Strong Link Found Between Dementia and Common Anticholinergic Drugs (2015)

My goto anti-hayfever drugs are Loratadine and Cetrizine in generic non-branded packets for cost reasons. OP's article worried me because I regularly take one or both of them for two months straight over summer.

The article states that Loratadine is recommended as an alternative for the relief of allergies. The article didn't explicitly mention Cetirizine but I have done some research and came across another article from 2012 which does include Cetirizine in the same category as Loratadine:

http://www.pharmacytimes.com/publications/issue/2012/april20...

I believe I am safe to continue using Cetirizine and thought some of you may have the same question. I am not an expert on these issues so if I'm mis-understood any of this please let me know.

> ...“basically any cold medications that make you sleepy might contain anticholinergics, so stay away from drugs that make you sleepy.” NyQuil is an exception, he said. It makes people sleepy, but does not contain an anti-cholinergic. Still, “if your solution for a sleep problem is a pill, a quick fix, do you want that?” Any drug taken for a long time could come with problems.

Over the counter sleep medicines lose their effectiveness when taken regularly, so it people are less likely to do so (vs. taking such medicines for allergy relief).

Also NyQuil contains doxylamine [1], which is an anticholinergic, and is listed with the other problematic medicines [2].

[1] https://www.google.com/search?q=nyquil%20active%20ingredient... [2] http://www.agingbraincare.org/uploads/products/ACB_scale_-_l...

As a narcoleptic, I have no trouble falling asleep, the trouble is with staying asleep and getting deep rest during my sleeping periods. I've found that some nutritional strategies work tremendously well.

http://main.poliquingroup.com/ArticlesMultimedia/Articles/Ar...

Personally, I only supplement 4 nutrients and it has been a tremendous sleep quality improvement.

Vitamin D3 in the AM Taurine & Magnesium Glycinate prior to sleep. L-Theanine is also added depending on whether I took caffeine during the day.

For my wife who also has sleep problems, she takes Ambien, but Ambien + Taurine will knock her out, while she can still wake up on Ambien alone.

Firstly, the article is open why not simply link it? Second -- people take these medications to help them sleep. Difficulty sleeping is a comorbidiy of dementia. I haven't made it through the paper yet -- but pointing out anything other than association seems awfully premature.

Link: http://archinte.jamanetwork.com/article.aspx?articleid=20917...

Poked around a bit and ran across at least one article [1] that advises caution but also points out that these results are seen in fairly high/frequent doses, are still being studied, and that anyone prescribed or currently taking an anticholinergic medication should check with their doctor before just stopping the drug. The way I see it, not everyone is necessarily at risk and as with many things, the outcome of not taking the medication could be worse than the potentially higher risk of negative outcomes from taking the medication.

Either way, something to consider.

[1] http://www.nhs.uk/news/2015/01January/Pages/media-dementia-s...

Can we have the data to see if their statistics are good and that they applied the right techniques to clean their data? I don't trust any medical study much anymore because next week one will come out refuting this claim.

Complete list (more or less) of affected drugs:

http://www.virginiageriatrics.org/consult/medications/medsLi...

I've seen many people claim choline has nootropic effects (i.e. that supplementing it is good for cognition), so this doesn't seem surprising.

Note: I am not a doctor, and this is not medical advice.

While not a new result, it is very scary none-the-less. Some of those drugs are a daily goto for many people to handle various issues. I hope medical professionals will take this result into account before recommending them for any longterm treatment.

Here is an article that talks about possible mechanisms: http://sci-hub.io/http://content.iospress.com/articles/journ...

"Another implication of the ability of cholinergic antagonists to promote dementing diseases is that sufficient choline needs to be provided so that adequate PC production can continue. This might most effectively be done by administering the choline as a component of a nutrient mixture that contains all three of the PC precursors which limit PC’s rate of synthesis: uridine as its monophosphate; DHA or EPA; and choline [24]. This mixture has been shown to diminish Aβ formation in experimental animals [32], and could have the added benefit of partially restoring the deficient brain synapses."

This is consistent with the Cholinergic hypothesis[1] of Alzheimer's disease. Also, note that the various hypotheses for Alzheimer's are not really "competing", so this doesn't mean that the more recent lines of research are any more or less valid.

Alarming stuff! I've no problem giving up Benydryl, but my partner takes Disiprimine,and it's the only drug she's found that works well for her depression :-(

[1] https://en.wikipedia.org/wiki/Alzheimer%27s_disease#Choliner...

