Talk:Alzheimer's disease/Archive 6

Cox-2 Inhibitors
This story describes a negative result (worse than placebo) from a halted large (n=2000) study on celecoxib and on naproxen sodium as prospective AD-protective agents. "The findings were posted online Monday and will appear in July's Archives of Neurology"
 * LeadSongDog (talk) 20:04, 9 June 2008 (UTC)

Causes -> "genetic" and "familial" inheritance ambiguity
"Most cases of Alzheimer's disease do not exhibit familial inheritance. At least 80% of sporadic AD cases involve genetic risk factors." There is no complete causal link between genes and alzheimers, but there are genes which increase it's likelyhood. I assume "familial" was used to describe genes which provide a causal link, such as the gene which causes cystic fibrosis, and "genetic risk factor" used to describe genes which only increase the risk. If this is the case wouldn't it be better to scrap the term "familial" in order to reduce ambiguity? I think it would be better to say something along the lines of... "80% of cases involve genetic risk factors suggesting alzheimers is not caused by a particular gene and it's likelyhood increases with certain genes." —Preceding unsigned comment added by Doctor Correct (talk • contribs) 17:14, 6 June 2008 (UTC)

Archive 4
I've just moved threads starting before 2008 to archive 4. LeadSongDog (talk) 20:04, 9 June 2008 (UTC)
 * Also sorted out a misplaced that was prematurely truncating the talk page rendering.LeadSongDog (talk) 20:10, 9 June 2008 (UTC)

24 million
(Following copied from my talk - LeadSongDog) Your change to the lead on Alzheimer's disease may have removed ambiguity about the extent of "affects" but reintroduced the false statement that the 24 million is cases of Alzheimers. It is an estimate for dementia as a whole. Since there doesn't seem to be a reliable estimate for AD worldwide, we need to find a way of saying that the 24 million is for dementia, of which Alzheimer's is a common cause. Colin°Talk 06:22, 9 June 2008 (UTC)
 * Took another go at it. See what you think.LeadSongDog (talk) 15:33, 9 June 2008 (UTC)
 * Too much jargon, too much information for the lead and the plural "dementias" doesn't work. Rethinking the "is the most common cause of dementia, which affects an estimated 24 million people worldwide." I think the extent of "affects" isn't really a problem. I don't think anyone's expecting a figure for indirect affect (where would one draw the line anyway). Perhaps we should take this to the talk page? Colin°Talk 16:56, 9 June 2008 (UTC)
 * Few people would consider that the primary caregiver is less affected than the AD patient, particularly in advanced stages. For familial forms, offspring living with the expectation that they too will develop the disease may have their entire life plan changed.  The term "affected" must not be conflated with "patient".  It is not a trivial point.   If you have another way of saying it, fine, but I believe it needs to be said. LeadSongDog (talk) 20:04, 9 June 2008 (UTC)
 * I think that shifting the default understanding of "affect" from direct to include indirect is campaign language. Makes you stop and think. But not encyclopaedic. I don't think there's confusion in the reader's mind. The word is used when quoting the prevalence of many diseases including, for example, serious congenital genetic illness, where the carer burden no less than with AD, and often longer. The article should be clear on the distinct and separate direct affect of dementia and the indirect affects on carers, family and society. If someone can think of an alternative word to "affect" then great, but this lead sentence must be simplified. The phrase "A Delphi study formed an expert concensus estimate" is pure jargon. Colin°Talk 22:44, 9 June 2008 (UTC)
 * That's why I linked Delphi method. See also the cited paper-the freely accessible pdf is linked in the citation.  Not everyone will trust Delphi technique results, but they are better than simply pulling one expert's number out of a hat.  In any case, remember WP:NOTTRUTH.  I'm thinking that the number is perhaps not so critical that it belongs as the second line of the lead.  Should we move it down a few lines? LeadSongDog (talk) 14:30, 10 June 2008 (UTC)
 * How about "afflicts" or is that too emotive? Fainites barley 22:15, 11 June 2008 (UTC)
 * I also gave it a try today. What do you think?--Garrondo (talk) 16:33, 14 June 2008 (UTC)
 * It reads better but I thought the problem was that the 24/6 million figure referred to dementia rather than just alzheimers - or have better figures been found? Fainites barley 08:44, 17 June 2008 (UTC)
 * Figures might not be very reliable but the figure right now is an estimation specific for alzheimer (I know that the estimation before was 24 million for dementia and this is 26.6 million only for AD... but that is the problem of trying to make a guess in such a complex problem).That is the reason why I also added that figures vary a lot.--Garrondo (talk) 09:31, 17 June 2008 (UTC)
 * OK. Fainites barley 22:54, 17 June 2008 (UTC)

