Researchers determined whether the longitudinal course of Parkinson's disease  in patients with the  LRRK2 mutation differs from the longitudinal course of PD in patients without the mutation . Patients with the  LRRK2  mutation demonstrate slower decline in motor functioning than patients without the mutation, which may have implications for the use of emerging disease-modifying agents.

A prospective comprehensive assessment of a large cohort of patients from 3 sites with  LRRK2  PD or with nonmutation PD was conducted from July 21, 2009, to September 30, 2016. All patients of Ashkenazi Jewish ancestry with PD were approached at each site; approximately 80% agreed to an initial visit.

A total of 545 patients of Ashkenazi Jewish descent with PD who had 1 to 4 study visits were evaluated. A total of 144 patients (26.4%) had the  LRRK2  G2019S mutation. Patients with  GBA  (OMIM 606463) mutations were excluded from the analysis.

Linear mixed-effects models for longitudinal motor scores were used to examine the association of  LRRK2 mutation status with the rate of change in Unified Parkinson's Disease Rating Scale III scores using disease duration as the time scale, adjusting for sex, site, age, disease duration , cognitive score, and levodopa-equivalent dose at baseline.

Mixed-effects models were used to assess change in cognition, as measured by Montreal Cognitive Assessment scores. Among the 545 participants, 233 were women, 312 were men, and the mean (SD) age was 68.2 (9.1) years for participants with the  LRRK2  mutation and 67.8 (10.7) years for those without it.

Seventy-two of 144 participants with the  LRRK2  mutation and 161 of 401 participants with no mutation were women. The estimate (SE) of the rate of change in the Unified PD Rating Scale III motor score per year among those with the LRRK2  mutation (0.689 [0.192] points per year) was less than between those without the mutation (1.056 [0.187] points per year; difference, -0.367 [0.149] points per year;  P  = .02).

The estimate ( SE ) of the difference in the rate of change of the Montreal Cognitive Assessment score between those with the  LRRK2  mutation (-0.096 [0.090] points per year) and those without the mutation (-0.192 [0.102] points per year) did not reach statistical significance (difference, 0.097 [0.055] points per year;  P  = .08).

Prospective longitudinal follow-up of patients with PDR or  LRRK2  G2019S mutation supports data from a cross-sectional study and demonstrates a slower decline in motor Unified Parkinson's Disease Rating Scale scores among those with  LRRK2  G2019S-associated PD.