We all trust that that medication is safe for us to use. We base this assumption on the fact that the development of the medication went through the rigorous process of clinical trials. Clinical trials do not only test whether a new medication is effective in treating the disease or symptom but importantly also whether it is safe to take.

Safety is often measured in clinical trials by detecting the unintended side effects the medication has on our body. There exists no medication which does not have side effects to some degree. The reason being that the medication changes the normal physiological functioning of our body, to treat the symptom or disease they are intended for but this can also affect other physiological functions which the medication was not intended for.

The key in clinical trials is to determine whether the benefit of the new medication outweighs the risks caused by the side effects. If the side effects are too severe then a new medication is unlikely to be realised to the public since one would do more harm than good to people taking this medication. We can therefore assume that any medication available on the market is safe to take and has limited side effects. This is particularly true for medication which is sold ‘over the counter’ as it requires no prescription and is therefore deemed to have a very low risk of side effects. But that is not necessarily the case.

A new study in the journal Neurology* adds to existing evidence showing that a class of popular ‘over the counter’ medications increase our risk for dementia. The class of medications is referred to as anticholinergic medications. Anticholinergic medications are commonly taken across a whole range of diseases and symptoms affecting our digestion, salivation, movement or urination. It is therefore commonly prescribed by doctors for a range of serious condition, such as Parkinson’s disease or asthma. But it anticholinergic medication is also available as ‘over the counter’ medication to treat everyday symptoms, such as indigestion or motion sickness.

As the name gives away, anticholinergic medication is against [anti] choline. Choline refers to ‘Acetylcholine’, a key neural messenger [neurotransmitter] molecule in our nervous system. The function of anticholinergic medication is to block the function of acetylcholine in our nervous system. The reason for blocking acetylcholine function is to suppress or inhibit its function, which in some of the above conditions or symptoms can be hyperactive. Therefore blocking acetylcholine allows reducing those symptoms.

Despite being regarded as a medication that is so safe that many of its variations can be sold ‘over the counter’, there has been emerging evidence that the long-term use of anticholinergic medication can affect our risk for dementia and particularly Alzheimer’s disease.

Why is that the case?

The main reason is that a reduction of acetylcholine is one of the first neurotransmitter changes in Alzheimer’s disease. Acetylcholine is not only important for our parasympathetic nervous system in our body to regulate movement, digestion, salivation or urination but also a key neurotransmitter in our brain for our healthy cognitive functioning. In particular, acetylcholine is important for our attention and memory systems in our brains. Since memory and attentional problems are some of the earliest cognitive changes in Alzheimer’s disease, it should come therefore not as a surprise that acetylcholine levels are reduced in people at risk or in the early stages of Alzheimer’s disease.

What has that to do with anticholinergic medication?

Imagine that we would be at risk or in the earliest stages of Alzheimer’s disease and we would be taking the anticholinergic medication regularly, say for our indigestion. The anticholinergic medication would reduce acetylcholine in our stomach to help with our indigestion and it would also reduce the acetylcholine levels in our brain. Since acetylcholine is reduced in our brain because of Alzheimer’s disease, we now further reduce the levels of acetylcholine by taking the anticholinergic medication for our indigestion. The anticholinergic medication creates therefore a second hit towards our acetylcholine levels and increases our risk for Alzheimer’s disease development further.

This effect has been indeed shown now across several scientific studies, that long-term anticholinergic medication increases our risk for Alzheimer’s disease or other forms of dementia. The new findings highlight that this risk is particularly large for older people taking anticholinergic medication for a prolonged time. Such people show a 47% increased risk of developing cognitive symptoms compared to people of a similar age who do not take anticholinergic medication. A similar effect was found for people who were at genetic risk of Alzheimer’s disease.

Does this mean I should not take any anticholinergic medication when I am older?

A fair question but not that easy to answer. Clearly taking anticholinergic medication is important for several conditions, in particular, more serious ones such as Parkinson’s disease or asthma. However, for more lifestyle-related symptoms, such as indigestion or travel sickness, it might be worth considering either changing lifestyle habits or considering other treatment options.

Another important finding in the recent study was that the results show that people who took anticholinergic medication at a much higher dosage than recommended, were at the highest risk for dementia. This suggests that if we take anticholinergic medication at the recommended dosages we are not necessarily at a higher risk for dementia. It raises the question whether such ‘over the counter’ medication should be therefore prescribed as it would allow regular reviews with our doctor to establish whether we are taking the right dosage or whether we still need anticholinergic medication at all anymore.

Taking ‘over the counter’ anticholinergic medication without medical advice might provide us therefore a short-term solution for symptoms but has long-term consequences for our dementia risk.

Original publication: * Association of anticholinergic medication and AD biomarkers with incidence of MCI among cognitively normal older adults Alexandra J. Weigand, Mark W. Bondi, Kelsey R. Thomas, Noll L. Campbell, Douglas R. Galasko, David P. Salmon, Daniel Sewell, James B. Brewer, Howard H. Feldman, Lisa Delano-Wood, for the Alzheimer’s Disease Neuroimaging Initiative Neurology Sep 2020, 10.1212/WNL.0000000000010643; DOI: 10.1212/WNL.0000000000010643

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