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The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is associated with slower motor function decline in Parkinson’s disease, according to data published in the March 1 issue of JAMA Neurology.
“Our findings of a slower decrease in motor Unified Parkinson’s Disease Rating Scale [UPDRS] score remained consistent even in sensitivity analyses that included only individuals who had two or more visits,” said Rachel Saunders-Pullman, MD, MPH, Associate Professor of Neurology at the Icahn School of Medicine at Mount Sinai in New York City. “The slower progression estimates could inform clinical trial design for emerging LRRK2-targeted agents.”
A cross-sectional study suggested that Parkinson’s disease associated with LRRK2 G2019S mutation among patients of Ashkenazi Jewish descent is milder and may progress more slowly, compared with idiopathic Parkinson’s disease. To determine whether the longitudinal course of Parkinson’s disease in patients with the LRRK2 mutation differs from that in patients without the mutation, Dr. Saunders-Pullman and colleagues conducted a prospective, comprehensive assessment of patients from July 21, 2009, to September 30, 2016.
Researchers recruited participants of Ashkenazi Jewish ancestry with LRRK2-associated Parkinson’s disease or with idiopathic Parkinson’s disease from three sites. The investigators evaluated 545 participants who had one to four study visits. Patients with the glucocerebrosidase 1 (GBA1) mutation were excluded from the analysis.
The investigators used linear mixed-effects models for longitudinal motor scores to examine the association of LRRK2 mutation status with the rate of change in UPDRS III scores. They used disease duration as the time scale and adjusted the data for sex, site, age, disease duration, cognitive score, and levodopa-equivalent dose at baseline. The researchers also used mixed-effects models to assess change in cognition, as measured by Montreal Cognitive Assessment scores.
Of the 545 participants, 233 were women. The mean age of patients with the LRRK2 mutation was 68.2, and the mean age of those without the mutation was 67.8. Seventy-two of the 144 participants with the LRRK2 mutation and 161 of the 401 participants with no mutation were women. Among patients with the LRRK2 mutation, the estimated rate of change in the UPDRS III motor score per year was lower (0.689 points/year), compared with those without the mutation (1.056 points/year).
“The present study is the first, to our knowledge, to demonstrate this milder progression using prospective analysis,” said Dr. Saunders-Pullman and colleagues. “It is unclear whether the overall milder course represents an average of divergent LRRK2 pathologic findings or less overall synuclein burden.
“Larger and longer-duration longitudinal studies, including those evaluating pathologic findings and nonmotor features, are warranted,” the researchers concluded.
—Erica Tricarico
Suggested Reading
Saunders-Pullman R, Mirelman A, Alcalay RN, et al. Progression in the LRRK2-associated Parkinson’s disease population. JAMA Neurol. 2018;75(3):312-319.
The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is associated with slower motor function decline in Parkinson’s disease, according to data published in the March 1 issue of JAMA Neurology.
“Our findings of a slower decrease in motor Unified Parkinson’s Disease Rating Scale [UPDRS] score remained consistent even in sensitivity analyses that included only individuals who had two or more visits,” said Rachel Saunders-Pullman, MD, MPH, Associate Professor of Neurology at the Icahn School of Medicine at Mount Sinai in New York City. “The slower progression estimates could inform clinical trial design for emerging LRRK2-targeted agents.”
A cross-sectional study suggested that Parkinson’s disease associated with LRRK2 G2019S mutation among patients of Ashkenazi Jewish descent is milder and may progress more slowly, compared with idiopathic Parkinson’s disease. To determine whether the longitudinal course of Parkinson’s disease in patients with the LRRK2 mutation differs from that in patients without the mutation, Dr. Saunders-Pullman and colleagues conducted a prospective, comprehensive assessment of patients from July 21, 2009, to September 30, 2016.
Researchers recruited participants of Ashkenazi Jewish ancestry with LRRK2-associated Parkinson’s disease or with idiopathic Parkinson’s disease from three sites. The investigators evaluated 545 participants who had one to four study visits. Patients with the glucocerebrosidase 1 (GBA1) mutation were excluded from the analysis.
