September 2, 2020

Anticholinergic Medications Linked to Increased Risk of Cognitive Decline

Anticholinergic medications appear to be associated with an increased risk of developing mild cognitive impairment (MCI) and cognitive decline, according to a study published in Neurology.

The study found that cognitively normal older adults taking at least 1 anticholinergic drug were 47% more likely to develop MCI over the next decade than people who were not taking such drugs.

“Our findings suggest that reducing the use of anticholinergic drugs before people develop any cognitive problems may be an important way to prevent the negative consequences of these drugs on thinking skills, especially for people who have an elevated risk of developing Alzheimer’s disease,” said Lisa Delano-Wood, PhD, University of California at San Diego, San Diego, California. “Future studies are needed to see if indeed stopping the use of these drugs could lead to a reduction in mild cognitive impairment and Alzheimer’s disease down the road.”

The study involved 688 people with an average age of 74 years who had no problems with thinking and memory skills at the start of the study. The participants reported if they were taking any anticholinergic drugs within 3 months of the start of the study at least once a week for more than 6 months. They took cognitive tests once a year for up to 10 years.

One-third of the participants were taking anticholinergic drugs, with an average of 4.7 anticholinergic drugs taken per person. Metoprolol, atenolol, loratadine, and bupropion were the most common.

Since different drugs have different levels of anticholinergic activity, the researchers also determined participants’ overall anticholinergic burden based on the number, dosage, and strength of anticholinergic drugs they were taking.

Of the 230 people who were taking anticholinergic drugs, 117 (51%) later developed MCI compared with 192 of the 458 (42%) people who were not taking the drugs. After adjusting for depression, number of medications being taken, and history of cardiac problems, individuals taking at least 1 anticholinergic drug had a 47% increased risk for developing MCI. Furthermore, those with higher overall exposure to anticholinergic drugs had additional increased risk.

The study also found that people with biomarkers for Alzheimer’s disease in their cerebrospinal fluid who were taking anticholinergic drugs were 4 times more likely to later develop MCI than people who were not taking the drugs and did not have the biomarkers. Similarly, people who had genetic risk factors for Alzheimer’s disease and took anticholinergic drugs were about 2.5 times as likely to later MCI than people without the genetic risk factors and who were not taking the drugs.

Because older people metabolise anticholinergic drugs differently than younger people, many anticholinergic drugs have different recommended daily dosages for elderly people than for younger people. Delano-Wood said that the majority of medications in the study 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 is of course concerning and is a potential area for improvement that could possibly lead to a reduction in cases of mild cognitive impairment,” said Delano-Wood said. “It is also a possible target toward a future precision medicine approach because we can more carefully consider and prescribe medications for people depending upon their risk profile for neurodegenerative disorders like Alzheimer’s disease.”

A limitation of the study was that only one-third of the participants in the study were taking anticholinergic medications, when other studies report that up to 70% of older people take them. However, Dr. Delano-Wood said that the “findings are compelling given that meaningful effects of these drugs on cognitive function were detected even though the volunteers in the study were generally very healthy and not taking as many medications as many older adults living in our communities.”

Reference: https://n.neurology.org/content/early/2020/09/02/WNL.0000000000010643

SOURCE: American Academy of Neurology
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