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)
Type
Research Project (R01)
Project #
5R01NS082386-02
Application #
8739321
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Babcock, Debra J
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Florida
Department
Other Health Professions
Type
Schools of Public Health
DUNS #
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Tanner, Jared J; Levy, Shellie-Anne; Schwab, Nadine A et al. (2016) Marked brain asymmetry with intact cognitive functioning in idiopathic Parkinson's disease: a longitudinal analysis. Clin Neuropsychol :1-22
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
Kuhn, T; Gullett, J M; Nguyen, P et al. (2016) Test-retest reliability of high angular resolution diffusion imaging acquisition within medial temporal lobe connections assessed via tract based spatial statistics, probabilistic tractography and a novel graph theory metric. Brain Imaging Behav 10:533-47
Colon-Perez, Luis M; Couret, Michelle; Triplett, William et al. (2016) Small Worldness in Dense and Weighted Connectomes. Front Phys 4:
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
Souillard-Mandar, William; Davis, Randall; Rudin, Cynthia et al. (2016) Learning Classification Models of Cognitive Conditions from Subtle Behaviors in the Digital Clock Drawing Test. Mach Learn 102:393-441
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
Özarslan, Evren; Westin, Carl-Fredrik; Mareci, Thomas H (2015) Characterizing magnetic resonance signal decay due to Gaussian diffusion: the path integral approach and a convenient computational method. Concepts Magn Reson Part A Bridg Educ Res 44:203-213
Price, Catherine C; Tanner, Jared J; Schmalfuss, Ilona M et al. (2015) Dissociating Statistically-Determined Alzheimer's Disease/Vascular Dementia Neuropsychological Syndromes Using White and Gray Neuroradiological Parameters. J Alzheimers Dis 48:833-47
Schwab, Nadine A; Tanner, Jared J; Nguyen, Peter T et al. (2015) Proof of principle: Transformation approach alters caudate nucleus volume and structure-function associations. Brain Imaging Behav 9:744-53

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