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Drugs With Anticholinergic Properties, Cognitive Decline, and Dementia in an Elderly General Population: The 3-City Study
Open accessAbstract
BACKGROUND: Despite the high intake of medications with anticholinergic properties by community-dwelling elderly persons, the effects on cognitive decline and dementia have rarely been evaluated. METHODS: Participants were 4128 women and 2784 men 65 years or older from a population-based cohort recruited from 3 French cities. Cognitive performance, clinical diagnosis of dementia, and anticholinergic use were evaluated at baseline and 2 and 4 years later. RESULTS: A total of 7.5% of the participants reported anticholinergic drug use at baseline. Multivariate-adjusted logistic regression indicated that women reporting use of anticholinergic drugs at baseline showed greater decline over 4 years in verbal fluency scores (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.11-1.79) and in global cognitive functioning (OR, 1.22; 95% CI, 0.96-1.55) than women not using anticholinergic drugs. In men, an association was found with decline in visual memory (OR, 1.63; 95% CI, 1.08-2.47) and to a lesser extent in executive function (OR, 1.47; 95% CI, 0.89-2.44). Notable interactions were observed in women between anticholinergic use and age, apolipoprotein E, or hormone therapy. A 1.4- to 2-fold higher risk of cognitive decline was observed for those who continuously used anticholinergic drugs but not for those who had discontinued use. The risk of incident dementia over the 4-year follow-up period was also increased in continuous users (hazard ratio [HR], 1.65; 95% CI, 1.00-2.73) but not in those who discontinued the use of anticholinergic drugs (HR, 1.28; 95% CI, 0.59-2.76). CONCLUSIONS: Elderly people taking anticholinergic drugs were at increased risk for cognitive decline and dementia. Discontinuing anticholinergic treatment was associated with a decreased risk. Physicians should carefully consider prescription of anticholinergic drugs in elderly people, especially in the very elderly and in persons at high genetic risk for cognitive disorder.
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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 [13]
The Discussion reports increased risks of cognitive decline and dementia among community-dwelling elderly people taking anticholinergic drugs, and the Dementia section links chronic use to incident dementia at four-year follow-up. The cited study does not report findings for nursing home residents, so it supports only the community-living part of the sentence. (LLM, conf=0.86)
Experimental — accuracy not yet measuredObservational studies of anticholinergic drugs and dementia risk have generally been relatively small, only assessed short-term exposure, or were subject to recall bias.
“Observational studies of anticholinergic drugs and dementia risk7,8,9,10 have generally been relatively small, only assessed short-term exposure, or were subject to recall bias.”
From Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study (2019) · cites this paper as [9]
The Anticholinergic drug use section says medication use was inventoried for the preceding month, and the Limitations section says precise treatment duration was unavailable. That supports the short-term exposure-measurement concern, but this was a large study with four-year follow-up (Study population), not a small study assessing only short-term outcomes. The Limitations section identifies possible recall bias in self-reported covariates, while the Strengths section says medication use was checked against prescriptions and medications. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA high risk of incident dementia was observed among continuous users of anticholinergics (HR=1.65, CI=1.00-2.73) but not among those who discontinued.
“A high risk of incident dementia was also observed among continuous users of anticholinergics (hazard ratio [HR]=1.65,CI=1.00-2.73)but not among those who discontinued the medications.”
From Risk of Dementia Among Elderly Nursing Home Patients Using Paroxetine and Other Selective Serotonin Reuptake Inhibitors (2015) · cites this paper as [13]
Previous literature suggests a strong association between anticholinergic use and risk of cognitive decline and dementia.
“Previous literature suggests a strong association between anticholinergic use and risk of cognitive decline and dementia (12)(13)(14).”
From Risk of Dementia Among Elderly Nursing Home Patients Using Paroxetine and Other Selective Serotonin Reuptake Inhibitors (2015) · cites this paper as [13]
Carrière and others found that use of anticholinergic medications in a prospective cohort of elderly patients was associated with cognitive decline during a follow-up period of four years.
“Carrière and others (13) found that the use of anticholinergic medications in a prospective cohort of elderly patients was associated with cognitive decline during a follow-up period of four years.”
From Risk of Dementia Among Elderly Nursing Home Patients Using Paroxetine and Other Selective Serotonin Reuptake Inhibitors (2015) · cites this paper as [13]
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 [14]
Several investigators have reported that anticholinergic medications may be associated with increased risk for sustained cognitive deficits such as mild cognitive impairment or dementia.
“However, several investigators have reported that anticholinergic medications may be associated with increased risk for sustained cognitive deficits such as mild cognitive impairment or dementia.1,2,14”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [14]
Prior observational studies of anticholinergic medications and dementia ascertained current anticholinergic use only at study entry and periodically during follow-up by conducting a medication inventory.
“First, current anticholinergic use was only ascertained at study entry and periodically during follow-up by conducting a medication inventory. 1,14”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [14]
The study findings are consistent with two cohort studies that examined anticholinergic use and incident dementia risk.
“Our study findings are consistent with two cohort studies that have examined anticholinergic use and incident dementia risk.1,14”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [14]
In a large population based cohort study of individuals age 65 years and older living in France, chronic anticholinergic use was associated with an increased risk for dementia (adjusted HR 1.65) and AD (adjusted HR 1.94) over 4 years of follow-up.
“In a large population based cohort study of individuals age 65 years and older living in France, chronic anticholinergic use was associated with an increased risk for dementia (adjusted HR 1.65) and AD (adjusted HR 1.94) over 4 years of follow-up.14”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [14]
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Metadata
- Authors
- Carrière, I., Fourrier-Reglat, A., Dartigues, J.-F., Rouaud, O., Pasquier, F., Ritchie, K., & Ancelin, M.-L.
- Affiliations
- Inserm (FR)
- Université de Bordeaux (FR)
- CHU Dijon Bourgogne (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- ORCID
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2009-07-27
- Volume
- 169
- Issue
- 14
- Pages
- 1317
- ISSN
- 0003-9926 (ISSN-L)
- PMC
- PMC2933398
- OpenAlex
- W1990263121
- Cited by
- 374
- References
- 1
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 16 · 2023: 11 · 2022: 12 · 2021: 39 · 2020: 37 · 2019: 32 · 2018: 29 · 2017: 21 · 2016: 22 · 2015: 29 · 2014: 28 · 2013: 17 · 2012: 23
- FWCI
- 19.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- 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 decline, dementia, older adults, community-dwelling older adults, verbal fluency, visual memory, executive function, apolipoprotein E, hormone therapy, drug discontinuation, sex differences, polypharmacy
- MeSH terms
- Aged, Aged, 80 and over, Cognition, Dementia, Female, Humans, Longitudinal Studies, Male, Sex Factors, Cholinergic Antagonists, Genetic Predisposition to Disease
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