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Classification

The classification section was created as a way of reducing the load of techinichal terms in the lead. However the lead has been greatly improved and includes all important information with a good equilibrium between technical and common terms. At this point the classification section is just "the poor sister of the lead" having less information, less citations and globally less quality than the lead, and not adding any extra information. Is it needeed right now? I clearly believe its not. Its elimination will supposse any problem and will be an improvement.--Garrondo (talk) 08:41, 6 March 2008 (UTC)

If word like "Aβ" and "ApoE" are happy lower down - I'm fairly OK with losing it. Classification is suggested in WP:MEDMOS, but it's only a guideline, of course - and it could always come back if needed. My worry is that those technical words might suddenly pop up in the lead! the Classification section could be useful simply to keep good-faith editors from looking to improve the Lead with those handful of ubiquitous technical terms - and in doing so compromising its readability.
Personally, I always think the term "progressive" should be in Classification and not the Lead -it means nothing to many people (simple though it sounds) and is fully covered in the lines on symptoms. We begin the article with a word that people don't really know, as many are obliged to wikilink away from the page before they read it! Maybe Classification just needs a re-write?--Matt Lewis (talk) 13:00, 6 March 2008 (UTC)
I believe that almost anybody understands progressive, and its not a medical term... I believe that if there is a good lead as we have now there is no sense in rewritting classification and the better it gets the more difficult would be to "pop up" technical words in the lead. One thing I have seen in wikipedia is that quality brings quality (and this article is a good example)... don´t worry about going back... :-) (and anyway we will be here to help...) Apart from all classification section should classify it... its not a summary of the article, and this classification has never done that. I'm going to eliminate it and see what happens. --Garrondo (talk) 08:36, 8 March 2008 (UTC)
I assume "Progressive illness" actually is a medical term? (if not it's definitely not the best word!). Alzheimer's is indiscriminate over education and country, remember. The USA is more fond of technical words that anywhere else in the world. You also have to pay for your own healthcare individually - so it is more of a personal concern, and it's a cultural thing too (using technical words that is). In the UK we have our healthcare paid for by the state. I would say possibly less than 50% of us here will provide you with an accurate definition of a "progressive illness"! "Progressive" is just not a household word here - and is a touch too abstract to be an obvious extension of "progress". Many (most) people asked will either define it as "continual", or need to think about it first. I know the UK pretty well! We let our GP's do everything. --Matt Lewis (talk) 16:17, 8 March 2008 (UTC)
Would "Degenerative disease" be more acceptable?LeadSongDog (talk) 16:34, 8 March 2008 (UTC)
It probably would be less ambiguous in the UK - but both these almost-identical aspects of AD (progessive and degenerative) are clearly described by the symptoms - so neither is actually needed in the opening line. The word "progressive" was repeated in Classification for sure - but rather than remove the Classification section, perhaps this word (and any others like it) should be there instead? --Matt Lewis (talk) 10:16, 10 March 2008 (UTC)
I don't really see much difference between both terms, but my mother language is spanish... so I'm not the most indicated to give an opinion. --Garrondo (talk) 17:28, 8 March 2008 (UTC)
I think this article having some level of technical terminology is fine. I dislike assuming the lowest common denominator for the readership. The lead should be easy to read, but the details need to be clear. The CAM woo that one finds on Wikipedia utilizes weak language and "friendly" terms to get convince people that diluting a compound retains a water memory. And Matt, you have a rather harsh assessment of the US and UK health care systems. OrangeMarlin Talk• Contributions 17:46, 8 March 2008 (UTC)
Sure, but we are talking about the Lead - we have the rest of the article for the technical terminology. I don't think you need worry about homeopathy etc appearing in here. We just need to follow medmos. We are moving away from General Practitioner authority in Wales (ie the local GP-run surgeries) - and most of us are looking forward to it, as it would mean a more controlled and specialised service in larger, better surgeries. Not sure how I was harsh on the US!? Unless it wasn't a fair judgement to say it isn't social care! People have to have more knowledge in the US - healthcare is a huge personal part of their lives. People in the UK have traditionally put themselves often unquestioningly in the trust of the NHS and their local GPs - but the service getting worse in many respects (GPs now earn about the equivalent to over 200,000 dollars a year, and are doing less work - and we can't guarantee how broad or uniform their knowledge is - and the NHS has some long waiting lists, which is simply due to its financing and structure as we all happily put a fortune into it). Finally we are looking at GP-level, which can only help the broader picture. I'm not knocking the NHS - it just started to get sectioned-off and over-consulted in the 80's and 90's, and the service has in many ways declined ever since - that's not a controversial statement over here. As for the US, that's up to the US people! --Matt Lewis (talk) 19:27, 8 March 2008 (UTC)
Just for curiosity. What do you mean with CAM woo? I didn´t understand you. --Garrondo (talk) 17:58, 8 March 2008 (UTC)
Yes, what's CAM woo? I got a digicam company on Google!--Matt Lewis (talk) 19:27, 8 March 2008 (UTC)
Funny, I asked the same Q recently. The dab page for CAM lists Complementary and alternative medicine.
Look up woo woo in Wiktionary, the free dictionary.

Put'em together. LeadSongDog (talk) 03:02, 9 March 2008 (UTC)

CAM is Complementary and alternative medicine. Woo is "non-science or anti-science". Some might define woo as bovine feces.  :) OrangeMarlin Talk• Contributions 16:11, 11 March 2008 (UTC)
I shared my worries with a mental health nurse (in a managerial role) whether "progressive" could easily be understood as "continual", and she agreed - many, if not most, people in the UK won't immediately assume the intended "changing-state" meaning. --Matt Lewis (talk) 10:16, 10 March 2008 (UTC)
I've changed to "Degenerative disease" as suggested by LeadSongDog above. Its article actually refers to the AD page - and seems to fit in well, or better at least. I also replaced "debilitating" with it towards the end of the Lead (as I was searching for something more like "degenerative" at the time).

AB image

The (in German) article has an interesting graphic. Anyone care to offer an opinion on whether it could be helpful if translated?LeadSongDog (talk) 20:19, 11 March 2008 (UTC)

Images

Last months there has been a clear improvement in the texts of the article, however no new images had been added. I have added seven images trying to create a more friendly-viewing article. I hope everybody likes them... :-) --Garrondo (talk) 18:04, 15 March 2008 (UTC)

Nice. There's also an image of the tangles that we may want in the US Surgeon General's report, presumably PD-USGov:

Satcher David; et al. (1999). "Alzheimer's Disease Mental Health: A report of the Surgeon General". {{cite web}}: Explicit use of et al. in: |author= (help) LeadSongDog (talk) 14:03, 19 March 2008 (UTC)

A review

Looking at this version. Be aware that I can't read any of the paid-for journals. I've looked (for now) at just one section (and its counterpart in the lead).

Herpes and Alzheimer's

Hey, I found some really interesting information about a link between Herpes Type 1 and Alzheimer's. I already put it in the herpes page. I thought I'd ask here first how it could be put in here before actually putting it in because I'm afraid of screwing up such a good article. Anyway, here's what I wrote on the herpes page:

Alzheimer's disease

Scientists have discovered a link between Herpes Simplex Type I and Alzheimer’s Disease. In the presence of a certain gene variation (APOE-epsilon4 allele carriers), HSV type 1 appears to be particularly damaging to the nervous system and increases one’s risk of developing Alzheimer’s disease. The virus interacts with lipoproteins, their components, and their receptors in the brain which may lead to the development of the disease.[41] This now makes the virus the pathogen most clearly linked to the establishment of Alzheimer’s.[42] It is important to note, however, that without the presence of the gene allele, HSV type 1 does not appear to cause any neurological damage and thus increase the risk of Alzheimer’s.[43]

I was thinking about using at least part of this (altered if needed) in the CAUSES section. What do you think? --Saritamackita (talk) 01:50, 17 March 2008 (UTC)

Search for pubmed.com to see how many articles the topic has. Observe not only the number but also the credibility (are there reviews on the topic?, what do they say?, all articles agree in the conclussions or there are more disagraing that agreeing?). If after that you are convinced on the importance be bold and edit the article. You should probably reduce it to a setence wich makes clear the importance it has; no more no less. An example would be something like "Some articles have found a relation between HSV and AD, althoug this findings are disputed.(REf).--Garrondo (talk) 13:30, 17 March 2008 (UTC)

Sounds good. I've seen a lot of articles about it. Doesn't seem to be disputed too much. I think I'll put in the sentence.

Saritamackita (talk) 17:25, 17 March 2008 (UTC)

I've done a quick search through articles regarding this link. It appears the link between Herpes simplex and AD genes is being uncovered, but it's not conclusive yet. I would reword any addition to this article to state "may play a role." OrangeMarlin Talk• Contributions 18:48, 17 March 2008 (UTC)
I don't know. What I saw seemed pretty conclusive. Are you sure it's not just scientists putting "and more research is needed..." because that's kind of a scientific tradition around.Saritamackita (talk) 21:57, 19 March 2008 (UTC)

Clinical Trials - Table?

