Parkinson’s stage “critical” to picking the best neuroimaging biomarker for clinical trials

Reuters Health - 31/08/2021 - Neuroimaging biomarkers are becoming increasingly important for monitoring progression of Parkinson disease (PD) in clinical trials and also have the potential to improve clinical care and management.

Yet, it's "critical" to consider the stage of disease when choosing an imaging biomarker as an outcome measure in clinical trials, as individual biomarkers may be better suited to assess the neurodegenerative process at different stages of disease, say the authors of a paper in JAMA Neurology.

In their review, Dr. David Vaillancourt with University of Florida, Gainesville and colleagues outline emerging neuroimaging biomarkers across various stages of PD.

"In the field of Parkinson's disease, neuroimaging has proven to be robust for characterizing and tracking progression," Dr. David Vaillancourt of the University of Florida, in Gainesville, commented in an email to Reuters Health.

"The purpose of the review is to synthesize the literature on the stages of Parkinson's disease from preclinical, early stage, and moderate to advanced stages. The goal is to provide a summary of the most promising methods at each stage of disease," Dr. Vaillancourt said.

The review provides the following advice and guidance:

- "If a clinical trial is being carried out in the preclinical and prodromal stages, potentially useful disease-state biomarkers include dopaminergic imaging of the striatum; metabolic imaging; free-water, neuromelanin-sensitive, and iron-sensitive imaging in the substantia nigra; and T1-weighted structural magnetic resonance imaging."

- "Disease-state biomarkers that can distinguish atypical parkinsonisms are metabolic imaging, free-water imaging, and T1-weighted imaging; dopaminergic imaging and other molecular imaging track progression in prodromal patients, whereas other established progression biomarkers need to be evaluated in prodromal cohorts."

- "Progression in early-stage PD can be monitored using dopaminergic imaging in the striatum, metabolic imaging, and free-water and neuromelanin-sensitive imaging in the posterior substantia nigra."

- "Progression in patients with moderate to late-stage PD can be monitored using free-water imaging in the anterior substantia nigra, R2* of substantia nigra, and metabolic imaging. Cortical thickness and gyrification might also be useful markers or predictors of progression."

- "Dopaminergic imaging and free-water imaging detect progression over 1 year, whereas other modalities detect progression over 18 months or longer."

- "The reliability of progression biomarkers varies with disease stage, whereas disease-state biomarkers are relatively consistent in individuals with preclinical, prodromal, early, and moderate to late-stage PD."

Dr. Vaillancourt told Reuters Health, "Clinicians will be able to use this review to better understand which neuroimaging techniques show the most promise at specific stages of disease. There may not be a one size fits all approach as the use a specific technique may depend on the disease stage."

He cautioned, "The literature on preclinical markers is still very early and more data is needed in this space going forward. We need assessments in preclinical stages including several different at risk cohorts."

This research was supported by grants from the National Institutes of Health. Dr. Vaillancourt is a cofounder of Neuroimaging Solutions LLC.

SOURCE: https://bit.ly/2UXzFcm JAMA Neurology, online August 30, 2021.

By Megan Brooks



Posted on 31 August 202113 September 2021