Emerging Evidence of Drug Induced Dementia

There is emerging evidence that anticholinergic drugs might cause vascular dementia in people age 50 years and older, who would otherwise not be expected to get dementia. This type of dementia is not genetic, like Alzheimer disease.

Anticholinergic drugs are on the Beer's list of drugs not to give people over 65 because they can cause short term confusion, memory loss and altered mental status.¹ It has also been observed that people who take cholinergic drugs for long periods have a higher rate of dementia.² There is even a list of anticholinergic drugs with a rating scale on the adverse cognitive side effects.³

More studies are being done to understand this connection. Most recently was a case control study recently published in JAMA.⁴

Information was gathered from the QResearch primary care database in England. The study looked at 58,769 patients with a diagnosis of dementia and 225,574 controls who did not have dementia. It specifically evaluated people age 55 years and older and the exposure to anticholinergic drugs.

Associations were strongest in cases diagnosed before the age of 80 years and in cases diagnosed with vascular dementia, rather than with Alzheimer disease. Population-attributable fractions indicate that approximately 10% of dementia diagnoses are attributable to anticholinergic drugs. There was nearly a 50% increased odds of dementia with the use of a strong anticholinergic drug consumed daily for 3 years.

The finding of this strong association between anticholinergic drugs and vascular dementia, rather than for other types of dementia, is new information. It raises questions how anticholinergic drugs cause permanent damage. Proposed mechanisms are vascular and inflammatory changes, as well as chronic cholinergic depletion.

Acetylcholine plays a role in the brain regarding cognitive function, learning and attention. It also plays a major role in the junctions between nerves and muscles, specifically at the neuromuscular junction.

Many anticholinergic drugs work at this location to improve the lives of patients suffering from muscle spasms, overactive bladder, and intestinal cramping. These drugs are also used to treat depression, mood disorders, Parkinson disease, and epilepsy, and exert their effects in the brain.

According to this study, there were no significant increased risks for antihistamines, gastrointestinal antispasmodics, antimuscarinic bronchodilators, antiarrhythmics, or skeletal muscle relaxants, although the numbers of patients prescribed these drugs were small. The highest association was with anticholinergic antidepressants, bladder antimuscarinics, antipsychotics, and antiepileptic drugs.

Researchers of this study concluded that 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 people middle-aged and older.

References

• American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc.
• Risacher SL, McDonald BC, Tallman EF, et al. Association Between Anticholinergic Medication Use and Cognition, Brain Metabolism, and Brain Atrophy in Cognitively Normal Older Adults. JAMA Neurol.2016;73(6):721—732. doi:10.1001/jamaneurol.2016.0580
• Campbell NL, Maidment I, Fox C, Khan B, Boustani M. The 2012 update to the anticholinergic cognitive burden scale. J Am Geriatr Soc. 2013;61 (S1):S142-S143.
• Coupland CAC, Hill T, Dening T, Morriss R, Moore M, Hippisley-Cox J. Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study. JAMA Intern Med. Published online June 24, 2019. doi:10.1001/jamainternmed.2019.0677