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Defining PD Subtypes Based on Patterns of Long-term Outcome

The purpose of our study is to identify Parkinson’s disease subtypes based on how individuals are doing approximately seven to eight years after diagnosis. Some patients have few symptoms at this time, while others may have problems with thinking and memory, balance, mood, motor fluctuations and dyskinesia, parkinsonism (slowness, stiffness, tremor), or autonomic function (blood pressure, urinary, and bowel function). We will analyze two long-term studies (DATATOP - Deprenyl and Tocopherol Antioxidant Therapy of Parkinsonism and CALM-PD - Comparison of the Agonist Pramipexole with Levodopa on Motor Complications of Parkinson’s Disease) and attempt to identify groups of patients with similar patterns of symptoms. We will then analyze characteristics of these patients when they were first diagnosed and treated to determine if we are able to predict their pattern of symptoms seven to eight years after diagnosis.

Early identification of patients who are anticipated to develop particular patterns of symptoms may allow selection of specific therapies that will improve long-term outcome and specific subtypes of patients may be selected for entry into clinical trials designed to evaluate therapies to forestall the development of that pattern of symptoms. In addition, identification of distinct PD subtypes may aid in delineating genetic and environmental causes of PD.

Final Outcome

Dr. Hauser used the long-term follow-up of the DATATOP and CALM-PD study populations to identify PD subgroups using cluster analysis based on domains of disability (cognitive, balance, motor function) at the last available clinical visit.

Drs. Hauser and McDermott identified specific clusters of patients ranging from a benign group to a malignant group (marked by posture problems and cognitive issues). From these two patient populations, four general patient subgroups were identified. These included a benign group (most common), benign depressed group (only found in DATATOP and not CALM-PD), benign fluctuators, and malignant group (PIGD, cognitive issues, higher UPDRS). Differences in the study populations were probably related to treatment differences (everyone in DATATOP got sinemet, while in CALM-PD it is split between Mirapex and sinemet). Though tremor was not found to be an important predictor of prognosis compared to existence of PIGD symptoms, other factors including bradykinesia, rigidity and bulbar symptoms (symptoms affecting the muscles of the throat, tongue, jaw and face) were found to be associated with cluster membership.


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