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Researchers investigated whether the use of anticholinergic drugs is associated with an increased incidence of dementia later in life.
Dementia is a disorder of the brain caused by neurodegenerative processes that lead to cognitive decline and the progressive loss of the ability to perform daily activities. Since there are no treatments to modify the disease activity of dementia, it is important to recognize and reduce the exposure to risk factors that may affect overall brain health in order to prevent it.
Anticholinergic drugs can cause short-term cognitive impairment
One potential risk factor is the exposure to anticholinergic drugs, which can be used in the treatment of depression, Parkinson’s disease, urinary incontinence, gastrointestinal disorders, and allergies. It has been well established that drugs with anticholinergic activity can cause short-term cognitive impairment, and there have been reports that anticholinergic drugs can cause future cognitive decline; however, whether these anticholinergic drugs are in fact contributing to future cognitive decline is not well known.
In a study published in The BMJ, researchers in the United Kingdom discuss their investigation into the long-term associations between anticholinergic drugs and the incidence of dementia.
The researchers performed a nested case-control study using data from the Clinical Practice Research Datalink (CPRD), which is representative of the United Kingdom population. To be included in the study, participants needed to be between the ages of 66 to 99 years, with at least six years of data before a dementia diagnosis and at least one year of exposure to an anticholinergic drug. Patients not included in the study were those with a diagnosis of HIV or AIDS, motor neuron disease, multiple sclerosis, Down’s syndrome or alcohol abuse before a dementia diagnosis.
Since the anticholinergic activity of drugs and their effects on the brain is difficult to measure, the researchers classified the anticholinergic effects of the drugs based on their Anticholinergic Cognitive Burden (ACB) scale. A score of 1 indicates possible anticholinergic activity based on lab experiments, a score of 2 indicates definitely anticholinergic based on blood-brain penetration that would result in clinically relevant anticholinergic effects, and a score of 3 is assigned to drugs that fulfill criteria for a score of 2 but also have reported associations with delirium.
Their analysis showed a significant association between dementia and the prescription of any drug with an ACB score of 1, 2 or 3, as well as a dose-response effect for anticholinergic drugs with an ACB score of 2 or 3.
Significant associations between dementia and antidepressants
When evaluated by drug class, they found a significant association between the incidence of dementia and the use of antidepressant, antiparkinson or urological drugs that have an ACB score of 3. Antidepressant drugs with an ACB score of 1 were found to have an increased incidence of dementia, whereas no other drugs with an ACB score of 1 had the same association. The researchers also found that those who were prescribed an anticholinergic drug with an ACB score of 3 fifteen to twenty years before a dementia diagnosis were associated with a significantly greater incidence of dementia.
Dementia is often under-diagnosed
The study’s findings are consistent with the few past studies that also examined long-term effects of anticholinergic drugs on cognition. The study’s use of a large population and longer patient history enabled a better estimate of the effects of different classes of anticholinergic drugs and their association with dementia incidence up to 20 years before a dementia diagnosis. With that said, dementia is often under-diagnosed, and misclassification of controls of who may have had undiagnosed dementia would reduce the estimated effects observed in this study.
The study may have also had some surveillance bias as patients taking anticholinergic drugs may have more frequent contact with healthcare services, thus be more likely to be diagnosed with dementia. Lastly, adherence to the prescribed anticholinergic drugs was not known and the use of over-the-counter drugs that may possess anticholinergic activity was not accounted for.
Clinicians should stay aware when analyzing risks and benefits in patients
Overall, despite the moderate associations between anticholinergic drugs and the incidence of dementia found in this study, the high incidence of dementia in the population should highlight this as a risk to be considered.
Further, studies in humans and mice examining the brain processes support the negative impact of anticholinergic drugs on brain cognition and overall brain health. Further research into individual drug classes with anticholinergic activity is warranted to investigate the potential harms of their use.
Clinicians should stay aware of the potential short-term and long-term risks with anticholinergic drug use, especially in particular drug classes, when analyzing the risks and benefits in their patients.
Written by Maggie Leung, PharmD
Reference: Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., . . . Savva, G. M. (2018). Anticholinergic drugs and risk of dementia: Case-control study. BMJ. doi:10.1136/bmj.k1315