Could medications contribute to dementia?

Robert H. Shmerling, MD

Faculty Editor, Harvard Health Publishing

Alzheimer’s disease and other illnesses that cause dementia are devastating, not only for those affected but also for their friends and family. For most forms of dementia, there is no highly effective treatment. For example, available treatments for Alzheimer’s disease may slow the deterioration a bit, but they don’t reverse the condition. In fact, for most people taking medications for dementia, it may be difficult to know if the treatment is working at all.

Experts predict that dementia will become much more common in the coming years. We badly need a better understanding of the cause of these conditions, as this could lead to better treatments and even preventive measures.

New research links certain medications to dementia risk

A new study raises the possibility that certain medications may contribute to the risk of developing dementia.

The focus of this study was on medications with “anticholinergic” effects. These are drugs that block a chemical messenger called acetylcholine, which affects muscle activity in the digestive and urinary tracts, lungs, and elsewhere in the body. It’s also involved in memory and learning.

Many medications have at least some anticholinergic effects, and it’s estimated that up to half of older adults in the US take one or more of these medications. Common examples include:

  • amitriptyline, paroxetine, and bupropion (most commonly taken for depression)
  • oxybutynin and tolterodine (taken for an overactive bladder)
  • diphenhydramine (a common antihistamine, as found in Benadryl).

In this new study, researchers collected detailed information from more than 300,000 adults ages 65 and older, and compared medication use among those diagnosed with dementia with those who were not. Those who had taken any medication with anticholinergic activity were 11% more likely to be eventually diagnosed with dementia; for those drugs with the most anticholinergic effects, the risk of dementia was 30% greater. The largest impact was found for drugs commonly taken for depression, bladder problems, and Parkinson’s disease; for antihistamines, and some other anticholinergic drugs, no increased risk of dementia was observed.

So should you be worried about your medications and dementia?

These findings are intriguing but they aren’t definitive, and they don’t mean you should stop taking a medication because you’re concerned about developing dementia.

First, this study found that use of certain medications was more common in people later diagnosed with dementia. That doesn’t mean these drugs caused dementia. There are other potential explanations for the findings. For example, some people develop depression during the early phases of dementia. Rather than antidepressants causing dementia, the medication might be prescribed for early symptoms of dementia that has already developed. This is called “confounding by indication” and it’s a potential flaw of studies like this one that attempt to link past medication use with future disease.

Another reason to be cautious about these results is that they cannot be used to estimate the impact of medication use on an individual person’s risk of dementia. This type of study looks at the risk in a large group, but individual factors (such as smoking or being sedentary) may have a much bigger impact on dementia risk.

Still, there is reason to be concerned about the possibility that anticholinergic drugs contribute to the risk of dementia. Acetylcholine is involved in memory and learning, and past research has demonstrated lower levels of acetylcholine in the brains of people with Alzheimer’s disease (the most common cause of dementia in the elderly). In addition, animal studies suggest that anticholinergic drugs may contribute to brain inflammation, a potential contributor to dementia.

What’s next?

Additional research will undoubtedly provide more information about the potential impact of medication use on dementia risk. In the meantime, it’s a good idea to review the medications you take with your doctor before making any changes.

And keep in mind that you may be able to reduce your risk of dementia by not smoking, getting regular exercise, and sticking to a healthy diet (that is rich in fiber, fruits, vegetables, and omega-3 fatty acids). Get your blood pressure and lipids checked regularly, and follow your doctor’s advice about ways to keep them in an optimal range.

The use of any medication comes with potential risks and benefits. This recent research linking certain medications with dementia risk reminds us that the risks of some medications are only uncovered years after their use becomes commonplace.

Follow me on Twitter @RobShmerling

Comments:

  1. Robert Shmerling

    Regarding whether the PDR is correct: I don’t think we can be absolutely sure any particular source is correct – but the PDR is well-respected and generally considered a reliable source of drug information. On the other hand, it’s true that there are bigger “offenders” than bupropion when it comes to anti-cholinergic effects.

