In a new study, researchers found that a class of drugs used for a broad array of conditions, from allergies and colds to hypertension and urinary incontinence, may be associated with an increased risk of cognitive decline, particularly in older adults at greater risk for Alzheimer’s disease (AD).
The research was conducted by a team at the University of California San Diego and elsewhere.
Anticholinergic drugs are widely used for dozens of conditions, minor and major. Some of these medications require a prescription, while others can be purchased over the counter.
They work by blocking acetylcholine — a type of neurotransmitter or chemical messenger known to be critical for memory function — from binding to receptors on certain nerve cells.
The effect is to inhibit parasympathetic nerve impulses, which are involved in a variety of involuntary muscle movements, such as those in the gastrointestinal tract and lungs, and bodily functions like salivation, digestion and urination.
In the study, researchers tested 688 adults. None of the participants displayed cognitive or memory problems at the beginning of the study.
Each reported whether they were taking anticholinergic drugs.
One-third were taking such medications, with an average of 4.7 anticholinergic drugs per person. Participants were given annual comprehensive cognitive tests for up to 10 years.
The team found that cognitively normal study participants who were taking at least one anticholinergic drug at baseline were 47% more likely to develop mild cognitive impairment (MCI), often a precursor to dementia such as AD.
They also looked at whether people had biomarkers for AD in their cerebrospinal fluid, such as certain types of proteins, or a well-known genetic risk factor for AD.
They found that participants with AD biomarkers who were taking anticholinergic drugs were four times more likely to develop MCI than persons lacking biomarkers and not taking the drugs.
The researchers believe this interaction between anticholinergic drugs and Alzheimer’s risk biomarkers acts in a ‘double hit’ manner.
In the first hit, Alzheimer’s biomarkers indicate that pathology has started to accumulate in and degenerate 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.
The findings suggest that reducing anticholinergic drug use before cognitive problems appear may be important for preventing future negative effects on memory and thinking skills, especially for people at greater risk for Alzheimer’s disease.
One author of the study is Lisa Delano-Wood, Ph.D., an associate professor in the Department of Psychiatry.
The study is published in Neurology.
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