Featured article
From a non-expert point of view this article is excellent. Editors should list issues that would prevent this article from becoming FA. On my reading, I see essentially none, but I am not an expert on the subject. The FA requirements can be found here: http://en.wikipedia.org/wiki/Wikipedia:Featured_article_criteria. This article is long, but Alzheimer's is a complex topic, so I would prefer the in-depth treatment.

Please respond with your opinions. —Preceding unsigned comment added by Lwnf360 (talk • contribs) 06:10, 12 June 2008 (UTC)


 * I think the prevention section deserves some expansion, especially since, without a cure, this is the most important area for lay readers who comprise the vast majority of Wikipedia's readers -- the professionals (medical and research) are probably not reading Wikipedia. There is a substantial amount of research on Alzheimer's and metals, yet this is relegated to a footnote, and the article cited is focused on aluminium when copper is found in high concentrations in the brains of patients (example). The other paper does not have a link -- we should look for good, accessible papers when possible. Incidentally, there's a new paper about Alzheimer drugs out. Another on a gene variation. ImpIn | (t - c) 13:28, 14 June 2008 (UTC)


 * As far as metals and AD, these perspectives are not the dominant view point in the AD research community. There are a couple of compounds in development that are looking at metal based strategies (PBT2), but the evidence on that is not in yet.  Aluminum has been discounted by most advocacy organizations, even though a study from France many years ago suggested a risk.  I think we want to be rather conservative about drugs in development since they often don't make it beyond clinical trials.  This article has come a long way in the two and a half years I have been working thanks to some great people and their efforts on it.  --Chrispounds (talk) 16:55, 15 June 2008 (UTC)


 * That doesn't mean the metals shouldn't be covered. Besides, I'd rather not take your word that these are not important -- show me a source. As far as drugs, the most important ones should be highlighted and all the others should be mentioned and linked in this article for it to become featured. There's not hundreds of drugs; at the most there are a dozen or so. ImpIn | (t - c) 10:50, 16 June 2008 (UTC)


 * No causal relation has been found for the disease and therefore no proposals are made from scientific-health authorities regarding prevention. The truth is that for the moment the disease can not be prevented. At most there are some facts that have been linked in some epidemiological studies with a lower risk but no causal relationship can be atributted. Of course that does not mean that some sections such as the role of metals can be improved, but always maintaining WP:weight and for the moment the view of metals in relation with AD are minority in the scientific community. As for the source you ask for: "Occupational risk factors in Alzheimer's disease: a review assessing the quality of published epidemiological studies." . I copy the abstract for informative porpuses only: Epidemiological evidence of an association between Alzheimer's disease (AD) and the most frequently studied occupational exposures--pesticides, solvents, electromagnetic fields (EMF), lead and aluminium--is inconsistent. Epidemiological studies published up to June of 2003 were systematically searched through PubMed and Toxline. Twenty-four studies (21 case-control and 3 cohort studies) were included. Median GQI was 36.6% (range 19.5-62.9%). Most of the case-control studies had a GQI of <50%. The study with the highest score was a cohort study. Likelihood of exposure misclassification bias affected 18 of the 24 studies. Opportunity for bias arising from the use of surrogate informants affected 17 studies, followed by disease misclassification (11 studies) and selection bias (10 studies). Eleven studies explored the relationship of AD with solvents, seven with EMF, six with pesticides, six with lead and three with aluminium. For pesticides, studies of greater quality and prospective design found increased and statistically significant associations. For the remaining occupational agents, the evidence of association is less consistent (for solvents and EMF) or absent (for lead and aluminium). Best regards. --Garrondo (talk) 12:31, 16 June 2008 (UTC)


 * Garrondo, when an editor says "prove to me that it doesn't work", they are asking you to prove a negative. That's difficult.  I read over the "press release" (read advertising" from the Mayo Clinic patting itself on the back.  I read the Nature article...not much there.  The work is speculative and a long way from being a part of this article.  And to ImperfectlyInformed, play nice, it's not the job to write a long article on speculative drugs for AD, although we've put together an article just for that, and well, be nice.   Orange Marlin  Talk• Contributions 14:12, 18 June 2008 (UTC)

