Home › Research › Caregiving
Anticholinergic Medication Burden-Associated Cognitive Impairment in Schizophrenia
Joshi YB, Thomas ML, Braff DL, Green MF, Gur RC, Gur RE, Nuechterlein KH, Stone WS et al.. The American journal of psychiatry, 2021-05-14
Topic: Risk, prevention and care in population studies
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.
Key findings
- Objective Many psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects.
- 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.
- 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.
Why it matters
This cross-sectional study found that higher anticholinergic medication burden was associated with worse cognitive performance across all domains tested in people with schizophrenia. It does not test any treatment, cure, or prevention for Alzheimer's disease.
New to this subject? Start with our plain-English guide: Caregiving →
Study details
- Study designcross-sectional
- Participants1,120
- Evidence strengthLow
How this study scored 60/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The American journal of psychiatry) |
| Journal's citation record | 4 / 4 | American Journal of Psychiatry: journal h-index 549 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,120 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 182 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 26.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 18.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 108 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Gregory A. Light: h-index 68 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33985348) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1176/appi.ajp.2020.20081212
- PubMed: 33985348
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Joshi, Y. B., Thomas, M. L., Braff, D. L., Green, M. F., Gur, R. C., Gur, R. E., et al. (2021). Anticholinergic Medication Burden-Associated Cognitive Impairment in Schizophrenia. The American journal of psychiatry. https://doi.org/10.1176/appi.ajp.2020.20081212
Vancouver
Joshi YB, Thomas ML, Braff DL, Green MF, Gur RC, Gur RE, et al. Anticholinergic Medication Burden-Associated Cognitive Impairment in Schizophrenia. The American journal of psychiatry. 2021. doi:10.1176/appi.ajp.2020.20081212. PMID: 33985348.
BibTeX
@article{joshi2021-33985348,
author = {Joshi, Y. B. and Thomas, M. L. and Braff, D. L. and Green, M. F. and Gur, R. C. and Gur, R. E. and Nuechterlein, K. H. and Stone, W. S. and others},
title = {{Anticholinergic Medication Burden-Associated Cognitive Impairment in Schizophrenia}},
journal = {The American journal of psychiatry},
year = {2021},
doi = {10.1176/appi.ajp.2020.20081212},
pmid = {33985348},
url = {https://doi.org/10.1176/appi.ajp.2020.20081212}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
1 study in the alzhub library lists this one in its references.