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Back in 2015 and 2016 some studies found a link between taking medicines that are anticholinergic and cognitive decline and dementia. Some examples of non-prescription anticholinergic medications are Chlor-Trimeton, Benadryl, Tavist, and Dimetapp. During this time a person also contacted me to report that his relative, who had Down's syndrome, had once participated in a study where he received cholinergic therapy, with the result that during the study he functioned better neurologically. Meanwhile I read several studies of older people that supported the result of a higher intake of foods with choline and better neurological functioning (e.g. verbal and visual memory).

A recent large study of men over a 4 year period found an association between a  higher intake of foods with choline (dietary choline) and better performance on several cognitive tests and lower risk of dementia. The research, which was conducted in Finland, found that the relationship seemed especially strong for a type of choline called phosphatidylcholine. Eggs (specifically the egg yolks) are a primary dietary source of phosphatidylcholine, and indeed, in the study, higher egg intake was associated with better performance on several measures, including verbal fluency, as well as lower risk of dementia.

Choline is an essential nutrient, found in some foods. Its role in the body is complex, but one of its roles is to produce acetylcholine, an important neurotransmitter for memory, mood, muscle control, and other brain and nervous system functions (NIH choline fact sheet). On the other hand, anticholinergic medications block the action of the neurotransmitter acetylcholine (which is involved with learning and memory). Anticholinergic medications include many common drugs, such as some antihistamines, sleeping aids, tricyclic antidepressants, medications to control overactive bladder, and drugs to relieve the symptoms of Parkinson’s disease.

What should one do? First, make sure to eat some foods rich in choline, especially eggs. The researchers themselves say that "consuming an adequate amount of foods high in choline may be an easy, effective, and affordable way to maintain cognitive functioning". Good sources of choline are meat, dairy products, poultry, and eggs - and it appears that eggs (the egg yolks) are especially beneficial. Second, one should also try to avoid non-prescription and prescription medicines known to be anti-cholinergic. For example switch from allergy medicines diphenhydramine or chlorpheniramine (Chlor-Trimeton) to one that isn't anticholinergic. [See list.]

From Science Daily: Dietary choline associates with reduced risk of dementia  ...continue reading "The Choline In Eggs Is Beneficial For the Brain"

Another study showing big problems with anticholinergics, which are in many popular medicines - both non-prescription and prescription (e.g., Chlor-Trimeton, Benadryl, Tavist, Dimetapp). An earlier study with older adults found a dose-response link with dementia, but the current study explored this issue further. They followed 2 groups of  "cognitively normal older adults" in their early 70s for several years: those who took anticholinergic medicines and those who did not take anticholinergic medicines. They found that those who took anticholinergic medicines had reduced brain volume (brain shrinking) and cognitive decline (when compared to those who did not take anticholinergic medicines). The researchers summarized their findings as the "use of anticholinergic medication was associated with increased brain atrophy and dysfunction and clinical decline". This finding was greatest for those taking drugs with the most anticholinergic activity.

See a list of anticholinergic medicines  from the Aging Brain Program of the Indiana University Center for Aging Research. Definitely try to avoid medicines with a score of 2 (medium effect) or 3 (high effect), but I would even be cautious about score 1 (low effect) medicines - use all medicines only as long as absolutely needed. My one very important question is: If these effects are found in older adults, what do anticholinergics do to younger brains, especially the developing brains of children? From Medical Xpress:

Brain scans link physical changes to cognitive risks of widely used class of drugs

Older adults might want to avoid a using class of drugs commonly used in over-the-counter products such as nighttime cold medicines due to their links to cognitive impairment, a research team led by scientists at Indiana University School of Medicine has recommended. Using brain imaging techniques, the researchers found lower metabolism and reduced brain sizes among study participants taking the drugs known to have an anticholinergic effect, meaning they block acetylcholine, a nervous system neurotransmitter.

Previous research found a link between between the anticholinergic drugs and cognitive impairment and increased risk of dementia.....Drugs with anticholinergic effects are sold over the counter and by prescription as sleep aids and for many chronic diseases including hypertension, cardiovascular disease, and chronic obstructive pulmonary disease. A list of anticholinergic drugs and their potential impact is at http://www.agingbraincare.org/uploads/products/ACB_scale_-_legal_size.pdf.

Scientists have linked anticholinergic drugs and cognitive problems among older adults for at least 10 years. A 2013 study by scientists at the IU Center for Aging Research and the Regenstrief Institute found that drugs with a strong anticholinergic effect cause cognitive problems when taken continuously for as few as 60 days. Drugs with a weaker effect could cause impairment within 90 days.