The investigators used linear mixed-effects models for longitudinal motor scores to examine the association of LRRK2 mutation status with the rate of change in UPDRS III scores. They used disease duration as the time scale and adjusted the data for sex, site, age, disease duration, cognitive score, and levodopa-equivalent dose at baseline. The researchers also used mixed-effects models to assess change in cognition, as measured by Montreal Cognitive Assessment scores.
Of the 545 participants, 233 were women. The mean age of patients with the LRRK2 mutation was 68.2, and the mean age of those without the mutation was 67.8. Seventy-two of the 144 participants with the LRRK2 mutation and 161 of the 401 participants with no mutation were women. Among patients with the LRRK2 mutation, the estimated rate of change in the UPDRS III motor score per year was lower (0.689 points/year), compared with those without the mutation (1.056 points/year).
“The present study is the first, to our knowledge, to demonstrate this milder progression using prospective analysis,” said Dr. Saunders-Pullman and colleagues. “It is unclear whether the overall milder course represents an average of divergent LRRK2 pathologic findings or less overall synuclein burden.
“Larger and longer-duration longitudinal studies, including those evaluating pathologic findings and nonmotor features, are warranted,” the researchers concluded.
—Erica Tricarico
Suggested Reading
Saunders-Pullman R, Mirelman A, Alcalay RN, et al. Progression in the LRRK2-associated Parkinson’s disease population. JAMA Neurol. 2018;75(3):312-319.
The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is associated with slower motor function decline in Parkinson’s disease, according to data published in the March 1 issue of JAMA Neurology.
“Our findings of a slower decrease in motor Unified Parkinson’s Disease Rating Scale [UPDRS] score remained consistent even in sensitivity analyses that included only individuals who had two or more visits,” said Rachel Saunders-Pullman, MD, MPH, Associate Professor of Neurology at the Icahn School of Medicine at Mount Sinai in New York City. “The slower progression estimates could inform clinical trial design for emerging LRRK2-targeted agents.”
A cross-sectional study suggested that Parkinson’s disease associated with LRRK2 G2019S mutation among patients of Ashkenazi Jewish descent is milder and may progress more slowly, compared with idiopathic Parkinson’s disease. To determine whether the longitudinal course of Parkinson’s disease in patients with the LRRK2 mutation differs from that in patients without the mutation, Dr. Saunders-Pullman and colleagues conducted a prospective, comprehensive assessment of patients from July 21, 2009, to September 30, 2016.
Researchers recruited participants of Ashkenazi Jewish ancestry with LRRK2-associated Parkinson’s disease or with idiopathic Parkinson’s disease from three sites. The investigators evaluated 545 participants who had one to four study visits. Patients with the glucocerebrosidase 1 (GBA1) mutation were excluded from the analysis.
The investigators used linear mixed-effects models for longitudinal motor scores to examine the association of LRRK2 mutation status with the rate of change in UPDRS III scores. They used disease duration as the time scale and adjusted the data for sex, site, age, disease duration, cognitive score, and levodopa-equivalent dose at baseline. The researchers also used mixed-effects models to assess change in cognition, as measured by Montreal Cognitive Assessment scores.
Of the 545 participants, 233 were women. The mean age of patients with the LRRK2 mutation was 68.2, and the mean age of those without the mutation was 67.8. Seventy-two of the 144 participants with the LRRK2 mutation and 161 of the 401 participants with no mutation were women. Among patients with the LRRK2 mutation, the estimated rate of change in the UPDRS III motor score per year was lower (0.689 points/year), compared with those without the mutation (1.056 points/year).
“The present study is the first, to our knowledge, to demonstrate this milder progression using prospective analysis,” said Dr. Saunders-Pullman and colleagues. “It is unclear whether the overall milder course represents an average of divergent LRRK2 pathologic findings or less overall synuclein burden.
“Larger and longer-duration longitudinal studies, including those evaluating pathologic findings and nonmotor features, are warranted,” the researchers concluded.
—Erica Tricarico
Suggested Reading
Saunders-Pullman R, Mirelman A, Alcalay RN, et al. Progression in the LRRK2-associated Parkinson’s disease population. JAMA Neurol. 2018;75(3):312-319.