Higher dementia risk linked to more use of common drugs

January 26, 2015
Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

A large study links a significantly increased risk for developing dementia, including Alzheimer's disease, to taking commonly used medications with anticholinergic effects at higher doses or for a longer time. Many older people take these medications, which include nonprescription diphenhydramine (Benadryl). JAMA Internal Medicine published the report, called "Cumulative Use of Strong Anticholinergic Medications and Incident Dementia."

The study used more rigorous methods, longer follow-up (more than seven years), and better assessment of medication use via pharmacy records (including substantial nonprescription use) to confirm this previously reported link. It is the first study to show a dose response: linking more risk for developing dementia to higher use of anticholinergic medications. And it is also the first to suggest that dementia risk linked to anticholinergic medications may persist—and may not be reversible even years after people stop taking these drugs.

"Older adults should be aware that many medications—including some available without a prescription, such as over-the-counter sleep aids—have strong ," said Shelly Gray, PharmD, MS, the first author of the report, which tracks nearly 3,500 Group Health seniors participating in the long-running Adult Changes in Thought (ACT), a joint Group Health-University of Washington (UW) study funded by the National Institute on Aging. "And they should tell their about all their over-the-counter use," she added.

"But of course, no one should stop taking any therapy without consulting their provider," said Dr. Gray, who is a professor, the vice chair of curriculum and instruction, and director of the geriatric pharmacy program at the UW School of Pharmacy. "Health care providers should regularly review their older patients' drug regimens—including over-the-counter medications—to look for chances to use fewer anticholinergic medications at lower doses."

For instance, the most commonly used medications in the study were tricyclic antidepressants like doxepin (Sinequan), first-generation antihistamines like chlorpheniramine (Chlor-Trimeton), and antimuscarinics for bladder control like oxybutynin (Ditropan). The study estimated that people taking at least 10 mg/day of doxepin, 4 mg/day of diphenhydramine, or 5 mg/day of oxybutynin for more than three years would be at greater risk for developing dementia. Dr. Gray said substitutes are available for the first two: a selective serotonin re-uptake inhibitor (SSRI) like citalopram (Celexa) or fluoxitene (Prozac) for depression and a second-generation antihistamine like loratadine (Claritin) for allergies. It's harder to find alternative medications for urinary incontinence, but some behavioral changes can reduce this problem.

"If providers need to prescribe a medication with anticholinergic effects because it is the best therapy for their patient," Dr. Gray said, "they should use the lowest effective dose, monitor the therapy regularly to ensure it's working, and stop the therapy if it's ineffective." Anticholinergic effects happen because some medications block the neurotransmitter called acetylcholine in the brain and body, she explained. That can cause many side effects, including drowsiness, sore throat, retaining urine, and dry mouth and eyes.

"With detailed information on thousands of patients for many years, the ACT study is a living laboratory for exploring risk factors for conditions like dementia," said Dr. Gray's coauthor Eric B. Larson, MD, MPH. "This latest study is a prime example of that work and has important implications for people taking medications—and for those prescribing medications for older patients." Dr. Larson is the ACT principal investigator, vice president for research at Group Health, and executive director of Group Health Research Institute (GHRI). He is also a clinical professor of medicine at the UW School of Medicine and of health services at the UW School of Public Health.

Some ACT participants agree to have their brains autopsied after they die. That will make it possible to follow up this research by examining whether participants who took anticholinergic medications have more Alzheimer's-related pathology in their brains compared to nonusers.

Explore further: Commonly used medications associated with impaired physical function in older adults

More information: Cumulative Use of Strong Anticholinergic Medications and Incident Dementia, JAMA Internal Medicine, 2015.

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9 comments

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monkerypiano
1 / 5 (3) Jan 26, 2015
Useless research.Insomnia is why people take the medications.Insomnia is a risk factor for dementia.
malapropism
5 / 5 (6) Jan 26, 2015
Useless research.Insomnia is why people take the medications.Insomnia is a risk factor for dementia.

Are you sure you've separated causation from correlation in this statement? That is, is it the insomnia that is the risk factor or the medication taken for insomnia, with the insomnia simply correlated with dementia due to taking that medication?

If you are certain, please cite your references.
rbncnklh
not rated yet Jan 26, 2015
Don't forget the impact of pollution of air, water, soil and processed foods..
mooster75
2.3 / 5 (3) Jan 27, 2015
Don't forget the impact of pollution of air, water, soil and processed foods..

Evidence?
foolspoo
5 / 5 (2) Jan 27, 2015
the correlation is irrefutable, monkey.
From the study;

Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses.
The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease)

as for causation, there are far too many unknowns. but that certainly doesn't render this useless. this is inspirational to many communities
Scottingham
not rated yet Jan 27, 2015
Wellll, I suppose I should stop taking Benadryl nightly...
vlaaing peerd
not rated yet Jan 28, 2015
Who on earth calls this "common drugs"? All the ones mentioned have a serious effect on daily routine and behaviour and should only be described if all else fails and should never be prescribed for long term usage. The article suggests that people pop these like candies.

I would not be surprised if such heavy drugs can have a detrimental effect on the brain or people's behaviour.
PhotonX
not rated yet Jan 29, 2015
Wellll, I suppose I should stop taking Benadryl nightly...
Yes, this article gave me pause, too, about that. I don't take 50 mg of diphenhydramine *every* night, but have doing it regularly for several years now. Maybe it needs to come back off of the counter?
.
.
flying_finn
not rated yet Feb 02, 2015
Terrible disease. More info ;

http://www.scienc...r&ut m_medium=email&utm_campaign=Feed%3A+sciencedaily+%28Latest+Science+News+--+ScienceDail y%29

http://www.scienc...Daily%29

http://www.scienc...r&ut m_medium=email&utm_campaign=Feed%3A+sciencedaily+%28Latest+Science+News+--+ScienceDail y%29

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