A new study in the University of Washington provides strong evidence that certain popular drugs may increase the risk of 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, cold, and allergy medicines as well as in the treatment of an overactive bladder and depression.
Drugs And Dementia
The most commonly used drug linked to dementia is diphenhydramine, which is used in many popular products such as Benadryl, Nytol Sominex, Theraflu, Triaminic Allergy, etc. It is also implicated in drugs containing chlorpheniramine (Aller-Chlor); oxybutynin (Ditropan) and tolterodine (Detrol) for overactive bladder; and tricyclic antidepressants, such as doxepin or amitriptyline.1
Acetylcholine is a critical brain chemical involved in the transmission of 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).2
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 earlier.
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.3 4 5
Other drugs, like sedative hypnotic drugs (sleeping pills) and antihistamines, have also been linked to an increased risk of dementia. All of these drugs, both prescription and over-the-counter, are used at an alarming rate by the elderly population, putting them at significant risk for dementia.
To evaluate whether cumulative anticholinergic use is associated with a higher risk of 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.6
Exposure to anticholinergic drugs 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’s disease. A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer’s. In other words, the higher the cumulative anticholinergic use, the greater the risk of dementia. The highest risk threshold was taking the minimum daily effective dose of one of the anticholinergic agents every day for 3 years.
Even at low dosage or recommended levels, chronic use of these drugs should be avoided.
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.
The results from this study highlight the importance of avoiding long-term use of such drugs, including diphenhydramine 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.
|↑1||Basu, Ranita, Hiroko Dodge, Gary P. Stoehr, and Mary Ganguli. “Sedative-hypnotic use of diphenhydramine in a rural, older adult, community-based cohort: effects on cognition.” The American journal of geriatric psychiatry 11, no. 2 (2003): 205-213.|
|↑2||Richter, Judith A., Elaine K. Perry, and Bernard E. Tomlinson. “Acetylcholine and choline levels in post-mortem human brain tissue: preliminary observations in Alzheimer’s disease.” Life sciences 26, no. 20 (1980): 1683-1689.|
|↑3||Starr, John M., and Lawrence J. Whalley. “Drug-induced dementia.” Drug safety 11, no. 5 (1994): 310-317.|
|↑4||Ancelin, Marie L., Sylvaine Artero, Florence Portet, Anne-Marie Dupuy, Jacques Touchon, and Karen Ritchie. “Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study.” Bmj 332, no. 7539 (2006): 455-459.|
|↑5||Mintzer, Jacobo, and Alistair Burns. “Anticholinergic side-effects of drugs in elderly people.” Journal of the Royal Society of Medicine 93, no. 9 (2000): 457.|
|↑6||Gray, Shelly L., Sascha Dublin, Onchee Yu, Rod Walker, Melissa Anderson, Rebecca A. Hubbard, Paul K. Crane, and Eric B. Larson. “Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study.” bmj 352 (2016): i90.|