The cognitive cost of anticholinergic burden: decreased response to cognitive training in schizophrenia.
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.


METHODS
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.
Vinogradov
Sophia
S
Department of Psychiatry, Langley Porter Psychiatric Institute, University of California, San Francisco, CA, USA. sophia.vinogradov@ucsf.edu
Fisher
Melissa
M
Warm
Heather
H
Holland
Christine
C
Kirshner
Margaret A
MA
Pollock
Bruce G
BG
D000328:Adult; D000818:Animals; D001285:Atropine / Q000097:blood; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis*; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D005260:Female; D005717:Games, Experimental; D006801:Humans; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D011569:Psychiatric Status Rating Scales; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D013813:Therapy, Computer-Assisted / Q000379:methods; D016896:Treatment Outcome
D018680:Cholinergic Antagonists; D001285:Atropine