Evolution of prodromal parkinsonian features in a cohort of <i>GBA</i> mutation-positive individuals: a 6-year longitudinal study.

Abstract

<i>GBA1</i> mutations are a frequent risk factor for Parkinson disease (PD). The aim of this study is to evaluate clinical features in a group of <i>GBA1</i> mutation-positive individuals over a 6-year follow-up. This is a longitudinal study on a cohort of <i>GBA1</i>-positive carriers. We enrolled 31 patients with Gaucher disease type 1 (GD), 29 <i>GBA1</i> heterozygous carriers (Het <i>GBA</i> 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. We 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 <i>GBA</i> groups. Intergroup comparisons showed that GD subjects had significantly worse scores in UPSIT, UMSARS, MoCA and MDS-UPDRS III than HC, while Het <i>GBA</i> displayed worse outcomes in UPSIT and MDS-UPDRS III compared with HC. In <i>GBA1</i> mutation-positive individuals (Het <i>GBA</i> 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. In this 6-year-long longitudinal study, <i>GBA1</i> mutation-positive subjects showed a worsening in motor and non-motor prodromal PD features.