    This study did not assess whether any particular drug contributes to dementia; rather, it found an association with a particular drug effect. And even drugs with low anti-cholinergic effects may matter in this regard since many people take more than one drug with anti-cholinergic effects.

  2. Anne Thompson

    Just to add–my understanding is that the ACB scale assigns a score of 1 (mild) to bupropion.

    Has this changed?

    Thank you.

  3. Anne Thompson

    Are you sure the PDR is correct in saying bupropion has moderate anticholinergic effects? Even this health letter has stated that its anticholinergic effects are very low. Perhaps there are new studies/analyses? You may be right, but I wonder if you could give some references to studies or analyses other than the PDR.

    It is an important question since bupropion has been thought to be one antidepressant not causing this particular problem for seniors.

    Looking forward to hearing about evidence. If you provided a link to something above, it’s not functional on my computer.

    Thank you!

  4. Rick

    I think you underestimate the causality of the relationship of anticholinergics to the underlying protein biochemistry and evolution of the dementia process. Yes, it is difficult to extrapolate from human population studies to causality, but the “entire body of work” which includes animal studies that can’t be done ethically in humans (even with PET antibody and receptor imaging techniques or fMRI protocols), indicates cholinergic receptor agonists and antagonists induce specific directional changes in post receptor neuronal protein turnover and accumulation that are pathognomonic for dementia. Furthermore, OTC diphenhydramine- containing meds are ubiquitous in the allergy, pain, and sleep aid aisles and come in a variety of liquid forms for children. The basal forebrain cholinergic nuclei project to the cognitive and memory areas of importance in dementia, and specific centrally acting anti cholinesterase drugs temporarily benefit people with dementia. Why then is there such a gap between late incorporation and early incorporation in human drug consumption behavior, clinical guidelines, and basic science ? The apparent fear of “upsetting the public with science” in the midst of a terrible epidemic reminds me of the 60 years of tobacco and public health policy. Having spent 13 years in basic neuroscience research before medical school and 25 years in general practice since, I must say there is a surprising significant gap between the two disciplines and a seeming lack of urgency in the mission statements of both.

  5. Anne Thompson PhD

    Are you sure bupropion is anticholinergic? Please doublecheck this claim for accuracy.

    • Nancy Ferrari

      Dear Anne,

      Surprising but the answer is yes, though mildly so. From the PDR section on mechanism of action: “….Bupropion does exhibit moderate anticholinergic effects, and produces a sensation of mild local anesthesia on the oral mucosa. Antidepressant activity is usually noted within 1—3 weeks of initiation of bupropion treatment; full effects may not be seen until 4 weeks of therapy.”

      You can see how the study investigators ranked anticholinergic effects for the medications by going to the study link in the blog.

  6. Mike

    Be cautious. The symptoms you describe could also be due to residual depression. It will not be hard to figure out which it is eg. begin to reduce the dose and see if you are worse or better. Good luck.

  7. Joanne E. Bucci

    Is Claratin and Zertex in that mix…Jb

  8. Patricia B.

    I believe this is true, at least in my case. I have depression and have been on bupropion (though I was unaware that this drug had any anticholinergic effects) 450mg along with escitalopram 20mg daily for about a year and a half after a life crisis, and have noticed a very noticeable difference in my ability to think or recall things in that time. I am getting quite annoyed by this, and it is also noticeable to my family. To me the mood regulation is definitely not worth the sensation of days passing without the ability to engage daily in real life. Hence I intend to address this with my psychiatrist at my upcoming appt. As he is very attuned to my opinion on how I’m handling my medications I know he will be willing to test how lowering them will or will not improve my cognitive issues. It will be interesting.

  9. NORMA LOEB

    All of these medications can certainly increase problems with severe side effects for people who already have Lewy Body Dementia.

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