The current research project involved 451 participants, 60 of whom were taking at least one medication with medium or high anticholinergic activity. The participants were drawn from a national Alzheimer's research project....and the Indiana Memory and Aging Study. To identify possible physical and physiological changes that could be associated with the reported effects, researchers assessed the results of memory and other cognitive tests, positron emission tests (PET) measuring brain metabolism, and magnetic resonance imaging (MRI) scans for brain structure.

The cognitive tests revealed that patients taking anticholinergic drugs performed worse than older adults not taking the drugs on short-term memory and some tests of executive function, which cover a range of activities such as verbal reasoning, planning, and problem solving. Anticholinergic drug users also showed lower levels of glucose metabolism—a biomarker for brain activity—in both the overall brain and in the hippocampus, a region of the brain associated with memory and which has been identified as affected early by Alzheimer's disease. The researchers also found significant links between brain structure revealed by the MRI scans and anticholinergic drug use, with the participants using anticholinergic drugs having reduced brain volume and larger ventricles, the cavities inside the brain.

Finding an increased risk of dementia and Alzheimer's with so many common over-the-counter medications such as Benadryl and  Chlortrimeton (the first generation allergy drug that so many people took for years) was an unpleasant surprise. Note: they found the link with high doses or heavy use (3 or more years). Some examples of common anticholinergics (from Wikipedia) are: atropine, benztropine (Cogentin), chlorpheniramine (Chlor-Trimeton), dimenhydrinate (Dramamine), diphenhydramine (Benadryl, Sominex, Advil PM, etc.), doxylamine (Unisom), hydroxyzine (Atarax, Vistaril), ipratropium (Atrovent), oxybutynin (Ditropan, Driptane, Lyrinel XL), tolterodine (Detrol, Detrusitol), tiotropium (Spiriva), and bupropion (Zyban, Wellbutrin). The message here: only take medications when absolutely needed and for as little a time as necessary. The study was done on older adults, so now the question is: what about children or young adults who take these drugs for years? Is there a similar increased risk later in life? From Medical Daily:

Common Over-The-Counter Anticholinergic Drugs Like Benadryl May Increase Your Risk Of Alzheimer's

Anticholinergic medications span a range of common drugs and include antihistamines, sleep aids, antidepressants, cardiovascular meds, gastrointestinal drugs (for diarrhea, incontinence, diverticulitis, and ulcers), and muscle relaxants. Now, a new study confirms the link between these everyday medications and dementia. Taking anticholinergic drugs at high doses or for a long time may significantly increase your risk for developing Alzheimer's disease and other dementias, say researchers from University of Washington School of Pharmacy.

“If providers need to prescribe a medication with anticholinergic effects because it is the best therapy for their patient, they should use the lowest effective dose, monitor the therapy regularly to ensure it's working, and stop the therapy if it's ineffective,” Dr. Shelly Gray, a professor and director of the geriatric pharmacy program at the UW School of Pharmacy said in a release.

On average, older people take four or five prescription drugs and two over-the-counter drugs each day. Clearly, drugs are an important part of medical care for older people; however, older people are more sensitive to the effects of many pills, including anticholinergics, which block the neurotransmitter acetylcholine and so effect the nervous system. While the drugs are too numerous to mention, those with anticholinergic effects — and these effects are sometimes dependent on the dose include Benadryl, Sominex, Xanax, Ativan, Valium, Luminal, Skelaxin, Limbitrol, and Tavist.

For the current study, the researchers investigated a previously reported link between anticholinergics, both prescription strength and over-the-counter, and dementia by employing more rigorous methods than in the past. Specifically, the researchers conducted a longer follow-up of more than seven years and more accurate use assessment via pharmacy records, which included nonprescription choices. The team tracked nearly 3,500 seniors participating in a long-running study, the Adult Changes in Thought (ACT), a joint project of UW and the National Institute on Aging.

The most commonly used medications in the study, the researchers discovered, were tricyclic antidepressants like doxepin (Sinequan), antihistamines like chlorpheniramine (Chlor-Trimeton), and antimuscarinics for bladder control like oxybutynin (Ditropan). 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, the researchers estimated, would be at greater risk for developing dementia. Importantly, substitutes are available for some of these drugs.  

While this study is the first to show a dose response — meaning, the more you use anticholinergic medications the greater your risk of developing Alzheimer’s — it also is the first to suggest this higher risk may persist, and may not be reversible, even years after you stop taking these drugs. 

Source: Gray S, Crane P, Dublin S, et al. Cumulative Use of Strong Anticholinergic Medications and Incident Dementia. JAMA Internal Medicine. 2015.