I have the idea to do a Table showing the various ongoing clinical trials in a possible DMD (not symptomatic-only) for AD - it would basically give the drug candidate name, the class/type (eg gamma secretase modulator, anti-amyloid-beta vaccine, antibody, etc), and a few other details (cite earlier results if published, perhaps the trial size, official start date, intended completion date). I think this will be a big focus in the next few years, and perhaps one will even work. BUT - has this been done already somewhere else? Is it in any of the citations that people here know of ? No use re-inventing the wheel if it exists already....thanks....io-io (talk) 22:59, 17 March 2008 (UTC)

Here's my concern with clinical trial tables--they give the impression that they both work and will be available soon. For example a Phase I drug may not be available for 5-10 years at best. A Phase III drug may fail. And labeling isn't available. I think that in a paragraph, a brief mention of the drugs in trial can be mentioned with appropriate citations. But this is MY opinion only. I just don't think Wikipedia articles should be advertisements for the drug companies. OrangeMarlin Talk• Contributions 23:49, 17 March 2008 (UTC)
How could such clinical trial lists on Wiki be advertisements for the drug companies if the drugs are not available, nor indeed, the trials are not even completed yet ? ...io-io (talk) 23:53, 17 March 2008 (UTC)
Because this article is #1 on Google, and people will read it, and push to get the drug. Again, it's my opinion, but I don't like discussing future drugs, except in context of research. I would suggest we take a look at all other medical articles and see how other articles handle it. Certainly, don't do what I think, I'm just giving you my opinion. OrangeMarlin Talk• Contributions 23:57, 17 March 2008 (UTC)
The clinical trials are designed not by demand, but by design (statistical basis)...the process is first clinical trials, and only if they succeed, apply and (hope to) get approval from FDA or EMEA for approval...until all that is done, no-one but the human guinea-pigs can get the drug. As for future drugs, they specifically target such things that are discussed in the disease pathology, such as A-beta, Tau, etc - that is what fascinates me, have they truly found the answer (or did the little white mice fool them)...io-io (talk) 00:08, 18 March 2008 (UTC)
There is simply no way that WP can do a good job of covering every trial. See Clinical Trials database to see how many are going on. There are 397 for AD alone, 144 of which are interventions at phase III or IV. What might be feasible is a tailored search query against clinicaltrials for inclusion in the article, such as: AD intervention trials at phase III or IV or similar.LeadSongDog (talk) 13:02, 18 March 2008 (UTC)
Most of these are for preventative or symptomatic-only trials - the number of advanced DMD (disease-modyfing) trials for AD is relatively small the Wiki page says just 2, but when I looked over weekend, I found 6 or 7 - of course there are more, but not a lot - its not easy for the drug candidates to advance as DMDs if they dont succeed with in their initial trials.......io-io (talk) 13:51, 18 March 2008 (UTC)
Part of the reason for limiting the discussion regarding drugs in clinical trials here is that so many of them have not successfully completed their trials. In the last 18 months, more than 4000 patients were in (at least 4) Phase 3 trials for AD that did not reach statistical significance in their primary endpoint. Garrondo created a page for Therapies_under_investigation_for_multiple_sclerosis and this might be one way to aggregate the information you want. A summary of late-stage trials from a new broader page would be appropriate for this article. DMD status for any compound in this area is going to be controversial since there are well-informed clinicians who say current therapies change the course of the disease. I think there are only two clinical programs for investigational new drugs seeking an indication for cognitive effects in Alzheimer's patients with active patients in Phase 3. A couple of others may add to this list soon. Medivation's Dimebon has announced Phase 3 but I have seen any indication they have patients enrolled yet. Lilly's LY450139 gamma secretase inhibitor may have enrolled patients and should be added to the section soon. --Chrispounds (talk) 19:31, 18 March 2008 (UTC)
Specifically I was intending to list drugs in clinical trials here that have not completed their trials at all. I am surprised you say that this is relevant: "there are well-informed clinicians who say current therapies change the course of the disease" - because if it were really true, I would think that, especially as these are known safe drugs (half the battle today), the drug companies would rush out to do trials to prove this, and announce it to the world (and make multi-billions, and a place in history). I was not thinking of a whole new section, as the pathology will have to be repeated in discussing the targets, and also it is hard to avoid speculation on what might work or not. Instead was thinking of a table with citations, I think that would be very easy-to-read, nuetral, and very effective in showing what we might hope (although not "expect") to see....io-io (talk) 20:11, 18 March 2008 (UTC)
I'd like to answer this from two different directions: the first as an encyclopedia and second from an ethical standpoint. As an encyclopedia, clinical trials will grow stale in just a few months. Editors come and go, and all of a sudden, no one is paying attention to the clinical studies section. As an example, AIDS is an FA, yet several of us had to spend a few days cleaning up sneaky vandalism, old information, bad information, and bad copyediting. As an encyclopedia, it is important to put the most current information, but it has to be notable and have some value over time. I don't recall the exact statistics, but the percentage of drugs that get launched from phase 3 trials is not 100%. And it could be years from now. From an ethical standpoint, someone might have a friend or relative that is afflicted by Alzheimer's and they read this article, thinking there is a "cure." I just don't think that's the right way to go. I would suggest that as we build this article, we'll come to a consensus, but three editors here are concerned about putting a chart of drugs in the article. I also haven't found any other article that does the same. OrangeMarlin Talk• Contributions 20:34, 18 March 2008 (UTC)
Well it already describes on the page that there are clincial trials ongoing. And is the word "trial" not a bit obvious in it's meaning? As for other articles, my point was that there is no treatment at all for this, the biggest/fastest-growing disease, and right now is when the pace of trials has accelerated to target the pathologies (amyloid-beta cascade, tau) already described on the page...Alz has been around for millenia, but only right now has the clinical work reached this moment.io-io (talk) 22:28, 18 March 2008 (UTC)
Based on previous WP:MED discussions, anything less than a large phase III trial isn't notable (unless it is notable--like major press coverage). We're not a crystal ball, nor a database. In the main AD article, I wouldn't really expect to see (or find room for) anything other than current treatments and broad brush strokes of what is on the horizon. Ask the Project if you want more opinions. Colin°Talk 21:27, 18 March 2008 (UTC)
Yes, I agree, these would have to be Phase III. But even so, I believe there are approx 6 - 8 of them. Well perhaps sooner or later, there will be a Therapies-under-Investigation page. Maybe I will do the table here, and it can be transported later.....io-io (talk) 22:28, 18 March 2008 (UTC)
You can create that page (Therapies under investigation for Alzheimer), as I did in MS (somebody has to do it). I agree with everybody else that a table won´t be approppiate for this article. I believe that it would be a too speccific information for a general article on AD and secondly is the fact of clinical trials continue evolving, so its very hard to maintain them uptodate. I believe that its preferred to simply name some prominent investigation trends in the main page (as in multiple sclerosis or treatment of multiple sclerosis being both featured articles, and leave such specific information for a subarticle. On the other hand right now there are other sections alredy written which requiere a lot of work if this article wants to become any time a FA, such as the epidemiology or causes subsections, so your help could be very welcomed in this other areas. Regards. --Garrondo (talk) 09:28, 19 March 2008 (UTC)
OK, thanks, a new trick I will have to learn, along with the others (apparently am technically a terrible editor, to judge from feedback) - but I will probably start the table on this talk page, where at least it will get some collaborative input before arriving on a Wiki page...in time I will start the Therapies-under-Investigation page too, or perhaps a Late-Stage Clinical Trials for AD page....also I can look at the causes section here, I may be able to contribute, probably only if there are obvious holes....io-io (talk) 13:31, 19 March 2008 (UTC)

draft table (for an "investigational therapies" page)

Table - Late-Stage Clinical Trials in Disease-Modyfing Candidates for Alzheimer's Disease
Target/Approach Notes (Theoretical) Candidate Name Trial Phase Trial Start Date Expected End Date Planned Enrollment AD population targeted (severity) AD population targeted (genetic) Comments
Selective A-Beta-42 lowering Agent Converts A-Beta-42 to less Toxic analogues MPC-7869[1]. Phase III Feb 2005 May 2008 1,600 Mild n/a 800-patient Trial also underway worldwide[2].
Gamma Secretase Inhibitor Inhibits Gamma Secretase, believed crucial to pathology LY451039[3] Phase III March 2008 March 2012 1,500 Mild-to-Moderate n/a Earlier 45-patient Trial completed early 2007, results not released[4].
Antibody to Amyloid-Beta Mimics Natural Antibody triggered by AN-1792 aab-001[5] Phase III Dec 2007 Dec 2010 800 Mild-to-Moderate Apolipoprotein E4 Carriers only Identical Trial also underway in Europe
Antibody to Amyloid-Beta Mimics Natural Antibody triggered by AN-1792 aab-001[6]. Phase III Dec 2007 Dec 2010 1,250 Mild-to-Moderate Apolipoprotein E4 Non-Carriers only Identical Trial also underway in Europe
Metal-Protein Interaction Attenuation Primary Target is Copper PBT2[7]. Phase II (completed) Dec 2006 Dec 2007 80 early Alzheimer's disease n/a Deemed a Success; Phase III to start
Fibrilization of Amyloid-Beta Prevents/Reverses Fibrilization of A-Beta AZD-103[8]. Phase II Dec 2007 May 2010 340 Mild-to-Moderate n/a Phase I was success
Neuroprotection Neuroprotective Peptide, intra-nasal AL-108[9]. Phase II (completed) Jan 2007 Jan 2008 120 Mild Cognitive Impairment n/a Deemed a Success; Phase III to start
Vaccine to Amyloid-Beta Injects modified A-Beta (active vaccine) acc-001[10]. Phase II Nov 2007 Mar 2012 228 Mild Cognitive Impairment n/a Sequel to famous AN-1792 Vaccine Trial
Notes
  • limited to DMD candidates, late-stage
  • a few more to be added?
  • comment welcome

article traffic statistics

I've found this - it's a beta, and not I'm sure how accurate it is. It gives the page hits for the last 90 days.

