title: Greater motor progression in patients with Parkinson disease who carry LRRK2 risk variants.
abstract: OBJECTIVE
  In a longitudinal follow-up study, we compared the clinical features and motor progression of patients with Parkinson disease (PD) who are carriers of the leucine-rich repeat kinase 2 (LRRK2) gene risk variants with patients who are noncarriers.
  
  
  METHODS
  We prospectively evaluated a cohort of patients with PD for their clinical characteristics, disease severity, and LRRK2 genotype. Carriers of risk variants (G2385R, R1628P, S1647T) and noncarriers were classified separately. A longitudinal, linear mixed model analysis of motor score progression was performed to compare motor progression between the 2 groups. Motor score progression was defined as the difference between Unified Parkinson's Disease Rating Scale motor score at baseline and follow-up scores.
  
  
  RESULTS
  A total of 184 patients (122 risk variant carriers and 62 noncarriers) were evaluated and followed up for up to 6.5 years. No differences in demographics and baseline disease characteristics were found. In the longitudinal, linear mixed model analysis, risk variant carriers experienced greater rate of motor progression than noncarriers after 4 years from the date of diagnosis (p ≤ 0.018).
  
  
  CONCLUSIONS
  PD LRRK2 risk variant carriers showed greater motor progression after 4 years of disease duration compared with noncarrier patients, suggesting that these risk variants may facilitate neurodegeneration with increasing disease duration.
authors: From the Department of Neurology (L.P.O., E.Y.L.N., S.-H.S., K.-Y.T., W.-L.A., E.-K.T., L.C.S.T.), Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute; and Duke-NUS Graduate Medical School (J.C.A., W.-L.A., E.-K.T., L.C.S.T.), Singapore.
authors: Linda P
authors: LP
authors: Oosterveld
authors: From the Department of Neurology (L.P.O., E.Y.L.N., S.-H.S., K.-Y.T., W.-L.A., E.-K.T., L.C.S.T.), Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute; and Duke-NUS Graduate Medical School (J.C.A., W.-L.A., E.-K.T., L.C.S.T.), Singapore.
authors: John C
authors: JC
authors: Allen
authors: From the Department of Neurology (L.P.O., E.Y.L.N., S.-H.S., K.-Y.T., W.-L.A., E.-K.T., L.C.S.T.), Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute; and Duke-NUS Graduate Medical School (J.C.A., W.-L.A., E.-K.T., L.C.S.T.), Singapore.
authors: Ebonne Y L
authors: EY
authors: Ng
authors: From the Department of Neurology (L.P.O., E.Y.L.N., S.-H.S., K.-Y.T., W.-L.A., E.-K.T., L.C.S.T.), Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute; and Duke-NUS Graduate Medical School (J.C.A., W.-L.A., E.-K.T., L.C.S.T.), Singapore.
authors: Soo-Hoon
authors: SH
authors: Seah
authors: From the Department of Neurology (L.P.O., E.Y.L.N., S.-H.S., K.-Y.T., W.-L.A., E.-K.T., L.C.S.T.), Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute; and Duke-NUS Graduate Medical School (J.C.A., W.-L.A., E.-K.T., L.C.S.T.), Singapore.
authors: Kay-Yaw
authors: KY
authors: Tay
authors: From the Department of Neurology (L.P.O., E.Y.L.N., S.-H.S., K.-Y.T., W.-L.A., E.-K.T., L.C.S.T.), Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute; and Duke-NUS Graduate Medical School (J.C.A., W.-L.A., E.-K.T., L.C.S.T.), Singapore.
authors: Wing-Lok
authors: WL
authors: Au
authors: From the Department of Neurology (L.P.O., E.Y.L.N., S.-H.S., K.-Y.T., W.-L.A., E.-K.T., L.C.S.T.), Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute; and Duke-NUS Graduate Medical School (J.C.A., W.-L.A., E.-K.T., L.C.S.T.), Singapore.
authors: Eng-King
authors: EK
authors: Tan
authors: From the Department of Neurology (L.P.O., E.Y.L.N., S.-H.S., K.-Y.T., W.-L.A., E.-K.T., L.C.S.T.), Parkinson's Disease and Movement Disorders Centre, USA National Parkinson Foundation Centre of Excellence, National Neuroscience Institute; and Duke-NUS Graduate Medical School (J.C.A., W.-L.A., E.-K.T., L.C.S.T.), Singapore. louis_tan@nni.com.sg.
authors: Louis C S
authors: LC
authors: Tan
mesh_terms: D000368:Aged; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics*; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases