GBA variants predict a more rapid progression of cognitive dysfunction and motor symptoms in patients with Parkinson disease (PD), with a greater effect on postural instability and gait difficulty (PIGD) scores than tremor, a recent study found. In order to determine whether GBA mutations and the E326K polymorphism modify PD symptom progression, researchers screened the entire GBA coding region for mutations and E326K in PD patients enrolled at 7 sites. A total sample of 733 patients underwent successful genotyping. They found:

• GBA mutations, E326K, and GBA variants combined as a single group were associated with a more rapid decline in the Movement Disorder Society-sponsored version of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) score.

• Combined GBA variants and E326K were associated with faster progression in PIGD scores, but not in tremor scores.

• A significantly higher proportion of E326K carriers (10 or 21 [47.6%]) and GBA variant carriers (15 of 39 [38.5%]) progressed to mild cognitive impairment or dementia.

Citation: Davis MY, Johnson CO, Leverenz JB, et al. Association of GBA mutations and the E326K polymorphism with motor and cognitive progression in Parkinson disease. [Published online ahead of print August 29, 2016]. JAMA Neurol. doi:10.1001/jamaneurol.2016.2245.