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Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis
Open accessAbstract
Background: the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear. Methods: we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I. Results: twenty-six studies (including 621,548 participants) met our inclusion criteria. ‘Any’ anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09–1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17–1.29, I2 = 2%; and OR 1.50, 95% CI 1.22–1.85, I2 = 90%). ‘Any’ anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09–0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97–1.59, I2 = 0%). Conclusions: anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.
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Previous longitudinal cohort studies indicate that anticholinergic medications negatively affect cognitive performance.
“This association between anticholinergic antidepressants and dementia aligns with previous longitudinal cohort studies indicating that anticholinergic medications negatively affect cognitive performance [15, 31, 32, 43, 44].”
From Long-Term Antidepressant Use and Dementia Risk: A Propensity Score-Matched Study of Swiss Older Adults, with an Anticholinergic-Specific Analysis (2026) · cites this paper as [44]
The Results (Anticholinergics and cognitive decline) report consistently greater cognitive decline among anticholinergic users across pooled studies. But the Introduction describes these as observational associations subject to confounding, so the claim’s wording that the medications negatively affect performance implies a causal conclusion the paper does not establish. (LLM, conf=0.83)
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Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study
Gray, S. L., Anderson, M. L., Dublin, S., Hanlon, J. T., Hubbard, R., Walker, R., Yu, O., Crane, P. K., & Larson, E. B. (2015) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2014.7663 · Cited by 1,111
Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study
Coupland, C. A. C., Hill, T., Dening, T., Morriss, R., Moore, M., & Hippisley-Cox, J. (2019) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2019.0677 · Cited by 637
Anticholinergic drugs and risk of dementia: case-control study
Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., Myint, P. K., Grossi, C. M., Mattishent, K., Bennett, K., et al. (2018) · BMJ · doi:10.1136/bmj.k1315 · Cited by 520
Self-citationBali, V., Chatterjee, S., Carnahan, R. M., Chen, H., Johnson, M. L., & Aparasu, R. R. (2015) · Psychiatric Services · doi:10.1176/appi.ps.201500011 · Cited by 23
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Research works printed but not linked: 26
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Amrein, M. A., Hengartner, M. P., Näpflin, M., Farcher, R., & Huber, C. A. (2026) · Drugs - Real World Outcomes · doi:10.1007/s40801-026-00560-y
Metadata
- Authors
- Pieper, N. T., Grossi, C. M., Chan, W.-Y., Loke, Y. K., Savva, G. M., Haroulis, C., Steel, N., Fox, C., Maidment, I. D., Arthur, A. J., Myint, P. K., Smith, T. O., Robinson, L., Matthews, F. E., Brayne, C., & Richardson, K.
- Affiliations
- University of East Anglia (GB)
- James Paget University Hospital (GB)
- Aston University (GB)
- University of Aberdeen (GB)
- University of Oxford (GB)
- Newcastle University (GB)
- University of Cambridge (GB)
- Corresponding author
- Richardson, Kathryn
- ORCID
- Venue
- Age and Ageing
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-06-29
- Volume
- 49
- Issue
- 6
- Pages
- 939-947
- ISSN
- 0002-0729 (ISSN-L)
- 1468-2834
- PMC
- PMC7583519
- OpenAlex
- W3013444166
- Cited by
- 138
- References
- 4
- Citations by year
- 2026: 29 · 2025: 32 · 2024: 25 · 2023: 15 · 2022: 20 · 2021: 17
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Age and Ageing (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Repository@Hull (Worktribe) (University of Hull) (publishedVersion, other-oa)
- Repository@Hull (Worktribe) (University of Hull) (submittedVersion, cc-by-nc)
- Aston Publications Explorer (Aston University) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc)
- Funders
- Alzheimer's Society (AS-PG-2013-017)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- anticholinergic agents, dementia, mild cognitive impairment, cognitive decline, older adults, drug exposure, chronic drug administration, cognitive function
- MeSH terms
- Cognition, Dementia, Pharmaceutical Preparations, Humans, Cholinergic Antagonists, Cognitive Dysfunction
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