Objective/Rationale:
A measurement tool which accurately reflects not only motor deficits but also a host of cognitive dysfunctions seen frequently in Parkinson’s disease (PD) would improve diagnosis of the disease and identify PD subtypes for more effective tailored treatment strategies.
Project Description:
We propose that an assessment of motor and cognitive deficits in PD together will lead to an improved characterization of PD, including a better classification of PD subtypes. To measure motor deficits, we will test PD patients on and off medication via the Unified PD Rating Scale. To measure PD-related cognitive deficits, we have selected a sensitive neurocognitive battery that tests specific aspects of executive functions, visual spatial cognition, and declarative memory. We will utilize multimodal MRI to capture images of what is happening in the brains of participants and identify relationships between what is seen in those images and the results of the motor and cognitive tests.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
A measurement tool which accurately reflects not only motor deficits but also a host of cognitive dysfunctions seen frequently in Parkinson’s disease (PD) would improve diagnosis of the disease and identify PD subtypes for more effective tailored treatment strategies.
Anticipated Outcome:
It is expected that the findings will increase diagnostic accuracy of the disease and thus will be a major step toward better health care for PD patients. Furthermore, it is expected the study will shed new light on the biological underpinnings of motor and cognitive deficits in PD. This information will permit more targeted enrollments of PD populations with specific clinical presentations of the disease for drug trials , thereby improving power of trials and potentially accelerating new drug discoveries.
Final Outcome
We have met our recruitment goal of 25 Parkinson’s disease (PD) patients and 15 controls. Cognitively, we found that PD patients had problems with their egocentric (self-based) spatial memory system but not with allocentric (landmark–based) memories. Furthermore, PD patients had worse executive function scores than controls. As for brain imaging, the most prominent signature of PD were alterations in functional connectivity and functional brain networks as seen with resting-state fMRI. In addition, PD patients showed a characteristic regional pattern of microstructural changes that involved the substantia nigra and supplementary motor regions, as seen with diffusion tensor imaging. Moreover, an initial analysis of microstructural alterations along specific fiber tracts show that motor deficits in PD are correlated with diminished integrity of fibers connections within basal ganglia, whereas the cognitive deficits are largely associated with fibers connections to the cortex. In summary, the findings indicate PD can involve selective impairment of cognitive functions in addition to motor impairments and this heterogeneity of symptoms is reflected in characteristic functional and microstructural brain alterations patterns seen on MRI. MRI of brain function and microstructural integrity are each potential markers of PD heterogeneity, which could aid early diagnosis and assessment of disease-modifying interventions.
Presentations & Publications
Michael A. Lones, Jane E. Alty, Stuart E. Lacy, D. R. Stuart Jamieson, Kate L. Possin, Norbert Schuff and Stephen L. Smith. Evolving Classifiers to Inform Clinical Assessment of Parkinson’s Disease. IEEE Symposium Series on Computational Intelligence (2013); Singapore.
Yu Zhang, Katherine Wu, Shannon Buckley, and Norbert Schuff. Visualization and Quantification of the Striato‐pallidonigral Fibers in Parkinson's Disease Using Diffusion Tensor. 11th International Conference on Alzheimer's & Parkinson's Diseases (2013). Florence, Italy.
J. Alty, M. Lones, S. Jamieson, K. Possin, N. Schuff, S. Lacy, S.L. Smith. Clinically ‘slight’ bradykinesia is accurately detected using a novel device that requires a one-minute test period. World Congress of Neurology (2013), Vienna, Austria.
Johnson, Bott, Kiely, Pollock, Kramer, Galifianakis, Smith, Alty, Lones, Lacy, Schuff, Possin. Egocentric Spatial Working Memory is Impaired in Parkinson’s Disease and May Contribute to Bradykinesia Severity. Meeting of the International Neuropsychological Society (2014). Seattle WA.
Nick Bott, Erica Johnson, Tom Kiely, Norbert Schuff, Nick Galifianakis, Joel Kramer, Katherine Possin. Sensitive Measures of Executive Function Deficits in Non-demented Parkinson’s Disease. Meeting of the International Neuropsychological Society (2014). Seattle WA.
Y. Zhang, K. Wu, S. Buckley, S. Mendick, J. Seibyl, E. Foster, C. Coffey, K. Marek, N. Schuff. Degeneration of corticostriatal fibers in Parkinson’s disease and their differential relations to cognitive and motor deficits. International Congress of Parkinson’s disease and movement disorders (2014). Stockholme, Sweden.
Y. Zhang, K. Wu, S. Buckley, N. Schuff. Differential Patterns of White Matter Degradation in Relation to Cognitive and Motor Deficits in Parkinson’s Disease. Annual Meeting of American Academy of Neurology (2014). Philadelphia, PA.
March 2014