COI
{| class="collapsible collapsed" style="width:100%;font-size:88%;text-align: left; border: 0px; margin-top: 0.2em;" ! style="background-color: #ffd8a0;" | Memeron – Nothing presently usable in article – 21:32, 19 June 2008 (UTC)
 * style="text-align:center;" | The following is an archived debate of the possible conflict of interest related to the article above. Please do not modify it. 
 * style="border: solid 1px silver; padding: 8px; background-color: white;" |LeadSongDog (talk) 21:32, 19 June 2008 (UTC)
 * style="border: solid 1px silver; padding: 8px; background-color: white;" |LeadSongDog (talk) 21:32, 19 June 2008 (UTC)
 * style="border: solid 1px silver; padding: 8px; background-color: white;" |LeadSongDog (talk) 21:32, 19 June 2008 (UTC)

Memeron Neuropharmaceutical
Just wanted to let editors know of a new neuropharmaceutical designed for Alzheimer's called "Memeron". The official release is scheduled for 7.1.2008. Memeron is a supercharged version of Galantamine hydrobromide. As an acetylcholinesterase inhibitor, galantamine should be taken with a strong choline source to balance it out and fuel the acetylcholine uptake. Memeron utilizes Alpha GPC which is probably the best acetylcholine precursor available. The Memeron website is at http://www.memeron.com for further information. As the developer of this medication, I would greatly appreciate it if there is any way to add Memeron to the Alzheimer's article under "Pharmaceutical Management". Philoprof (talk) —Preceding comment was added at 13:54, 18 June 2008 (UTC)
 * Please provide reliable sources that verify any claims made. I am personally reluctant to use a corporate website as a citation for anything about this compound.  Orange Marlin  Talk• Contributions 14:07, 18 June 2008 (UTC)
 * Never mind, this isn't a pharmaceutical, your website is officially advertising, and there are no reliable sources. It's never going to be added to this article, and I think this discussion should be deleted, but I need to review the rules on that.   Orange Marlin  Talk• Contributions 14:09, 18 June 2008 (UTC)

Galantamine is a prescribed pharmaceutical AND available OTC. Its in a gray area. When its combined with Alpha GPC (which is a pharmaceutical level lecithin) is it a pharmaceutical or not? Is a pharmaceutical just something that gets prescribed? Or is it a level of the medication? Does it refer to efficacy? Philoprof (talk)
 * There are plenty of reliable efficacy studies on both galantamine and alpha gpc in the treatment of neurological conditions. Just check Google scholar or PubMed. The FDA approved galantamine as a treatment for mild to moderate Alzheimer's and not any name brand per say.Philoprof (talk)
 * The Memeron website is a corporate website with information about a particular product. Name brands are referred to in the article and I simply wanted to politely ask editors to consider Memeron as a candidate in the article.  I am biased because I am the developer of the drug, but I am convinced Memeron is one of the most effective (if not the most effective) pharmaceutical level treatment for Alzheimer's currently on the market.  We have learned that acetylcholinesterase inhibitors are much more effective when taken with acetlycholine precursors.  The nootropic community is particularly savy on this point because many of them have experienced it for themselves or did their homework on the synergy that is created when you combime the two.Philoprof (talk)  —Preceding comment was added at 14:46, 18 June 2008 (UTC)
 * We have learned that acetylcholinesterase inhibitors are much more effective when taken with acetlycholine precursors. Have we? A good starting point would be to provide articles on this issue. Search in pubmed and give the references (the editor that includes any new information is the one responsible of finding the references not the other editors). If it is so the addition of such info might be valuable. --Garrondo (talk) 14:58, 18 June 2008 (UTC)
 * Garrondo- I am going to work on providing spefic references for you and include them here for consideration.Philoprof (talk) —Preceding comment was added at 15:01, 18 June 2008 (UTC)
 * I go on holiday in an hour, but other editors will be here. Understand that many people try to include their products in the article and we have to be very careful so only include those really proved. In this sense it praises you to have addmitted your conflict of interest and try to provide reliable verications to your claims.--Garrondo (talk) 15:07, 18 June 2008 (UTC)
 * Thank you Garrondo. Your comments are well taken and I want to be careful with how I approach the issue with Wikipedia editors and feel that is best to bring it up in the discussions area for consideration.  Hope you enjoy your holiday!  —Preceding unsigned comment added by Philoprof (talk • contribs) 15:12, 18 June 2008 (UTC)

