Influence of Antipsychotic and Anticholinergic Loads onCognitive Functions in Patients with Schizophrenia

Many patients with schizophrenia show cognitive impairment. There is evidence that, beyond a certain dose of antipsychoticmedication, the antipsychotic daily dose (ADD) may impair cognitive performance. Parallel to their D2 receptor antagonism,many antipsychotics show a significant binding affinity to cholinergic muscarinic receptors. Pharmacological treatment with ahigh anticholinergic daily dose (CDD) significantly impairs attention and memory performance. To examine the relationshipsbetween individual cognitive performance and ADD and/or CDD, we conducted a retrospective record-based analysis of a sampleof𝑛=104in patients with a diagnosis of schizophrenia, all of whom had completed a comprehensive neuropsychological testbattery. To calculate the individual ADD and CDD, the medication at the time of testing was converted according to equivalencemodels. After extracting five principal cognitive components, we examined the impact of ADD and CDD on cognitive performancein the medicated sample and subgroups using multiple regression analysis. Finally, locally weighted scatterplot smoothing (Loess)was applied to further explore the course of cognitive performance under increasing dosage. Results showed significant negativeeffects of ADD on performance in tests of information processing speed and verbal memory. No effects were found for CDD. Thepotential neuropsychopharmacological and clinical implications are discussed.