As full months, Jan shows 68,666, and Feb shows 79,990. Jan being 'slow' perhaps(?), and Feb being a 28 day month - I would guess this gets about 100,000 a month as a yearly average, possibly more - it will be interesting to see what transpires! (we are around 45,000 in March so far) --Matt Lewis (talk) 14:01, 18 March 2008 (UTC)

Yes, that's an interesting tool. Makes you realise how important WP is. This article has >10x more readers than the stuff I normally write about. Mind you, if you're after readership then Simpsons articles and lists of sex positions make this look positively ignored. Colin°Talk 22:55, 18 March 2008 (UTC)
It would be interesting to see how many of these are first-time hits. My guess is that many people are coming back to the article at various times, as they are connected to AD in some way. I did originally think this article would have been read by many many millions - it doesn't quite look like that's the case now - a few million unique visitors perhaps. The search "Alzheimer's disease" is no.1 in Google, and no.13 in Yahoo - I wonder if Wikipedia's bad rep is putting people off - or if it's getting the 'lion's share' of Google's AD searches? I'll see if I can find the Google stats for "Alzheimer's disease". It's not easy to spell either - people might be getting to non-WP websites that way! --Matt Lewis (talk) 23:20, 18 March 2008 (UTC)
I have no proof, so please don't shoot me. But I actually believe for medical articles, as they get better and more informative, more people read them. They get linked to emails to friends and family, blogs, etc. This article is getting better everyday. Also, I don't think Google's ranking is just for visitors, it includes how many links there are, etc. I forget where the description is located, but it's a complex formula. I wanted some information a few weeks ago, and I googled AD. There were a few good articles, but none really informative (and the number that said you can be cured by eating ginkgo and olive oil were amazing). I can't remember where this article was located, but it was down in the 20's, I believe. I couldn't believe that, so when I came here, I did a few things to up the ranking (like wikilinking where appropriate), cleaning up the references with PMID and DOI numbers (which are links). Readership has gone up as we get more and more links. And now that it's #1 on Google, we can expect people to come to read the article. One of my "beliefs" about Wikipedia medical articles is that unlike articles about The Simpsons or Sex positions, people could be helped or hurt by what we write here. That's why I fight the CAM nutjobs so much, because they write articles as if it is true. We write this article, for example, as if it were verified by a lot of strong research. Those of us dedicated to fixing these articles have a responsibility to give the best possible information to someone who comes hear to read about Alzheimer's disease. Honestly, without sounding arrogant or condescending, the medical articles that get the really good editors (such as this one) and follow WP:MEDMOS are some of the best review articles out there. I almost wish Wikipedia split off it's medical articles (without the CAM promoters), because it can really raise the reputation of Wikipedia. A big group of very devoted editors keep these articles clean. But I bet there are only 10-20 medical articles that are really well written. I keep running across articles that either have COI problems (one article was being attacked by one company's promoters) or CAM woo all through them. This article is moving up to one of the better ones. OrangeMarlin Talk• Contributions 17:08, 19 March 2008 (UTC)
I agree that more people come back as articles improve - that might account for the lower than expected hits for this article (for me at least) - ie it hasn't yet built a readership, or reputation to pass on. Unfortunately we can't see the stats going back for longer. There are some very poor and excellent pages out there (we’ve been both imo over different times!), but we can become potentially the best AD ‘page’ bar none, because of the nature of the Wikipedia (all theoretical until achieved though!).
RE Google position,
I think the AD article has been no.1 on Google for a while - the reason I edit Wikipedia (which I originally thought was an insane idea – and still do sometimes!) is because I realised it was no.1 for so many searches I was making. A lot of people are still 'snooty' and ignore it - they foolish to do so though, imo. The reason for the amount of no.1 positions is in Google's page ranking system - which has a complicated algorithm, as you say. The principal factor is not 'page hits', but actually 'Link Popularity' - which means how many sites link to the page. Crucially, Google also looks at the 'link popularity' of the "homepage" or higher-domain: with "Wikipedia" the results are awesome. I doubt that anyone, including Amazon, has a better score. There is another, better, Wiki site called "Citizendium" (which vets articles, and was set up by Jimbo Wales' original partner) - but it just can't get anywhere near Wikipedia's page ranking, and is stuck in a cycle of not been seen, and so not being edited. Because of Wikipedia's massive Link Pop, all of its pages get a high ranking on Google. Yahoo has a different - and probably fairer - formula. The reason Wikipedia has so much high-ranking porn, advertising sites and general junk - is partly due to its preference for link popularity, and those sites notoriously link to each other.
RE Ginkgo etc,
Most sites I see admit AD is incurable, but then ‘sell’ you the plethora of readily available supplements for profit: the exaggeration (and sometimes pure deceit) that we see is simply advertising hype. Ginkgo Biloba always struck me principally as another blood regulator (to whatever effect) - which may give secondary help in that way. I personally suspect a number of "supplements" could help some AD sufferers from possible wider angles - it's all up to the buyers imo. The important thing is that they know the score, and ideally they see the available evidence, so they are not sold 'snake oil'! I actually recommend a number of things, with the usual caveats - ironically (given its constant recommendations) I'm not big on Ginkgo, as the evidence doesn't strike me as all that great apart from blood regulation. Over both Ginkgo and olive oil (?- do you mean the ‘Mediterranean diet’?) I might suggest garlic - as a blood regulator that we know is good for you too (advising to be careful with blood-thinning medications, see the GP etc). In my experience people want other options (I'm always asked) - it's just human nature in the face of a cruel impending death. The lack of options GP’s and other health practitioners have for AD have a lot to do with it too (which is why many do suggest E, etc). And scandalously, we don't get Galanthamine in the UK unless someone decides we have progressed enough to warrant the expense. Many GP’s often just look blank when asked about things like Gingko too, which is increasingly more dangerous imo (specifically in the sense of GPs and patients staying 'in touch'). --Matt Lewis (talk) 19:07, 19 March 2008 (UTC)

Stages of Alzheimer's

When I read this section, it seemed to me that it was missing the approximate lengths of time that each stage lasts (1 year? 4 years? 5 years? etc). I think that kind of information would be very helpful to a lot of people. Saritamackita (talk) 18:20, 20 March 2008 (UTC)

A quick comment is that it is not easy, because it is hard to define the lines between the stages; even the tests are being continually questioned, and new ones proposed (typically composites of cognitive and functional performances). But I agree with your intent, perhaps there is a great paper somewhere.....io_editor (talk) 21:11, 22 March 2008 (UTC)
The problem is that what you seek does not exist. You wouldn't get an "answer," except with very wide time limits, because the rate of AD disease-progression varies quite a lot from person to person. Going from mild IADL dysfunction to not knowing your kids or wife, can happen in 2 years or 10. SBHarris 02:43, 23 March 2008 (UTC)
ok. I guess that makes sense. If good research is found on it, though, it should definitely be put in. Saritamackita (talk) 08:45, 26 March 2008 (UTC)

Summary of therapies under investigation and creation of subpage

This section was growing continously with no order or criteria. I have summarised the section trying to name different investigation approaches but not being exhaustive and I have moved all info, and de table created by io io to a new article centered on investigation. I believe in that it will help to mantain stable the main article while increasing all the info in the secondary article. --Garrondo (talk) 11:29, 23 March 2008 (UTC)

Would propose that the new article be limited to investigation in halting disease (far more interesting/focussed) - that was my intention in doing the table?...io_editor (talk) 17:15, 23 March 2008 (UTC)
Deleting so much information from the section made it difficult to understand. For example, I had to revert a big section deleted, because the whole explanation of why vaccinations might work with AD was deleted. I think for massive changes, should post them here. Moreover, I'm going to take the time to review why certain drugs are being highlighted in the section. I know drug trials well enough to know that being in Phase III doesn't mean anything. Approval is still years away. OrangeMarlin Talk• Contributions 17:17, 23 March 2008 (UTC)
The section must either be very large, or just small. I think the way that Garrondo had it was closer to what is appropriate, as it is indeed disordered; especially as the area is A) broad B) incomplete and C) not yet proven. Much of the stuff about statins and enbrel should not be there at all, as it is extremely speculative, and even obsolete at that. Also, there is already a "Disease mechanism" sub-section describing the A-Beta cascade theory. Perhaps a line could be added to what Garrondo wrote, stating that following earlier AN-1792 work, vaccine that had triggered the antibdy, there are follow-on approaches....io_editor (talk) 19:18, 23 March 2008 (UTC)
My suggestion would be to reduce back and for copyediting, why don't you and Garrando set up a sandbox for this section (it can be done as page off of this talk page). It would be helpful. OrangeMarlin Talk• Contributions 19:23, 23 March 2008 (UTC)


Maybe this time I was too eager to delete info. Sorry. Thankfully anything can be reverted if somebody feels it wasn´t appropiate. Nevertheless I want to explain my reasons and my action may serve to boost this section. First of all I want to say that I was thinking on doing it for some time, and has been an action on my own. I have been rewritting the treatmens section in order for a month. First it was cognitive therapies (which is my speciality), then approved treatments, and finally I wanted to touch the investigation section.

Investigation sections usually get "cracy". With cracy I mean that they just become a compilation of random info, that do not give an accurate overview of a field. The more complex a disease is the more easy this happens. This is what has happened in Alzheimer: only a few products appear, with a lot of weight given to them, while many others are not even named. See for example this lines: In 2002 it was reported that 6% of multi-dosed participants (18 of 300) developed symptoms resembling meningoencephalitis, and the trials were stopped. Participants in the halted trials continued to be followed, and 20% "developed high levels of antibodies to beta-amyloid" and some showed slower progression of the disease, maintaining memory-test levels while placebo-patients worsened. Micro-cererebral hemorrhages during passive immunisation and meningoencephalitis with active immunisation still remain potent threats to this strategy.[141] Does it have sense to have more than five lines for just an investigation that failed when there are 400 ongoing trials?

