Objective: To systematically evaluate and quantitatively synthesize evidence on the effects of novel antipsychotic agents (Clozapine, Olanzapine, Risperidone, and Aripiprazole) on cognitive domains in Parkinson’s disease patients.

Background: Cognitive impairment is a prevalent and disabling non-motor feature of Parkinson’s disease (PD), affecting executive function, memory, attention, and processing speed. Neuropsychiatric symptoms in PD are frequently managed with atypical antipsychotics; however, their potential influence on cognitive performance remains insufficiently characterized.

Method: Following PRISMA guidelines, we included 25 randomized controlled trials and 11 cohort studies comprising 2,533 PD patients receiving novel antipsychotic therapy. A comprehensive search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library databases. Study quality was assessed using ROB2 and the Newcastle–Ottawa Scale. Quantitative synthesis was performed using RevMan

Results: Meta-analysis demonstrated significant cognitive improvements associated with novel antipsychotics across multiple domains. Verbal learning (SMD = 0.60), attention and processing speed (SMD = 0.45), verbal fluency (SMD = 0.14), and motor-associated cognitive performance (SMD = 0.35) showed notable enhancement. Executive function improved as reflected by Trails B (SMD = −0.39) and reduced perseverative errors on the Wisconsin Card Sorting Test (SMD = −0.16). WAIS-R measures indicated significant gains in abstract reasoning (Similarities, SMD = 0.77) and visuospatial problem-solving (Block Design, SMD = 0.31), while Digit Symbol performance improved markedly (SMD = 0.64). Memory domains assessed by WMS-R Logical Memory and Visual Reproduction also showed significant benefits. No significant changes were observed in MMSE scores or delayed visual pairing tasks. Among agents, Olanzapine and Risperidone demonstrated the most consistent cognitive benefits.

Conclusion: Novel antipsychotic medications may provide measurable cognitive benefits in Parkinson’s disease across executive, memory, and processing domains. These findings suggest a potential adjunctive role for selected antipsychotics in addressing cognitive dysfunction in PD

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-of-novel-antipsychotic-agents-on-cognitive-functions-in-parkinsons-disease-a-systematic-review-and-meta-analysis-of-2533-patients/