Imaging biomarker proposed for Parkinson’s disease

By Eleanor McDermid, Senior medwireNews Reporter

Reduced off-medication connectivity in the basal ganglia network (BGN) separates patients with early Parkinson’s disease (PD) from healthy controls with high accuracy, preliminary findings suggest.

Furthermore, the differences in BGN connectivity disappeared when the PD patients in the study were taking dopaminergic medication.

“This finding suggests that reduced connectivity in the BGN is a functional rather than structural phenomenon and is related to PD-specific dopamine-dependent processes”, write senior study authors Michele Hu and Clare Mackay, from the University of Oxford in the UK, and team in Neurology.

The researchers created a BGN template using an observer-independent technique on data from 80 healthy elderly controls who underwent resting-state functional magnetic resonance imaging (RS-fMRI). They then created BGN connectivity maps of 19 PD patients and 19 age- and gender-matched healthy controls.

The PD patients had been diagnosed within the past 3 years and were taking medication. When scanned 12 to 17 hours after medication withdrawal these patients had significantly reduced connectivity relative to controls in nine clusters across the BGN: the putamen and caudate bilaterally, midbrain, superior temporal gyrus bilaterally, dorsolateral prefrontal cortex bilaterally, medial prefrontal cortex, and precuneus.

BGN connectivity significantly increased in the patients when they were scanned on medication, abolishing the differences relative to the controls.

The average connectivity parameter estimates (PE) value for the significantly different clusters was 1.04 in the PD patients versus 7.59 in controls. In a post-hoc analysis, a PE value of 3.88 distinguished between patients and controls with 100% sensitivity and 89.5% specificity.

The researchers applied this cutoff to a validation cohort of 13 PD patients, including five drug-naïve patients, and it classified these individuals with 85% accuracy (two were misclassified). It correctly classified four of the five drug-naïve patients, which the team says increases the “robustness of the finding and speaks against it being a simple effect of short-term medication withdrawal.”

BGN connectivity was not associated with clinical measures of PD symptom severity, which the team says may mean that it “is a trait marker of disease, reflecting a constitutional fault of the network and not the resulting clinical symptoms.”

In an editorial accompanying the study, Nicolaas Bohnen (University of Michigan, Ann Arbor, USA) and WR Wayne Martin (University of Alberta, Edmonton, Canada) say: “Although clinical translation of RS-fMRI to real-world neurology practice will need to clear many more hurdles, this proof-of-concept study offers great promise for the future.

“It demonstrates the potential for a functional and dopaminergic medication-responsive MRI technique to characterize disease-specific brain networks that can be quantitatively expressed and provide a reader-independent diagnosis.”

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