I believe that a good idea is draw the main tendencies of research of the field and give some examples of each one, going away from detailing every investigation or clinical trial. Respective to why some drugs are highlighted... Well, be sure it was not my intention... What I precisely intended was exactly the opposite, I tried to give examples (and they were presented as such) of a inmense amount of trials. Right now as I show in the lines before is when there are some drugs highlighted. Respective vaccines: Is it really informative to know why a possible future treatment might work? I believe its just giving to much details. Finally I also agree that being in phase III doesn´t mean anything.

Well as I said: sorry to everybody, I´m no expert in pharma and this might have been a too much of an edit, but lets look in positive for the future:

My aim was to give the big picture of AD investigations and center the section in tendencies and not in specific drugs: I named 3:

  • Amyloid beta fight; (which would include vaccines)
  • Neuroprotection
  • Metal-protein interaction attenuation

Can anybody give other examples of main trends in AD treatments investigation?

Bests to everybody. --Garrondo (talk) 11:43, 24 March 2008 (UTC)

  • Agreed - these sections become a mess, as everybody comes along to place some speculative idea they saw in the newspapers, some of it homeopathic, some alternative, etc - and even the better material becomes uncoordinated (in fact even in diseases where there are already treatments - I am thinking of the MS page - these sections can look very poor). In terms of the treatments you mention, in fact almost all the late-stage ones (even the metal attenuation ones target a catalyst) are aimed at what is called the "Amyloid Cascade", it just depends on whether they are aimed at what is considered "upstream" or "downstream" (and even this is not known for sure) in the process. I will come back later with a suggestion....io_editor (talk) 13:50, 24 March 2008 (UTC)

A new alternative

A possibility to summarize vaccines into first paragraph eliminating info on the last trial failure would be the following. (New additions in black). What does people think?

Many different investigation approaches coexist. Amyloid beta is a common target of clinical trials of compounds which aim to reduce it using different agents such as bapineuzumab, an antibody in Phase III tirals for patients in the mild to moderate stages of AD,[137] and MPC-7869, a selective amyloid beta-42 lowering agent in Phase III trials for mild AD.[138] This is also the case of vaccines or immunotherapy, which would be used to treat diagnosed patients rather than for disease prevention and are based on the idea that, by training the immune system to recognize and attack beta-amyloid , it might reverse deposition of amyloid and thus stop the disease. An example of vaccine under investigation is acc-001. Other approaches to treating AD are neuroprotective agents, such as AL-108, which has just completed its Phase II clinical trial,[139] and metal-protein interaction attenuation agents, such as PBT2, which has also just completed its Phase II trial.[140] There are also many basic investigations attempting to increase the knowledge on the origin and mechanisms of the disease that will lead to new treatments.

I had missed this earlier. I made edits; see if you like them or not. I agree that the trial failure (or partial success) should be out as it was a vague result (it is not surprising that 20% developed antibodies to somtheing they were injected with). The bapineuzumab MaB is an offspring of immunotherapy. Recently statins failed in a huge trial, so that's out. Also the enbrel story on a single patient is a red herring, there are no AD trials in enbrel, so out it goes too....io_editor (talk) 02:03, 25 March 2008 (UTC)
I dont agree with the 2nd-last edit by Garrondo. To say there is just no cure, is of course true, but alone it sounds naive, especially when research has no hope of really reversing the patient back to full health. The hope right now is to to delay or halt. Also for the drugs under trials, many of the established symptomatic drugs - or new drugs in the same class - and also generic competition is on the way, as 1 or 2 of gthem are now very old - are being tried in different doses, different combinations with each other, different stages of disease, and there will be some efficacy. The burning question is not here, but in the area of the disease itself....io_editor (talk) 14:09, 26 March 2008 (UTC)
It's not only said that there is no cure, but that is palliative and sytomatic treatment which from my point of view is saying almost the same as "Does not delay or halt". I think its an important sentence for the pharma section (and it continues there), and finally there is really no much point in saying it again in investigation since it can't be known which will be the results of those investigations... Maybe a combination of approved treatments is the key, or maybe is one of those more risky investigations... maybe the only investigation on a new treatment has more funds that all the others..who knows... In the investigation section I think it does not give a lot of info saying one more time "do not intend to halt or delay". Finally I not only reverted it becose I felt it was unncesary but becouse it was a copy-paste three times of the same exact sentences which does not sound very encyclopedic. Lets see if anybody else gives their opinion or make new edits. --Garrondo (talk) 15:18, 26 March 2008 (UTC)
OK, I think sooner or later someone will change it again though........also think about my second point as well, because there will be more symptomatic drugs....io_editor (talk) 18:31, 26 March 2008 (UTC)

Public health cost impact of therapies

Reviewing much of what has been discussed about the various rear-guard-action therapies it struck me that we may not be giving them their due. While not cures, any therapies that significantly postpone the time at which a patient must move on to a more intensive stage of care can be seen as (at least potentially) providing a reduction in the social cost of delivering that care or allowing supply-constrained social resources to be marshalled towards other services. Am I missing something here or should this be discussed in the article?LeadSongDog (talk) 21:55, 25 March 2008 (UTC)

I think these therapies modestly rather than significantly postpone such an event. These symptomatic drugs right now have shown only modest benefits over short periods (6-months is the standard)). Remember the course of the disease pathology is believed to be unaltered, drug or no drug. All the reports are that future costs will be enormous to care for the exploding population and that the current drugs are not good enough. Even now there must be a benefit, but the UK body (NICE) did cost-benefit analyses in the last few years and said that no such benefit existed - relative that is, to the price of these drugs themselves...io_editor (talk) 22:20, 25 March 2008 (UTC)
Then lets find a referencer for those economic public health studies, since it seems important enough.--Garrondo (talk) 08:20, 26 March 2008 (UTC)
Perhaps this will serve:Getsios D, Migliaccio-Walle K, Caro JJ (2007). "NICE cost-effectiveness appraisal of cholinesterase inhibitors: was the right question posed? Were the best tools used?". Pharmacoeconomics. 25 (12): 997–1006. PMID 18047386.{{cite journal}}: CS1 maint: multiple names: authors list (link) LeadSongDog (talk) 13:37, 26 March 2008 (UTC)
That is a start. I believe the full NICE assessment should be findable, as it is a government document, and would have been released at one time. The UK authority is called NIH (NICE is their consultant), so that might be a place to search....back later....io_editor (talk) 13:56, 26 March 2008 (UTC)
Got the abstract. Here's the cite:

Green C, Picot J, Loveman E, Takeda A, Kirby J, Clegg A. (2005). "Modelling the cost effectiveness of cholinesterase inhibitors in the management of mild to moderately severe Alzheimer's disease". Pharmacoeconomics. 23 (12): 1271–1282. PMID 16336020.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Cheers, LeadSongDog (talk) 19:06, 26 March 2008 (UTC)
Well it did assess the benefit of the "delay" - my comments in italics.... RESULTS: The clinical benefits on cognition from treatment ....... incremental (= extra) cost per QALY gained ranging from 53,780 pounds sterling to 74,735 pounds sterling... (vs usual care).... the probability of ....incremental cost per QALY of < 30,000 pounds (this seems to have been the benchmark) sterling is < 21%. The key determinants of cost effectiveness were the effectiveness of treatment, the mean treatment cost and the cost savings associated with an expected delay in disease progression (which is how we started)." .......It looks as if the study felt that the delay was worth 30k, but to get there, the drugs spending would be more than double that. However there is something I don't understand, why they appear to average this over 5 years, as I believe that the average usage of these drugs is only 8-9 months due to efficacy wearing off...io_editor (talk) 23:36, 26 March 2008 (UTC)
Both studies disagree in their conclussions. I propose the following:
There is also evidence for the efficacy of these medications in mild to moderate Alzheimer’s disease,[112] and some evidence for their use in the advanced stage. Only donepezil is approved for treatment of AD dementia during this stage.[113] Their cost-effectiveness is disputed.
adding both references after it. Would it be enough?--Garrondo (talk) 15:27, 27 March 2008 (UTC)
That might be just a little too concise. See Matt Lewis' words above re protests (under Political element). How about An NHS sponsored study found insufficient effect to justify funding their cost, but the premises of that study are disputed. (plus the refs)LeadSongDog (talk) 18:42, 27 March 2008 (UTC)
Re the UK protests over Aricept's limited availability - Donepezil (Aricept) does have this against it [1] and [2]. Also this on cholinesterase inhibitors in general [3] (I don't think we are using these Pubmeds).
I have to go out now - but I'll certainly help regarding social aspects. --Matt Lewis (talk) 20:09, 27 March 2008 (UTC)
I'm certainly for covering it all, btw! It's just about getting it right. --Matt Lewis (talk) 20:12, 27 March 2008 (UTC)
I don't think the point is to say if anticonlinestares inhibitors are effective, since it is well proved they are, even if their effects are very mild. If they had the prize of aspirine no government would doubt on its use. I think the other two references are much more interesting, since they try to balance effectiveness and costs both of drugs and cares. --Garrondo (talk) 09:24, 28 March 2008 (UTC)
If we say that "cost-effectiveness" is disputed - and pose this difficult question of what is costly and what is effective in example form - such as the UK criticisms of the decision over Aricept and the subsequent protests (over the 'cost/availability' side), surely we would then need to show the extremes of opinion over anticholinesterase inhibitors? (ie the 'effectiveness' side of the dispute)?

