Nottingham, UK—Regular use of some anticholinergic medications in patients aged 55 years and older appears to increase their risk of dementia nearly 50%.

That’s according to a study published recently in JAMA Internal Medicine that looked at longer-term use of the medications for 3 years or more. The drugs help to contract and relax muscles by blocking acetylcholine and are prescribed for chronic obstructive pulmonary disease, bladder conditions, allergies, gastrointestinal disorders, and symptoms of Parkinson’s disease.

The United Kingdom researchers point out that while the medications are known to have short-term side effects, including confusion and memory loss, not enough information was available on whether long-term use increases the risk of dementia.

In an effort to remedy that, the study team focused on the medical records of 58,769 patients with a diagnosis of dementia and 225,574 patients without a diagnosis of dementia, all aged 55 years and older and registered with UK general practitioners (GPs) contributing data to the QResearch database. Most of the participants were female, with an average age of 82.2 years in the study, which was conducted between January 1, 2004, and January 31, 2016.

For the nested case-control study, information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Primary exposure was defined as the total standardized daily doses (TSDDs) of anticholinergic drugs prescribed in the 1 to 11 years prior to the date of diagnosis of dementia, or equivalent date, in matched controls.

Results indicated that the adjusted odds ratio (OR) for dementia increased from 1.06 (95% CI, 1.03-1.09) in the lowest overall anticholinergic exposure category (total exposure of 1-90 TSDDs) to 1.49 (95% CI, 1.44-1.54) in the highest category (>1,095 TSDDs), compared with no anticholinergic drug prescriptions in the 1 to 11 years before the index date.

Researchers identified significant increases in dementia risk for:
• The anticholinergic antidepressants (adjusted OR [AOR], 1.29; 95% CI, 1.24-1.34)
• Antiparkinson drugs (AOR, 1.52; 95% CI, 1.16-2.00)
• Antipsychotics (AOR, 1.70; 95% CI, 1.53-1.90)
• Bladder antimuscarinic drugs (AOR, 1.65; 95% CI, 1.56-1.75)
• Antiepileptic drugs (AOR, 1.39; 95% CI, 1.22-1.57)

No increased risks were documented, however, for the other types of anticholinergic drug studied, including antihistamines and gastrointestinal drugs.

The study team notes that results were similar when exposures were restricted to exposure windows of 3 to 13 years (AOR, 1.46; 95% CI, 1.41-1.52) and 5 to 20 years (AOR, 1.44; 95% CI, 1.32-1.57) before the index date for more than 1,095 TSDDs.

The study emphasizes that associations were stronger in cases diagnosed before the age of 80 years.

“Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These findings highlight the importance of reducing exposure to anticholinergic drugs in middle-aged and older people,” study authors conclude.

“This study provides further evidence that doctors should be careful when prescribing certain drugs that have anticholinergic properties,” explained coauthor Tom Dening, MD, who heads the Centre for Dementia at the University of Nottingham. “However, it’s important that patients taking medications of this kind don’t just stop them abruptly as this may be much more harmful. If patients have concerns, then they should discuss them with their doctor to consider the pros and cons of the treatment they are receiving.”

“Our study adds further evidence of the potential risks associated with strong anticholinergic drugs, particularly antidepressants, bladder antimuscarinic drugs, anti-Parkinson drugs and epilepsy drugs,” added lead author Carol Coupland, PhD, of the University’s Division of Primary Care. Coupland also called for regular medication reviews and suggested that might apply to middle-aged as well as elderly patients.

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