‘FRONTAL’ COGNITIVE FUNCTION IN PATIENTS WITH PARKINSON'S DISEASE ‘ON’AND ‘OFF’ LEVODOPA

TLDR

Parkinson’s disease is associated with a range of cognitive deficits that parallel those seen after prefrontal cortex damage, and anatomical studies show dopamine‑dependent frontal‑basal ganglia circuits that may influence performance on frontal‑lobe tests. The study examined whether levodopa status modulates frontal cognitive function by testing Parkinson’s patients on and off levodopa on tasks sensitive to prefrontal cortex disruption. Patients were evaluated on a battery of prefrontal‑sensitive tests while on and off levodopa, and the authors discussed two explanatory mechanisms: dopamine depletion and dopamine overstimulation. Results were variable: verbal fluency was impaired only off levodopa, associative conditional learning and subject‑ordered pointing only on levodopa, and Wisconsin Card Sorting was impaired both on and off, indicating that distinct prefrontal regions and differing dopamine levels in cortex and caudate contribute to task performance.

Abstract

A wide range of cognitive impairments can be observed in patients with Parkinson's disease. A close parallel exists between these deficits and those found following damage to prefrontal cortex. Anatomical evidence is reviewed which reveals a complex pattern of neuronal circuits connecting the frontal cortex and basal ganglia. All these circuits are in some way dependent upon dopamine, suggesting that changes in the levels of dopamine stimulation may alter performance on 'frontal' tests. To test this hypothesis, a group of patients with Parkinson's disease were assessed both on and off levodopa treatment, on a range of tests selected from the human and animal experimental literature as being sensitive to disruption of prefrontal cortex. A variable pattern of results was obtained. On one test, a measure of verbal fluency, patients were impaired, compared with normal controls, only when off levodopa. On two measures, associative conditional learning and subject- ordered pointing, patients were impaired only when on levodopa, while on the final measures, the Wisconsin Card Sorting Test, patients were impaired both on and off levodopa. Two mechanisms are discussed to explain these results, one based on the effects of dopamine depletion, and the other based on the adverse effects of dopamine overstimulation. The results suggest that different areas of prefrontal cortex are involved in the tasks employed, and that functional levels of dopamine in separate areas of cortex and caudate may differ crucially in Parkinson's disease.