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Journal Articles Annals of Neurology Year : 2022

Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers

Gian Pal
Emily Hill
  • Function : Author
Bichun Ouyang
  • Function : Author
Yuanqing Liu
  • Function : Author
Vanessa Lythe
  • Function : Author
Debra Ehrlich
  • Function : Author
Rachel Saunders-Pullman
  • Function : Author
Vicki Shanker
  • Function : Author
Susan Bressman
  • Function : Author
Roy Alcalay
  • Function : Author
Priscilla Garcia
  • Function : Author
Karen Marder
  • Function : Author
Jan Aasly
  • Function : Author
M. Maral Mouradian
  • Function : Author
Samantha Link
  • Function : Author
Marc Rosenbaum
  • Function : Author
Sharlet Anderson
  • Function : Author
Bryan Bernard
  • Function : Author
Robert Wilson
  • Function : Author
Glenn Stebbins
  • Function : Author
William Nichols
  • Function : Author
Sepehr Sani
  • Function : Author
Mitra Afshari
  • Function : Author
Leo Verhagen
  • Function : Author
Rob M.A. de Bie
  • Function : Author
Tom Foltynie
  • Function : Author
Deborah Hall
Christopher Goetz

Abstract

Objective: This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. Methods: Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and noncarriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. Results: Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects), who were longitudinally followed (range = 36-60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA-DBS- subjects (95% confidence interval [CI] = -2.35 to -1.69), 1.71 points/yr more than GBA+DBS- subjects (95% CI = -2.14 to -1.28), and 1.49 points/yr more than GBA-DBS+ subjects (95% CI = -1.80 to -1.18). Interpretation: Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS so that alternative options may be considered. ANN NEUROL 2022;91:424-435.

Dates and versions

hal-04588567 , version 1 (27-05-2024)

Identifiers

Cite

Gian Pal, Graziella Mangone, Emily Hill, Bichun Ouyang, Yuanqing Liu, et al.. Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers. Annals of Neurology, 2022, 91 (3), pp.424-435. ⟨10.1002/ana.26302⟩. ⟨hal-04588567⟩
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