Acetylcholine (ACh) plays a major role in neurotransmission controlling the activity of various organs in the body. It has been postulated in the past that the decline in cognitive functions in dementia is predominantly related to a decrease in cholinergic neurotransmission.

An anticholinergic agent is a substance that blocks the neurotransmitter by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. Anticholinergic drugs are used in the treatment of a variety of conditions:
• Hyperactive Bladder and urinary incontinence
• Gastrointestinal cramps, nausea, and vomiting
• Respiratory disorders like COPD, asthma and chronic bronchitis
• Hay fever and other allergies
• Sinus bradycardia due to a hypersensitive vagus nerve.
• Depression and Insomnia
• Vertigo and motion sickness
• Muscular spasm

A new paper from Indiana University School of Medicine now suggests that drugs that have a strong “anticholinergic effect” shrink the brain and decrease brain metabolism. This is not a new finding: earlier research has found a link between anticholinergic drugs and cognitive impairment among older adults. Shannon Risacher, an assistant professor of radiology and imaging sciences at Indiana University School of Medicine said the findings provide us with a much better understanding of how this class of drugs may act upon the brain in ways that might raise the risk of cognitive impairment and dementia.

In this present study there were 451 participants between the ages of 70 and 75, 60 of them were taking at least one medication with medium or high anticholinergic activity. All of them had memory and other cognitive tests, positron emission tests (PET) measuring brain metabolism, and magnetic resonance imaging (MRI) scans for brain structure. The cognitive tests revealed that patients taking anticholinergic drugs performed worse than older adults not taking the drugs on short-term memory and some tests of executive function, which cover a range of activities such as verbal reasoning, planning, and problem solving. The researchers also found significant links between brain structure and anticholinergic drug use revealed by the MRI scans. The participants using anticholinergic drugs had reduced brain volume and larger ventricles. The brains were, on average, four per cent smaller, while the cavities inside the brain were 12 per cent larger. The participants taking anticholinergic drugs also had lower levels of glucose metabolism, which is a “biomarker” indicating brain activity and Alzheimer’s disease.

Scientists have linked anticholinergic drugs and cognitive problems among older adults for at least 10 years. People with Alzheimer’s disease are known to lack acetylcholine and it is feared that the use of anticholinergic pills may exacerbate or trigger the condition. A 2013 study by scientists at the IU Center for Aging Research and the Regenstrief Institute found that drugs with a strong anticholinergic effect cause cognitive problems when taken continuously for as few as 60 days. Drugs with a weaker effect could cause impairment within 90 days. Last year a study in the US found that taking a daily dose of pills like, Clarityn, Piriton and Nytol, for at least three years, raised the chance of getting Alzheimer’s disease by more than 60 per cent. The new paper published in the journal JAMA Neurology, is believed to be the first to study the potential underlying biology of those clinical links using neuroimaging measurements of brain metabolism and atrophy.

Although Dr. Risacher Shannon said additional studies are needed if we are to truly understand the mechanisms involved, the authors concluded: “The use of anticholinergic medication was associated with increased brain atrophy and dysfunction and clinical decline. Thus, use of anticholinergic medication among older adults should likely be discouraged if alternative therapies are available.”