Anticholinergic Medication Burden-Associated Cognitive Impairment in Schizophrenia
Yash B Joshi1, Michael L Thomas1, David L Braff1
1Desert Pacific Mental Illness Research, Education, and Clinical Center, VA San Diego Healthcare System, San Diego (Joshi, Braff, MacDonald, Molina, Light, Sprock); Department of Psychiatry, University of California, San Diego, La Jolla (Joshi, Braff, Swerdlow, Greenwood, MacDonald, Molina, Nungaray, Sprock, M.T. Tsuang, Light); Department of Psychology, Colorado State University, Fort Collins (Thomas); Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles (Green, Nuechterlein, Sugar); Desert Pacific Mental Illness Research, Education, and Clinical Center, VA Greater Los Angeles Healthcare System, Los Angeles (Green); Department of Psychiatry, University of Pennsylvania, Philadelphia (R.C. Gur, R.E. Gur, Turetsky); Department of Psychiatry, Harvard Medical School, and Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Boston (Stone); Department of Psychiatry and Behavioral Sciences and Department of Biomedical Data Science, Stanford University, Stanford, Calif. (Lazzeroni); Sierra Pacific Mental Illness Research, Education, and Clinical Center, VA Health Care System, Palo Alto, Calif. (Lazzeroni); Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle (Radant, D.W. Tsuang); Northwest Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle (Radant, D.W. Tsuang); Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York (Silverman); Research and Development, James J. Peters VA Medical Center, New York (Silverman); Department of Biostatistics, UCLA School of Public Health, Los Angeles (Sugar).
Objective:
Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients.
Methods:
Cross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia-2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).
Results:
ACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage.
Conclusions:
Anticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes-including psychotropics used in usual care-should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.
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