The three most commonly used subtypes of anticholinergics in this cohort were tricyclic antidepressants, first-generation antihistamines, and bladder anti-muscarinics.
The researchers accounted for age and gender differences, as well as APOE genotype (a genetic marker of risk for Alzheimer’s), and found that these variables did not in any way mitigate or account for the observed association between the medication exposure and the risk of dementia.
Dr. Gray and colleagues believe their findings have major clinical significance.
“We found that among the heaviest users, people who had past heavy use had a similar dementia risk as those with recent or continued heavy use. This suggests that the risk for dementia with anticholinergic use may persist despite discontinuation,” the authors note.
In light of the findings, older patients and their caregivers need to take a big, deep breath and a healthy dose of caution before going for an anticholinergic drug.
The authors urge clinicians to take the risk seriously, and to consider alternatives to anticholinergics whenever possible. “For conditions where therapeutic anternatives may not be available, prescribers should use the lowest effective dose and discontinue therapy if ineffective.”
They note that OTC anticholinergics pose a significant public health issue because people who buy them may be entirely unaware of the damage they might be causing their brains.
“Given the devastating consequences of dementia, informing older adults about this potential modifiable risk would allow them to choose alternative products and collaborate with their health professionals to minimize overall anticholinergic use.”
Assessing Anticholinergic Burden
The Gray study is one of a number of relatively recent studies underscoring the cognitive problems associated with anticholinergics.
One of the challenges in this line of research has been that there is no standardized tool for measuring anticholinergic burden.
Analysis of several individual scales proposed for this purpose showed that the Anticholinergic Cognitive Burden (ACB) scale was the most frequently validated expert-based assessment tool for adverse outcomes.
The ACB was developed by Indiana University School of Medicine geriatrician Malaz Boustani; it ranks these drugs according to the severity of their effects on cognitive function. The intent of the tool is lower overall anticholinergic cognitive burden by lowering the collective score of the drugs an individual is taking. Drugs are given a score of 0 to 3 across several parameters. If the score for a particular drug is 3 or more, one should consider medications with lower scores.
According to a 2013 study by Pasina and colleagues, wider use of the ACB scale rapidly identify drugs that show dose-dependent associations with cognitive impairment (Pasina L, et al. Drugs Aging. 2013: 30: 103-112).
That said, a different rating system–the Anticholinergic Risk Scale (ARS)–seems better for identifying patients with impairment in activities of daily living (Rudolph JL, et al. Arch Intern Med. 2008; 168(5): 508-513).
Simple Switches
Benadryl (diphenhydramine) remains one of the most widely used anticholinergics for extensive allergic symptoms, particularly at night. Newer antihistamines such as loratadine (Claritin) can replace diphenhydramine or chlorpheniramine.
