Anticholinergic drug exposure increases risk of dementia, study finds

An observational study published in JAMA Internal Medicine found that middle-aged and older adults who used anticholinergic drugs such as antidepressants, antiparkinson agents, antipsychotics, antimuscarinics, and antiepileptics had an increased risk of dementia.

Researchers from the United Kingdom conducted a nested case-control study of 58,769 patients with dementia and 225,574 matched control participants to assess the association between cumulative anticholinergic drug exposure and risk of dementia. Data were obtained from the QResearch database, which contains information on more than 30 million British patients from over 1,500 general practices. The base cohort included patients aged 55 years or older without dementia at study entry, with some developing dementia during the follow-up period.

Patients who developed dementia were matched to five controls on the basis of age, sex, general practice, and calendar time using incidence-density sampling. Patients who developed dementia and control participants were included if they had at least 11 years of recorded data before the date of diagnosis (or index date for controls) to account for at least 10 years of anticholinergic exposure. A total of 56 anticholinergic drugs were included in the analysis.

The results showed that patients exposed to anticholinergic agents had a significant increase in the risk of dementia, with the greatest risk observed in those who had the highest anticholinergic exposure. The adjusted odds ratio for risk of dementia increased from 1.06 for patients with the lowest anticholinergic exposure to 1.49 for those in the highest category, compared with those not exposed to anticholinergic agents. This equated to a nearly 50% increase in the risk of dementia for patients exposed to an equivalent of 3 years of daily use of a single strong anticholinergic medication at the recommended minimum effective dose for older people. 

“Because of their training, education, and patient care experiences, pharmacists are generally aware that anticholinergic medications are associated with harmful treatment-emergent adverse effects, particularly in frail older individuals,” noted Jack Chen, PharmD, BCPS, CGP, FASCP, professor in the neurology department of Loma Linda University in California, in response to the study results. “This potential harm may be minimized by regular medication reviews to determine if there is a high anticholinergic burden and, if so, to assess whether contributing medications can be deprescribed or whether there is a better alternative medication.”

Chen noted that the increased risk of dementia appeared to be dose and time related, the risk extended to middle-aged individuals, and the detrimental effect manifested insidiously over several years. There are several noteworthy caveats to keep in mind. Although this type of study can demonstrate associations, it cannot determine causality. In addition, some anticholinergic medications may have important benefits and cannot be discontinued. Therefore, application of the current study may simply translate into more careful prescribing of anticholinergic medications for middle-aged and older adults. For those in which the benefits of anticholinergic agents outweigh the risks, careful monitoring and follow-up are advised.  

For the full article, please visit for the August 2019 issue of Pharmacy Today.