Protocol
Reducing anticholinergic drug burden
Higher cumulative anticholinergic burden is associated with cognitive decline and cardiovascular events in observational Research that watches what people already do rather than assigning a treatment. It can show that two things travel together, not that one causes the other. data, which carries no grade.
Grade D, tested: a human randomized trial looked for a benefit on the endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. graded and did not find one. How to read a grade →
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How this letter has changedLatest: October 2026 · Corrected.
The D Route 2 Human randomized trials have been run and did not show benefit on the stated outcome. One of the two routes to the lowest letter on EBL's scale. rested on two pooled analyses without naming a trial. Added: Kersten et al. (J Gerontol A, 2013; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 22982689), the one trial that clearly lowered the burden, null on cognition at 8 weeks, and van der Meer et al. (BMJ Open, 2018; PMID 30030308), which did not lower the burden and found no difference in falls, admissions or mortality. The endpoint type is corrected to the measured cognition and function outcomes the trials used; cardiovascular events, the only hard outcome the observational study links to burden, are marked as never tested. The sentence calling the observational harm signal real is replaced: association carries no grade in either direction. The track field no longer tells the reader what to do. D Route 2 unchanged. Applied the written grade definition under the editor's standing instruction of October 2026 (Arnold Sandlow, D.C.).PMID 22982689 PMID 30030308
Every change to a letter on this site is dated and published. The full evidence log →
Some common drugs block a brain chemical called acetylcholine, and taking several can add up. Studies tested cutting back these drugs in older adults. A careful review found no clear gain in thinking, falls, quality of life or survival. In the one study that clearly cut the load, thinking did not improve.
Higher cumulative anticholinergic burden is associated with cognitive decline and cardiovascular events in observational data, which carries no grade. Randomized deprescribing trials have been run: the one that clearly lowered the burden found no improvement in measured cognition, most of the others failed to lower the burden at all, and pooled analyses find no benefit on cognition, falls, quality of life or mortality.
Why this gradeGrade D, tested, no benefit. The reasoning, and what the grade does not cover.
Grade D, Route 2. Randomized deprescribing trials have been run, and the Cochrane review (PMID 38063254) and a meta-analysis A study that pools the numbers from several trials into one combined estimate. of 7 trials (PMID 37740900) found no clear benefit on cognition, falls, quality of life, cardiovascular disease or mortality. The one trial that clearly lowered the burden (Kersten et al., 2013; PMID 22982689) found no cognitive improvement at 8 weeks; most other trials, including van der Meer 2018 (PMID 30030308), did not manage to lower the burden, so they tested whether an intervention changes prescribing more than whether a lower burden improves health. The observational association between anticholinergic burden and harm carries no grade in either direction; people taking more of these medicines are sicker, so it cannot be read as cause. Moved from Route 1 No human randomized trial has been run, so the record rests on animal or mechanistic evidence only. One of the two routes to the lowest letter on EBL's scale. in October 2026; the letter is unchanged. Incident cardiovascular events, the outcome the observational study links to burden, have never been tested in a trial, so for that outcome alone the position is untested rather than tested without benefit.
WHAT THIS GRADE DOES NOT COVERwhether a particular anticholinergic medicine is still needed for a particular person, which is a prescribing judgment for their clinician; deprescribing of other drug classes; and avoiding anticholinergic drugs around surgery, which is a different question.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
The evidence, in fullFive papers, each linked to its PubMed record.
Zhu et al. (BMC Medicine, 2026; PMID 41761231): population-based observational study associating higher anticholinergic burden with incident cardiovascular events. Taylor-Rowan et al. (Cochrane Database Syst Rev, 2023; PMID 38063254): Cochrane review of anticholinergic deprescribing trials; very low certainty and no between-group differences for mortality, falls, cardiovascular disease or other clinical outcomes. Braithwaite et al. (Age Ageing, 2023; PMID 37740900): meta-analysis of 7 randomized trials; no significant effect on falls, cognition, burden score or quality of life. Kersten et al. (J Gerontol A, 2013; PMID 22982689): 87 frail nursing-home residents in Norway, pharmacist-initiated reduction of the anticholinergic drug scale score by a median of 2 points; no improvement in immediate recall, the primary endpoint The one outcome a trial names in advance as its main test. Results on other outcomes carry less weight., or any other cognitive measure at 8 weeks. van der Meer et al. (BMJ Open, 2018; PMID 30030308): 157 community-dwelling older adults, pharmacist-led review; the burden index did not fall more than in controls, one secondary cognitive test and reported sedative side effects improved, falls, admissions and mortality did not differ. Grade D, Route 2: deprescribing has been tested in randomized trials and no clinical benefit was shown. The observational association with harm carries no grade in either direction.
The Anticholinergic Cognitive Burden scale scores a medication list at baseline and after any change, which is what the trials measured as their process outcome. Cognitive function on the MoCA at baseline and every 6 months is the clinical outcome the trials did not move. Medication changes are made by the prescribing clinician.
Evidence notes: observational
Endpoint graded: Cognition, falls, quality of life and mortality (functional)
Last reviewed: July 2026
Educational use only · Not medical advice · EBL grades published human evidence and does not recommend treatment. Stopping a prescription is a decision for your physician.
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These statements have not been evaluated by the Food and Drug Administration. Any grade on this page describes the strength of published human trial evidence in the populations studied. It is not a recommendation for any individual and is not medical advice. Starting, stopping or changing any supplement or medication is a decision for your physician.
How EBL searched for the trials (1 search)
The search that was run, what it returned, and what was left out and why, so the absence of evidence can be checked as well as its presence.
anticholinergic[tiab] AND (deprescrib*[tiab] OR burden[tiab]) AND (randomized controlled trial[pt] OR meta-analysis[pt] OR systematic review[pt])Grades move when new trials publish. A free monthly email lists every grade EBL moved, with the reason and the trial behind it: the sign-up is on the Evidence Log →