Linda P Oosterveld1, John C Allen1, Ebonne Y L Ng1, Soo-Hoon Seah1, Kay-Yaw Tay1, Wing-Lok Au1, Eng-King Tan1, Louis C S Tan2. 1. 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. 2. 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.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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:PDLRRK2 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: Rachel Saunders-Pullman; Anat Mirelman; Roy N Alcalay; Cuiling Wang; Roberto A Ortega; Deborah Raymond; Helen Mejia-Santana; Martha Orbe-Reilly; Brooke A Johannes; Avner Thaler; Laurie Ozelius; Avi Orr-Urtreger; Karen S Marder; Nir Giladi; Susan B Bressman Journal: JAMA Neurol Date: 2018-03-01 Impact factor: 18.302
Authors: Xiao Deng; Bin Xiao; John Carson Allen; Ebonne Ng; Jia Nee Foo; Yew-Long Lo; Louis C S Tan; Eng-King Tan Journal: J Med Genet Date: 2019-02-27 Impact factor: 6.318