Neuropsychological performance in LRRK2 G2019S carriers with Parkinson's disease

• LRRK2-PD patients perform better than iPD on neuropsychological tests, including executive, attention and language tasks.
• LRRK2-related PD patient perform similarly to iPD on the MoCA.
• Ashkenazi Jewish patients with LRRK2-PD have less tremor and more gait difficulty.

BackgroundAshkenazi Jewish (AJ) LRRK2 carriers are more likely to manifest the postural instability gait difficulty (PIGD) motor phenotype than non-carriers but perform similarly to non-carriers on cognitive screening tests.ObjectiveTo compare the cognitive profiles of AJ with Parkinson's disease (PD) with and without LRRK2 G2019S mutations using a comprehensive neuropsychological battery.MethodsWe administered a neuropsychological battery to PD participants in the Michael J. Fox Foundation AJ consortium. Participants (n = 236) from Beth Israel Medical Center, NY, Columbia University Medical Center, NY and Tel Aviv Medical Center, Israel included 116 LRRK2 G2019S carriers and 120 non-carriers. Glucocerbrosidase mutation carriers were excluded. We compared performance on each neuropsychological test between carriers and non-carriers. Participants in New York (n = 112) were evaluated with the entire battery. Tel Aviv participants (n = 124) were evaluated on attention, executive function and psychomotor speed tasks. The association between G2019S mutation status (predictor) and each neuropsychological test (outcome) was assessed using linear regression models adjusted for PIGD motor phenotype, site, sex, age, disease duration, education, Unified Parkinson's Disease Rating Scale (UPDRS) Part III, levodopa equivalent dose, and Geriatric Depression Score (GDS).ResultsCarriers had longer disease duration (p < 0.001) and were more likely to manifest the PIGD phenotype (p = 0.024). In adjusted regression models, carriers performed better than non-carriers in Stroop Word Reading (p < 0.001), Stroop Interference (p = 0.011) and Category Fluency (p = 0.026).ConclusionIn AJ-PD, G2019S mutation status is associated with better attention (Stroop Word Reading), executive function (Stroop Interference) and language (Category Fluency) after adjustment for PIGD motor phenotype.