'Strongest Evidence Yet' Links Anticholinergic Drugs, Dementia

[MarcR]

The study was published yesterday. The Medscape summary is more informative than the abstract:

'Strongest Evidence Yet' Links Anticholinergic Drugs, Dementia

"We found an obvious dose-response relationship between anticholinergic drug use and risk of developing dementia: the higher the usage, the greater the risk," Dr Gray commented to Medscape Medical News.

Even Low Doses Implicated

But people taking just the minimum effective dose of these agents for prolonged periods qualified as having high use and were found to be at greater risk for dementia compared with those not taking such medicines.

"This is not excessive use," Dr Gray said. "Many of these agents are used chronically, and chronic use — even at low doses — would put you in the highest risk category."

While on Medscape I also noticed these related articles:

Just 2 Months' Exposure to Anticholinergics Affects Cognition
Pain Patients at Cognitive Risk From Anticholinergic Burden?

Here's a link to Silverlining's topic listing common anticholinergics:

List of Anticholinergic Drugs with Burden Assessment

[Stavia]

good find!
Scary stuff.
I'm SO glad I got off my amitryptilene....

[TheBrain]

Thanks, merouleau. This is, indeed, scary stuff.

I took Doxepin for at least 13 years for sleep and chronic pain. Yesterday, I ordered a choline supplement. Not only because of this connection but because I also have the SNP variant that makes me most at risk (rs7946 = TT).

Here's some information I found:

Acetylcholine/Choline Deficiency in Chronic Illness – The Hunt for the Missing Egg
http://geneticgenie.org/blog/2013/10/21 ... ssing-egg/

According the National Health and Nutrition Examination Survey (NHANES) in 2003-2004, only about 10% of the population have an adequate intake of choline. This means about 90% of the population consumes a diet deficient in choline. Furthermore, those without an adequate intake of choline may not have symptoms.

Along with folate and B12 deficiency, inadequate consumption of choline can lead to high homocysteine and all the risks associated with hyperhomocysteinaemia, such as cardiovascular disease, neuropsychiatric illness (Alzheimer’s disease, schizophrenia) and osteoporosis. Inadequate choline intake can also lead to fatty liver or non-alcoholic fatty liver disease (NAFLD).

The most common symptoms of choline deficiency are fatty liver and/or hemorrhagic kidney necrosis. Consuming choline rich foods usually relieve these deficiency symptoms.

SNP: rs7946 (C or T) on PEMT (chromosome 17)

TT Moderately higher odds of developing Non-alcoholic fatty liver disease
CC Typical odds of developing Non-alcoholic fatty liver disease
CT Slightly higher odds of developing Non-alcoholic fatty liver disease

[Sandraz]

Hi all!
I looked at the list at this link from Silverling via Merlou and here is the direct link
http://www.magellanofaz.com/media/75730 ... e_2014.pdf

So they divide the drugs up as a risk 1 (lowest) 3 (highest risk) with the caveat from the article and Merlou that even low doses or low risk taken regulularly becomes a high risk!,

Looking at the list I was shocked at how many OTC drugs are on it. So what is an apoe4 to take if allergies are a problem? The ONLY antihistamine I know of that is not on the list is Allegra (fexofenadine). No more Claritin for me. Sudafed is on there, so maybe Afrin nose spray if very bad congestion for a few days if bad cold.

I see that all the anti-dizzy drugs are on there, so if going on a cruise or something, no transderm Scop(rx), no meclizine, no Dramamine. But I notice Zofran (ondansetron rx) is not listed so that would be good for seasickness induced nausea.
For sleep all the benzos are listed as 1's but Benadryl , which is tylenolol pm is a 3!!
Zantac and Tagamet for stomach acid issues are a 1 & 2, but none of the proton pump inhibitors are listed so looks like Prilosec and Prevacid and nexium are ok.

This article real eye opener for me because I will be changing what I tell people to try OTC especially if they are older!

No wonder AD is on the rise if the everyday available drugs increase risk along with lifestyle, food choices, and of course, genetics.

[Julie G]

Not so fast on the PPIs I remembered reading about a study last year that linked them to dementia:

Study: Long-Term Use of Acid Reflux Meds May Increase Dementia
http://charlottesville.legalexaminer.co ... ntia-risk/

And this older paper:

Proton pump inhibitors: predisposers to Alzheimer disease
http://www.ncbi.nlm.nih.gov/pubmed/20456731

As if that wasn't enough to scare us off...I found this:

Research shows proton pump inhibitors may cause cardiovascular problems
http://www.news-medical.net/news/201307 ... ovascular-

Maybe Cimetidine (Tagamet), an H2, but NOT anticholinergic medication may be the safest antacid to use- especially on a long term basis.
---------
I dug a little deeper and found that fexofenadine/Allegra IS an anticholinergic medication. Maybe it didn't make the list because it's anticholinergic properties are lower?

I found this paper comparing the anticholinergic effect of ten different H1s:

Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models.
http://www.ncbi.nlm.nih.gov/pubmed/1562743

They conclude that fexofenadine (Allegra) AND ceretizine (Zyrtec) have the lowest anticholinergic properties. However, given the fact that fexofenadine didn't make Silverlining's link, I'm guessing that may be our safest bet

I'd love to hear your thoughts, Sandra. We're lucky to have a resident pharmacist

[RichardS]

It's been a while, but I previously did an extensive review of the cognitive effects of anti-histamines for a published paper. The bottom line for cognitive effects was that if the anti-histamine caused sedation, adverse cognitive effects were found. All the newer anti-histamines advertised as non-sedating should not be a cause for concern in the short- to medium-term. Long-term controlled trials (>6 months) are basically absent from the literature. The essential factor for whether or not an anti-histamine caused sedation was its ability to cross the blood brain barrier.

Please forgive the lack of a citation here. I'm still trying to maintain some modicum of anonymity online.

[Stavia]

It would make sense intuitively. No sedation can happen without crossing the BBB. Once thru the BBB bad things can happen.
Btw corticosteroid nasal sprays and antihistamine eye drops are an option for hayfever. But seriously the occasional cetirizine or loratidine has to have very teeny risk, prolly less than breathing in polluted city air. We shouldn't be too paranoid.
And sedatives - I don't think there are any that are safe from a cognitive point of view.

[pgf54]

well that's a bit of synchronicity for you , I intended to ask the group about ppi's today and I read Julies post.
I was put on a ppi last year and I noticed two things , my blood pressure began to slowly increase and it caused shall we say a mens health issue. I went back to the pharmacist and he retorted no such side effects had ever been noted. I was also worried about B12 absorption issues. At the time I began to drink beetroot juice as a natural source of nitric acid and vasodilator, to counteract the effects , though probably not so good from the natural sugar point of view,..........Until I read Julies link I thought perhaps it was just me but the article on ppi's and cardiovascular disease confirms my suspicions. I wouldn't take it after two months....
Incidentally I was scoped in September and have minor gastric erosions and was told to go back on the ppi.
I haven't as yet..because of my previous experience.

[Stavia]

Btw Julie we don't use cimetidine anymore. It has numerous interactions thru its effect on the cytochrome P450 pathway. I haven't prescribed it in over 20 years since there have been safer alternatives. Ranitidine is currently the H2 of choice safety wise, looking at the whole side effect profile.

[Julie G]

Good to know, Richard. Thanks.

Also, good to know, Stavia. Scratch that one. It looked like an option when I saw that ranitidine was anticholinergic and cimetidine wasn't. Tagamet/cimetidine is still available OTC, I think, but you've talked me out of it.

We're lucky to have you both.

I've decided that E4s must pursue optimal health as zero medications are safe for us