Paradoxical effect of dopamine medication on cognition in Parkinson's disease: relationship to side of motor onset.
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.
1Departments of Neurology,Psychiatry,and Diagnostic Radiology and Nuclear Medicine,University of Maryland School of Medicine,Baltimore,Maryland.
Brenda
B
Hanna-Pladdy
2Parkinson's Disease and Movement Disorder Center,Department of Neurology,University of Kansas Medical Center,Kansas City,Kansas.
Rajesh
R
Pahwa
2Parkinson's Disease and Movement Disorder Center,Department of Neurology,University of Kansas Medical Center,Kansas City,Kansas.
Kelly E
KE
Lyons
D000368:Aged; D001288:Attention / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D056344:Executive Function / Q000187:drug effects; D005260:Female; D007839:Functional Laterality / Q000502:physiology*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy; D011597:Psychomotor Performance / Q000187:drug effects; D012720:Severity of Illness Index; D013028:Space Perception / Q000187:drug effects; D014706:Verbal Learning / Q000187:drug effects
D018491:Dopamine Agonists; D007980:Levodopa
Cognition; Dopamine; Memory; Motor asymmetry; Parkinson’s disease