From the source [1]: "study participants 65 years or older were sampled randomly from Seattle-area GH members. Participants with dementia were excluded. The original cohort of 2581 participants was enrolled from 1994 through 1996. An additional 811 participants were enrolled from 2000 through 2003. In 2004, the study began continuous enrollment to replace those who died or dropped out."

[1] http://archinte.jamanetwork.com/article.aspx?articleid=20917...

This result echoes previous research into links between cognitive decay and use of paracetemol:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921468/

The suggested mechanism is that coal tar derived medicines trigger a self sustaining inflammation reaction which causes generation and accumulation of amyloid plaques.

Most peoples anti-hayfever drugs will be 'second generation' antihistamines, like loratadine and cetirizine, which are not problematic.

More worrying to me is the fact that OTC antiemetic (motion sickness) drugs like Gravol/Dramamine/Vomex/Dramina are made of dimenhydrinate, which is 50% diphenhydramine, which in turn is what the mentioned 'first generation' antihistamines are made of.

What is the difference between a branded drug like Tylenol and paracetamol?

Does anybody know if this also concerns drugs taken with an inhaler? I use an inhaler for allergic asthma and am not sure if the drug is "anticholinergic".

Great, I took berodual for years because of asthma :/

Interesting, especially the finding that the dementia is correlated with multiple different anticholinergic drugs, but the counter-argument is simple: people taking lots of medications are probably less healthy in general, and therefore more likely to develop dementia.

Since there's no ethical way to do a prospective study, this is more suggestive than anything else. They admit they don't know the mechanism yet, so take with a grain of salt.

SSRIs, contrary to the article are all potent anticholinergic.

Got around to reading the primary source. I am surprised there isn't more skepticism from this group, but it may have to do with not having time to read the paper. A few reasons to be skeptical of the results (some are stronger than others):

1) First, required reading for anyone interpreting medical studies: http://jama.jamanetwork.com/article.aspx?.articleid=201218 TLDR; is that ~40% of _randomized_ (generally considered highest level of quality) studies and maybe more are proven wrong by subsequent ones resulting from publication bias. Consider that this would not have been published in a high profile journal if it showed no effect, hence pub bias. In other words, we're not seeing the similarly large analyses that show no effect because they're not published.

2) The adjusted analyses have confidence intervals on the odds ratio that overlap with 1.0 except for the highest dose group. There is evidence of a dose response relationship, but there is a problem in how they measure dose response. Cumulative dose biases towards people who have been on medications for a long time. People who are able to take medications (ie are older) for a long time are at greater risk for dementia.

3) It is problematic that they assume any effect on their endpoint is a class effect (ie true of all anticholinergics). The relationship with one medication may be driving this effect entirely. I would like to see, for example, oxybutynin pulled out of the analysis which is never prescribed for allergies and more often for neurological conditions, which could be an unmeasured confounder depending on how they modeled the comorbidities.

4) Controlled analyses are difficult to do well. Most of the time it controls for linear effects, meaning synergistic effects (which are probably involved in development of dementia) are not captured unless explicitly modeled. I do not see that they did this here.

5) I am further suspicious of the way they obtained fill data. As you are noting, many OTC anticholinergics are not "dispensed" in a way typical of prescription anti-cholinergics. If I bought Benadryl at CVS or even if I bought the pre-packaged bottle at the Group Health pharmacy, it's pretty clear to me that neither of these would be reflected in the data. This skews heavily toward prescription anti-cholinergics, which tend to be given for psych/neuro indications which themselves have an association (though likely not a causal one) with dementia. Again, unclear if they modeled all of these.

Overall, I share the sentiment that medical literature needs to be more open. I think it's unfortunate that current state makes it hard to confirm analyses like these with a great degree of certainty.

Should have 2015 in the title, it's not a new finding at all.

For those like myself that freak about this kind of stuff, and did not read through carefully, the effect is pretty small and requires taking a lot of benadryl:

"Three years of taking either daily Benadryl, Advil PM, Tylenol PM, or Motrin PM, for example, is associated with about a ten percentage point increase in the probability of experiencing dementia or Alzheimer's compared to no use."

As usual big pharma is poisoning us in the name of profits.

I have lost all trust in modern medicine. It doesn't mean I don't use it, but I avoid it and find alternatives whenever I can.