Numerically, the most important genetic risk factor for the development of Parkinson disease (PD) is the presence of a glucocerebrosidase gene (GBA) mutation.
The purpose of this study was the longitudinal clinical evaluation of a GBA mutation positive cohort and the evolution of the prodromal features of PD.
Individuals were participants in a study of the aetiology and prodrome of PD and have been re-evaluated in this 2 year follow-up report.
Type 1 GD patients and heterozygous GBA mutation positive carriers were recruited in 2010 from the Lysosomal Storage Disorder Unit at the Royal Free Hospital, London. Thirty previously diagnosed Type 1 GD patients, twenty-eight heterozygous GBA mutation carriers and twenty-six genetically unrelated controls were included. For both GD and carrier subjects, exclusion criteria included a diagnosis of PD or dementia and for controls, any existing neurological disease.
Main Outcome(s) and Measure(s)
Assessment was performed for clinical markers including hyposmia, rapid eye movement sleep behaviour disorder (RBD), depression, autonomic dysfunction, cognitive function and parkinsonian motor signs (UPDRS part III).
Over 2 years, depression scores were significantly worse in heterozygotes (P = ·01), RBD scores were significantly worse in GD patients (P < ·001) and heterozygotes (P < ·001), and UPDRS III scores were significantly worse in GD patients (P < ·001) and heterozygotes (P < ·001). In controls, there was a small but significant deterioration in the UPDRS II score (P = ·006). At 2 years, olfactory and cognitive assessment scores were lower in GD patients and heterozygotes compared to controls, but did not differ significantly from baseline. When the results from GD patients and heterozygotes were combined, there was a significant deterioration from baseline in RBD, BDI, UPDRS II and III scores (in all, P < ·01), and at 2 years, significant differences in UPSIT, UMSARS, MMSE, MoCA, UPDRS II and UPDRS III scores when compared to controls (in all, P < ·05).
Conclusions and Relevance
This study indicates that as a group, GBA mutation positive individuals show deterioration in clinical markers consistent with the prodrome of PD. Within this group, 10% appear to be evolving at a more rapid rate.