• Micol Avenali, Marco Toffoli, Stephen Mullin, Alisdair McNeil, Derralynn A Hughes, A Mehta, Fabio Blandini, and Schapira Anthony H V AHV 0000-0002-3018-3966 Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK a..
• Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.
• J. Neurol. Neurosurg. Psychiatr. 2019 Oct 1; 90 (10): 1091-1097.

ObjectivesGBA1 mutations are a frequent risk factor for Parkinson disease (PD). The aim of this study is to evaluate clinical features in a group of GBA1 mutation-positive individuals over a 6-year follow-up.MethodsThis is a longitudinal study on a cohort of GBA1-positive carriers. We enrolled 31 patients with Gaucher disease type 1 (GD), 29 GBA1 heterozygous carriers (Het GBA group) and 30 controls (HC) at baseline and followed them for 6 years. We assessed baseline motor and non-motor signs of PD in all subjects using clinical questionnaires and scales (reduced Unified Multiple System Atrophy Rating Scale (UMSARS), Montreal Cognitive assessment (MoCA), University of Pennsylvania Smell Identification Test (UPSIT), REM Sleep Behavior Disorder screening questionnaire (RBDsq), Movement Disorders Society Unified Parkinson's Disease Rating Scale motor subscale (MDS-UPDRS III) and Beck Depression Inventory (BDI). We repeated these at the 6-year follow-up alongside venous blood sampling for measurement of glucocerebrosidase enzymatic activity (GCase). We explored whether the GCase activity level was altered in leucocytes of these subjects and how it was related to development of PD.ResultsWe observed a significant worsening in UMSARS, RBDsq, MDS-UPDRS III and BDI scores at the 6-year follow-up compared with baseline in both the GD and Het GBA groups. Intergroup comparisons showed that GD subjects had significantly worse scores in UPSIT, UMSARS, MoCA and MDS-UPDRS III than HC, while Het GBA displayed worse outcomes in UPSIT and MDS-UPDRS III compared with HC. In GBA1 mutation-positive individuals (Het GBA and GD), an UPSIT score of 23 at baseline was correlated with worse outcome at 6 years in UPSIT, MoCA, MDS-UPDRS III and BDI.ConclusionIn this 6-year-long longitudinal study, GBA1 mutation-positive subjects showed a worsening in motor and non-motor prodromal PD features.© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

55 keywords...

hide…