Nonmotor features may predict PD progression

By Eleanor McDermid, Senior medwireNews Reporter

The presence of mild cognitive impairment (MCI), orthostatic hypotension, and rapid eye movement sleep behaviour disorder (RBD) may identify a subset of Parkinson’s disease (PD) patients with a poor prognosis, research suggests.

The results emerge from a cluster analysis of 113 prospectively recruited patients with idiopathic PD. They were aged an average of 66.7 years and had PD diagnosed an average of 5.7 years previously.

Ronald Postuma (McGill University, Montreal, Quebec, Canada) and study co-authors used cluster analysis because it is “a hypothesis-free data-driven approach”. They found that MCI, RBD and orthostatic hypotension were the predominant factors determining three subgroups of patients, with the Unified Parkinson’s Disease Rating Scale parts II and III scores, and depression and anxiety also contributing.

These three subgroups had similar durations of PD and were readily identifiable among patients who were less than 3 years from diagnosis, suggesting that the cluster analysis had identified disease subtypes rather than stages. Moreover, the three subgroups had markedly different outcomes over an average 4.5 years of follow-up.

One subgroup of 40 patients all had MCI and orthostatic hypotension and 92.5% had RBD. The team termed this the “diffuse” group, because their defining features “are related to dysfunction of very different anatomical systems [so] their simultaneous impairment may mark a relatively diffuse neurodegenerative process.”

The diffuse subgroup had a “dramatically worse prognosis” than a subgroup of 43 patients who had no orthostatic hypotension and a low rate of RBD (18.6%), with 44.2% having MCI; their symptoms were mainly restricted to motor symptoms of moderate severity.

Compared with the motor subgroup, the diffuse subgroup had a significantly increased likelihood of progressing in all domains, with odds ratios ranging from 2.9 for motor symptoms to 10.0 for other nonmotor symptoms (those not defining the subgroup).

Another subgroup, of 30 patients, had an intermediate prognosis, with the likelihood of progression being slightly but not significantly greater than that in the motor subgroup. They were characterised by orthostatic hypotension, but no MCI and an intermediate (60.0%) rate of RBD.

“Interestingly, our model did not find large baseline differences in motor signs and symptoms, yet it strongly predicted motor progression on follow-up”, write Postuma et al in JAMA Neurology. They attribute this to the clusters being based largely on three “critical nonmotor variables”.

The team also assessed seven previously published and validated cluster solutions, but found that just one of these previous solutions predicted progression in their cohort.

In an accompanying editorial, Mya Caryn Schiess and Jessika Suescun, both from The University of Texas Medical School at Houston, USA, note the “striking” lack of consistent motor and nonmotor determinants between the previous cluster solutions. They observe that the baseline global composite outcome scores also varied between cohorts, “suggesting that the subtype may be a stage in the evolution of the disease.”

They conclude that the “true benefit” of the current findings is the shift of focus from motor to nonmotor phenotyping “and that they provide a compelling reason for all clinicians to screen patients with PD at initial visits for [orthostatic hypotension], cognitive impairment, and sleep disorders in order to predict prognosis and tailor a management regimen.”

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