According to the latest statistics1 for 2019, 14% of Americans aged 71 or older have some form of dementia. Alzheimer's disease, which is the most severe and lethal form of dementia, affects an estimated 5.8 million Americans. Of those, 81% are over the age of 75, but approximately 200,000 are younger than 65. In all, 1 in 10 seniors over the age of 65 has Alzheimer's dementia.
Due to the high prevalence of dementia and the scarcity of effective conventional treatments, prevention is paramount. I've written many articles on this topic, highlighting several of the most important prevention strategies, including dietary recommendations and the need for exercise, sun exposure and avoidance of toxins.
One risk factor that has received far less attention is medication side effects, which we'll focus on here. One class of drugs shown to be of great concern in this regard are anticholinergics — drugs that block acetylcholine, a neurotransmitter that performs important functions in your brain and peripheral and central nervous systems.
In your nervous systems, it acts both as an activator and an inhibitor,2 which is in part why it's used in such a wide variety of drugs. For example, acetylcholine triggers muscle contractions and pain responses, and is involved in the regulation of your endocrine system and REM sleep cycle.
Acetylcholine blockers can trigger dementia symptoms
Anticholinergic drugs are prescribed for a wide variety of conditions, including depression, incontinence, diarrhea, dizziness, motion sickness, insomnia, allergies and epilepsy.6,7 You can find a long list of anticholinergic drugs and the different conditions they're used for on seniorlist.com.8 As reported in a July 2019 article on KHN.org:9
"By all accounts the woman, in her late 60s, appeared to have severe dementia. She was largely incoherent. Her short-term memory was terrible. She couldn't focus on questions that medical professionals asked her.
But Dr. Malaz Boustani, a professor of aging research at Indiana University School of Medicine, suspected something else might be going on. The patient was taking Benadryl for seasonal allergies, another antihistamine for itching, Seroquel (an antipsychotic medication) for mood fluctuations, as well as medications for urinary incontinence and gastrointestinal upset.
To various degrees, each of these drugs blocks an important chemical messenger in the brain, acetylcholine. Boustani thought the cumulative impact might be causing the woman's cognitive difficulties. He was right."
As the patient was taken off these medications over a period of six months, she made what appeared to be a "miraculous" recovery; her scores on the Mini-Mental State Exam going from indicating severe dementia back to normal.
Recent research highlights risks of anticholinergic drugs
A June 2019 study10 in JAMA that assessed the dementia risk associated with various anticholinergic drugs found the link was strongest for:
- Antidepressants (tricyclic antidepressants such as imipramine,11 doxepine or amitriptyline have strong anticholinergic effects, whereas SSRIs such as citalopram and duloxetine have lower anticholinergic effects12)
- Antiparkinson drugs
- Antipsychotics (such as clozapine,13 chlorpromazine or olanzapine14)
- Bladder antimuscarinics (such as oxybutynin or tolterodine,15 prescribed for overactive bladder)
- Antiepileptic drugs (such as oxcarbazepine or carbamazepine16)
A case-control study17 published in 2018 in the BMJ — which like the JAMA study just mentioned looked at the effects of various classes of anticholinergics — also found that antidepressant, urological and antiparkinson drugs posed the greatest risk.
Similarly, an earlier study,18 published in JAMA Internal Medicine in 2015, found "Higher cumulative anticholinergic medication use is associated with an increased risk for dementia," including Alzheimer's, and that anticholinergic use should be minimized to avoid this medication-related risk.
Overall, high use of anticholinergic medications for three years or more was associated with a 54% increased risk for dementia, compared to nonuse.19 What's more, they concluded that this heightened risk remained even after the drug or drugs were discontinued.
According to KHN,20 a new trial will look into this further, to see whether patients taking anticholinergics whose cognition has already started to decline can regain their brain function, or whether the drugs' effects have a more permanent impact.