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Drugs That May Put You at Risk for Alzheimer’s Disease

Research in JAMA Neurology this week noted a link between popular drugs and Alzheimer's disease. What other kinds of medications may also raise this risk?

This week we read that many popular prescription and over-the-counter medications may increase the risk for dementia. This is not the first time we have learned that tens of millions of people are taking drugs that make them vulnerable to brain fog or even Alzheimer’s disease.

It’s not just anticholinergic (AC) drugs, though they affect an enormous number of patients. Proton Pump Inhibitors (PPIs) have also been implicated, along with sleeping pills and anti-anxiety agents. So many people could be impacted that it is literally mind-blowing (pardon the pun).

The Latest Research:

The study in JAMA Neurology (online Apr. 18, 2016) recruited 451 people who had no cognitive decline at the start of the trial. Their average age was 73.

Participants were involved in two different studies. They were given cognitive tests and also underwent imaging studies to explore brain function and structure.

People who were taking anticholinergic medications that interfere with the neurotransmitter acetylcholine were more likely to score poorly on tests of problem solving, memory, and executive function. They also had lower metabolic activity in the part of the brain responsible for memory. In addition, MRIs showed changes in the structure and size of the brain.

Many over-the-counter antihistamines have strong anticholinergic activity. One ingredient, diphenhydramine, is found in many nighttime pain relievers. If the drug has PM in its name, there is a strong likelihood it contains diphenhydramine. This medicine is best known under its brand name Benadryl.

Antidepressants like amitripytyline and paroxetine (Paxil) also have anticholinergic action, as do many drugs for overactive bladder. If a person is taking more than one anticholinergic medicine, the chances for a negative impact on the brain are increased.

To see a more comprehensive list of anticholinergic drugs visit this link:

Heartburn Drugs and Dementia:

Proton pump inhibitors (PPIs) are taken daily by tens of millions of people worldwide. (It is estimated that at least 15 million Americans take these medications regularly) We’re talking about drugs such as dexlansoprazole (Dexilant), esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), rabeprazole (Aciphex) and pantoprazole (Protonix).

PPIs are considered so safe you can now buy Nexium 24HR, Prevacid 24HR and Prilosec OTC without a doctor’s prescription. Although the labels of these OTC versions come with cautions about how long to use these acid-suppressing drugs, we fear that many people may not bother to read the instructions or might ignore them.

In JAMA Neurology (online, April, 2016) we were told the findings of a German epidemiological study:

“In this cohort study including more than 70 000 participants and using longitudinal observational data derived from the German statutory health insurer Allgemeine Ortskrankenkassen (AOK), elderly patients 75 years of age or older receiving PPI medication had a significantly increased risk of incident dementia compared with patients 75 years of age or older not receiving PPI medication.”

The authors concluded:

“The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice.”

We don’t know about you, but avoiding drugs that might prevent Alzheimer’s disease or dementia seems like a pretty good idea to us.

Anti-Anxiety Agents and Alzheimer’s:

Benzodiazepines (“benzos”) such as alprazolam, chlordiazepoxide, clonazepam, diazepam, lorazepam and midazolam have been prescribed to tens of millions of people for many decades. They are perceived as safe sedatives and sleeping pills. They work by affecting the activity of a neurochemical called GABA (gamma-aminobutyric acid) the the brain receptors that respond to this compound.

An article in the BMJ (Sept. 9, 2014) concluded:

“Benzodiazepine use is associated with an increased risk of Alzheimer’s disease…Unwarranted long term use of these drugs should be considered as a public health concern.”

The authors commented on the implications of their study:

“Our study reinforces the suspicion of an increased risk of Alzheimer type dementia among benzodiazepine users, particularly long term users, and provides arguments for carefully evaluating the indications for use of this drug class. Our findings are of major importance for public health, especially considering the prevalence and chronicity of benzodiazepine use in older people and the high and increasing incidence of dementia in developed countries. In such conditions, a risk increased by 43-51% in users would generate a huge number of excess cases, even in countries where the prevalence of use of these drugs is not high.”

Contrary Evidence:

A more recent study (BMJ, Feb. 2, 2016) of benzodiazepine use in older people reported that “Contrary to expectations, we found a small increased risk for dementia in people with low (that is, up to one month) or moderate (one to four months) use.” Higher doses, though, were not linked to dementia or cognitive decline, so the question of benzo use and alzheimer’s disease remains unresolved at this time. The authors conclude:

“It should be noted that our study did not examine the acute cognitive adverse events that can occur when treatment with a benzodiazepine is started in older adults and careful monitoring is recommended in this situation. Nonetheless, given the mixed evidence regarding benzodiazepines and risk of dementia and that these drugs are associated with many adverse events, healthcare providers are still advised to avoid benzodiazepines in older adults to prevent important adverse health outcomes, withdrawal, and dependence.”

The Bottom Line on Drugs and Alzheimer’s Disease:

Most health professionals have blamed Alzheimer’s disease on bad genes or bad luck. Although we have known for a very long time that head injuries and concussions could increase the risk for dementia, the assumption was that this was due to physical trauma. And yet underlying physical trauma to the brain is a disruption in neuronal function at the cellular level. Why wouldn’t drugs that affect neuronal function also have an impact on learning, memory and a risk for Alzheimer’s disease?

We now know that anticholinergic drugs affect brain function and have been linked to dementia. It is entirely conceivable that many other medications may also increase the risk for Alzheimer’s disease. Until such drugs are proven completely safe for the brain, we would urge health professionals to exercise caution in prescribing them for long periods of time, especially for older people.

Learn more about medications that could be hazardous to older people in our Guide to Drugs and Older People.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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