Influence of Antipsychotic and Anticholinergic Loads on Cognitive Functions in Patients with Schizophrenia

Abstract

Many patients with schizophrenia show cognitive impairment. There is evidence that, beyond a certain dose of antipsychotic medication, 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 a high anticholinergic daily dose (CDD) significantly impairs attention and memory performance. To examine the relationships between individual cognitive performance and ADD and/or CDD, we conducted a retrospective record-based analysis of a sample of n = 104 in patients with a diagnosis of schizophrenia, all of whom had completed a comprehensive neuropsychological test battery. To calculate the individual ADD and CDD, the medication at the time of testing was converted according to equivalence models. After extracting five principal cognitive components, we examined the impact of ADD and CDD on cognitive performance in 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 negative effects of ADD on performance in tests of information processing speed and verbal memory. No effects were found for CDD. The potential neuropsychopharmacological and clinical implications are discussed.

Association between using medications with anticholinergic properties and short‐term cognitive decline among older men: A retrospective cohort study in Taiwan

“…Among the studies investigating the adverse effect of anticholinergics, the majority of them were focused on its impact on cognitive performance, which consistently identified the association between exposure to medications with anticholinergic properties with increased risk of cognitive impairment and incident dementia in older adults, and worsened cognitive deterioration in patients with dementia . It is noteworthy that antipsychotics contribute substantially to the adverse effects of anticholinergics on cognition . Many typical and atypical antipsychotics have been shown to have anticholinergic properties, and would impair cognition or deteriorate cognitive decline .…”

“…14,15 It is noteworthy that antipsychotics contribute substantially to the adverse effects of anticholinergics on cognition. 16 Many typical and atypical antipsychotics have been shown to have anticholinergic properties, and would impair cognition or deteriorate cognitive decline. [17][18][19] Furthermore, antipsychotics would lead to a subtle, but measurable, influence on brain tissue loss when prescribed for a long time and at high dosages.…”

Successful management of persistent distressing neuropsychiatric symptoms by clozapine in a patient suffering from dementia with Lewy bodies

“…The high anticholinergic burden and sedative properties of clozapine may also contribute to cognitive deficits 18. However, there are suggestions that the N-methyl-D-aspartate (NMDA) and M4 agonistic properties of clozapine may enhance cognition and compensate for deficits due to anticholinergic burden 19. In this case, clozapine appeared to have no cognitive benefit, and could have even contributed to further cognitive deterioration.…”

A Study of the Association between Psychotropic Drugs and Cognitive Dysfunction in Patients with Schizophrenia

“…It is possible that some of these drugs may have an adverse impact on cognition. Two mechanisms may explain cognitive dysfunction under antipsychotic medication [4]. One is the dopamine receptor blockade.…”