[olsen]

http://jnnp.bmj.com/cgi/content/shor...186239v1?rss=1

Neurol Neurosurg Psychiatry. Published Online First: 21 September 2009...


Use of drugs with anticholinergic effect and impact on cognition in Parkinson’s disease: A cohort study
Uwe Ehrt 1*, Karl Broich 2, Jan Petter| Larsen 1, Clive Ballard 3 and Dag Aarsland 4

1 The Norwegian Centre for Movement Disorders, Stavanger University Hospital, Norway...



Abstract

Background: Cognitive decline is common in Parkinson’s disease (PD). Although some of the etiological factors are known, it is not yet known whether drugs with anticholinergic activity (AA) contribute to this cognitive decline. Such knowledge would provide opportunities to prevent acceleration of cognitive decline in PD.

Objective: To study whether the use of agents with anticholinergic properties is an independent risk factor for cognitive decline in patients with PD...

Methods: A community-based cohort of patients with PD (n=235) were included and assessed at baseline. They were re-assessed four and 8 years later...
Results: More than 40% used drugs with AA at baseline. During the 8-year follow-up, the cognitive decline was higher in those who had been taking AA drugs (median decline on MMSE 6.5 points) compared to those who had not taken such drugs ... significant associations with decline on MMSE were found for total AA load (standardised Beta=0.229, p=0.04) as well as duration of using AA drugs (standardized beta 0.231, p=0.032).

Conclusion: Our findings suggest that there is an association between the use of drugs with anticholinergic properties and cognitive decline in PD. This may provide an important opportunity for clinicians to avoid increasing progression of cognitive decline by avoiding such drugs if possible. Increased awareness by clinicians is required about the classes of drugs that have anticholinergic properties.

[BEMM]

Oh no, this is very bad new indeed. AMANTADINE, the only medicine that can keep me in balance, is causing dementia. Devastating!
And the three years of taking it can not be reversed. It does make my head buzz, but without it I can't walk, I can't turn, it has been my miracle drug. What a dilemma - choosing between body and mind. Thank you Olsen, I am thankful to be told, at least I now know the gruesome truth, so the decision to take it or not is an educated, knowing decision.
But what to do?
birte

[mrsD]

There is a movement in geriatric medicine today to avoid
anticholinergic drugs in ALL elderly patients.

That even includes Benadryl!

All those ads you see on TV for overactive bladder? All are anticholinergic!

[BEMM]

After a lot of frantic search I am happy to report that though Amantadine appeared on the list of anticholinergic drugs I found yesterday, I have found more research results that claim Amantadine is neuroprotective. Now I have hope again.
Is it or is it not?
bad or good?


http://www.springerlink.com/content/rmu18yj1xt1d55gm/

Co-administration of memantine and amantadine with sub/suprathreshold doses of L-Dopa restores motor behaviour of MPTP-treated mice

[olsen]

I know most of the individuals on this forum are not considered "elderly", thought I would share this link anyway--list of drugs elderly should avoid and reasons why:
http://www.cbc.ca/news/background/se...able_more.html

[Conductor71]

Originally Posted by BEMM

After a lot of frantic search I am happy to report that though Amantadine appeared on the list of anticholinergic drugs I found yesterday, I have found more research results that claim Amantadine is neuroprotective. Now I have hope again.
Is it or is it not?
bad or good?

In the quest for better treatments and just to simply feel better, it seems like we run across so very much contradictory research. I would say check with your neurologist-take in the citation from the Norwegian study and he or she will look into it for you. Keep in mind, we only see part of the picture as we're usually given abstract access only. Without the full study, it's hard to extrapolate this research study. It seems a rather small sample and it is only ONE study. Also, what were the ages of those in the study group. Did it primarily affect people with older onset PD or young too? What were the rates of decline in both age groups (if both were even measured)- is there any statistical validity to it? Lots of questions to ask before you get super upset. I know it is incredibly frustrating; I was thinking of trying Amantadine as part of new treatment regimen but am also now fearful. Keep in mind that much of neurology thought that levodopa was toxic to us in the sense that it fostered cell death. It has been proven that this is not the case.

Hang in there!

Laura

[lindylanka]

Was taking an anticholinergic for hyperactive bladder till a few months ago, for approx 4 years. It began to lose it's effect, so I came off it, and some of the abulia affects that I had been suffering seemed to go, I am now using a patch, also anticholinergic, that does not seem to have the same effect, in fact the opposite, I am mentally a bit hyper! This world of meds is mystifying sometimes.....the cocktail thing is scary too......
Lindy

[girija]

Thanks for your analysis of abstracts Laura. I have posted similar messages a few times in the past. It is probably a good idea to repeat this message once in a while as several of us depend on PubMed for info.

