Freely available drugs used for allergies and colds may be associated with an increased risk of cognitive decline, including those at risk of Alzheimer’s disease.
The researchers reported that cognitively normal study participants taking at least one anticholinergic drug were 47 per cent more likely to develop mild cognitive impairment (MCI), often a precursor to various types of dementia including Alzheimer’s.
“This study suggests that reducing anticholinergic drug use before cognitive problems appear may be important for preventing future negative effects on memory and thinking skills,” said study author Associate Professor Lisa Delano-Wood, from the University of California San Diego in the US.
Anticholinergics are often used to inhibit the involuntary movements of muscles or balance the production of chemicals in the body. They are used to treat conditions as varied as depression, epilepsy, urinary incontinence and hypertension, but some cold and flu medications also contain anticholinergic properties.
Dementia Australia says anticholinergic drugs may be used by up to 60 per cent of older Australians at some time and an estimated 33 per cent of Australians over the age of 65 take enough medications with anticholinergic effects to potentially increase their risk of harm.
None of the study’s 688 participants, with an average age of 74, displayed cognitive or memory problems at the start of the study. One-third were taking anticholinergic medications, with an average of 4.7 anticholinergic drugs per person. Participants undertook annual cognitive tests for up to 10 years.
The scientists also examined whether participants had biomarkers for Alzheimer’s in their cerebrospinal fluid. They found that participants with Alzheimer’s biomarkers who took anticholinergic drugs were four times more likely to develop MCI than those without biomarkers and not taking the drugs.
People with a genetic risk for Alzheimer’s who took anticholinergic drugs were 2.5 times more likely to develop MCI than those without genetic risk factors who were not taking the drugs.
“We believe this interaction between anticholinergic drugs and Alzheimer’s risk biomarkers acts in a ‘double hit’ manner,” said Alexandra Weigand, the study’s lead author.
“In the first hit, Alzheimer’s biomarkers indicate that pathology has started to accumulate and degenerate in a small region called the basal forebrain that produces the chemical acetylcholine, which promotes thinking and memory.
“In the second hit, anticholinergic drugs further deplete the brain’s store of acetylcholine. This combined effect most significantly impacts a person’s thinking and memory.”
Study authors noted that older adults often took anticholinergic medications at levels much higher than the lowest effective dose recommended for older adults, with 57 per cent taken at twice the recommended dosage and 18 per cent at four times the recommended dosage.
“This points to a potential area for improvement, since reducing anticholinergic drug dosages may possibly delay cognitive decline,” said Ms Weigand.
“It’s important for older adults who take anticholinergic medications to regularly consult with their doctors and discuss medication use and dosages.
“Clinical ‘deprescribing’ studies are currently underway at certain research sites across the nation in an effort to investigate whether reducing or stopping use of these drugs does, in fact, lead to reductions in progressive cognitive impairment,” Assoc. Prof. Delano-Wood said.
The study confirms the findings of a 2015 study undertaken by the Group Health Research Institute and the University of Washington, Seattle. The Cumulative Use of Strong Anticholinergic Medications and Incident Dementia study concluded: “Higher cumulative anticholinergic medication use is associated with an increased risk for dementia. Efforts to increase awareness among health professionals and older adults about this potential medication-related risk are important to minimise anticholinergic use over time.”
That study began in 1994, with follow-ups every two years and involved 3434 participants aged 65 and older who had no dementia when the study began.
It found that higher cumulative use of anticholinergic medications was associated with “an increased risk of all-cause dementia and Alzheimer’s disease”.
“It is worth noting that the increased risk for dementia was consistent across anticholinergic subclasses, with increased risk found for people with high use of anticholinergic medications other than antidepressants, such as first generation antihistamines and bladder antimuscarinics.
“We found that among the heaviest users, people who had past heavy use had a similar dementia risk as those with recent or continued heavy use. This suggests that the risk for dementia with anticholinergic use may persist despite discontinuation.
“In a small autopsy study of patients with Parkinson’s disease, participants that were receiving anticholinergic drugs for two years or longer had increased levels of AD neuropathology compared with those using for shorter durations.
“Prescribers should be aware of this potential association when considering anticholinergic medications for their older patients and should consider alternatives when possible. For conditions where therapeutic alternatives may not be available, prescribers should use the lowest effective dose and discontinue therapy if ineffective. These findings also have public health implications for education of older adults about potential safety risks since some anticholinergic medications are available as over the counter (OTC) products.
“Given the devastating consequences of dementia, informing older adults about this potential modifiable risk would allow them to choose alternative products and collaborate with their health professionals to minimise overall anticholinergic use.”
The June 2019 study Anticholinergic Drug Exposure and the Risk of Dementiaanalysed associations between anticholinergic drug treatments and risk of dementia in persons 55 years or older.
It was unequivocal about the danger of such medications.
“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.
“In this nested case-control study of 58,769 patients with a diagnosis of dementia and 225,574 matched controls, there were statistically significant associations of dementia risk with exposure to anticholinergic antidepressants, anti-Parkinson’s drugs, antipsychotic drugs, bladder antimuscarinics and antiepileptic drugs after adjusting for confounding variables.
“The associations observed for specific types of anticholinergic medication suggest that these drugs should be prescribed with caution in middle-aged and older adults.”
Are you concerned about medications you take? Has your doctor discussed the dangers of any medications he or she may have prescribed?
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