Approximately 10% of dementia diagnoses might be attributable to long-term use of anticholinergic drugs, according to investigators.
In a comparison of 58,769 dementia patients and 225,574 dementia-free individuals aged 55 years or older (mean age 82 years) matched by sex and age, exposure to anticholinergics significantly correlated with increased dementia risk. Excess risk increased from 6% to 49% for individuals with the lowest (1-90 total standardized daily doses; TSDDs) and highest anticholinergic use (more than 1095 TSDDs) over 10 years compared with nonuse, Carol Coupland, PhD, of the University of Nottingham in the United Kingdom, and colleagues reported in JAMA Internal Medicine.
The investigators acknowledged that their observational study cannot evaluate causality. If the association between anticholinergic use is causal, the population-attributable fractions indicate that about 10% of dementia diagnosis are attributable to anticholinergic drug exposure.
In adjusted analyses, use of bladder antimuscarinics, antipsychotic drugs, anti-Parkinson drugs, antiepileptic drugs, and antidepressants was significantly associated with 65%, 70%, 52%, 39%, and 29% increased odds of dementia, respectively, among individuals with the highest anticholinergic use compared with nonuse. The associations were stronger in individuals diagnosed before the age of 80 and in cases of vascular dementia (vs Alzheimer’s disease).
At the population level, anticholinergic drug exposure was associated with a 10.3% excess risk of dementia. This magnitude is comparable to other modifiable risk factors for dementia such as smoking, physical inactivity, midlife hypertension, and diabetes.
“The associations observed for specific types of anticholinergic medication suggest that these drugs should be prescribed with caution in middle-aged and older adults,” Dr Coupland and her colleagues wrote.
Given that association does not prove causation, editorialists Noll Campbell, PharmD, MS, Richard Holden, PhD, and Malaz Boustani, MD, MPH, of Regenstrief Institute, in Indianapolis recommended deprescribing trials: “Given the ultimate goal of improving clinical outcomes by reducing population-level exposure to high-risk medications, such as anticholinergic medications, a comparison of the efficiency and safety of various deprescribing intervention approaches and targets should be considered.”
Coupland CAC, Hill T, Dening T, Morriss R, Moore M, and Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. doi:10.1001/jamainternmed.2019.0677
Campbell NL, Holden R, and Boustani MA. Preventing Alzheimer Disease by Deprescribing Anticholinergic Medications. JAMA Intern Med.