"If we say that "cost-effectiveness" is disputed" - I agree that this leads to 2 difficult questions - the "cost" (net) and the "effect" (QoL being hard to define) - and the NIH studies are often seen as politicaly tainted - perhaps we say nothing about "cost-effectiveness", beacuse it would take almost another page to explain what is meant by that. I think it is enough to say that their usefulness is limited, and that they make no difference to the long-term prognosis....io_editor (talk) 14:23, 28 March 2008 (UTC)

The new page could be "Sociological and cultural aspects of Alzheimer's disease" (per the Autism sub article). We would still need a comment here though. We must always remember WP:MEDMOS (and it's always easy to forget) - Wikipedia is not stirictly intended to be a "pharmaceutical resource", so this article is about Alzheimer's disease in the 'broad sense' first and foremost - though it is great that it goes beyond the "general", of course.
"Wikipedia is written for the general reader. It is an encyclopaedia, not a comprehensive medical or pharmaceutical resource, nor a first-aid (how-to) manual. Although healthcare professionals and patients may find much of interest, they are not the target audience."
--Matt Lewis (talk) 12:46, 29 March 2008 (UTC) (didn't sign, sorry)
If you really want this new page, then I cannot help much, but Garrondo would almost certainly be at home (unless you are Garrondo?). But I think we agree, it is beyond the scope of the AD page itself.io_editor (talk) 22:40, 28 March 2008 (UTC)
My point is actually that it is within the scope of a broad article on AD - but I feel it needs to be developed under a sub-article too. I misleadingly said it needs "a comment" in here (which does sound dismissive) - actually I meant a couple of nicely-packed well-written sentences - whatever can cover it best, with a "Further information" leading to the sub-article! It's definitely part of the subject of AD. --Matt Lewis (talk) 12:46, 29 March 2008 (UTC)

I note at AmJ Managed Care (page 811) that theres a decent estimate of savings per month admission is deferred. Later stages aside, it ought to be possible to find an estimate of how many months deferral can be obtained with various treatments. LeadSongDog (talk) 01:28, 29 March 2008 (UTC)

Having just attended the 5th IPECAD conference on AD pharmacoeconomics, I would say that current therapies are questioned first on the magnitude of their clinical effect (4 ADAS-cog points being a clinically significant standard that they are not consistently beating) and second on their cost effectiveness. NICE's modeling has been criticized because they made several simplifying assumptions in the AHEAD/Caro model that very much changed the results in terms of value per QALY. Looking at an outcome like nursing home admission is done via population cohort studies that measure healthcare utilization parameters and then linking those back to the clinical variables that were observed in the regulatory submission trials. The AD2000 trial tried to be an effectiveness study, but it perhaps was too small and broad in its entry criteria to give the best picture of effectiveness. Nonetheless, it did recruit a large number of APO E4+ patients (like 60%). Which costs get accounted for in the value of these drugs is a key element in the effectiveness results. Unpaid caregiver time has what benefit? What about healthcare outcomes for the caregiver? What about health system benefits in the long run (which may include long term care)? These are tough questions to answer. --Chrispounds (talk) 04:13, 31 March 2008 (UTC)
This just came in from BMC. Open access. Zhao Yang, Kuo Tzu-Chun, Weir Sharada, Kramer Marilyn S, Ash Arlene S (2008-05-22). "Healthcare costs and utilization for Medicare beneficiaries with Alzheimer's". BMC Health Services Research. 8: 108. doi:10.1186/1472-6963-8-108.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)LeadSongDog (talk) 04:36, 30 May 2008 (UTC)

PiB-PET imaging

I was bold and added in a new result, now in preprint from Brain. Check out the lay summary's attached image. Stunning.LeadSongDog (talk) 20:19, 26 March 2008 (UTC)

It looks indeed groundbreaking, and the sort of tool needed to help clinical research make progress. When I looked, there was actually anotehr paper by the smae team, this time showing correlation between PiB and MRI (not so exciting I suppose), so I added it too....io_editor (talk) 00:06, 27 March 2008 (UTC)
Sounds impressive, and it also shows one of the most impressive things of wiki: the article was pubblished barely a month ago and we alredy have it in the article. Well done. --Garrondo (talk) 08:27, 27 March 2008 (UTC)
When you say "combined with a tracer" - it is in fact only the tracer that the imaging sees.....I will changeio_editor (talk) 13:38, 27 March 2008 (UTC)
Good job LeadDogSong. Man that was hard to type. Let's try to remember to change the reference to it's actual listing once it's published. OrangeMarlin Talk• Contributions 23:05, 28 March 2008 (UTC)
Thank you.LeadSongDog (talk) 00:44, 29 March 2008 (UTC)

Neuroleptics for agitation found to be of negligible benefit and substantial risk

A multi-year UK study by the Alzheimer's Research Trust suggested that this and other neuroleptic anti-psychotic drugs commonly given to Alzheimer's patients with mild behavioural problems often make their condition worse. [11] The study concluded that

Cochrane database trial registration (not sure how to cite)

So does this not belong in the article?LeadSongDog (talk) 20:40, 1 April 2008 (UTC)

Well, we don't mention it elsewhere in the article. The article could get really long if we list out everything that doesn't work. That was my point.OrangeMarlin Talk• Contributions 20:47, 1 April 2008 (UTC)
This might be worth a mention, because neuroleptics are/were very widely used in patients with Alzheimer's. It's not exactly a garden variety treatment-that-didn't-work; it's more like a widely used treatment that recent evidence suggests may not be beneficial and may even be harmful. MastCell Talk 20:52, 1 April 2008 (UTC)
I did a search and found lots of articles over the past two years that state it doesn't work. I'm wondering why the BBC News article seems to make it appear that one guy figured this out??? Anyways, I'm not opposed to putting it in, but the sentence should say something to the effect of: "Neuroleptics had been widely used with patients with AD, but recent evidence suggests it has limited effect on the course and severity of the disease, and may be harmful to the patient." Use some citations that don't include the BBC News, since it's unpublished, and the interviewed researcher is not alone. OrangeMarlin Talk• Contributions 21:25, 1 April 2008 (UTC)
Sorry, I've gone retroactive and edited my above out-of-sequence to clarify the citation somewhat, make it readable in the talkpage, and add the Cochrane database link. I'll try not to make a habit of it ;/) LeadSongDog (talk) 05:48, 2 April 2008 (UTC)
I have reverted last edition. The editor said it worsens the state of AD patients, when at most in the article says it does not have much effect. Lets get to a consensus and then add it again if we believe it is a good idea. In the read also section there is a 2007 guide from the apa. It has a lot of up-to-date info on articles on neuropsychiatric treatments in dementia. It may serve as an initial revision for a guided search of info. Right now I have a lot of work out of wiki so I won't be able to help much the following weeks.--Garrondo (talk) 12:18, 2 April 2008 (UTC)
Disagree. The ref says

I think that's pretty unambiguous.LeadSongDog (talk) 14:07, 2 April 2008 (UTC)

I think we're in agreement that it belongs. But let's use the best possible source. And LDS, almost any clinical trial can be referenced with a peer-reviewed article. I'll try to search for one. OrangeMarlin Talk• Contributions 17:08, 2 April 2008 (UTC)
Try a pubmed search on "dementia[ti] AND neuroleptic[ti]" (less quotes)...lots to choose from.LeadSongDog (talk) 19:06, 2 April 2008 (UTC)

Structure

The article structure needs some rethinking. The Prognosis section is particularly strange, including subsections that really don't belong. Suggestions? LeadSongDog (talk) 17:10, 5 April 2008 (UTC)

