Anticholinergic Medications Linked to Cognitive Decline

Although anticholinergic medications are used in a wide array of conditions, including allergies, basic colds, and hypertension, they may be associated with an increased risk of cognitive decline, especially in older adults at greater risk for Alzheimer disease, according to researchers from University of California San Diego School of Medicine.

Anticholinergic drugs include a wide range of medications and treat many conditions, both major and minor, some requiring a prescription and others available as OTC options. The drugs work by blocking acetylcholine—a type of neurotransmitter or chemical messenger known to be critical for memory function—from binding to receptors on certain nerve cells, thus inhibiting parasympathetic nerve impulses.

The study authors found that cognitively normal study participants who were taking at least 1 anticholinergic drug at baseline were 47% more likely to develop mild cognitive impairment, which is often a precursor to dementia. Study participants were tracked for up to 10 years and compared with participants who did not take such drugs.

A total of 688 adults were included in the study, evenly divided by sex with an average age of 74. No participants displayed cognitive or memory problems at the beginning of the study. One-third of the participants were taking anticholinergic drugs, with an average of 4.7 anticholinergic drugs per person. All participants were given annual comprehensive cognitive tests for up to 10 years.

“This study, led by Alexandra Weigand, suggests that reducing anticholinergic drug use before cognitive problems appear may be important for preventing future negative effects on memory and thinking skills, especially for people at greater risk for Alzheimer’s disease,” said senior author Lisa Delano-Wood, PhD, in a press release.

The investigators analyzed whether participants had biomarkers for Alzheimer disease in their cerebrospinal fluid or a well-known genetic risk factor. They found that participants with biomarkers who were taking anticholinergic drugs were 4 times more likely to develop mild cognitive impairment than participants who lacked biomarkers and were not taking the drugs.

Similarly, participants at genetic risk for Alzheimer disease who took anticholinergic medications were approximately 2.5 times more likely to develop mild cognitive impairment than those without the genetic risk factors who were not taking the medications.

“We believe this interaction between anticholinergic drugs and Alzheimer’s risk biomarkers acts in a ‘double hit’ manner,” Weigand said in a press release. “In the first hit, Alzheimer’s biomarkers indicate that pathology has started to accumulate in and degenerate a small region called the basal forebrain that produces the chemical acetylcholine, which promotes thinking and memory. In the second hit, anticholinergic drugs further deplete the brain’s store of acetylcholine. This combined effect most significantly impacts a person’s thinking and memory.”

Significantly, the authors found that although older adults metabolize anticholinergic drugs differently than younger people, anticholinergic medications were being taken at levels much higher than the lowest effective dose recommended for older adults, with 57% taken at twice the recommended dosage and 18% at least 4 times the recommended dosage.

“This points to a potential area for improvement since reducing anticholinergic drug dosages may possibly delay cognitive decline,” Weigand said. “It’s important for older adults who take anticholinergic medications to regularly consult with their doctors and discuss medication use and dosages.”

REFERENCE

Common Class of Drugs Linked to Increased Risk of Alzheimer’s Disease [news release]. UC San Diego Health; September 4, 2020. https://health.ucsd.edu/news/releases/Pages/2020-09-04-common-class-of-drugs-linked-to-increased-risk-of-alzheimers.aspx#:~:text=A%20team%20of%20scientists%2C%20led,cognitive%20decline%2C%20particularly%20in%20older. Accessed September 10, 2020.