The Cognitive Cost of Anticholinergic Burden: Decreased Response to Cognitive Training in Schizophrenia

Abstract

Objective Schizophrenia is treated with medications that raise serum anticholinergic activity and are known to adversely affect cognition. The authors examined the relationship between serum anticholinergic activity and baseline cognitive performance and response to computerized cognitive training in outpatients with schizophrenia. Method Fifty-five patients were randomly assigned to either computerized cognitive training or a computer games control condition. A neurocognitive battery based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was performed at baseline and after the intervention. Serum anticholinergic activity, measured at study entry by radioreceptor assay, was available for 49 patients. Results Serum anticholinergic activity showed a significant negative correlation with baseline performance in verbal working memory and verbal learning and memory, accounting for 7% of the variance in these measures, independent of age, IQ, or symptom severity. Patients in the cognitive training condition (N=25) showed a significant gain in global cognition compared to those in the control condition, but this improvement was negatively correlated with anticholinergic burden. Serum anticholinergic activity uniquely accounted for 20% of the variance in global cognition change, independent of age, IQ, or symptom severity. Conclusions Serum anticholinergic activity in schizophrenia patients shows a significant association with impaired performance in MATRICS-based measures of verbal working memory and verbal learning and memory and is significantly associated with a lowered response to an intensive course of computerized cognitive training. These findings underscore the cognitive cost of medications that carry a high anticholinergic burden. The findings also have implications for the design and evaluation of cognitive treatments for schizophrenia.

Association of impaired reality processing with psychotic symptoms in schizophrenia

“…Third, all patients were taking medications and had experienced a relatively long duration of illness. Although there is no evidence regarding the effects of medication on reality processing, it is possible that these factors are related to cognition in patients with schizophrenia (Mishara and Goldberg, 2004;Vinogradov et al, 2009;Shah et al, 2012). Fourth, it is not clear whether the relationship between impairment in reality evaluation and psychotic symptoms are specific to schizophrenia or nonspecifically present in other psychotic disorders, and whether such relationship is stable over time or changed in different phases of illness.…”

Neuroplasticity-Based Auditory Training Via Laptop Computer Improves Cognition in Young Individuals With Recent Onset Schizophrenia

“…Based on Mean and SD of chlorpromazine equivalents. 21 our previous finding that medication-induced anticholinergic burden adversely affects training response, 38 we excluded from analysis 2 subjects (1 in each condition) who were prescribed an increased dose of benztropine mesylate while in the study. All variables were screened and normally distributed after winsorising of outlying values.…”

The muscarinic system, cognition and schizophrenia

“…The administration of anti-cholinergic and anti-muscarinic agents was once common practice amongst schizophrenia patients due to the capacity of these drugs to alleviate parkinsonism-like side effects commonly caused by typical antipsychotic medications (Tandon et al, 1990(Tandon et al, -1992. In addition to proliferating the severity of positive symptoms, it was discovered that the administration of muscarinic antagonists potentiated the cognitive impairments prevalent amongst patients (see Desmarais et al, 2012;Tandon, 2011;Vinogradov et al, 2009). With the advent of atypical antipsychotic medications, the concurrent administration of anti-muscarinic drugs ceased and so to the drug-induced potentiation of symptoms.…”