The quality of evidence is downgraded by study limitations (possible reverse causation) but upgraded by large magnitude of effect.
Anticholinergic drugs cannot be recommended as a first line of treatment for older adults.
The recommendation is weak because the certainty of evidence is low from the observational studies, and there is no evidence from a randomized trial that deprescribing of anticholinergics would improve cognition in the short term. However, the recommendation to avoid anticholinergic drugs is also supported by observational evidence of association with increased mortality, impaired physical function, and reduced quality of life. The balance of benefits and harms of avoiding anticholinergic drugs is uncertain, as alternatives e.g. for chronic pain also cause adverse effects or they are not effective, and individual patient preferences for symptomatic treatment probably differ.
A Cochrane review [Abstract] 1 included 25 prospective and retrospective longitudinal cohort and case-control observational studies with a total of 968,428 people aged 50 years or more. Eight studies (320,906 participants) provided suitable data for meta-analysis. The Anticholinergic Cognitive Burden scale (ACB scale) was the only scale with sufficient data for 'scale-based' meta-analysis. Unadjusted ORs suggested an increased risk for cognitive decline or dementia in older adults with an anticholinergic burden (OR 1.47, 95% CI 1.09 to 1.96) and adjusted ORs similarly suggested an increased risk for anticholinergic burden, defined according to the ACB scale (OR 2.63, 95% CI 1.09 to 6.29).
Overall GRADE evaluation of certainty of the evidence was low. The evidence may have exaggerated the strength of the association between anticholinergic medicines and dementia. For example, anticholinergic medicines may be prescribed for the early symptoms of dementia. This would give a strong link but would not imply that the medicine caused the memory problems. Similarly, there is a risk that studies are only published when they show an association between anticholinergic medicines and future dementia.
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