By Noll Campbell, Craig A. Solid and Malaz Boustani
Alzheimer’s disease and Related Dementia (ADRD) is a national public health issue and a growing concern. Risk factors for ADRD, such as age and family history, are not modifiable. However, the use of certain prescribed or over-the-counter (OTC) medications known as anticholinergics are associated with adverse cognitive effects and have recently been considered a modifiable risk factor for ADRD. Despite this knowledge, a significant portion of community-dwelling older adults takes anticholinergics every year. Increasing awareness among consumers of the brain health risks of anticholinergics and of providing viable pharmacological or non-pharmacological alternatives are important strategies to reduce the societal burden of ADRD.
Studies Confirm Risks of Anticholinergic Use
Anticholinergics are used to treat a broad spectrum of diseases and symptoms. Some require a prescription by a clinical provider and others are available over the counter. Despite decades of repeated admonition about potentially inappropriate prescribing of anticholinergics, older adults continue to receive anticholinergics that have both short-term and long-term adverse cognitive effects such as delirium or dementia.
Our work and that of others demonstrates that long-term exposure to anticholinergics increases the risk of developing neurodegenerative brain disorders such as Alzheimer’s disease. This potential for long-term brain harm is in addition to the potential for short-term adverse cognitive effects. Recently, Drs. Campbell and Boustani and collaborators in the United Kingdom completed a 20-year longitudinal study of more than 300,000 older adults to evaluate the ADRD risk associated with anticholinergics. The study confirmed the increased risk for ADRD associated with anticholinergics and demonstrated that the risk was detectable up to 20 years before ADRD diagnosis.
In another recent study, we used the Alzheimer’s Disease Neuroimaging Initiative database to show declines in both cognitive performance and brain structure in domains important to the diagnosis of ADRD among users of anticholinergics compared with non-users. Specifically, we observed deficits in memory, processing speed and executive function among those taking anticholinergics. These results support the hypothesis that anticholinergics negatively affect cognition through a mechanism that destroys specific neurons, which in turn speeds ADRD progression. The existing evidence is limited to older adult populations, and further research is necessary to understand whether the same risks are evident in adults or younger populations.
Access to and Use of Anticholinergics
Although some anticholinergics are prescribed by physicians, many of these medications are available without prescriptions. These medications were specifically identified in the April 2015 Institute of Medicine report on cognitive aging, which includes a recommendation for improved strategies and “guidelines for Over-The-Counter (OTC) medications (such as antihistamines, sedatives, and other medications that have strong anticholinergic activity) that may affect cognitive function.”
Many anticholinergics are prescribed for symptomatic relief from conditions of uncertain etiology and some have uncertain benefit. For example, one group of antidepressant anticholinergics often are prescribed to treat forms of nerve pain, but are known to provide a clinically significant benefit in only 30 percent of people who use them. Many times, these medications are prescribed or purchased because there are no perceived alternatives and the medications are believed to be safe, and often the risk of adverse events is unknown or thought to take years to manifest.
Unfortunately, there is little evidence that the anticholinergics use has decreased over the past 20 years at the population level. The above-noted Institute of Medicine report strongly recommends developing comprehensive solutions to reduce exposure to anticholinergics to prevent brain harm.
Currently, anticholinergics are among the top three most frequently used OTC drugs; this includes medications for motion sickness (meclizine), insomnia (doxylamine) and allergies and colds (diphenhydramine). OTC medications exist under many brand names such as Dramamine, Unisom and Benadryl. Common prescription anticholinergics include tricyclic antidepressants (amitriptyline [Elavil], paroxetine [Paxil]) and bladder muscle relaxants (oxybutynin and tolterodine).
Educating Patients, Caregivers Is Key
Despite the body of evidence produced by researchers, many community-dwelling older adults are unaware of the association between anticholinergic use and ADRD. Educating patients and their informal caregivers (through additional written materials or by encouraging education from providers) to increase awareness of this association should be a principal goal in ADRD prevention. Once the risks are understood, patients currently using anticholinergics should be provided with the opportunity to consider discontinuing such medication or transitioning to safer alternatives (in collaboration with their provider).
We recently interviewed 24 older adults currently using anticholinergics and found that none were aware of the adverse cognitive effects of their medications, and many were willing to consider an alternative therapy under the direction of their healthcare provider.
While it is true that randomized clinical trials are needed to test the impact of an anticholinergic de-prescribing intervention and determine whether there can be a sustainable improvement in cognition, the strength of available evidence, and the availability of alternatives, indicate that more should be done within the patient-provider relationship. Healthcare providers should initiate conversations with patients who are using anticholinergics to ensure they understand the risks and to allow them to participate in decisions regarding their care. These efforts can help to increase awareness among patients and potentially help to reduce anticholinergic-associated cognitive decline in older patients.
Noll Campbell, Pharm.D., M.S., is assistant professor for Pharmacy Practice at the Center on Aging and Life Course at Purdue University College of Pharmacy in West Lafayette, Ind. Craig A. Solid, Ph.D., is owner and principal of Solid Research Group, LLC, in St. Paul, Minn. Malaz Boustani, M.D., M.P.H., is Richard M. Fairbanks Professor of Aging Research at Indiana University School of Medicine in Indianapolis.
Editor’s Note: This article appears in the September/October 2018 issue of Aging Today, ASA’s bi-monthly newspaper covering issues in aging research, practice and policy nationwide. ASA members receive Aging Today as a member benefit; non-members may purchase subscriptions at our online store.