To evaluate differences in Parkinson’s disease (PD) between patients with LRRK2 and GBA mutations and those without.

Mutations in the LRRK2 and GBA genes influence the phenotypic presentation and progression of PD. The LRRK2-G2019S mutation and the GBA-N370S mutation are frequently identified in patients diagnosed with and treated for “idiopathic PD.”

We evaluated LRRK2 and GBA mutations in a predominantly elderly Ashkenazi Jewish population of patients with PD. Onset age, disease duration, UPDRS subscores, Hoehn-Yahr stage, and cognitive tests were queried from the most recent clinical evaluation.

Among 330 elderly patients, 30 (9.1%) had LRRK2-G2019S mutation and 21 (6.3%) had GBA-N370S mutation. Of the 279 patients without either mutation, 81 had family history of PD and 198 had neither mutation nor family history of PD. Compared to those without these two mutations and without family history of PD, patients with LRRK2 and GBA mutations had earlier onset age and higher UPDRS-I scores. Patients with GBA mutation had higher UPDRS-II scores and earlier Hoehn-Yahr stage >2. At similar time points, cognitive scores were more impaired in patients with GBA and less impaired in LRRK2 mutations.

As previously reported in relatively younger cohorts, this analysis of the role of these two genes in elderly patients with PD suggest that those with a LRRK2-G2019S mutation have a slower course and those with GBA-N370S mutation have a more progressive course, as compared to PD without these genes nor family history.