I would suggest that the subsections under Prognosis be put into a new section called "Social Impact" or something like that. --Gimme danger (talk) 18:09, 5 April 2008 (UTC)
I agree they look odd, and technically not part of Prognosis, but I am not sure they should be removed off the page. Of the 2 burdens - Caregiving is already staggerring and the Cost is headed that way, as the numbers boom. They are really central issues for society today. Can I suggest though that half (the middle paragraph or most) of Caregiving burden could be removed?io_editor (talk) 18:16, 5 April 2008 (UTC)
The reason why it is under prognosis is becouse its is advised so in MEDMOS, however it might be a good idea to make an exception here and create an indepndent subsection. Nevertheless not to follow the manual of style is an important decision so lets ask everybody else. --Garrondo (talk) 14:28, 6 April 2008 (UTC)
Thanks for directing attention back to WP:MEDMOS. It was very direct:
So, rather than having Treatment followed by Prognosis, we would have Prognosis followed by Management. I don't see anything in MEDMOS that guides the the subsections' form. LeadSongDog (talk) 17:11, 6 April 2008 (UTC)
Very good, as the Prognosis is univerally bad. Within Management I would suggest that the middle paragraph in caregiving burden be substantially dropped/summarized for brevity.io_editor (talk) 18:31, 6 April 2008 (UTC)
I was about to do this, and I suddenly realised that this would mean Management would replace Treatment. While I would agree with this (completely!), it may be controversial as others have seen "treatment" to be mean all drugs....io_editor (talk) 18:48, 6 April 2008 (UTC)
Surely the parag on caregiving your refer to is pretty concise - why lose it? Please give reasons - is any part of it wrong? I'll point to my comments above re "general reader is the audience" and "full topic coverage" (per medmos etc).--Matt Lewis (talk) 22:19, 6 April 2008 (UTC)
I don't see problems with a management section. It would only change the name, not the content of the treatment section, since two sub-sub-sections right now are not pharma treatments and everybody has agreed to it. Neverteless maintaining its actual name is no innacuracy either. However the question was if creating a section of "social impact" was appropiate (I believe there is no such section in MEDMOS).--Garrondo (talk) 14:33, 7 April 2008 (UTC)
MEDMOS suggested section list includes "Prognosis (social impact may also be discussed)", but doesn't speak to whether a distinct subsection should be used for social impact. Presumably we make that call based on size/importance. If sufficiently important that we give it lots of space, then make a separate subsection. In this case we may need to go past that to a separate article, in which case there's little point to a separate subsection. Question: Is the social impact of AD sufficiently distinct from that of other dementias to have a distinct AD impact article? I'd suggest that we should simply cover the topic under Caregiving and dementiaLeadSongDog (talk) 16:07, 7 April 2008 (UTC)
All the main points in a proper "daughter article" needs to be covered in the parent article - it's actually required (I asked someone in FA once). So we will always need these sub-sections, at very least. I want to stress again that these “non-technical” factors of AD as no less worthy of main-article space than the technical factors - far from it, the ethos of Wikipedia is about the whole subject, and the general reader. What will the word "Alzheimer's" mean to a general reader? What will he/she want/expect to know? I can't stress this enough, as most people here are natural to the sciences.
In MEDMOS, the line "(social impact may also be discussed)" does sound a bit like a rather patronising aside (!) - it should be more affirmative: eg. "If "social aspects" are important they need to be addressed here, in sub-sections if necessary". It perhaps shouln't be left as 'obvious' that some articles have highly-relevant "social aspects" (like AD), whereas others obviously do not. I think I'll look at slightly re-wording MEDMOS here. --Matt Lewis (talk) 19:15, 7 April 2008 (UTC)
You are absolutely correct, in a way the social impact the whole point. I had thought earlier that perhaps the Caregiving section was too wordy, and could lose most of middle paragraph without losing meaning.io_editor (talk) 19:27, 7 April 2008 (UTC)
I probably included most of that parag, but if you can make it even more direct than fine. I try and get things as concise as I can without losing any of the points I want to include. AD is a dementia (and very much its own disease too), that causes a few core behavioural symptoms that caregivers will tell you are very common, and I think the parag covers them. Of course a sub-article (its own or the dementia one) could give even more detail, but I think we've covered the main aspects here. Initially it was part bullet-form, then was made converted to a parag.
I've tried a change to MEDMOS by the way - what does anyone think?--Matt Lewis (talk) 19:48, 7 April 2008 (UTC)
(this is the diff - it was removed quickly by someone who believes that each social aspect will have a corresponding section in the article as its home - but I just can't see it. I've stated a discusion here in MEDMOS talk). --Matt Lewis (talk) 20:19, 7 April 2008 (UTC)
Having fought it out at MADMOS (for far too long) I can report that changes have been made to society. Cultural references no longer covers it all, as apparently it was supposed to do. I have made the changes in line. It clearly needs an introduction. --Matt Lewis (talk) 00:42, 15 April 2008 (UTC)
Sometimes I think I should stop asking questions ;/) Thanks for toughing it out Matt.LeadSongDog (talk) 20:14, 15 April 2008 (UTC)

Blood/brain leakage

Another interesting item has come out here. It indicates that the heritable ALS-linked gene SOD-1 leads to low levels of ZO-1, occludin and claudin-5 (proteins in the barrier) and to early failure of the barrier within the spinal column, before the loss of motor neurons. Note too the final para referring to "In January [2008], Zlokovic reviewed the evidence for involvement of the barrier in diseases like Alzheimer’s, ALS, and multiple sclerosis in a 24-page review in Neuron." Relevant? LeadSongDog (talk) 19:01, 7 April 2008 (UTC)

I feel it is too much specific for main page. Maybe suitable for secondary article on phathology. Only my opinion.--Garrondo (talk) 13:41, 8 April 2008 (UTC)
Sorry, I got lazy with the above. The papers are
  • Zhong Z, Deane R, Ali Z, Parisi M, Shapovalov Y, O'Banion MK, Stojanovic K, Sagare A, Boillee S, Cleveland DW, Zlokovic BV (2008 Apr). "ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration". Nat Neurosci. 11 (4): 420–422. PMID 18344992. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |epub= ignored (help)CS1 maint: multiple names: authors list (link)
  • Zlokovic BV (2008-01-24). "The blood-brain barrier in health and chronic neurodegenerative disorders". Neuron. 57 (2): 178–201. PMID 18215617. and
  • Deane R, Zlokovic BV (2007 Apr). "Role of the blood-brain barrier in the pathogenesis of Alzheimer's disease". Curr Alzheimer Res. 4 (2): 191–197. PMID 17430246. {{cite journal}}: Check date values in: |date= (help) Review.
It was mainly the reviews that I wanted to draw attention to.LeadSongDog (talk) 16:07, 8 April 2008 (UTC)

Treatments in clinical development

Getting close to 3RR guys. Better talk it out instead.LeadSongDog (talk) 01:55, 9 April 2008 (UTC)

If you want, decide with OM - actually even better, I will take AD off my watch-list NOW, this moment - and I will not return, ever, so feel free....io_editor (talk) 01:58, 9 April 2008 (UTC)

TNF-alpha/inflammation

I think the AD page is great--kudos! There was this wacky story on BBC4 radio this morning about a guy in a private clinic in California who is giving perispinal injections of etanercept (TNF-alpha inhibitor) and turning the poor patients upside down--with remarkable, almost immediate, but somewhat anecdotal amelioration of impairment with some months' or years' duration. My first reaction was an eye-roll... But the more I looked into it, the more it started to make sense... and the more literature I found suggesting that -- while this is a very shaky first start in the Tobinick's non-placebo-controlled trials -- this is definitely consistent with some things other people have been thinking about w/r/to TNF-alpha, inflammatory processes, etc. So I added a couple of sentences to the AD page -- in the neuropathology section and in the pharmaceutical management section. I couldn't decide whether to put the first bit in neuropathology, biochemical, or disease mechanisms, and just went with the first. In hindsight, maybe one of the latter would have been better.Celia Kozlowski (talk) 16:40, 11 April 2008 (UTC)

Although there are often stories about compounds in development for Alzheimer's, we have tried to take the strategy that only products in Phase 3 or later would be listed because of the high failure rate in this disease. Yes, the mechanism is interesting, but the patient population so far has been small. Over the last two years, 4000 patients in 5 different 18-month trials did not find compounds that could change clinical symptoms of the disease (on average). --Chrispounds (talk) 10:06, 13 April 2008 (UTC)

pressure ulcer picture

The topic of pressure ulcers seems too peripheral to this article to warrant an illustration. I propose we remove that image, the image page of which doesn't even indicate that the person shown has Alzheimer's disease. --Allen (talk) 21:53, 15 April 2008 (UTC)

Pressure sores

I am a little concerned that pressure sores are considered one of the causes of death for people with Alzheimer's Disease. In my experience (30+ years as a registered nurse) bed sores are the result of bad nursing. There exists in the UK and the majority of other countries technology capable of avoiding the pressure which leads to these sores. The initial development of pressure sores indicates poor assessment of the patient's nursing needs, in this case relief of pressure on certain body points and the subsequent action to ameliorate that pressure. Pressure sores are always avoidable. It is the lack of health resources (i.e. lack of skill of the carers, lack of funds for equipment, lack of awareness of relatives) that leads to their formation. Having cared for over 200 individuals in their final stages of life with AD I believe I am able to offer an informed opinion. In my opinion the commonest cause of death from AD is pneumonia (sometimes leading to septicaemia) caused by the lack of activity of the individual. Not a single patient in my team's care ever developed a pressure sore. with kind regards, Richard Avery (talk) 06:56, 16 April 2008 (UTC)

