{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:43:58Z","timestamp":1790883838044,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K23\u2010NS097625"],"award-info":[{"award-number":["K23\u2010NS097625"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (<jats:italic>GBA<\/jats:italic>) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN\u2010DBS) in Parkinson disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 <jats:italic>GBA<\/jats:italic> and categorized as <jats:italic>GBA<\/jats:italic> carriers with or without DBS (<jats:italic>GBA<\/jats:italic>+DBS+, <jats:italic>GBA<\/jats:italic>+DBS\u2010), and noncarriers with or without DBS (<jats:italic>GBA<\/jats:italic>\u2010DBS+, <jats:italic>GBA<\/jats:italic>\u2010DBS\u2010). <jats:italic>GBA<\/jats:italic> 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 <jats:italic>GBA<\/jats:italic> and DBS status and then according to <jats:italic>GBA<\/jats:italic> severity and DBS status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Data were available for 366 subjects (58 <jats:italic>GBA<\/jats:italic>+DBS+, 82 <jats:italic>GBA<\/jats:italic>+DBS\u2010, 98 <jats:italic>GBA<\/jats:italic>\u2010DBS+, and 128 <jats:italic>GBA<\/jats:italic>\u2010DBS\u2010 subjects), who were longitudinally followed (range\u00a0=\u00a036\u201360\u00a0months after surgery). Using the MDRS, <jats:italic>GBA<\/jats:italic>+DBS+ subjects declined on average 2.02 points\/yr more than <jats:italic>GBA<\/jats:italic>\u2010DBS\u2010 subjects (95% confidence interval [CI]\u00a0=\u00a0\u22122.35 to \u22121.69), 1.71 points\/yr more than <jats:italic>GBA<\/jats:italic>+DBS\u2010 subjects (95% CI\u00a0=\u00a0\u22122.14 to \u22121.28), and 1.49 points\/yr more than <jats:italic>GBA<\/jats:italic>\u2010DBS+ subjects (95% CI\u00a0=\u00a0\u22121.80 to \u22121.18).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Although not randomized, this composite analysis suggests that the combined effects of <jats:italic>GBA<\/jats:italic> mutations and STN\u2010DBS negatively impact cognition. We advise that DBS candidates be screened for <jats:italic>GBA<\/jats:italic> mutations as part of the presurgical decision\u2010making process. We advise that <jats:italic>GBA<\/jats:italic> mutation carriers be counseled regarding potential risks associated with STN\u2010DBS so that alternative options may be considered. 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