Anticholinergics, Dementia, and the Need for Deprescribing

A recent study published in JAMA, August 2019 suggests that in a large population prior exposure to strong anticholinergic drugs is associated with the risk of dementia. Previous studies by Richardson (2018) and Gray (2015) were small case-control cohort studies while these studies suggested an association between anticholinergics and dementia the sample size were too small to draw conclusions.  The findings of this large middle-aged to elderly cohort study by Coupland, advocates for deprescribing of anticholinergic agents in middle-aged to older adults (e.g. 55 years and older) to reduce the risk of dementia. 

Coupland, (2019), looked at a nested case-control cohort total of over 280,000 patients (225,500 control group; 58,700 at risk) in England with the diagnosis of dementia and the intervention group with 56 drugs with strong anticholinergic properties for exposure (from 1 to 20 years) prior to dementia diagnosis.  The population consisted 63.1% female, 97% Caucasian, 85.4% nonsmokers/ex-smokers and 67.2% non-alcohol or 1 drink daily users with an average age of 82.2 years.

The results of this study by Coupland, showed the 5 top anticholinergic drug classes for associated increased risk of dementia: 1) anticholinergic antidepressants, 2) antiparkinson’s agents, 3) anticholinergic antipsychotic medications, 4) bladder antimuscarinic agents, and 5) anticholinergic anticonvulsants. Furthermore, the greater increased risk of anticholinergic exposure and dementia occurred in participants less than 80 years of age. 

Anticholinergic burden is potentially a modifiable risk factor for dementia yet there have been no studies establishing the causation.  Perhaps as Campbell, Holden, & Boustani (2019) propose looking to a deprescribing trial that potentially demonstrates the restoring of cholinergic function in areas of the brain important for cognition could reduce the risk or delay the onset of dementia. However, deprescribing of anticholinergic agents can lead to the worsening of the symptoms/conditions they were initially prescribed to treat such as depression or urinary incontinence. Working with pharmacists to assist with the selection of alternative agents to reduce the anticholinergic burden may alleviate the risk of worsening originally treated conditions/symptoms. Hopefully there will be more research done looking at the deprescribing of anticholinergic burden agents and the causative links with dementia. Moreover, working as an interdisciplinary team particularly with a pharmacist, deprescribing anticholinergic as well as any unnecessary medications may improve quality of life and health care utilization in our elderly patients.  


Campbell NL, Holden R, Boustani M. Preventing Alzheimer disease by deprescribing anticholinergic medications. JAMA Intern Med, 2019, 179(8):1093-1094.

Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic drug exposure and the risk of dementia: a nested case-control study [published online June 24, 2019].  JAMA Intern Med.Doi:10/1001/jamainternmed.2019.0677

Gray SL, Anderson ML, Dublin S, Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015:175(3): 401-407. Doi:10.1001/jamainternmed.2014.7663

Richardson K, Fox C, Maidment I, Anticholinergic drugs and risk of dementia: case-control study. BMJ, 2018; 361:k1315 doi:10.1136/bmj.k1315
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