etiology
Deep Brain Stimulation
/ adverse effects
Disease Progression
Female
Glucosylceramidase
/ genetics
Humans
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
/ genetics
Male
Middle Aged
Neuropsychological Tests
Parkinson Disease
/ complications
Retrospective Studies
Subthalamic Nucleus
/ surgery
Ubiquitin-Protein Ligases
/ genetics
Cognitive decline
Genetic risk factors
Parkinson's disease
Retrospective study
Subthalamic nucleus deep brain stimulation
Journal
Parkinsonism & related disorders
ISSN: 1873-5126
Titre abrégé: Parkinsonism Relat Disord
Pays: England
ID NLM: 9513583
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
05
12
2019
revised:
25
02
2020
accepted:
03
04
2020
pubmed:
1
9
2020
medline:
13
8
2021
entrez:
1
9
2020
Statut:
ppublish
Résumé
Subthalamic nucleus deep brain stimulation (STN-DBS) has demonstrated its efficacy on motor complications in advanced Parkinson's disease (PD) but does not modify disease progression. Genetic forms of PD have been associated with different cognitive progression profiles. To assess the effect of PD-related genetic mutations on cognitive outcome after STN-DBS. Patients with STN-DBS were screened for LRRK2, GBA, and PRKN mutations at the Pitié-Salpêtrière Hospital between 1997 and 2009. Patients with known monogenetic forms of PD from six other centers were also included. The Mattis Dementia Rating Scale (MDRS) was used to evaluate cognition at baseline and one-year post-surgery. The standardized Unified PD Rating Scale (UPDRS) evaluation On and Off medication/DBS was also administered. A generalized linear model adjusted for sex, ethnicity, age at onset, and disease duration was used to evaluate the effect of genetic factors on MDRS changes. We analyzed 208 patients (131 males, 77 females, 54.3 ± 8.8 years) including 25 GBA, 18 LRRK2, 22 PRKN, and 143 PD patients without mutations. PRKN patients were younger and had a longer disease duration at baseline. A GBA mutation was the only significant genetic factor associated with MDRS change (β = -2.51, p = 0.009). GBA mutation carriers had a more pronounced post-operative MDRS decline (3.2 ± 5.1) than patients with LRRK2 (0.9 ± 4.8), PRKN (0.5 ± 2.7) or controls (1.4 ± 4.4). The motor response to DBS was similar between groups. GBA mutations are associated with early cognitive decline following STN-DBS. Neuropsychological assessment and discussions on the benefit/risk ratio of DBS are particularly important for this population.
Sections du résumé
BACKGROUND
Subthalamic nucleus deep brain stimulation (STN-DBS) has demonstrated its efficacy on motor complications in advanced Parkinson's disease (PD) but does not modify disease progression. Genetic forms of PD have been associated with different cognitive progression profiles.
OBJECTIVE
To assess the effect of PD-related genetic mutations on cognitive outcome after STN-DBS.
METHODS
Patients with STN-DBS were screened for LRRK2, GBA, and PRKN mutations at the Pitié-Salpêtrière Hospital between 1997 and 2009. Patients with known monogenetic forms of PD from six other centers were also included. The Mattis Dementia Rating Scale (MDRS) was used to evaluate cognition at baseline and one-year post-surgery. The standardized Unified PD Rating Scale (UPDRS) evaluation On and Off medication/DBS was also administered. A generalized linear model adjusted for sex, ethnicity, age at onset, and disease duration was used to evaluate the effect of genetic factors on MDRS changes.
RESULTS
We analyzed 208 patients (131 males, 77 females, 54.3 ± 8.8 years) including 25 GBA, 18 LRRK2, 22 PRKN, and 143 PD patients without mutations. PRKN patients were younger and had a longer disease duration at baseline. A GBA mutation was the only significant genetic factor associated with MDRS change (β = -2.51, p = 0.009). GBA mutation carriers had a more pronounced post-operative MDRS decline (3.2 ± 5.1) than patients with LRRK2 (0.9 ± 4.8), PRKN (0.5 ± 2.7) or controls (1.4 ± 4.4). The motor response to DBS was similar between groups.
CONCLUSION
GBA mutations are associated with early cognitive decline following STN-DBS. Neuropsychological assessment and discussions on the benefit/risk ratio of DBS are particularly important for this population.
Identifiants
pubmed: 32866938
pii: S1353-8020(20)30097-3
doi: 10.1016/j.parkreldis.2020.04.002
pii:
doi:
Substances chimiques
Ubiquitin-Protein Ligases
EC 2.3.2.27
parkin protein
EC 2.3.2.27
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
EC 2.7.11.1
GBA protein, human
EC 3.2.1.45
Glucosylceramidase
EC 3.2.1.45
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
56-62Investigateurs
Eve Benchetrit
(E)
Laure Delaby
(L)
Deborah Berthet
(D)
Fabrice Danjou
(F)
Marie Vidaihlet
(M)
Paul Krack
(P)
Pierre Pelissier
(P)
Dominique Morand
(D)
Christine Delaigue
(C)
Nadia Barun
(N)
Mathieu Anheim
(M)
Marie Pleuvret
(M)
Alain Destée
(A)
Luc Defebvre
(L)
Caroline Moreau
(C)
Clémence Simonin
(C)
Gilles Ryckewaert
(G)
Alexandre Kreisler
(A)
Eugénie Mutez
(E)
Nicolas Carrière
(N)
Lucie Hopes
(L)
Céline Tard
(C)
Guillaume Grolez
(G)
Kathy Dujardin
(K)
Nathalie Pecheux
(N)
Marie Delliaux
(M)
Anne-Sophie Rolland
(AS)
Emmanuel Broussolle
(E)
Chloè Laurencin
(C)
François Tison
(F)
Pierre Burbaud
(P)
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.