Cognitive profile of LRRK2-related Parkinson's disease.

Author(s): Srivatsal, S; Cholerton, B; Leverenz, JB; Wszolek, ZK; Uitti, RJ; Dickson, DW; Weintraub, D; Trojanowski, JQ; Van Deerlin, VM; Quinn, JF; Chung, KA; Peterson, AL; Factor, SA; Wood-Siverio, C; Goldman, JG; Stebbins, GT; Bernard, B; Ritz, B; Rausch, R; Espay, AJ; Revilla, FJ; Devoto, J; Rosenthal, LS; Dawson, TM; Albert, MS; Mata, IF; Hu, SC; Montine, KS; Johnson, C; Montine, TJ; Edwards, KL; Zhang, J; Zabetian, CP | Abstract: © 2015 International Parkinson and Movement Disorder Society. Background: Increasing evidence suggests that genetic factors play a role in the variability associated with cognitive performance in Parkinson's disease (PD). Mutations in the LRRK2gene are the most common cause of monogenicPD; however, the cognitive profile of LRRK2-related PD is not well-characterized. Methods: A cohort of 1,447 PD patients enrolled in the PD Cognitive Genetics Consortium was screened for LRRK2mutations and completed detailed cognitive testing. Associations between mutation carrier status and cognitive testscores were assessed using linear regression models. Results: LRRK2mutation carriers (n=29) demonstrated better performance on the Mini Mental State Examination(P=0.03) and the Letter-Number Sequencing Test (P=0.005). A smaller proportion of LRRK2carriers were demented (P=0.03). Conclusions: Our cross-sectional study demonstrates better performance on certain cognitive tests, as well as lower rates of dementia in LRRK2-related PD. Future longitudinal studies are needed to determine whether LRRK2mutation carriers exhibit slower cognitive decline.