In light of the above two comments I'm going to delete it for the moment. It's evocative certainly - but there nothing to prove the patient has AD, it's quite extreme, and it should be regarded as generally untypical (surely to this degree), rather than appearing the norm. The text is "Pressure ulcers are a common complication in advanced AD.": Perhaps a more typical pressure ulcer can be found (?), with some surrounding article text too, clarifying the reasons why it could happen. If the picture is a typical sore (when they occur) - the text in the caption and the article needs to better explain why and how often they occur. the question is - is the picture a typical example of how a sore develops when it is allowed to?--Matt Lewis (talk) 11:33, 16 April 2008 (UTC)
I have work with inbedded people (not exactly AD) and the thruth is that altough it is rare to reach this degrees of sores it is possible... and these kind of ulcers are the ones that kill people. Of course thankfully many times prevention or cures evitate reaching this state. On the other hand it does not really matter if the person in picture has alzheimer or not, since pressure ulcers are not disease dependant but due to inmovility.--Garrondo (talk) 13:57, 16 April 2008 (UTC)
Maybe a solution is just to say in caption "a picture of a very advanced pressure ulcer", or something like that. --Garrondo (talk) 13:59, 16 April 2008 (UTC)
Regarding richard avery comment: I suspect (I have not read about it) that being attended by a professional team reduces the posibilites of having such ulcers. Probably those AD patients inbedded at home cared by families and specilly by non sanitary and non family carers may be at greater risk... Nevertheless the picture is not so important.--Garrondo (talk) 14:03, 16 April 2008 (UTC)
I agree that the pic's origins don't matter so much as it's a pressure sore, but I'd like to read the source text that came with the picture (if there was any). How long does it take to get a sore like that? - that might be a useful fact to add in the image comment. - I notice you suggest "advanced" - but I think the nurse had a point about how 'bad' it looks - this is a scary image for people to see. I'm happy with it in the article with the right text to explain it fairly (I don't mind giving it a go) - I do feel I need more information on the pic though. Can someone estimate the time it takes to get a sore like that? --Matt Lewis (talk) 14:17, 16 April 2008 (UTC)
According to the pressure ulcer link in the text, which leads to bedsore this is a 'Stage IV' ulcer - "the deepest, extending into the muscle, tendon or even bone.". The image title is in a foreign language, so I guess it's corresponding source text could be too. Images are hard to find I know, but we could do with a lower stage really. I've got a bit of time so I'll have a search for: Alzheimer's ulcer/sore stage etc to see if any stage is typical. (maybe stage 1 is hard to avoid if someone is static all day). --Matt Lewis (talk) 14:25, 16 April 2008 (UTC)
Found this Guardian link. Someone with AD died of MRSI via a bedsore contracted in a care home. Looks like stage IV can develop "quickly". Spoke to soon - I have to go! (the link looks like it could be a good one if anyone wants to follow this up now). --Matt Lewis (talk) 14:36, 16 April 2008 (UTC)
This discussion of typicality and the details of the picture is good, but what about the relevance of pressure sores to AD in general? Sure, it may be a common complication, but isn't that true of any disease or condition that causes someone to spend a lot of time in bed? Would we want to put this image (or any bedsore image) in the articles for each such condition? --Allen (talk) 14:55, 16 April 2008 (UTC)
Well said Allen, the point I'm making is the development of pressure sores has more to do with inadequate care than the illness of the sufferer. Richard Avery (talk) 17:50, 16 April 2008 (UTC)
I would say in its defence that it highlights probably will happen with late-stage AD sufferers if not attended to, as sufferers become unaware/unable to deal with themselves and any pain they may/may not fully perceive. The seriousness of bed sores with AD needs highlighting and I think the link is good enough - but it doesn't necessarily need a picture (though that is true of most things). They can develop quite quickly with unrelieved pressure apparently, so this would need to be included in the caption for this particular pic if it was included. It's all in the caption I would say. --Matt Lewis (talk) 19:58, 18 April 2008 (UTC)
If there was a vote, I'd say remove it, since it's not a consequence of the disease itself, but as someone said above, from poor care. In fact, there's no way to state that the picture is of an AD patient, it could be someone with a coma. And it's one disgusting picture. I hate reading that section of the article, just because the picture is there. However, that picture probably should be in the ulcer section. OrangeMarlin Talk• Contributions 17:55, 16 April 2008 (UTC)
It's from the ulcer section. I thought you were made of tougher stuff marlin! I'll hold back on my suggested caption then ("Some jam tarts are sticky on the bottom")--Matt Lewis (talk) 19:58, 18 April 2008 (UTC)

Research directions

I just don't like this section here. I'm not sure how it happened, because I can't find anything in this discussion about it, but it's going to be a great catch-basin for fringe ideas. It belongs in the treatment section, but that's just my opinion. What say you editors? OrangeMarlin Talk• Contributions 17:35, 16 April 2008 (UTC)

It was me. I did not ask simply becouse right now is the place for this kind of info in MEDMOS. I think it has some advantages and disadvantages to former placement. Advantages are that the treatment section keeps more neat since I did not like much putting toguether proved treatments and investigations, since it gave the idea that they "are almost there". It does not have to be in the treatment section, since right now they are not "real treatment options". Worst problem may be what you say about fringe ideas, but right now we are asking for a high level of excelence in citations, and secondly I am not sure that being placed here should attract more than before.

Nevertheless I don't really care much where should it be placed, but if we move it back we have to be aware that we are not following current MEDMOS.--Garrondo (talk) 08:23, 19 April 2008 (UTC)

Yes, the MEDMOS 'sections' section was revised in a couple of places in the end, maybe a day before Garrondo made the change. Regarding fringe stuff: I've been reading about sub-articles lately as I thought some information in MEDMOS would be useful. Wikipedia suggests moving fringe information to a sub-article - or, if it's not notable for a sub-article - deleting it. It's interesting that Wikipedia prefers sub-articles to deleting information - which is frowns upon unless absolutely necessary: I didn't know Wikipedias editing policy advocated 'splitting' quite to that degree. But it's supposed to be the "encyclopaedia of everything", I suppose.--Matt Lewis (talk) 14:15, 19 April 2008 (UTC)
I have created again "Research directions section" since it is the reccomended section in MEDMOS: if somebody disagress lets discuss it here.--Garrondo (talk) 16:58, 14 June 2008 (UTC)

Regan's letter

On the page it refers to this letter and says "clear signs of the disease can be recognised", but that's never addressed - which clear signs are shown? What other signs are there that aren't shown? Can someone knowledgeable about this add to either here or to the letter's page? peterl (talk) 07:21, 21 April 2008 (UTC)

I'll try to find a reference for that... but that writting is clearly of a person with alzheimer... infant writting, not keeping margins... but as you say there is no reference. --Garrondo (talk) 07:37, 21 April 2008 (UTC)

OK... that might have been original research. I have not found references for it (although I'm sure that Alzheimer signs are clear...). Would it be a solution to say that writing is usually affected in the first stages of the disease? --Garrondo (talk) 07:54, 21 April 2008 (UTC)
Thanks Garrondo. peterl (talk) 10:38, 21 April 2008 (UTC)

New result we need eyes on

Can somebody have a look into this one: Hébert SS; et al. (2008). "Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/β-secretase expression". Proceedings of the National Academy of Sciences. {{cite journal}}: Explicit use of et al. in: |author= (help) (not yet in Pubmed) From the press release it looks like it might shed some light on etiology.LeadSongDog (talk) 16:43, 23 April 2008 (UTC)


Phosphorylation of Tau protein

In the section on Biochemical Characteristics, it appears that the action of phosphorylating tau is reversed from what is should be. According to other sources (and wiki articles on Tau protein and Microtubule-associated protein), phosphorylation of tau causes dissociation from (not association with) the microtubules. So it should say something like hyperphosphorylation causes tau to dissociate, resulting in the breakdown of microtubule integrity, which cuases the microtubules to aggregate and cause the formation of neurofibrillary tangles. Can someone (an expert, preferably) confirm and amend this if necessary?

Quartertone (talk) 20:19, 24 April 2008 (UTC)

I reverted the following addition from the article, but other opinions are welcome:LeadSongDog (talk) 21:24, 24 April 2008 (UTC)

No treatment has been proven to stop or reverse the disease although German scientists from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden believe that they have created a drug that when injected into the brains of mice with AD reversed signs of the disease. The drug is said to effectively block the enzyme responsible for the build up of sticky deposits or plaque in the brain , attaching itself to the spot where toxic activity takes place.[12]
Still it is not known whether current treatments slow the progression, or simply manage the symptoms. Many preventative measures have been suggested for Alzheimer's disease, but their value is unproven in reducing the course and severity of the disease. Mental stimulation, exercise and a balanced diet are often recommended, both as a possible prevention and as a sensible way of managing the disease.

A chimpanzee model has been found:

  • "Tauopathy with paired helical filaments in an aged chimpanzee". The Journal of Comparative Neurology. 509 (3): 259–270. 2008-07-20. Published online May 14, 2008

ACC-001 trial has been suspended

Corrected. I have added that it was suspended.--Garrondo (talk) 16:50, 14 June 2008 (UTC)

Correcting apparent vandalism

I corrected the apparent vandalism of this article by user 69.66.31.204. —Preceding unsigned comment added by Mojomama (talk • contribs) 15:47, 7 May 2008 (UTC)

ToDo list

See /ToDo. LeadSongDog (talk) 16:39, 12 June 2008 (UTC)

Epidemiology

This is User:Eubulides expert topic and I recommend asking his opinion prior to FAC.

  • The lead say "24 million people worldwide" are afflicted by AD. The source for this is given two sentences later. While those two sentences may well come from that epidemiological source (they aren't in the abstract) it would be best if they were sourced to a general review rather than a comment in a paper whose main purpose is elsewhere. Anyway... the abstract gives an estimate of 24.3 million and 4.6 million new cases "of dementia". Now, you've just said AD is "the most common cause of dementia", meaning it isn't synonymous with it. The epidemiology section later tells us it is associated with "almost half of all patients with dementia". So what is that paper telling us? The total figure for all dementias or do they mean AD and aren't being precise with their language? In addition, this fact isn't repeated in the body text--a clue is that the source is only used in the lead.

