Background Anticholinergic medications are widely used, however their use in older people has been linked to cognitive decline, dementia and increased mortality. This systematic review examines the literature investigating relationships between anticholinergic burden and risk of dementia, cognitive impairment, and outcomes in dementia. Methods Cochrane database and PubMed searches using the terms anticholinergic and dementia or cognition were performed up to May 2023. Outcomes included: (i) dementia diagnosis, (ii) cognitive outcomes in people without dementia (iii) cognitive outcomes, hospitalisation and death in people with dementia. Inclusion and exclusion criteria were defined, and papers were evaluated for inclusion by two researchers independently. Papers examining these relationships specifically for urinary drugs and antidepressants were also analysed separately. Results Sixty observational studies met our criteria across the three outcomes of interest. Anticholinergic burden was found to be consistently associated with increased risk of dementia however the relationships with cognitive outcomes were less clear. In people with dementia, there were consistent associations between the anticholinergic burden and mortality (hazard ratio (HR) range: 1.04-1.23) or hospitalisation (HR range: 1.13-4.54) but not for cognitive outcomes. Urological drugs with high anticholinergic burden were associated with a ≥50% increased mortality risk in people with dementia. Conclusion Anticholinergic burden has been consistently associated with increased dementia incidence. Furthermore, in people with existing dementia, anticholinergic burden is associated with increased mortality and hospitalisation. Associations with cognitive outcomes in people without/with dementia remains uncertain. Clinicians should be advised to exercise caution with anticholinergic medication use in older people.

RS has received research support in the last 3 years from Janssen, GSK and Takeda. DT receives research funding from Janssen Pharmaceuticals and Lundbeck speaking honoraria from Janssen, Lundbeck, Sunovion, and Recordati but no sources of funding were received for the preparation of this article.

This study did not receive any funding

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