Chronic effects of dopaminergic replacement on cognitive function in Parkinson's disease: A two-year follow-up study of previously untreated patients

Abstract

BACKGROUND: The cognitive effects of dopaminergic treatment in Parkinson's disease (PD) are still controversial.OBJECTIVE: To evaluate, in previously untreated patients with PD, whether chronic dopaminergic stimulation produces significant cognitive changes; whether they are sustained beyond the period of a few months; and whether the cognitive status of two motor-comparable groups is differently affected by levodopa and pergolide.DESIGN AND SUBJECTS: Parallel, randomized open study with blind neuropsychologic evaluation of 20 consecutive de novo patients with PD before and 3, 6, 12, 18, and 24 months after monotherapy with levodopa (n ‫ס‬ 10) or pergolide (n ‫ס‬ 10; 6-month monotherapy; pergolide + levodopa thereafter).RESULTS: Both treatments were associated with a signifi-cant improvement in motor scores and in tests assessing learning and long-term verbal and visual memory, visuospatial abilities, and various frontal tasks. While improvement in motor scores persisted, improvement in activities of daily living and in semantic fluency, Luria's rhythm and motor and long-term memory tests was not sustained at the 24-month examination. Further, performance on attentional, short-term memory, and the Stroop tests did not change over the course of the study. CONCLUSIONS: Both treatments were associated with incomplete but long-lasting (18 mos) improvement in many cognitive tasks which declined thereafter, suggesting that dopaminergic replacement is not enough to compensate for all cognitive deficits of PD.

l‐Dopa/carbidopa intestinal gel and subthalamic nucleus stimulation: Effects on cognition and behavior

“…In our study, cognitive changes in the LCIG group could be related to a positive effect of l‐ dopa on some aspects of cognition (Cools, Stefanova, Barker, Robbins, & Owen, 2002; Kulisevsky et al., 2000; Muslimovic, Post, Speelman, & Schmand, 2005). Experimental fMRI studies have shown that l‐ dopa administration enhances prefrontal cortex activity, improves cognition in de novo patients and induces blood flow changes in right dorsolateral prefrontal cortex (Poletti et al., 2012).…”

Role of Cholinesterase Inhibitors in Parkinson’s Disease and dementia with Lewy Bodies

“…No studies of drugs other than ChEIs have reliably shown cognitive improvement in PDD or DLB, although dopaminergic agents may have a beneficial effect on some cognitive functions early in course. 52 Atypical antipsychotic drugs have been shown to improve psychosis in PDD 53 and possibly in DLB as well, but risperidone and olanzapine are associated with a higher stroke risk in demented patients, and there is a high risk for marked sensitivity reactions related to neuroleptic drugs in DLB 54 and probably also in PDD, 55 and these potential risks need to be taken into account when prescribing neuroleptics. Studies of nonpharmacological interventions in PDD and DLB do not exist.…”

Tonic Dopaminergic Stimulation Impairs Associative Learning in Healthy Subjects

“…In healthy humans, only subjects with high as compared to low baseline (prefrontal) dopaminergic functioning performed worse in a working memory task after administration of a D2-receptor dopamine agonist (Bitsios et al, 2005;Gibbs and D'Esposito, 2005;Kimberg et al, 1997) or Damphetamine (Mattay et al, 2003). Conversely, de novo patients with Parkinson's disease suffering from decreased dopamine levels improved on learning tasks after treatment with pergolide (Kulisevsky et al, 2000), consistent with other findings that a tonic hypodopaminergic condition is associated with decreased efficiency of prefrontal cortical information processing in Parkinson's disease (Mattay et al, 2002). This underscores the beneficial potential of dopamine agonists on cognitive processes in hypodopaminergic conditions like Parkinson's disease, possibly by improving tonic functions like attention or working memory.…”