Commonly used anticholinergic drugs were associated with an increased risk of dementia in older adults, according to a study published in JAMA Internal Medicine.
It is well known that anticholinergic drugs have short-term effects, such as confusion and memory loss. However, their long-term effect on the risk of dementia is unknown.
Researcher conducted a nested case-control study of 58,769 patients with dementia (cases) and 225,574 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 more than 1,500 general practices. The base cohort included patients who were aged 55 years or older without dementia at study entry. Cases developed dementia during the follow-up period. Cases were matched to five controls on the basis of age (<1 y), sex, general practice, and calendar time using incidence-density sampling. Both cases and controls 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 primary exposure was calculated as the total standardized daily doses (TSDDs) of anticholinergic drugs in the 1 to 11 years before the index date.
Cases had a mean age at diagnosis of 82.4 years, most were women (63.1%), and white/not recorded (97.0%), and common comorbidities were hypertension (33.9%), depression (13.8%), and coronary heart disease (13.2%). The adjusted odds ratio (aOR) for dementia increased as anticholinergic exposure increased, with an aOR of 1.06 (95% CI 1.03–1.09) for a total exposure of 1 to 90 TSDDs to an aOR of 1.49 (1.44–1.54) for more than 1095 TSDDs. Significant increases were observed for more than 1095 TSDDs for anticholinergic antidepressants (1.29, 1.24–1.34), antiparkinson drugs (1.52, 1.16–2.00), antipsychotics (1.70, 1.53–1.90), bladder antimuscarinic drugs (1.65, 1.56–1.75), and antiepileptics (1.39, 1.22–1.57).
The current analysis suggests there may be an increased risk of dementia in older adults who take anticholinergic drugs, especially with more prolonged exposure. A nearly 50% increased odds of dementia was associated with exposure of more than 1,095 TSDDs within a 10-year period, which is equivalent to 3 years’ daily use of a single strong anticholinergic medication at the minimum effective dose recommended for older people. Clinicians should be familiar with drugs with anticholinergic properties listed on the 2019 Beers Criteria for potentially inappropriate medication use in older adults. The authors of the current analysis concluded, “Adverse effects should be considered alongside benefits when these drugs are prescribed, and alternative treatments should be considered where possible, such as other types of antidepressant or nonpharmacological treatments for depression, alternative antiparkinsonian drugs, and bladder training or mirabegron [Myrbetriq—Astellas] for overactive bladders.”
Authors of an accompanying commentary noted that the current research adds to the knowledge of anticholinergic use and dementia. However, causation cannot be established. The authors advocated for a deprescribing trial to test the association between anticholinergic medication use and diagnosis of dementia. They wrote, “Given that anticholinergic medications represent a potentially reversible risk factor for ADRD [Alzheimer disease and related dementias]—with deprescribing potentially reducing ADRD prevalence more than interventions for midlife hypertension, diabetes, or physical inactivity—we propose deprescribing research as a high priority in the effort to reduce the burden of ADRD, while also learning about efficient and safe approaches to optimize medication use in older adults.”
Inform patients that select anticholinergic medications may increase their risk of dementia. However, they should not stop taking any medications without discussing their concerns with the prescriber. Patients can ask their prescriber to determine if alternatives are available and if the medications should be switched. Patients should also be educated about the “Beers list” and encouraged to speak to their providers if any of their drugs are on this list or if they are experiencing any adverse effects.
Coupland CAC, et al. Anticholinergic drug exposure and the risk of dementia: a nested case-control study. JAMA Intern Med. 2019;[Epub ahead of print].
Campbell NL, et al. Preventing Alzheimer disease by deprescribing anticholinergic medications. JAMA Intern Med. 2019;[Epub ahead of print].
American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674–94.
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