Pal, G;
Mangone, G;
Hill, EJ;
Ouyang, B;
Liu, Y;
Lythe, V;
Ehrlich, D;
... Goetz, CG; + view all
(2022)
Parkinson disease and STN-DBS: cognitive effects in GBA mutation carriers.
Annals of Neurology
, 91
(3)
pp. 424-435.
10.1002/ana.26302.
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Abstract
OBJECTIVE: To compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and non-carriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). 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 non-carriers 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 367 subjects: 58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects who were longitudinal followed (range 36 to 60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/year more than GBA-DBS- subjects (95% CI = -2.35, -1.69), 1.71 points/year more than GBA+DBS- subjects (95% CI = -2.14, -1.28), and 1.49 points/year more than GBA-DBS+ subjects (95% CI = -1.80, -1.18). INTERPRETATION: Although non-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 pre-surgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS and alternative options may be considered. This article is protected by copyright. All rights reserved.
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