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Anticholinergic Medication Use and Cognitive Impairment in the Older Population: The Medical Research Council Cognitive Function and Ageing Study
Open accessAbstract
OBJECTIVES: To determine whether the use of medications with possible and definite anticholinergic activity increases the risk of cognitive impairment and mortality in older people and whether risk is cumulative. DESIGN: A 2‐year longitudinal study of participants enrolled in the Medical Research Council Cognitive Function and Ageing Study between 1991 and 1993. SETTING: Community‐dwelling and institutionalized participants. PARTICIPANTS: Thirteen thousand four participants aged 65 and older. MEASUREMENTS: Baseline use of possible or definite anticholinergics determined according to the Anticholinergic Cognitive Burden Scale and cognition determined using the Mini‐Mental State Examination (MMSE). The main outcome measure was decline in the MMSE score at 2 years. RESULTS: At baseline, 47% of the population used a medication with possible anticholinergic properties, and 4% used a drug with definite anticholinergic properties. After adjusting for age, sex, educational level, social class, number of nonanticholinergic medications, number of comorbid health conditions, and cognitive performance at baseline, use of medication with definite anticholinergic effects was associated with a 0.33‐point greater decline in MMSE score (95% confidence interval (CI)=0.03–0.64, P =.03) than not taking anticholinergics, whereas the use of possible anticholinergics at baseline was not associated with further decline (0.02, 95% CI=−0.14–0.11, P =.79). Two‐year mortality was greater for those taking definite (OR=1.68; 95% CI=1.30–2.16; P <.001) and possible (OR=1.56; 95% CI=1.36–1.79; P <.001) anticholinergics. CONCLUSION: The use of medications with anticholinergic activity increases the cumulative risk of cognitive impairment and mortality.
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Over the past decade, prolonged exposure to anticholinergic drugs has been linked to long term cognitive decline or dementia incidence among community living cohorts and nursing home residents.
“Over the past decade, prolonged exposure to anticholinergic drugs has been linked to long term cognitive decline or dementia incidence among community living cohorts and nursing home residents.12 13 14 15 16 17”
From Anticholinergic drugs and risk of dementia: case-control study (2018) · cites this paper as [14]
Covariates were selected based on literature review to confound the relationship between anticholinergic medication use and dementia.
“Based on literature review we selected covariates that may confound the relationship between anticholinergic medication use and dementia.13,14”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [13]
Anticholinergics may be associated with global cognitive impairment.
“In addition, anticholinergics may be associated with global cognitive impairment.13”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [13]
A well-known risk with anticholinergic medications is acute impairment in specific aspects of cognition (e.g., working memory, attention, psychomotor speed), demonstrated in single dose experimental studies and cohort studies.
“A well-known risk with anticholinergic medications is acute impairment in specific aspects of cognition (e.g., working memory, attention, psychomotor speed) which has been demonstrated in single dose experimental studies 9-12 and cohort studies.13”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [13]
Anticholinergic use was defined as those medications deemed to have strong anticholinergic activity as per consensus by an expert panel of health care professionals.
“Anticholinergic use was defined as those medications deemed to have strong anticholinergic activity as per consensus by an expert panel of health care professionals.8,13”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [13]
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Sorted by citations
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-citationAnticholinergics: theoretical and clinical overview
Nishtala, P. S., Salahudeen, M. S., & Hilmer, S. N. (2016) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2016.1165664 · Cited by 167
Anticholinergic Drug Burden in Older People's Brain - How well is it Measured?
Kersten, H., & Wyller, T. B. (2014) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12140 · Cited by 112
Identifying potentially inappropriate prescribing in older people with dementia: a systematic review
Hukins, D., Macleod, U., & Boland, J. W. (2019) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-018-02612-x · Cited by 84
van Beers, M., Janssen, D. J. A., Gosker, H. R., & Schols, A. M. W. J. (2018) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2018.1533405 · Cited by 77
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Merrick, R., & Brayne, C. (2024) · Journal of Alzheimer's Disease · doi:10.3233/jad-240358 · Cited by 10
Self-citation
Metadata
- Authors
- Fox, C., Richardson, K., Maidment, I. D., Savva, G. M., Matthews, F. E., Smithard, D., Coulton, S., Katona, C., Boustani, M. A., & Brayne, C.
- Affiliations
- University of East Anglia (GB)
- National Health Service (GB)
- University of Cambridge (GB)
- MRC Biostatistics Unit (GB)
- National Institute for Health and Care Research (GB)
- University of Kent (GB)
- University College London (GB)
- Regenstrief Institute (US)
- ORCID
- Venue
- Journal of the American Geriatrics Society
- Publisher
- Wiley
- Published
- 2011-06-24
- Volume
- 59
- Issue
- 8
- Pages
- 1477-1483
- ISSN
- 0002-8614 (ISSN-L)
- 1532-5415
- OpenAlex
- W2139337687
- Cited by
- 655
- References
- 3
- Citations by year
- 2026: 29 · 2025: 36 · 2024: 31 · 2023: 36 · 2022: 27 · 2021: 86 · 2020: 68 · 2019: 59 · 2018: 41 · 2017: 49 · 2016: 42 · 2015: 53 · 2014: 32 · 2013: 33 · 2012: 24
- FWCI
- 25.37
- Type
- journal article
- Language
- en
- Open access
- Locations
- Journal of the American Geriatrics Society (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Repository@Hull (Worktribe) (University of Hull) (submittedVersion, cc-by)
- Kent Academic Repository (University of Kent) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- 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 › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Keywords
- anticholinergic agents, cognitive impairment, cognitive decline, older adults, mortality, polypharmacy, cumulative drug effects, Anticholinergic Cognitive Burden Scale, community-dwelling older adults, institutionalized elderly
- MeSH terms
- Aged, Aged, 80 and over, Cognition Disorders, England, Female, Health Surveys, Humans, Longitudinal Studies, Male, Mental Status Schedule, Prospective Studies, Psychometrics, Risk Factors, Wales, Geriatric Assessment, Comorbidity, Odds Ratio, Cholinergic Antagonists
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