A new study out of the University of Washington provides the strong evidence that certain popular drugs may increase the risk for dementia in older adults. The drugs share some common mechanisms within key areas of the brain, but are used primarily as ingredients in over-the-counter sleep, cough and cold, and allergy medicines as well as in the treatment of an overactive bladder and depression.

The most commonly used drug linked to dementia was diphenhydramine, which is used in many popular products such as Benadryl, Nytol Sominex, Theraflu, Triaminic Allergy, plus many others. Also implicated where drugs containing chlorpheniramine (Aller-Chlor); oxybutynin (Ditropan) and tolterodine (Detrol) for overactive bladder; and the tricyclic antidepressants, such as doxepin or amitriptyline.

Background Data:

Acetylcholine is a critical brain chemical involved in the transmission of the nerve impulse and is especially important for proper memory and cognitive function. For example, Alzheimer’s disease is associated with a severe reduction in acetylcholine levels due to reduced activity of the enzyme that manufactures acetylcholine (choline acetyltransferase).

Given the link between low acetylcholine levels and poor brain function, including dementia, previous studies have linked drugs to reduced acetylcholine activity as well as mild cognitive impairment. These drugs include the ones mentioned in the introduction above. While discontinuation of the drugs is thought to reverse the mental deficit, there is evidence that anticholinergic drugs may produce permanent changes leading to irreversible dementia. These drugs are known to cause short-term drowsiness or confusion, which is included in the prescribing information, but the long-term effects these drugs have on mental function are generally not known by physicians or the people taking them.

Other drugs, like sedative hypnotic drugs (sleeping pills) and antihistamines have also been linked to an increased risk for dementia. All of these types of drugs, both prescription and over-the-counter, are used at an alarming rate by the elderly population putting them at significant risk for dementia.

New Data:

To evaluate whether cumulative anticholinergic use is associated with a higher risk for incident dementia, researchers examined medical records from 3,434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003 and data through September 30, 2012 were also included in these analyses

Exposure to anticholinergic was determined from computerized pharmacy records. Cumulative exposure was updated as participants were followed up over a 10-year period. About 20% of the population was found to be using anticholinergic drugs.

During the evaluation period, 797 participants (23.2%) developed dementia with 637 of these (80%) developing Alzheimer disease. A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease. In other words, the higher the cumulative anticholinergic use, the greater the increased risk for dementia. The highest risk threshold was taking the minimum daily effective dose of one the anticholinergic agents every day for 3 years.

Based upon these results, the authors of the study propose efforts to increase awareness among health care professionals and older adults about the risk of the use of these drugs over time. Even at low dosage or recommended levels chronic use of these drugs should be avoided.


The results from this study highlight the importance of avoiding long-term use of these sorts of drugs, including Benadryl and over-the-counter sleeping pills. What this research further establishes is that the human brain can be adversely affected by minor pharmacological agents highlighting the importance of using natural approaches that not only address the key issue (e.g., insomnia, allergies, etc.), but also have a positive effect on brain function. For example, the natural compound enzymatically modified isoquercitrin (EMIQ) has demonstrated significant anti-allergy effects and also has been shown to block the formation of beta-amyloid – a protein that is linked to causing the brain damage in Alzheimer’s disease.


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Gray SL, Anderson ML, Dublin S, et al. Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study. JAMA Intern Med. 2015 Jan 26. doi: 10.1001/jamainternmed.2014.7663.

Dr. Michael Murray

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