NIH Awards Grant For Parkinson Disease Dementia Research

Virendra Mishra, PhD

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The National Institute of Neurological Disorders and Stroke at the National Institutes of Health (NIH) has awarded a grant expected to total $3.8 million to Virendra Mishra, PhD, associate staff at Cleveland Clinic Lou Ruvo Center for Brain Health, to identify biomarkers – or disease indicators – to predict dementia in patients with Parkinson disease.

“Although dementia affects approximately 50-80% of those living with Parkinson’s disease within 12 years of diagnosis, currently there are no means for predicting dementia in specific individuals,” said Mishra. “The possibility of identifying who will develop dementia with Parkinson’s disease progression has several clinical benefits, including providing individuals with greater clarity on their future and helping clinicians better manage disease progression.”

The five-year grant supports the project, “Towards Generating a Multimodal and Multivarate Classification Model from Imaging and Non-Imaging Measures for Accurate Diagnosis and Monitoring of Dementia in Parkinson’s Disease,” which will use biomarkers spanning imaging, blood, cerebrospinal fluid and genetics to develop a predictive mathematical model to identify specific individuals with Parkinson disease who may develop dementia as their disease progresses.

Utilizing sophisticated and pathologically relevant neuroimaging measures — such as diffusion-weighted MRI and resting state functional MRI — with non-imaging measures, including clinical data, demographics, genetics and cerebrospinal fluid, Mishra aims to:

• Understand how functional brain connectivity (interaction between different brain regions to complete the task at hand) and structural brain connectivity (information flow between brain regions responsible for completing the task at hand) differ in dementia in Parkinson’s disease
• Identify the best biomarkers that predict dementia in Parkinson’s disease through multivariate statistical modeling

Through this research, Mishra plans to develop a method that can be applied in clinical care with a greater-than-chance success rate to improve patient outcomes. In addition to clinical implications, identifying pathophysiology-based biomarkers for dementia in Parkinson disease is critical for selecting appropriate individuals for participation in clinical trials of potential new disease-modifying therapies, and better understanding of the underlining pathophysiological processes.

Additionally, the novel imaging techniques developed for this research also can be applied in other neurodegenerative diseases such as Alzheimer’s disease to help advance the understanding of disease-specific neuroanatomical changes indicative of dementia.

This project is supported by NIH grant award R01NS117547.

For more information about ongoing research at Cleveland Clinic Lou Ruvo Center for Brain Health, visit ClevelandClinic.org/Nevada or call 702-701-7944.