Tag Archives: Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study

Some prescription drugs, incl. antidepressants, have 50% higher dementia risk

Dementia, also known as senility, is a broad category of brain diseases that cause a long term decrease in the ability to think, remember, and speak. such that a person’s daily functioning is affected. Approximately 7.7 million new cases of dementia are identified every year—which amounts to one new case every four seconds.

The most common type of dementia is Alzheimer’s disease, a severe form of dementia that makes up 50% to 70% of all cases of senile dementia, affecting an estimated 5.2 million Americans, according to 2013 statistics. As many as 1 in 9 seniors over the age of 65 has Alzheimer’s, and the disease is the third leading cause of death in the U.S., right behind heart disease and cancer.

Other common types of senile dementia include vascular dementia (25%), Lewy body dementia (15%), and frontotemporal dementia.

While we cannot change your age and family history, there are modifiable lifestyle factors we can control to reduce our risk for developing senile dementia. Those factors include diet, physical activity, weight (obesity), cognitive activitysmoking (tobacco), and diabetes.

Now comes news that certain prescription drugs, specifically anticholinergic drugs, carry a 50% higher dementia risk.

Anticholinergic drugs inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles in the gastrointestinal tract, urinary tract, lungs, and many other parts of the body.

Anticholinergic medicines have short-term cognitive adverse effects, but scientists have also long found a possible link between those drugs and an increased risk of dementia

The link is now confirmed by a recent study of more than 284,000 UK adults, aged 55 and older, by a team of 6 medical scientists in England who found statistically significant associations of dementia risk with exposure to the following anticholinergic prescription drugs:

  • Antidepressants such as paroxetine or amitriptyline.
  • Antiparkinson drugs.
  • Antipsychotics such as chlorpromazine or olanzapine.
  • Anti-epileptic drugs such as oxcarbazepine or carbamazepine.
  • Bladder antimuscarinics such as oxybutynin or tolterodine to treat overactive bladder.

The study is published as “Anticholinergic Drug Exposure and the Risk of Dementia: A Nested Case-Control Study” in the journal JAMA Internal Medicine, June 24, 2019. The authors are Carol A. Coupland, PhD; Trevor Hill, MSc; Trevor Hill, MSc; Tom Dening, MD; Richard Morriss, MD; Michael Moore, MSc; and Julia Hippisley-Cox, MD.

The study:

58, 769 patients with a diagnosis of dementia and 225, 574 controls 55 years or older were matched by age, sex, general practice, and calendar time. Information on prescriptions for 56 drugs with strong anticholinergic properties was used to calculate measures of cumulative anticholinergic drug exposure. Data were analyzed from May 2016 to June 2018.

Of the entire study population (284 343 case patients and matched controls), 179, 365 (63.1%) were women, and the mean (SD) age was 82.2 (6.8) years.


The researchers found “there was nearly a 50% increased odds of dementia” associated with a total anticholinergic exposure of more than 1,095 daily doses within a 10-year period, which is equivalent to an older adult taking a strong anticholinergic medication daily for at least three years.

The odds of dementia increased from 1.06 among those with the lowest anticholinergic exposure to 1.49 among those with the highest exposure, compared with having no prescriptions for anticholinergic drugs.

Happily, the study found no significant increases in dementia risk associated with other classes of anticholinergic drugs, such as antihistamines, skeletal muscle relaxants, gastrointestinal antispasmodics, antiarrhythmics, or antimuscarinic bronchodilators.


Exposure to several types of strong anticholinergic drugs is associated with an increased risk of dementia. These drugs should be prescribed with caution in middle-aged and older adults. 

Carol Coupland, the leading author of the study who is professor of medical statistics in primary care at the University of Nottingham, England, said: “The study is important because it strengthens a growing body of evidence showing that strong anticholinergic drugs have long term associations with dementia risk. It also highlights which types of anticholinergic drugs have the strongest associations. This is important information for physicians to know when considering whether to prescribe these drugs.”

Coupland cautions that “this is an observational study so no firm conclusions can be drawn about whether these anticholinergic drugs cause dementia,” and that people taking these medications are advised to consult with their doctor first before discontinuing the meds. 

However, if the association between these anticholinergic drugs and senile dementia is causal, this could mean that around 10% of dementia diagnoses are attributable to anticholinergic drug exposure, which would equate to around 20,000 of the 209,600 new cases of dementia per year in the United Kingdom.

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