Anticholinergic drug exposure increases risk of dementia

Abstract

Middle-aged and older adults who used anticholinergic drugs such as antidepressants, antiparkinson agents, antipsychotics, antimuscarinics, and antiepileptics had an increased risk of dementia, according to an observational study published in JAMA Internal Medicine.1.Coupland C.S. et al.JAMA Intern Med. 2019; (Epub ahead of print)https://doi.org/10.1001/jamainternmed.2019.0677Crossref Scopus (153) Google Scholar “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.” U.K. researchers conducted a nested case-control study of 58,769 patients with dementia and 225,574 matched controls to assess the association between cumulative anticholinergic drug exposure and dementia risk. They obtained data 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. Chen noted that the increased risk of dementia appeared to be related to dose and time and extended to middle-aged individuals. 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. Pharmacists should be familiar with the anticholinergic drugs listed in the 2019 Beers Criteria for potentially inappropriate medication use in older adults.2.J Am Geriatr Soc. 2019; 67: 674-694Crossref PubMed Scopus (764) Google Scholar Clinicians should thoroughly assess medication profiles to identify anticholinergic agents and determine which ones can be safely switched (e.g., agents for depression, Parkinson’s, or overactive bladder) or discontinued. It’s important to educate patients on the study results and to inform them which of their medications have a high anticholinergic burden. Emphasize to patients that they should not stop taking any medication without first discussing their concerns and viable solutions with their doctor or pharmacist.