In Search of Predictive Biomarkers of Dementia in Parkinson Disease

$3.8M NIH grant fuels effort to develop a multimodal and multivariate model

The National Institute of Neurological Disorders and Stroke 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 to predict dementia in patients with Parkinson disease (PD).

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“Although dementia affects approximately 50% to 80% of those living with Parkinson disease within 12 years of diagnosis, currently there are no means for predicting dementia in specific individuals,” says Dr. Mishra. “The possibility of identifying who will develop dementia with Parkinson 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 a project titled, “Towards Generating a Multimodal and Multivariate Classification Model from Imaging and Non-Imaging Measures for Accurate Diagnosis and Monitoring of Dementia in Parkinson’s Disease.” The project 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.

Drawing on imaging and non-imaging measures

Dr. Mishra and colleagues will combine sophisticated and pathologically relevant neuroimaging measures, such as diffusion-weighted MRI and resting-state functional MRI, with patients’ clinical, demographic and genetic data, as well as cerebrospinal fluid analysis, in an effort to:

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  • Understand how functional brain connectivity and structural brain connectivity differ in dementia in individuals with Parkinson disease
  • Identify the best biomarkers that predict dementia in Parkinson disease through multivariate statistical modeling

The researchers aim to use their findings to develop a method that can be applied in clinical care with a greater-than-chance success rate to improve patient outcomes.

Clinical implications and beyond

In addition to clinical implications, identifying pathophysiology-based biomarkers for dementia in Parkinson disease is critical to better understanding of underlying pathophysiological processes. And it can guide selection of appropriate candidates for clinical trials of potential new disease-modifying therapies.

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