Body:

  • "affects almost half of all patients with dementia" doesn't come from (Gorelick, 2004).
  • "Correspondingly, " redundant word.
  • "Among people aged 65, 2–3% show signs of the disease". But (Gorelick, 2004) says "It is estimated that the prevalence is around 1.5% at age 65 years".
  • "while 25–50% of people aged 85 have symptoms of Alzheimer's and an even greater number have some of the pathological hallmarks of the disease without the characteristic symptoms" doesn't come from (Gorelick, 2004).
  • "Every five years after the age of 65, the probability of having the disease doubles". But (Gorelick, 2004) says "doubles every 4 years to reach about 30% at age 80 years" which is not only a different rate but indicates a peak.
  • "The share of Alzheimer's patients over the age of 85 is the fastest growing segment of the Alzheimer's disease population in the US" is not supported by (Hebert, 2003). That five-year-old paper uses a single study to estimate prevalence of AD in the US through to 2050. The paper speculates that the 85+ group will quadruple by 2050 compared to the 75-84 group merely doubling. However, the chart doesn't show any growth in that group till after 2020. So to say it "is the fastest growing segment" isn't supportable. Better to find a secondary (review) source to comment on this aspect rather than a primary source.
  • "A study in Denmark found that women aged 65 are at significantly higher risk (22 percent) of developing AD by age 95 than their male counterparts (9 percent), while vascular dementias were nearly equal." This is the first and only time vascular dementias are mentioned in this article. It would be useful to indicate earlier that vascular (multi-infarct) dementia is the second most common form of dementia and clarify it is not the same as AD. Although this 1999 study pools four previous studies, it is still original research rather than a review paper. The phrase "A study in Denmark" shouldn't really appear outside of a history section. Either women are at increased risk or they aren't. Find a high quality review, cite that, and state the facts not the history.
    • I've revised my opinion on that article and think it is significant enough to cite directly rather than insist on a secondary source. However, if the abstract's concluding sentence is fair, then you can just say "Compared with men, women have an increased risk for AD." without quoting the study by name/location. Colin°Talk 12:48, 3 June 2008 (UTC)
  • "Some studies have shown a relationship between Alzheimer's Disease and magnetic field exposure, although the mechanism is unknown. Other research does not confirm this link." Selecting (potentially, cherry-picking) primary research studies that support or contradict a controversial "fact" should not be done by WP editors. Find a review that discusses this link and use it to help gauge the weight you should give to each side. If the studies are seminal then link to them as an aid to the inquisitive reader but don't use them to support the statement. One way to do this is to cite the study after the words "some studies" or "other research" but cite the review after the "fact" you wish to state.
  • "The role of metals in the disease is also controversial." This is too vague to be helpful. One assumes the "role" is a negative one but it isn't made clear (e.g., perhaps some metal supplement is supposed to prevent AD). Aluminium is the most commonly suspected metal so should be highlighted. The citation lists three sources. Of these, (Rondeau, 2000) is primary research and probably should be dropped in favour of a more recent review. (Shcherbatykh, 2007) looks good from the abstract but I've no way to judge. I think you need to expand this sentence indicating the lack of causal evidence but noting "elevated levels of these metals in the brain may be linked to the development or progression of AD". (Santibáñez, 2007) also looks interesting from the abstract and covers several risks such as solvents, EMP, pesticides, lead and aluminium. However, its focus is to examine the quality of the research rather than to come to any conclusion. Its value as a source for this article is less certain -- but I haven't read the full text.

Looking at just this one section doesn't fill me with hope that this article is close to FA. There's too much text that deviates from the cited sources. For such a common disease, I'd expect the epidemiology section to be more comprehensive than this. I'd like to know whether the disease affects all ethnic groups equally and all countries equally (e.g, rich vs poor). The gender difference isn't adequately covered. Has the epidemiology of Alzheimer's changed over the years, and if so, is that purely down to age-population changes in society.

The editors of this article (who presumably have better access to the sources than me) need to review every sentence to ensure it is supported by the sources. Do this section by section and finish with the lead (making sure it is based on the body text). Once this is done, the ongoing challenge that all committed WP editors face is to ensure all additions/changes are policed to make sure they still match the sources. Well meaning and expert editors can ruin a potential FA by adding text sourced to their own brains. Alzheimer's is, unfortunately, a topic where everyone thinks they know something whether that is off the news or out of this week's BMJ/NEJM. However, the big advantage such an important topic has is that you should have no problem finding high quality review articles in respected journals. Use them as the foundation of your article, rather than citing primary research. The good news is that once you do reach the quality and comprehensiveness of an FA, people do show some respect and the rubbish edits are easier to handle.

Please check each cited paper to see if a free online version is available. PubMed's link can help but isn't 100% reliable at spotting (or linking to) the free papers. If you Google for the "Paper title", then this can often locate PDF/HTML copies at the publisher's site. Being able to located and read the free full paper makes it much easier for folk like me to look up the facts.

This is a very important disease topic. I urge you to continue working towards FAC. Colin°Talk 00:02, 17 March 2008 (UTC)

I agree that right now the two lowest quality sections are epidemiology and causes, which have to be completely reviewed. I suppose I will get to them at some time, but it won´t be soon... so if anybody wants to rewritte any of these sections it will be very welcomed. --Garrondo (talk) 08:01, 17 March 2008 (UTC)
I am at an Alzheimer's conference and the question came up of what source of prevalence is best. The delphi consensus in the Lancet 2006 is the one that folks were speaking up for. --Chrispounds (talk) 01:37, 28 March 2008 (UTC)
That one is "Global prevalence of dementia: a Delphi consensus study". PMID 16360788. {{cite journal}}: Cite journal requires |journal= (help) but see also "The epidemiology of the dementias: an update". PMID 17551353. {{cite journal}}: Cite journal requires |journal= (help) and "An estimate of the worldwide prevalence and direct costs of dementia in 2003". PMID 16401889. {{cite journal}}: Cite journal requires |journal= (help)LeadSongDog (talk) 03:58, 28 March 2008 (UTC)
The "affects almost half of all patients with dimentia" that Colin takes issue with appears in page 2 of Ren Yimin (2008-10-27). "Consequences of the interaction of Amyloid Beta with Amyloid Binding Alcohol Dehydrogenase and the Receptor for Advanced Glycation End products". {{cite journal}}: Cite journal requires |journal= (help)CS1 maint: year (link) which refs Jones JA, Lavallee N, Alman J, Sinclair C, Garcia RI (1993). "Caries incidence in patients with dementia". Gerodonto. 10: 76–82.{{cite journal}}: CS1 maint: multiple names: authors list (link) (questionable) and Brookmeyer 2007. Further on worldwide prevalence to 2050 is in: Brookmeyer R; et al. "Forecasting the global burden of Alzheimer's disease". {{cite journal}}: Cite journal requires |journal= (help); Explicit use of et al. in: |author= (help) lay summary in Peck Peggy (2007-06-11). "AAICPD: More than 100 Million Alzheimer's Patients Predicted Worldwide by 2050". Psychiatric Times. It doesn't appear though that we have a clear WP:RS for the statement as it reads at present. LeadSongDog (talk) 15:46, 3 June 2008 (UTC)
This website puts Alzheimer's at 50–60% of all dementia, vascular dementia at 20% and Dementia with Lewy bodies at 20%, with the other causes rare. I don't know much about the subject, but I guess much of what the Alzheimer charities concern themselves with is common to all causes of dementia and it suits them to just quote the bigger "all dementia" figure. Maybe there is no accurate figure for global Alzheimer's and you need to rephrase the lead to just give the figure for dementia, along with the approximate proportion due to Alzheimer's. I don't see where Brookmeyer gets his 2006 data from; looks rather speculative to me. Colin°Talk 19:43, 3 June 2008 (UTC)
  1. ^ Clinical Trial. FDA/clinicaltrials.gov. 2007-12-11 = "Efficacy Study of MPC-7869 to Treat Patients With Alzheimer's" http://clinicaltrials.gov/ct2/show/NCT00105547 = "Efficacy Study of MPC-7869 to Treat Patients With Alzheimer's". {{cite web}}: Check |url= value (help); Missing or empty |title= (help)
  2. ^ Clinical Trial. FDA/clinicaltrials.gov. 2007-12-11 = "Global Efficacy Study of MPC-7869 to Treat Patients With Alzheimer's" http://clinicaltrials.gov/ct2/show/NCT00322036 = "Global Efficacy Study of MPC-7869 to Treat Patients With Alzheimer's". {{cite web}}: Check |url= value (help); Missing or empty |title= (help)
  3. ^ ""Effect of LY451039 on the Long Term Progression of Alzheimer's Disease"". Clinical Trial. FDA/clinicaltrials.gov. 2008-01-11.
  4. ^ Clinical Trial. FDA/clinicaltrials.gov. 2007-05-24 = "Effects of LY450139 Dihydrate on Subjects With Mild to Moderate Alzheimer's Disease" http://clinicaltrials.gov/ct/show/NCT00244322 = "Effects of LY450139 Dihydrate on Subjects With Mild to Moderate Alzheimer's Disease". {{cite web}}: Check |url= value (help); Missing or empty |title= (help)
  5. ^ ""Bapineuzumab in Patients With Mild to Moderate Alzheimer's Disease/ Apo_e4 carriers"". Clinical Trial. FDA/clinicaltrials.gov. 2008-02-29.
  6. ^ ""Bapineuzumab in Patients With Mild to Moderate Alzheimer's Disease/ Apo_e4 non-carriers "". Clinical Trial. FDA/clinicaltrials.gov. 2008-02-29.
  7. ^ ""Study Evaluating the Safety, Tolerability and Efficacy of PBT2 in Patients With Early Alzheimer's Disease"". Clinical Trial. FDA/clinicaltrials.gov. 2008-01-13.
  8. ^ ""ELND005 in Patients With Mild to Moderate Alzheimer's Disease"". Clinical Trial. FDA/clinicaltrials.gov. 2008-02-29.
  9. ^ ""Safety, Tolerability and Efficacy Study to Evaluate Subjects With Mild Cognitive Impairment"". Clinical Trial. FDA/clinicaltrials.gov. 2008-03-11.
  10. ^ ""Study Evaluating ACC-001 in Mild to Moderate Alzheimers Disease Subjects"". Clinical Trial. FDA/clinicaltrials.gov. 2008-03-11.
  11. ^ "Medication 'worsens Alzheimer's'". BBC News. Tuesday, 1 April 2008. Retrieved 2008-04-01. Neuroleptics provided no benefit for patients with mild behavioural problems, but were associated with a marked deterioration in verbal skills. {{cite news}}: Check date values in: |date= (help); Cite has empty unknown parameter: |coauthors= (help)
  12. ^ [4]
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