This project will examine novel cognitive and structural imaging predictors of future cognitive and functional decline in patients with Parkinson's disease (PD). Previous studies have shown that cognitive measures of anterior brain functioning within the anterior brain regions, are somewhat predictive of future cognitive decline in PD. However, recent research suggests that cognitive measures of posterior brain functioning may be better predictors of cognitive decline and Parkinson's Disease Dementia (PDD). To date, no studies have directly contrasted anterior vs. posterior brain functioning using sensitive cognitive measures and no study has attempted to determine whether separating ventral or dorsal aspects of these brain regions leads to greater predictability. The proposed project will determine whether such cognitive measures can predict which patients develop future decline global cognitive status and instrumental activities of daily living (e.g., medication management). We will enroll 70 PD patients who currently do not meet formal criteria for PDD and 50 Healthy Comparison (HC) participants who will be evaluated neuropsychologically at baseline (Time 1) and at follow-up 2-2.5 years later (Time 2). Participants will also be administered a structural magnetic resonance imaging protocol to evaluate cortical and subcortical brain volume. Four visual cognitive tests will be administered that are believed to be associated with posterior cortical functioning. Two of these measures are thought to rely on the posterior ventral object-based system (PVOBS) and two of these measures rely on the posterior dorsal spatial based system (PDSBS). Participants will also be administered a decision-making task thought to be sensitive to the integrity of the Anterior Decision Making System (ADMS), and has been shown to be differentially impaired in PD patients, and a learning task that is thought to be sensitive to the integrity of the Anterior Cognitive Control System (ACCS). It is anticipated that, in general, cognitive processes sensitive to the integrity of the PVOBS as compared to the other systems will be better predictors of cognitive and functional longitudinal decline. Further, sMRI volume of structures within the PVOBS will be better predictors of cognitive and functional decline. The results of this study will provide novel predictors of future changes in global cognition and functional decline.

Public Health Relevance

There is an increasing need to better understand the progression of the cognitive symptoms of Parkinson's disease (PD). Once thought to be primarily a disease impacting only movement, it is now becoming increasingly clear that cognition and psychiatric functions are equally impacted, and in fact, can be more debilitating for patients and their caregivers. From a clinical perspective, it is important to be able to evaluate patients and have some prognostic indicators that can help predict which patients will go on to develop cognitive changes. The risk of developing PD increases substantially with age. At the time of the 2010 Veteran's census, there were over 6.7 million Veterans 65 years of age or older, suggesting that approximately 33 to 100 thousand Veterans were diagnosed with PD at that time, with the likelihood of half having some level of cognitive impairment. With our growing Veteran population over the age of 65, it is anticipated that these numbers will grow markedly in the future.

National Institute of Health (NIH)
Non-HHS Research Projects (I01)
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Mental Health and Behavioral Science B (MHBB)
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VA San Diego Healthcare System
San Diego
United States
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