Clinical markers help identify PD patients with cholinergic deficits

By Joanna Lyford, Senior medwireNews Reporter

Assessing patients for clinical markers of cholinergic system denervation is viable and can help identify suitable individuals for trials of new anticholinergic drugs, researchers believe.

In this retrospective study, Martijn Müller, from the University of Michigan in Ann Arbor, USA, and colleagues assessed 137 patients with Parkinson’s disease (PD) who were participating in a separate ongoing cohort study.

Their aim was to identify conventional, cost-effective and noninvasive clinical markers of cholinergic deficits in PD patients. Cholinergic system degeneration is heterogeneous in PD, they note, and this variability may explain clinical variation in the condition.

The patients’ average age was 65.6 years, the average duration of motor symptoms was 6.0 years and 34 patients were female. Patients were classified as hypocholinergic, based on brain imaging data, if they were below the 5th percentile for neocortical or thalamic cholinergic innervation.

Forty-nine (35.8%) patients were found to be hypocholinergic, of whom 23 had thalamic cholinergic denervation, with or without cortical denervation, and 26 had only cortical denervation.

In the thalamic denervation group, there were two significant predictors of cholinergic deficits: rapid eye movement sleep behaviour disorder and a history of falls. The best diagnostic test was obtained with both factors combined, which gave a sensitivity of 34.8%, a specificity of 93.2% and an area under the receiver operating characteristic curve of 0.64.

In the group with cortical-only denervation, there were four significant predictors: longer 8.5 m walk time, lower Montreal cognitive assessment test (MoCA) score, higher age and male gender. The best diagnostic test was a combination of walk time and MoCa score, which had a sensitivity of 19.2%, a specificity of 98.9% and an area under the curve of 0.59.

Writing in Movement Disorders, Müller and his co-authors admit that ideally studies should be conducted to identify markers that are specific to cholinergic system degeneration. This is challenging, however, given the multisystem neurodegenerative nature of PD and the effect of comorbidities on PD features, they write.

“Selection of effective cut-off criteria of the clinical features was based on high specificity but at the expense of lower sensitivity”, the authors conclude.

They add: “[W]e believe that in the presence of multisystem neurodegeneration recruitment for cholinergic augmentation therapy should prioritize specificity above sensitivity to maximize clinical response and minimize side effects.”

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