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.
| Original language | English |
|---|---|
| Pages (from-to) | 424-435 |
| Number of pages | 12 |
| Journal | Annals of neurology |
| Volume | 91 |
| Issue number | 3 |
| Early online date | 2022 |
| DOIs | |
| Publication status | Published - Mar 2022 |
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In: Annals of neurology, Vol. 91, No. 3, 03.2022, p. 424-435.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation
T2 - Cognitive Effects in GBA Mutation Carriers
AU - Pal, Gian
AU - Mangone, Graziella
AU - Hill, Emily J.
AU - Ouyang, Bichun
AU - Liu, Yuanqing
AU - Lythe, Vanessa
AU - Ehrlich, Debra
AU - Saunders-Pullman, Rachel
AU - Shanker, Vicki
AU - Bressman, Susan
AU - Alcalay, Roy N.
AU - Garcia, Priscilla
AU - Marder, Karen S.
AU - Aasly, Jan
AU - Mouradian, M. Maral
AU - Link, Samantha
AU - Rosenbaum, Marc
AU - Anderson, Sharlet
AU - Bernard, Bryan
AU - Wilson, Robert
AU - Stebbins, Glenn
AU - Nichols, William C.
AU - Welter, Marie-Laure
AU - Sani, Sepehr
AU - Afshari, Mitra
AU - Verhagen, Leo
AU - de Bie, Rob M. A.
AU - Foltynie, Tom
AU - Hall, Deborah
AU - Corvol, Jean-Christophe
AU - Goetz, Christopher G.
N1 - Funding Information: We thank our patients, who inspire us daily and have contributed to this research. This research was supported by the Parkinson Disease Foundation and the National Institute of Neurological Disorders and Stroke (K23‐NS097625‐05). Collection from Mount Sinai was supported by U01‐NS094148‐01 and U01‐NS107016‐01A1. The French collection was supported by the program Investissements d'Avenir (ANR‐10‐IAIHU‐06). Data from the NIH Parkinson's Clinic were supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. R.M.A.d.B. received research grants from Medtronic and Lysosomal Therapeutics, paid to the institution. Funding Information: Data used in the preparation of this article were obtained from the Accelerating Medicine Partnership® (AMP®) Parkinson’s Disease (AMP PD) Knowledge Platform. For up‐to‐date information on the study, visit https://www.amp-pd.org . The AMP® PD program is a public‐private partnership managed by the Foundation for the National Institutes of Health and funded by the National Institute of Neurological Disorders and Stroke (NINDS) in partnership with the Aligning Science Across Parkinson's (ASAP) initiative; Celgene Corporation, a subsidiary of Bristol‐Myers Squibb Company; GlaxoSmithKline plc (GSK); The Michael J. Fox Foundation for Parkinson's Research; Pfizer Inc.; Sanofi US Services Inc.; and Verily Life Sciences. ACCELERATING MEDICINES PARTNERSHIP and AMP are registered service marks of the U.S. Department of Health and Human Services. Funding Information: We thank our patients, who inspire us daily and have contributed to this research. This research was supported by the Parkinson Disease Foundation and the National Institute of Neurological Disorders and Stroke (K23-NS097625-05). Collection from Mount Sinai was supported by U01-NS094148-01 and U01-NS107016-01A1. The French collection was supported by the program Investissements d'Avenir (ANR-10-IAIHU-06). Data from the NIH Parkinson's Clinic were supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. R.M.A.d.B. received research grants from Medtronic and Lysosomal Therapeutics, paid to the institution. Data used in the preparation of this article were obtained from the Accelerating Medicine Partnership® (AMP®) Parkinson’s Disease (AMP PD) Knowledge Platform. For up-to-date information on the study, visit https://www.amp-pd.org. The AMP® PD program is a public-private partnership managed by the Foundation for the National Institutes of Health and funded by the National Institute of Neurological Disorders and Stroke (NINDS) in partnership with the Aligning Science Across Parkinson's (ASAP) initiative; Celgene Corporation, a subsidiary of Bristol-Myers Squibb Company; GlaxoSmithKline plc (GSK); The Michael J. Fox Foundation for Parkinson's Research; Pfizer Inc.; Sanofi US Services Inc.; and Verily Life Sciences. ACCELERATING MEDICINES PARTNERSHIP and AMP are registered service marks of the U.S. Department of Health and Human Services. Funding Information: Parkinson’s Disease Biomarker Program (PDBP) consortium is supported by the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health. A full list of PDBP investigators can be found at https://pdbp.ninds.nih.gov/policy . The PDBP Investigators have not participated in reviewing the data analysis or content of the manuscript. Publisher Copyright: © 2022 American Neurological Association.
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85123557609&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ana.26302
DO - https://doi.org/10.1002/ana.26302
M3 - Article
C2 - 34984729
SN - 0364-5134
VL - 91
SP - 424
EP - 435
JO - Annals of neurology
JF - Annals of neurology
IS - 3
ER -