精神分裂症中抗胆碱能药物负担相关的认知障碍
Anticholinergic Medication Burden-Associated Cognitive Impairment in Schizophrenia.
作者信息
Joshi Yash B, Thomas Michael L, Braff David L, Green Michael F, Gur Ruben C, Gur Raquel E, Nuechterlein Keith H, Stone William S, Greenwood Tiffany A, Lazzeroni Laura C, MacDonald Laura R, Molina Juan L, Nungaray John A, Radant Allen D, Silverman Jeremy M, Sprock Joyce, Sugar Catherine A, Tsuang Debby W, Tsuang Ming T, Turetsky Bruce I, Swerdlow Neal R, Light Gregory A
机构信息
Desert 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).
出版信息
Am J Psychiatry. 2021 Sep 1;178(9):838-847. doi: 10.1176/appi.ajp.2020.20081212. Epub 2021 May 14.
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.
目的
许多用于治疗精神分裂症的精神药物具有显著的抗胆碱能特性，这与健康受试者的认知障碍和痴呆风险相关。阐明抗胆碱能药物负担所致认知障碍的影响，可能有助于优化精神分裂症患者的认知结局。本研究的目的是全面描述这种负担如何影响精神分裂症门诊患者多个认知领域的功能。
方法
使用推断统计和探索性结构方程模型分析横断面数据，以确定抗胆碱能药物负担与认知之间的关系。作为精神分裂症遗传学联盟-2的一部分，在美国五所大学的社区招募了诊断为精神分裂症或分裂情感性障碍的患者（N = 1120）。对于每位参与者，根据改良的抗胆碱能认知负担（ACB）量表对处方药物进行评分并求和。通过宾夕法尼亚计算机化神经认知测验（PCNB）各领域的表现评估认知功能。
结果
ACB评分与认知表现显著相关，在PCNB测试的所有领域中，ACB评分较高的组比ACB评分较低的组表现更差。在其他认知测试中也观察到类似的效果。在控制了人口统计学特征和疾病严重程度的潜在替代指标（包括临床症状和氯丙嗪等效抗精神病药物剂量）后，效应仍然显著。
结论
精神分裂症患者的抗胆碱能药物负担较重、普遍存在，由多种药物类别导致，并且与所有认知领域的认知障碍相关。在治疗决策中应考虑所有药物类别（包括常规护理中使用的精神药物）的抗胆碱能药物负担，并在精神分裂症认知功能研究中予以考虑。
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