Neurocognitive Signatures of Parkinson's and Alzheimer's Disease

• Main Author: Bodi, Nikoletta
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01.01.2012
• Subjects: Mental health
• ISBN: 9781303008559; 1303008556

Neurodegenerative diseases comprise one of the major public health concerns in our aging population. Parkinson’s disease (PD), Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are characterized by marked cognitive dysfunctions. The aim of our study was to find neuropsychological assessments which could be the early indicators of selective deficits of these dementias and the connected brain structures. PD is characterized by the degeneration of dopaminergic pathways projecting to the striatum. These pathways are implicated in reward prediction. In this study, we investigated reward and punishment processing in young, never-medicated (nmed) PD patients, recently-medicated (med PD) patients receiving the dopamine receptor agonists pramipexole and ropinirole, and healthy controls. The nmed PD patients were also re-evaluated after 12 weeks of treatment with dopamine agonists. Reward and punishment processing was assessed by a feedback-based probabilistic classification task that enabled us to investigate stimulus-response learning guided by positive and negative feedback. Personality characteristics were measured by the Temperament and Character Inventory (TCI). Acquired equivalence is a phenomenon in which prior training to treat two stimuli as equivalent increases generalization between them. Previous studies demonstrated that the hippocampal complex may play an important role in acquired equivalence associative learning. We investigated feedback-guided stimulus-response learning in early AD and tested the generalization and flexibility of these associations. The data analysis was focused on acquired equivalence and on the retrieval of associations in a free task context (non-directed card pairing) instead of instrumental responding. The clock drawing test (CDT) is a widely used cognitive screening test. We investigated that the command condition of the CDT was able to discriminate between AD, FTD and controls. We examined quantitative (global) and qualitative (specific error type) differences. The data analysis was focused on errors related to visuospatial difficulties and conceptual problems, as visuospatial skill can be relatively preserved in FTD patients, and AD patients are expected to display more conceptual errors. Results revealed that nmed PD patients showed selective deficits on reward processing and novelty seeking, which were remediated by dopamine agonists. These medications disrupted punishment processing. In addition, dopamine agonists increased the correlation between reward processing and novelty seeking, whereas these drugs decreased the correlation between punishment processing and harm avoidance. Our finding that dopamine agonist administration in young patients with PD resulted in increased novelty seeking, enhanced reward processing, and decreased punishment processing may shed light on the cognitive and personality bases of the impulse control disorders, which arise as side effects of dopamine agonist therapy in some PD patients. Patients with early AD exhibited mild impairments in the training phase, they were able to learn stimulus-response associations using trial-by-trial feedback following decisions. Generalization of these associations, as measured by acquired equivalence, was impaired. Associative knowledge could not be transferred to a more flexible retrieval condition requiring flexible declarative knowledge. These results suggest that acquired equivalence learning is a markedly sensitive marker of early AD which may indicate the pathology of the hippocampal complex. In the CDT investigations both global and error analysis helped discriminate the FTD group from controls and AD patients. Results showed significantly lower overall scores in the dementia groups compared to the control group, whereas FTD patients scored significantly higher than the AD group. On qualitative analysis, the FTD group had fewer stimulus bound responses, conceptual deficits, and spatial or planning errors compared to the AD group.