{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:32:58Z","timestamp":1782977578082,"version":"3.54.5"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["MJFF\u2010010551"],"award-info":[{"award-number":["MJFF\u2010010551"]}],"id":[{"id":"10.13039\/100000864","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":[[2025,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The phenotype of patients with Parkinson's disease carrying <jats:italic>GBA<\/jats:italic>1 variants (GBA\u2010PD) suggest similarities to symptomatology associated with early cholinergic system degeneration. Therefore, this study aims to investigate the clinical features and the cholinergic innervation pattern in patients with early GBA\u2010PD versus those without the <jats:italic>GBA1<\/jats:italic> mutation (non\u2010GBA\u2010PD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 46 GBA\u2010PD and 104 non\u2010GBA\u2010PD subjects were included. Clinical assessments included motor and non\u2010motor evaluation, as well as a comprehensive neuropsychological examination. Cholinergic system integrity was assessed using <jats:sup>1<\/jats:sup><jats:sup>8<\/jats:sup>F\u2010Fluoroethoxybenzovesamicol (<jats:sup>18<\/jats:sup>F\u2010FEOBV) positron emission tomography (PET) to investigate the differences between GBA\u2010PD and non\u2010GBA\u2010PD. Given the higher prevalence of females in GBA\u2010PD, analyses were repeated when stratified by sex. Additionally, we examined the association between cognitive domains and whole\u2010brain cholinergic binding in both groups. Exploratory analyses examined clinical and <jats:sup>18<\/jats:sup>F\u2010FEOBV binding differences among <jats:italic>GBA1<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GBA\u2010PD patients exhibited a higher burden of non\u2010motor symptoms and lower cognitive performance on executive functions and attention. We observed a more pronounced cholinergic denervation in GBA\u2010PD, compared to non\u2010GBA\u2010PD, primarily in the anterior, central, and limbic regions. However, the distribution of cholinergic loss and its association with attention and executive dysfunction was comparable between GBA\u2010PD and non\u2010GBA\u2010PD. In addition, the clinical presentation and cholinergic binding differed significantly between sexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These results suggest an important role of early cholinergic denervation in GBA\u2010PD patients, which is related to more severe cognitive dysfunction. 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