Movement Disorders: Project Description

Parkinson’s disease (PD) is a complex neurodegenerative disorder that progressively affects multiple regions of the brain, and increases in severity over time. PD is characterized both by motor deficits such as tremor and gait ataxia, and by non-motor deficits such as cognitive decline and loss of REM sleep. PD is the second most prevalent neurodegenerative disorder behind Alzheimer’s disease (AD), and affects about 1-2% of the global population. The incidence of PD increases steadily with age, and is more prevalent in men than women due to a variety of genetic and environmental factors. As the global population ages and health burden associated with PD increases, the effective and holistic treatment of PD will become more important. Though PD has been extensively studied, clinical diagnostic accuracy is generally poor, and treatment efficacy is low.

Parkinson’s disease has typically been investigated from a motor symptom perspective. Most of what is known about the progression of PD has focused on decline in the basal ganglia and midbrain, regions that have been shown to be affected by the pathology of PD. Historically less studied are the numerous non-motor symptoms that have been found to precede the clinical diagnosis of PD by many years, and increase in frequency and severity after the onset of motor symptoms. The appearance of non-motor symptoms such as constipation or loss of REM sleep constitute a pre-motor or “prodromal” phase of PD, and have been shown to appear up to 20 years before the onset of motor symptoms. In many cases, little is known about the cause of these symptoms or their potential to serve as an early warning sign for PD.

Because the “gold standard” for identifying deficits associated with PD has long been post-mortem pathology, identifying the pathological progression of non-motor symptoms has been challenging. In order to visualize the PD brain during development of disease rather than post-mortem, attention has shifted to neuroimaging for an in-vivo approach. One of the most powerful tools for investigating regional involvement in disease symptomology is magnetic resonance imaging (MRI). MRI is a relatively recent addition to the PD literature because it has not been validated for use in the clinical diagnosis of PD. Advanced image analysis techniques have the potential to reveal new relationships between non-motor symptomology and brain volume, and to view the change in that relationship over time in longitudinal cohorts of PD that are publically available and continue to grow. The purpose of this project is to summarize the current state of the PD imaging field from the perspective of structural MRI. It will discuss known associations between brain morphology and non-motor symptoms, and argue that advanced neuroimaging techniques allow for the identification of non-motor specific regional atrophy that is distinct from the decline that is typically associated with motor symptoms. It will also argue that individual non-motor symptoms can be localized to regions associated with normal functioning, and that decline in these regions over time as measured by MRI will follow an increase in severity of these symptoms.