Levodopa and Dopamine Agonists

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Findings concerning the impact of levodopa on cognitive functions are inconsistent, with studies showing improvement, decrements, and an absence of significant cognitive changes associated with levodopa therapy or its withdrawal (124). Despite these inconsistent findings, evidence is accumulating that levodopa has short-term effects on certain aspects of memory and executive functions, perhaps as mediated by disease stage. Kulisevsky et al. (125) reported that short-term improvements in learning and memory, visuoperception, and certain executive functions were associated with dopamine replacement therapies, but stated that these cognitive improvements were not maintained over time. Owen et al. (126) found that only certain aspects of executive functioning (i.e., planning accuracy) were improved with levodopa therapy early in the disease, whereas other aspects (response latency)

remained relatively unaffected. That levodopa affects only certain components of cognitive functions is consistent with the findings of Fournet et al. (127), who reported poorer performance only on working memory tasks in patients with PD after withdrawal from levodopa, and of Lange et al. (128), who also found that levodopa withdrawal impacted performance on only a minority of executive function measures. Levodopa's rather selective effects on working memory and certain executive functions may be related to its mediation of dorsolateral frontal cortex blood flow in response to executive task activation (129).

Dopamine agonists such as pergolide (130,131) and bromocriptine (132-134) have limited, if any, cognitive effects at therapeutic doses, acutely or after chronic administration. However, pramipexole may have negative effects on attention, verbal memory, and verbal fluency (135). Catechol-O-methyl-transferase (COMT) inhibitors are used to reduce peripheral breakdown of levodopa and thereby increase the amount of levodopa reaching the brain. One study found that after six months of treatment with the COMT-inhibitor tolcapone patients demonstrated improved attention, memory, and constructional skills (136).

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