Parkinson's Disease (PD) affects at least 1.5 million people in the United States alone. One of the most severe non-motor symptoms of PD is cognitive dysfunction involving reduced processing speed/working memory, and/or episodic memory. Relative to other neurodegenerative disorders with cognitive impairment, we know little about the neuroanatomical correlates of cognitive decline in PD. In preliminary work, we have examined brain connectivity associated with cognition in a group of idiopathic non-dementia PD relative to non- PD age-matched peers. Three distinct cognitive phenotypes were observed: a) slow information processing speed with preserved episodic memory, b) episodic memory difficulty with subtle slow information processing speed; and c) normal functioning with no deficits relative to age matched peers. Preliminary results of high angular resolution diffusion imaging suggest unique white matter and gray matter profiles: PD with episodic memory deficits exhibited mesial temporal circuit disruption (i.e., entorhinal-hippocampal connectivity); PD with primary processing speed deficits displayed aberration in the frontal-subcortical white matter circuitry (DLPFcircuit) between the dorsolateral prefrontal cortex and caudate; and PD without cognitive deficits showed circuitry similar to age-matched controls. The present study will recruit from one of the largest movement disorder databases in the country to investigate working hypotheses regarding memory and processing speed/executive difficulties and regional white matter connectivity within the temporal and frontal-subcortical regions, respectively.
Three specific aims will be addressed.
Aim 1 : to demonstrate the association between memory function and the connectivity between the entorhinal cortex and hippocampus;
Aim 2 : to examine the relation between reduced processing speed/working memory and integrity within the DLPF cortex to caudate;
and Aim 3 : to reveal the significance of regional brain connectivity on memory or executive function decline at one and two years post-baseline. A research team specialized in movement disorders, functional and diffusion imaging, neuropsychological assessment, reliable change analyses, and longitudinal statistical modeling will carry out these aims. Study methods will draw from unique PD patient database, state-of-the art imaging techniques, and resources from the General Clinical Research Center within the Clinical and Translational Science Institute.

Public Health Relevance

Dementia related to advancing Parkinson's disease (PD) is more common than in the standard population. PD dementia profiles are heterogeneous and warrant close examination if we are going to facilitate clinical interventions and stall dementia development. We propose three aims to examine hypotheses relating specific regions of white matter connectivity to memory/ cognitive functions in idiopathic non-dementia PD. The study incorporates possibly one of largest clinical databases of PD for recruitment, advanced high resolution neuroimaging approaches, and annual neuropsychological testing to examine the proposed hypotheses. We will use the findings to direct behavioral interventions designed to reduce PD cognitive decline.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS082386-05
Application #
9328166
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Babcock, Debra J
Project Start
2013-09-25
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2019-08-31
Support Year
5
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Florida
Department
Other Health Professions
Type
Schools of Public Health
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Wiggins, Margaret E; Tanner, Jared; Schwab, Nadine et al. (2018) Regional leukoaraiosis and cognition in non-demented older adults. Brain Imaging Behav :
Crowley, Samuel; Huang, Haiqing; Tanner, Jared et al. (2018) Considering total intracranial volume and other nuisance variables in brain voxel based morphometry in idiopathic PD. Brain Imaging Behav 12:1-12
Tanner, Jared J; McFarland, Nikolaus R; Price, Catherine C (2017) Striatal and Hippocampal Atrophy in Idiopathic Parkinson's Disease Patients without Dementia: A Morphometric Analysis. Front Neurol 8:139
Huang, Haiqing; Nguyen, Peter T; Schwab, Nadine A et al. (2017) Mapping Dorsal and Ventral Caudate in Older Adults: Method and Validation. Front Aging Neurosci 9:91
Jones, Jacob D; Tanner, Jared J; Okun, Michael et al. (2017) Are Parkinson's Patients More Vulnerable to the Effects of Cardiovascular Risk: A Neuroimaging and Neuropsychological Study. J Int Neuropsychol Soc 23:322-331
Tanner, Jared J; Levy, Shellie-Anne; Schwab, Nadine A et al. (2017) Marked brain asymmetry with intact cognitive functioning in idiopathic Parkinson's disease: a longitudinal analysis. Clin Neuropsychol 31:654-675
Colon-Perez, Luis M; Couret, Michelle; Triplett, William et al. (2016) Small Worldness in Dense and Weighted Connectomes. Front Phys 4:
Colon-Perez, L M; Triplett, W; Bohsali, A et al. (2016) A majority rule approach for region-of-interest-guided streamline fiber tractography. Brain Imaging Behav 10:1137-1147
Sisco, Shannon M; Slonena, Elizabeth; Okun, Michael S et al. (2016) Parkinson's disease and the Stroop color word test: processing speed and interference algorithms. Clin Neuropsychol 30:1104-17
Price, Catherine C; Tanner, Jared; Nguyen, Peter T et al. (2016) Gray and White Matter Contributions to Cognitive Frontostriatal Deficits in Non-Demented Parkinson's Disease. PLoS One 11:e0147332

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