title: Association of anticholinergic load with impairment of complex attention and memory in schizophrenia.
abstract: OBJECTIVE
  The authors' goals were 1) to establish a clinically useful standard index of the relative anticholinergic potency of psychiatric medications; 2) to determine which cognitive functions are most affected by the administration of anticholinergic medications to patients with schizophrenia; and 3) to compare in vitro and clinically derived indexes of anticholinergic load in predicting these cognitive impairments.
  
  
  METHODS
  One hundred six clinically stable patients with schizophrenia were given a brief neuropsychological battery and evaluated on a standard symptom rating scale. The anticholinergic load associated with their psychiatric medications was estimated by using 1) a pharmacological index, calculated from a compilation of published studies reporting in vitro brain muscarinic receptor antagonism, and 2) a clinical index, based on clinician ratings of the anticholinergic side effects of medications. The authors analyzed the correlations of both indexes with the neuropsychological measures and with summary neuropsychological factor scores.
  
  
  RESULTS
  The clinical and pharmacological anticholinergic indexes were highly correlated with each other and showed virtually identical associations with neuropsychological measures. Anticholinergic load was associated with lower scores on measures of attention and declarative memory, including several measures of auditory and visual memory and two tests of complex attention, but was unrelated to intelligence, simple attention, working memory, executive functions, conceptual fluency, or motor speed.
  
  
  CONCLUSIONS
  This pattern of cognitive impairment with central cholinergic antagonism is consistent with emerging models of the functional anatomy of ascending forebrain cholinergic subsystems. Both pharmacological and clinical indexes show utility in predicting the effects of anticholinergic load on cognition in schizophrenia. Doses of psychiatric medication within the range of routine pharmacotherapy practice may have clinically significant effects on memory and complex attention in patients with schizophrenia; these effects may contribute as much as one-third to two-thirds of the memory deficit typically seen in patients with schizophrenia.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine and VA Medical Center, Bronx, NY, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Minzenberg
authors.forename: John H
authors.initials: JH
authors.lastname: Poole
authors.forename: Cynthia
authors.initials: C
authors.lastname: Benton
authors.forename: Sophia
authors.initials: S
authors.lastname: Vinogradov
mesh_terms: D000328:Adult; D000339:Affect; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000145:classification / Q000627:therapeutic use*; D001288:Attention; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D002799:Cholinergic Fibers / Q000187:drug effects*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004522:Educational Status; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000175:diagnosis / Q000209:etiology*; D011618:Psychotic Disorders / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D012559:Schizophrenia / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D014888:Wechsler Scales
chemical_list: D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists