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<jats:title>Abstract</jats:title><jats:p>With disease-modifying treatment for Parkinson’s disease (PD) associated with variants in the glucocerebrosidase gene (<jats:italic>GBA1</jats:italic>) under way, the challenge to design clinical trials with non-PD-manifest <jats:italic>GBA</jats:italic> mutation carriers (GBA1<jats:sub>NMC</jats:sub>) comes within close reach. To delineate trajectories of motor and non-motor markers as well as serum neurofilament light (sNfL) levels and to evaluate clinical endpoints as outcomes for clinical trials in GBA1<jats:sub>NMC</jats:sub>, longitudinal data of 56 GBA1<jats:sub>NMC</jats:sub> carriers and 112 age- and sex-matched <jats:italic>GBA1</jats:italic> wildtype participants (GBA1<jats:sub>wildtype</jats:sub>) with up to 9 years of follow-up was analyzed using linear mixed-effects models (LMEM) and Kaplan–Meier survival analysis of clinical endpoints for motor and cognitive function. GBA1<jats:sub>NMC</jats:sub> showed worse performance in Pegboard, 20 m fast walking, global cognition as well as in executive and memory function at baseline. Longitudinally, LMEM revealed a higher annual increase of the MDS-UPDRS III bradykinesia subscore in GBA1<jats:sub>NMC</jats:sub> compared to GBA1<jats:sub>wildtype</jats:sub>, but comparable trajectories of all other motor and non-motor markers as well as sNfL. Kaplan–Meier survival analysis showed a significantly earlier progression to clinical endpoints of cognitive decline in GBA1<jats:sub>NMC</jats:sub>. Incidence of PD was significantly higher in GBA1<jats:sub>NMC</jats:sub>. In conclusion, our study extends data on GBA1<jats:sub>NMC</jats:sub> indicating early cognitive decline as a potentially characteristic feature. Comprehensive longitudinal assessments of cognitive function are crucial to delineate the evolution of early changes in GBA1<jats:sub>NMC</jats:sub> enabling a more accurate stratification and allow for a more precise definition of trial design and sample size.</jats:p>
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Hinweis
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DeepGreen-ID: 2b286813480b4deaa5b0a917b869c12f ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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