Dopaminergic Treatment and Episodic Memory in Parkinson's Disease: A Meta-analysis of the Literature

Abstract

To date, few studies have focused on the benefits of dopaminergic treatment on episodic memory functions in patients affected by Parkinson's disease (PD). We conducted a meta-analysis to determine the effects of pharmacological therapy with dopamine in alleviating episodic memory deficits in Parkinson's patients. A secondary aim was to evaluate the role of dopamine in episodic memory circuits and thus in different memory systems. We conducted a comprehensive literature search in PubMed (1971-2022) to find studies that met specific inclusion criteria. The studies had to provide sufficient data (means and standard deviations) to evaluate performance on neuropsychological tests of episodic memory. A total of k = 36 measures were included in the analysis. A statistically significant difference suggested better performance following dopaminergic therapy assumption (ON condition) than following dopaminergic withdrawal (OFF condition), specifically the estimated pooled effect calculated through a random-effects restricted maximum likelihood model was log ratio of means (RoM) = 0.047 (p = 0.011). The back-transformed RoM, indicating a 4.8% improvement, provides an interpretable measure of the effect size, as it reflects the multiplicative change in performance associated with the ON condition. A meta-regression analysis was also performed to assess the influence of specific memory tasks and relevant covariates/factors on the overall meta-analytic effect: four memory contrasts (verbal/visual, immediate/delayed, recall/recognition, word-list/short-story), age of participants, years of education, severity of illness, duration of illness in years, country of study, proportion of women in the sample, type of medication, counterbalancing. Word list/short story and proportion of women in the sample were the only two statistically significant predictors in the model, both associated with a positive higher pooled effect size. The present study revealed a significant overall difference between the results obtained in the ON and OFF conditions. We also found a significantly greater pharmacological effect in the recall of short stories than word lists, which supports the hypothesis of a beneficial effect of dopamine on the hippocampal circuit rather than on prefrontal cortical areas.

Keywords: Hippocampus; L-dopa; Memory; Parkinson’s disease.