By Will Boggs MD
NEW YORK (Reuters Health) - A clinical-subtype classification can be used to predict outcomes in patients with Parkinson disease, researchers in the UK report.
Patients with Parkinson disease (PD) have widely divergent outcomes, but there is little information on clinical subtypes and their impact on meaningful outcomes.
Dr. Thomas T. Warner and colleagues at the University College London Queen Square Institute of Neurology divided 111 PD patients into three subtypes based on motor scores, autonomic dysfunction, rapid-eye-movement behavior disorder (RBD), and cognitive dysfunction.
The subtypes were: mild-motor predominant (with motor and all nonmotor scores less than the 75th percentile); diffuse malignant (with either motor score greater than the 75th percentile and at least one nonmotor score greater than the 75th percentile or all three nonmotor scores greater than the 75th percentile; and intermediate (all individuals not meeting criteria for the other subtypes).
They then evaluated time from diagnosis to death and time of onset from diagnosis to disease progression, as measured by four specific disease milestones (regular falls, wheelchair dependence, dementia and placement in residential or nursing home care), for the three clinical subtypes.
Mean survival from diagnosis was longest in the mild-motor predominant group (20.2 years), shortest in the diffuse malignant group (8.1 years), and intermediate in the intermediate group (13.2 years), the team reports in JAMA Neurology, online January 14.
Similarly, rates of disease progression were slowest in the mild-motor predominant group, intermediate in the intermediate group, and fastest in the diffuse malignant group.
Neuropathology, including Lewy pathology and Alzheimer disease-related neuropathologic changes, were similar among the different PD clinical subtypes. Neurofibrillary tangles, neuritic plaques and Alzheimer disease-related pathology were significantly associated with increased age at death, whereas neocortical Lewy pathology was not significantly associated with disease duration.
"Clinical subtyping of PD based on motor symptoms, RBD, and autonomic and cognitive dysfunction at diagnosis is feasible in clinical practice and provides accurate long-term estimation of disease progression and survival," the researchers conclude. "Different pathologies with differing rates of progression are important determinants of clinical subtypes, and age at diagnosis should be included in future subtype classification systems."
Dr. Alberto J. Espay from the UC Gardner Center for Parkinson's Disease and Movement Disorders, at the University of Cincinnati Academic Health Center, told Reuters Health by email, "I think these clinicopathologic exercises are of intellectual curiosity but of little clinical utility in prognosticating a given patient's course - much less in defining the management of a patient."
"The story line basically goes like this: If someone with PD has an aggressive first couple of years, that sets a bad track record that will likely be kept over the years and lead to early death," he said. "If someone has a fairly benign early course, that kind of track record will also be kept and people have longer lives with less disability."
"What is fascinating is that the Lewy and Alzheimer pathologies do not serve to distinguish these subtypes," Dr. Espay said. "In fact, and perhaps paradoxically according to our prevailing disease model for PD and AD, pathology of AD showed a significant association with increased age. That is, those with more AD pathology lived longer. This ostensible paradox may be explained by a compensatory role that protein aggregates play against any of a range of molecular derangements, allowing cells to work longer, even if this strategy is ultimately overwhelmed."
He added that a forthcoming paper will challenge current notions regarding the causality of both PD and AD pathology.
Dr. Ronald B. Postuma from McGill University, in Montreal, Canada, who has also researched clinical criteria for subtyping PD, told Reuters Health by email, "PD is not one thing. There are huge differences in prognosis and the types of manifestations that will develop. To predict prognosis, in addition to the well-known importance of gait impairment, watch for the non-motor complications, particularly mild cognitive impairment, severe autonomic dysfunction (especially cardiovascular), and REM-sleep behavior disorder."
"There are some limitations to the (authors') conclusions, because one cannot collect all the data on an autopsy cohort using retrospective chart review," he said. "Still, this is a terrific study. It really demonstrates that we can subtype PD."
Dr. Warner did not respond to a request for comments.
JAMA Neurol 2019.
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