Roger Kurlan1, Bernard Ravina2, Shirley Eberly3, Anthony E Lang4, Caroline M Tanner5, Kenneth Marek6, Karen Marder7, James Beck8, Robin Elliott8, David Oakes3, Ira Shoulson9. 1. Atlantic Neuroscience Institute Summit New Jersey USA. 2. Voyager Therapeutics Cambridge Massachusetts USA. 3. Department of Biostatistics and Computational Biology University of Rochester Rochester New York USA. 4. Toronto Western Hospital Toronto Ontario Canada. 5. The Parkinson's Institute Sunnyvale California USA. 6. Institute for Neurodegenerative Disorders New Haven Connecticut USA. 7. Columbia University New York New York USA. 8. Parkinson's Disease Foundation New York New York USA. 9. Georgetown University Washington District of Columbia USA.
Abstract
BACKGROUND: The aim of this work was to identify early clinical predictors of important outcomes in Parkinson's disease (PD). In PD, treatment-resistant (e.g., dementia, falling) and other important functional outcomes (e.g., declines in quality of life [QOL] and activities of daily living [ADL]) emerge and become increasingly disabling. METHODS: We analyzed longitudinal data from 491 early, untreated PD subjects who enrolled in the PreCEPT trial, had baseline SPECT dopamine transporter deficit, and have continued in the PostCEPT observational cohort. After PreCEPT, antiparkinsonian medications were added if needed. Baseline clinical precursors were examined as potential predictors of selected outcomes. Separate and multivariate logistic regressions, adjusted for certain baseline factors, were performed for dichotomized outcomes evaluated at the last PostCEPT visit. RESULTS: On enrollment, subjects had average disease duration of 0.8 years and were followed for an average of 5.5 years. Some baseline precursors were found to be predictive: disease stage, cognitive, and ADL scores for dementia; disease stage, ADL, and motor and freezing scores for hallucinations; disease stage, depression, ADL, and freezing and walking scores for falling; and ADL, depression, and motor and walking scores and disease stage for QOL decline. No baseline clinical feature predicted decline in ADL. Being on levodopa was not a significant predictor of any outcome, but subjects on a dopamine agonist were significantly less impaired with respect to falling, abnormal Mini-Mental State Examination, and QOL. CONCLUSIONS: Although there are limitations, results support the value of longitudinal follow-up of clinical trial populations to identify early clinical precursors of important outcomes and thereby identify high-risk patients early on.
BACKGROUND: The aim of this work was to identify early clinical predictors of important outcomes in Parkinson's disease (PD). In PD, treatment-resistant (e.g., dementia, falling) and other important functional outcomes (e.g., declines in quality of life [QOL] and activities of daily living [ADL]) emerge and become increasingly disabling. METHODS: We analyzed longitudinal data from 491 early, untreated PD subjects who enrolled in the PreCEPT trial, had baseline SPECT dopamine transporter deficit, and have continued in the PostCEPT observational cohort. After PreCEPT, antiparkinsonian medications were added if needed. Baseline clinical precursors were examined as potential predictors of selected outcomes. Separate and multivariate logistic regressions, adjusted for certain baseline factors, were performed for dichotomized outcomes evaluated at the last PostCEPT visit. RESULTS: On enrollment, subjects had average disease duration of 0.8 years and were followed for an average of 5.5 years. Some baseline precursors were found to be predictive: disease stage, cognitive, and ADL scores for dementia; disease stage, ADL, and motor and freezing scores for hallucinations; disease stage, depression, ADL, and freezing and walking scores for falling; and ADL, depression, and motor and walking scores and disease stage for QOL decline. No baseline clinical feature predicted decline in ADL. Being on levodopa was not a significant predictor of any outcome, but subjects on a dopamine agonist were significantly less impaired with respect to falling, abnormal Mini-Mental State Examination, and QOL. CONCLUSIONS: Although there are limitations, results support the value of longitudinal follow-up of clinical trial populations to identify early clinical precursors of important outcomes and thereby identify high-risk patients early on.
Authors: Bernard Ravina; Karen Marder; Hubert H Fernandez; Joseph H Friedman; William McDonald; Diane Murphy; Dag Aarsland; Debra Babcock; Jefferey Cummings; Jean Endicott; Stewart Factor; Wendy Galpern; Andrew Lees; Laura Marsh; Mark Stacy; Katrina Gwinn-Hardy; Valerie Voon; Christopher Goetz Journal: Mov Disord Date: 2007-06-15 Impact factor: 10.338
Authors: J L Neumeyer; S Y Wang; R A Milius; R M Baldwin; Y Zea-Ponce; P B Hoffer; E Sybirska; M al-Tikriti; D S Charney; R T Malison Journal: J Med Chem Date: 1991-10 Impact factor: 7.446
Authors: Bernard Ravina; Caroline Tanner; Diane Dieuliis; Shirley Eberly; Emily Flagg; Wendy R Galpern; Stanley Fahn; Christopher G Goetz; Stephen Grate; Roger Kurlan; Anthony E Lang; Kenneth Marek; Karl Kieburtz; David Oakes; Robin Elliott; Ira Shoulson Journal: Mov Disord Date: 2009-10-30 Impact factor: 10.338
Authors: Connie Marras; Michael P McDermott; Paula A Rochon; Caroline M Tanner; Gary Naglie; Anthony E Lang Journal: Mov Disord Date: 2008-04-15 Impact factor: 10.338
Authors: Bruno Dubois; David Burn; Christopher Goetz; Dag Aarsland; Richard G Brown; Gerald A Broe; Dennis Dickson; Charles Duyckaerts; Jefferey Cummings; Serge Gauthier; Amos Korczyn; Andrew Lees; Richard Levy; Irene Litvan; Yoshikuni Mizuno; Ian G McKeith; C Warren Olanow; Werner Poewe; Cristina Sampaio; Eduardo Tolosa; Murat Emre Journal: Mov Disord Date: 2007-12 Impact factor: 10.338
Authors: Mariese A Hely; Wayne G J Reid; Michael A Adena; Glenda M Halliday; John G L Morris Journal: Mov Disord Date: 2008-04-30 Impact factor: 10.338