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Paradoxical Effect of Dopamine Medication on Cognition in Parkinson’s Disease: Relationship to Side of Motor Onset

Published online by Cambridge University Press:  29 April 2015

Brenda Hanna-Pladdy*
Affiliation:
Departments of Neurology, Psychiatry, and Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland
Rajesh Pahwa
Affiliation:
Parkinson’s Disease and Movement Disorder Center, Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas
Kelly E. Lyons
Affiliation:
Parkinson’s Disease and Movement Disorder Center, Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas
*
Correspondence and reprint requests to: Brenda Hanna-Pladdy, Department of Neurology, University of Maryland School of Medicine, 110 South Paca Street 3rd Floor, Baltimore, MD 21201. E-mail: bhanna-pladdy@som.umaryland.edu

Abstract

Parkinson’s disease (PD) is characterized by asymmetric motor symptom onset attributed to greater degeneration of dopamine neurons contralateral to the affected side. However, whether motor asymmetries predict cognitive profiles in PD, and to what extent dopamine influences cognition remains controversial. This study evaluated cognitive variability in PD by measuring differential response to dopamine replacement therapy (DRT) based on hemispheric asymmetries. The influence of DRT on cognition was evaluated in mild PD patients (n=36) with left or right motor onset symptoms. All subjects were evaluated on neuropsychological measures on and off DRT and compared to controls (n=42). PD patients were impaired in executive, memory and motor domains irrespective of side of motor onset, although patients with left hemisphere deficit displayed greater cognitive impairment. Patients with right hemisphere deficit responded to DRT with significant improvement in sensorimotor deficits, and with corresponding improvement in attention and verbal memory functions. Conversely, patients with greater left hemisphere dopamine deficiency did not improve in attentional functions and declined in verbal memory recall following DRT. These findings support the presence of extensive mild cognitive deficits in early PD not fully explained by dopamine depletion alone. The paradoxical effects of levodopa on verbal memory were predicted by extent of fine motor impairment and sensorimotor response to levodopa, which reflects extent of dopamine depletion. The findings are discussed with respect to factors influencing variable cognitive profiles in early PD, including hemispheric asymmetries and differential response to levodopa based on dopamine levels predicting amelioration or overdosing. (JINS, 2015, 21, 259–270)

Type
Research Articles
Copyright
Copyright © The International Neuropsychological Society 2015 

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