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Neurodegenerative Disease Parkinson’s Disease


Use of the Unified Parkinson’s Disease Rating Scale Activities of Daily Living Subscale to Assess Response to Rasagiline in Early Parkinson’s Disease


Daniel E Kremens, MD, JD1 and James Gilbart, PhD2


1. Assistant Professor of Neurology and Co-Director, Parkinson’s Disease and Movement Disorders Center, Jefferson Medical College, Thomas Jefferson University; 2. Principal Medical Writer, Touch Briefings


Abstract


Various assessment scales are used to measure the severity and rate of progression of Parkinson’s disease (PD)—for example, the Unified Parkinson's Disease Rating Scale (UPDRS) and its Activities of Daily Living (ADL) subscale. The relative merits of these scales for accurately determining the degree of disease progression have recently come under scrutiny. Analyses of data from the recent Attenuation of disease progression with Azilect given once daily (ADAGIO) trial demonstrated that patients receiving early-start rasagiline (Azilect®, Teva Neuroscience, North Wales, PA) 1 mg/day experienced slower disease progression, as assessed by their mean total UPDRS score, than patients receiving placebo followed by delayed-start rasagiline treatment. Subsequent secondary analyses showed that 1 and 2 mg/day doses of early-start rasagiline delayed the need for antiparkinsonian drugs and improved other parameters, including ADL scores and fatigue, when compared with placebo followed by delayed-start rasagiline. Furthermore, the analyses highlighted that, over time, the motor and mentation sections of the UPDRS-ADL subscale increasingly reflect the response to treatment of the early- and delayed-start rasagiline 1 mg/day patient groups. The results from the ADAGIO trial suggest that rasagiline has potential disease-modifying effects, but more clinical data are required to confirm their effect on PD progression.


Keywords Early Parkinson’s disease, Unified Parkinson’s Disease Rating Scale, Activities of Daily Living subscale, rasagiline, ADAGIO trial


Disclosure: Daniel Kremens, MD, JD, has served on the speaker's bureau for Teva Neuroscience, Allergan, Merz, and Novartis, and as a consultant to Teva Neuroscience, Allergan, Merz, and Impax. James Gilbart, PhD, is an employee of Touch Briefings. Received: November 29, 2011 Accepted: December 23, 2011 Citation: US Neurology, 2011;7(2):91–9 Correspondence: Daniel Kremens, MD, JD, Thomas Jefferson University Hospitals, 900 Walnut Street, Ste. 200, Philadelphia, PA 19107. E: Daniel.Kremens@jefferson.edu


Support: The publication of this article was funded by Teva Neuroscience. The views and opinions expressed are those of the authors and not necessarily those of Teva Neuroscience.


Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder, affecting 1−2 % of people aged more than 60 years.1


behavioral, and autonomic systems.2


It is a complex disorder that affects the motor, cognitive, PD can be hard to diagnose early


because mild parkinsonian signs are often detected in elderly patients who are not known to have neurological disease.3


Many patients who


have parkinsonian signs, such as gait and balance changes, rigidity, bradykinesia, and tremor do not technically fulfill the stringent diagnostic criteria for confirmed PD.3–5


These patients have a predisposition to develop PD, but not all will go on to develop clinically manifest PD.5


Many of the signs of PD are associated with the age-related decline of dopamine-producing neurons in the substantia nigra. It is thought that approximately 50 to 80 % of dopaminergic neurons are lost prior to the emergence of the typical motor signs of PD.6


More recent studies


have suggested that motor symptoms may emerge when as few as 30 % of dopaminergic neurons in the substantia nigra are lost.7


© TOUCH BRIEFINGS 2011


Levodopa, in combination with a dopa decarboxylase inhibitor, is well established for the treatment of PD. Long-term use, however, is associated with the development of motor fluctuations and dyskinesias.8–12 Furthermore, dopamine replacement often does not alleviate non-motor symptoms, including sleep disturbances, depression, orthostatic hypotension, and dementia.13


It is, therefore, important to explore alternative treatment options, including potential disease-modifying drugs.


Assessing the Clinical Severity of Parkinson’s Disease


The evaluation of PD requires sensitive and accurate rating scales to assess clinical severity and treatment-related changes.14


Observer-rated


scales have been used to evaluate the clinical severity of PD, including the Hoehn and Yahr scale, the Columbia University Rating Scale, the Webster Scale, the Hamilton Depression Rating Scale, and the mini–mental state examination.15–17


A number of limitations and issues arise regarding the use of these scales for the assessment of PD.18


For example, some 91


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