I thought I would add a few points to Laura's message. There are a few things one can do to evaluate an abstract. Like everything in biology there are always exceptions to the rules!

Impact factor of the Journal. Generally high impact journals have solid papers that are comprehensive and data is reproducible and stands the test of time. Manuscripts go through peer review, usually 3 reviewers per paper. I think Pubmed has a link to impact factors of various journals.

Some of the low impact journals, do not even have peer review therefore whatever the author wants gets into the paper.

Prior history of the senior author, usually the last name on the abstract.
If the last authors' name brings in several papers on the same or similar topic, we can be assured that she/he knows the subject. It may not be mainstream and could be a controversial paper, at least there is a basis for their thinking

Time gap between the papers on the same subject. The last paper you see on topic X is in 1994 and if there are no other publications after that, I would take the conclusions of 1994 paper wiht a pinch of salt!

If you have the energy, getting the fulll length article and reading is the best!

I hope this information helps!

Girija




to simply feel better, it seems like we run across so very much contradictory research. I would say check with your neurologist-take in the citation from the Norwegian study and he or she will look into it for you. Keep in mind, we only see part of the picture as we're usually given abstract access only. Without the full study, it's hard to extrapolate this research study. It seems a rather small sample and it is only ONE study. Also, what were the ages of those in the study group. Did it primarily affect people with older onset PD or young too? What were the rates of decline in both age groups (if both were even measured)- is there any statistical validity to it? Lots of questions to ask before you get super upset. I know it is incredibly frustrating; I was thinking of trying Amantadine as part of new treatment regimen but am also now fearful. Keep in mind that much of neurology thought that levodopa was toxic to us in the sense that it fostered cell death. It has been proven that this is not the case.

Hang in there!

Laura[/QUOTE]

[Jaye]

AMANTADINE?????

Somebody who prescribed 3 amantadine a day for me is going to be hearing a question on this. Any ideas how to keep the adversarial tone out of my voice?

I should have looked it up on rxlist.com a long time ago, but after ten years of following every drug that looks interesting, I got lazy.

Memo to self: don't put anything in your mouth that you haven't investigated personally. Or at least, don't swallow!

[olsen]

First off a word of caution--consult with your physician about amantadine and One MUST NOT "cold turkey" off amantadine. If one were to discontinue this drug for any reason, one must be weaned off it.

Let's not beat ourselves up yet, though will join with you should amantadine turn out to be a major player vis a vis anticholinergic effect. I recall (and found thru recent (yesterday and today!) research that amantadine's 2 primary modes of action are that it is a dopamine releasing drug (causes a release of dopamine in the neurons increasing concentration of dopamine in the synaptic cleft and inhibits its reuptake) and it is an NMDA antagonist (see Rick's posting about glutamate and a new way to look at PD), and several references note this anti NMDA action is its predominate antiparkinson action. It's antichonlinergic effects are reported to be "indirect" in some references(ie amantadine was found to depress NMDA evoked acetylcholine release), barely detectable in some studies, though direct in others.

The following study is cited ONLY because of the description of amantadine--this was indeed a very poorly designed study, despite the fact it came out of johns hopkins
http://psy.psychiatryonline.org/cgi/.../full/45/3/205
"The precise mechanism of amantadine's brain action is unknown. It appears to have dopamine-modulating activity in the peripheral and CNS by augmenting the release and inhibiting the cellular reuptake of dopamine.10 Amantadine is also a N-methyl-D-aspartic acid receptor antagonist, which may indirectly enhance dopaminergic transmission and confer neuroprotective effects, similar to its analogue, memantine.11 Moreover, amantadine is known to alter the function of nicotinic acetylcholine receptors in muscle and has a weak antagonist effect on mammalian hippocampal nicotinic acetylcholine receptors. This may signify protective effects in neurodegenerative disorders or in cholinergic toxicity.12"
(my total knowledge of what "nicotinic acetylcholine receptors" function happens to be is from wikipedia...)

All this contradictory information is hurting my head; i am going to bed, to take up the investigation in the morning. My husband takes amantadine; it is the first drug prescribed for him during his first consultation with a neurologist. We have emailed his neurologist for assistance.