Anticholinergic medications increase risk of mild cognitive impairment, study suggests

A study published in Neurology, which followed 688 patients over ten years, has found that the use of anticholinergic medicines more than double the risk of mild cognitive impairment in those predisposed to Alzheimer’s disease.

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Anticholinergic (aCH) medicines more than double the risk of mild cognitive impairment (MCI) and accelerated memory and language decline in those predisposed to Alzheimer’s disease (AD), a study in Neurology has suggested.

The researchers evaluated 688 “cognitively normal”, highly educated and healthy participants with a mean age of 73.5 years and followed them up over a 10-year period to examine aCH use and risk of progression to MCI.

Overall, 33% (230) of the patients were recorded as taking aCH medications, and were referred to as aCH+, with an average of 4.7 medications being taken per aCH+ person. Metoprolol, atenolol, loratadine and bupropion were the most common medications taken.

Due to the fact that different aCH medications have different levels of anticholinergic activity, the researchers also determined participants’ overall anticholinergic burden based on the number, dosage and strength of aCH drugs they were taking.

The researchers found that participants who had taken at least one aCH medicine during the 10-year period had a 47% increased risk of progression to MCI (hazard ratio [HR]=1.47, 95% confidence interval [CI]=1.10–1.98, P=0.02) compared with those who had not taken them. This risk increased with higher overall exposure to aCH medications.

Participants with a genetic predisposition to AD who had also taken an aCH had a greater than two-fold (HR=2.69, 95% CI=1.78–4.07, < 0.001) increased risk of progression to MCI compared with those who were not predisposed and had not taken aCH medications.

Further to this, patients with biomarkers for AD in their cerebrospinal fluid who had taken aCH medications had a nearly five-fold increased risk of MCI (HR=4.89, 95% CI=2.86–8.36, < 0.001).

“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, a neuropsychologist at the University of California, San Diego, and lead author on the study.

“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.”

Anne Child, pharmacy and dementia specialist lead at the Royal Masonic Benevolent Institution Care Company, said she did not consider the findings to be unexpected and that more investigation to include deprescribing trials would be the “natural next step”.

“All too often people living with dementias have anything and everything ascribed to their condition; asking ourselves ’why’ can only help to increase our understanding and, more importantly, improve how we support individual outcomes,” she said. 

David de Monteverde-Robb, lead pharmacist at Addenbrooke’s Hospital in Cambridge and a specialist in neurology, said that the study was “robustly designed” and added “high quality real-life data to a subject that has shown increasing interest in recent years”. 

“The study … highlights that there is a wide range of commonly prescribed drugs that can display anticholinergic side effects,” he said. 

“This major limitation of appropriately identifying the drugs which may display anticholinergic effects will limit the applicability of the study to the individual patient and the identification of at-risk patients. As such, it is dependent on clinicians and pharmacists being conversant with the range of drugs with possible anticholinergic activity and considering this risk in the long-term management of the patient, when the acute management may commonly divert from such long-term considerations.”

He also pointed out that the study found that 98 of the 688 patients who developed MCI improved to become cognitively normal again.

“Further data is needed on the reversibility of the effects of anticholinergics, but it is worth considering the reversibility of cognitive impairment when reviewing a patient’s medicines,” de Monteverde-Robb said.

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Citation
The Pharmaceutical Journal, September 2020;Online:DOI:10.1211/PJ.2020.20208322