Parkinson disease (PD) is characterized by cardinal symptoms of bradykinesia, rigidity, and resting tremor considered reflective of dopaminergic (DA) neuronal loss in the nigrostriatal tract. These motor symptoms can be accompanied by impairments in cognition, although there is heterogeneity in the cognitive deficits associated with PD. While DA depletion has been correlated with the severity of motor impairment in PD, prior studies investigating the effects of DA medication on cognitive tasks have been inconsistent and the role of the basal ganglia in cognition is controversial. Few studies have evaluated patients in both on and off medication states, and there are inconsistent results in the studies which have been conducted. Thus, the neuroanatomical and neurochemical correlates of cognitive dysfunction in PD are uncertain. The specific hypothesis behind the research is that only some PD disordered behaviors are mediated by DA, and that DA treatment has differential effects depending on task demands. We base that hypothesis on the following observations: First, not all behavioral deficits of PD can be accounted for on the basis of pure motor impairment, and/ or DA depletion. Second, dopaminergic treatment differentially impacts performance depending on task demands, and is related to the extent of dopamine-depletion in the affected circuits. Based on these observations, the experimental focus of this proposal is on determining in PD under which conditions (i.e., task demands) DA regulatory mechanisms influence performance.
The specific aims are designed to provide an assessment of the dopaminergic modulation of the cognitive aspects of motor control in PD.
The specific aims are the following: (1) To determine the role of DA in regulating incremental skill acquisition, feedback control processes, and movement amplitude in PD. (2) To characterize implicit memory deficits in PD and investigate DA modulation. (3) To determine the role of DA in regulating spatiotemporal features of limb sequences in PD. We propose that DA regulates planning aspects of incremental skill acquisition when reliant on internal cues, but not PD deficits in movement amplitude or limb sequence acquisition. Conversely, DA will have a detrimental effect on spatial features of limb sequences. We predict that implicit memory deficits in PD can be divided into subtypes only some of which are mediated by DA. We base these hypotheses on dissociations in our pilot data that exist across various task demands. The proposed aims will help elucidate DA regulatory mechanisms controlling motor and cognitive symptoms of PD, as a necessary prerequisite to development of therapeutic protocols capable of treating all aspects of PD disordered behavior.
Parkinson disease (PD) is a progressive disease that usually affects the motor system, but it is also associated with a non-motor symptom complex that contributes significantly to morbidity and institutionalization, more than quadrupling the cost of care. Recent evidence suggests that non-motor symptoms such as cognitive dysfunction may be markers of a preclinical stage of PD, although cognitive symptoms in PD are not well recognized in clinical practice and it is uncertain how current treatments with dopamine agonists affect cognition. The proposed study will characterize cognitive symptoms in PD and evaluate treatment with dopaminergic medication as a necessary prerequisite to the development of therapeutic protocols capable of treating the full constellation of PD symptoms.
| Hanna-Pladdy, Brenda; Pahwa, Rajesh; Lyons, Kelly E (2015) Paradoxical effect of dopamine medication on cognition in Parkinson's disease: relationship to side of motor onset. J Int Neuropsychol Soc 21:259-70 |
| Hanna-Pladdy, Brenda; Jones, Katherine; Cabanban, Romeo et al. (2013) Predictors of mild cognitive impairment in early-stage Parkinson's disease. Dement Geriatr Cogn Dis Extra 3:168-78 |
| Hanna-Pladdy, B; Enslein, A; Fray, M et al. (2010) Utility of the NeuroTrax computerized battery for cognitive screening in Parkinson's disease: comparison with the MMSE and the MoCA. Int J Neurosci 120:538-43 |
| Hanna-Pladdy, Brenda; Heilman, Kenneth M (2010) Dopaminergic modulation of the planning phase of skill acquisition in Parkinson's disease. Neurocase 16:182-90 |
