Can Anticholinergic Drugs Increase Risk of Dementia?

Highlights:

• Commonly prescribed anticholinergic drugs for various conditions may increase dementia risk if used long term (three years or more) and should be prescribed with caution
• Anticholinergic drugs are known to cause short-term side effects such as confusion and memory but long term effects have remained unclear
• Anticholinergic drugs block the neurotransmitter acetylcholine and are routinely prescribed for a wide variety of conditions such as depression, Parkinson’s disease, seizures and bladder problems

Commonly prescribed anticholinergic drugs for various conditions including depression and Parkinson’s disease may increase dementia risk if used long term (three years or more) as per a recent observational study and doctors should weigh the risk-benefit balance before prescribing these drugs long term, according to a recent observational study at the University of Nottingham and sponsored by the NIHR School for Primary Care Research. The study was led by Professor Carol Coupland from the University's Division of Primary Care and the findings of the research appear in the journal JAMA Internal Medicine.

Do Anticholinergic Drugs Increase Dementia Risk?

• The study team analyzed the medical records of 58,769 patients diagnosed with dementia and 225,574 patients without dementia. All participants were aged 55 years and above and registered with UK GPs, who provided these data to the QResearch registry, between 1st January 2004 and 31st January 2016
• The average age of the 58,769 dementia patients was 82 years and 63% were women. Each
• dementia patient was matched to five control patients of the same sex, age, and belonging to the same GP (general practitioner) surgery.
• Exposure to anticholinergic drugs was assessed using prescriptions over a duration of 10 years and 1 to 11 years dementia was diagnosed and a similar period in control patients, and the data were compared to assess dementia risk
• During the 1-11 year period of follow-up before dementia diagnosis, it was noted that nearly 57% of those diagnosed with dementia and 51% of control patients were prescribed at least one strong anticholinergic drug, averaging six prescriptions in patients and 4 in controls.
• This observational study found an increased risk of dementia in patients on anticholinergic drugs overall and especially those on anticholinergic antidepressants, anti-Parkinsons drugs, bladder drugs, antipsychotics and epilepsy drugs after excluding other contributing risk factors
• However, there was no increased risk found for other types of anticholinergic drugs such as gastrointestinal drugs and antihistamines. Additionally, the team analyzed prescriptions for anticholinergic drugs up to 20 years before the diagnosis of dementia was made.

The findings of the study suggest that long term use of strong anticholinergic drugs, especially to treat depression, Parkinson’s disease, seizure disorder and bladder problems may increase dementia risk. From the observed findings, the team believes that patients who used strong anticholinergic drugs daily for three years or more had a nearly 50% increased risk of dementia. The findings of the current study echo the results of a similar study done in 2018.

Professor Tom Dening, Head of the Centre for Dementia at the University of Nottingham and a member of the research study team, said: "This study provides further evidence that doctors should be careful when prescribing certain drugs that have anticholinergic properties. 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."

However, the study team caution that this is an observational study and definite conclusions cannot be drawn between the use of anticholinergic drugs and increased dementia risk and that that in some cases, the drugs may have been prescribed for early symptoms of dementia.

Takeaways From Study

• Physicians should prescribe strong anticholinergic agents with caution only after weighing the risk-benefit balance
• The observed risk was most marked in anticholinergic drugs prescribed to treat Parkinson’s disease, depression and overactive bladder
• Whenever possible alternative agents should be prescribed
• If anticholinergics are still prescribed, regular patient reviews must be carried out
• Several cases of dementia were diagnosed before 80 years suggesting that anticholinergics must be prescribed with caution both in middle-aged as well as elderly patients
• Should a causal relationship be proved between anticholinergic drugs and dementia, this would account for about 10% of dementia diagnosis or nearly 20,000 of the 209,600 new cases of dementia annually in the UK
• Around 10% of dementia cases attributable to anticholinergic drugs is indeed a significant proportion along with other modifiable risk factors including 5% for high blood pressure in middle age, 3% for diabetes, 6.5% for a sedentary life and 14.5% for smoking in later life.

In summary, long term prescription of anticholinergic drugs to treat depression, overactive bladder or Parkinson’s disease may increase dementia risk and doctors should prescribe these agents with caution or prefer other alternatives to reduce patient’s risk of dementia.

References:

1. Anticholinergic Drug Exposure and the Risk of Dementia doi:10.1001/jamainternmed.2019.0677

Source-Medindia