Studies pertaining to Memeron efficacy claims: —Preceding unsigned comment added by Philoprof (talk • contribs) And cites tweaked by me. LeadSongDog (talk) 15:50, 18 June 2008 (UTC)
 * Is there any clinical trial showing that there is any difference between galantamine and galantamine combined with alpha gpc? Is there any clinical trial on the efficacy of alpha gcp alone? We don't need articles on the efficacy of galantamine (its moderate efficacy is alredy stated in the article). --Garrondo (talk) 15:34, 18 June 2008 (UTC)



Thanks LeadSongDog for the cite tweaks. --Philoprof (talk) 15:53, 18 June 2008 (UTC)Philoprof
 * Happy to do that. Still, Garrondo's 14:58 post stands.  The only thing I see so far that speaks to that question is, which is only in rats.  The standard for inclusion here is (at minimum) phase III trial results.  There have been too many promising failures.LeadSongDog (talk) 16:11, 18 June 2008 (UTC)
 * Phase III trials have been conducted on Galantamine alone, so the efficacy on that end of things is well established. The FDA has approved Galantamine for mild to moderate Alzheimer's (this I'm sure you're already familiar with however).  Galantamine has been used in Europe for over 50 years now and is well-tolerated.  The efficacy of Galantamine plus Alpha GPC is a new discovery incorporated into the Memeron formula.  To be honest, the mainstream big-business pharmaceutical companies are a bit behind the times.  The cognitive enhancement community seems to me much further ahead on some of these issues.  They have first-hand  experiences of the combination.  The so-called "scientific" community is just catching up even though there are a fair amount of studies circulating about referencing acetylcholinesterase inhibitor and precursor synergy.  We have really only learned the extent of this synergy within the past five years or so.  Until neuroscience was able to identify and learn more about the acetylcholine neurotransmitter system have we really began to understand the roles of acetylcholine precursors and cholinesterase inhibitors. --Philoprof (talk) 20:22, 18 June 2008 (UTC)Philoprof
 * " there are a fair amount of studies circulating about referencing acetylcholinesterase inhibitor and precursor synergy" — So show us the citations. LeadSongDog (talk) 21:26, 18 June 2008 (UTC)
 * --Philoprof (talk) 13:34, 19 June 2008 (UTC)Philoprof
 * A study published this year on Alpha GPC efficacy compared to other choline precursors:
 * The Memeron formula is based squarely on the cholinergic hypothesis of Alzheimer's disease. Memeron works specifically on the acetylcholine neurotransmitter system.  However, whereas the other acetylcholinesterase inhibitors on the market today such as Aricept (donepezil), Razadyne (galantamine alone), and Rivastigmine (Exelon) just inhibit the breakdown of acetylcholine, Memeron provides additional acetylcholine to the brain through acetylcholine synthesis utilizing Alpha GPC as a precursor. Memeron does the two tasks simultaneously- prevent the breakdown of acetylcholine AND produce additional acetylcholine.  Its not enough simply to slow down the breakdown of acetylcholine in the Alzheimer's brain.  You have to produce more through acetylcholine synthesis.  Alzheimer's sufferers need additional acetylcholine pumped into their neurotransmitter system and not just prevent the breakdown of what little acetylcholine is left.--Philoprof (talk) 14:09, 19 June 2008 (UTC)Philprof
 * The Memeron formula is based squarely on the cholinergic hypothesis of Alzheimer's disease. Memeron works specifically on the acetylcholine neurotransmitter system.  However, whereas the other acetylcholinesterase inhibitors on the market today such as Aricept (donepezil), Razadyne (galantamine alone), and Rivastigmine (Exelon) just inhibit the breakdown of acetylcholine, Memeron provides additional acetylcholine to the brain through acetylcholine synthesis utilizing Alpha GPC as a precursor. Memeron does the two tasks simultaneously- prevent the breakdown of acetylcholine AND produce additional acetylcholine.  Its not enough simply to slow down the breakdown of acetylcholine in the Alzheimer's brain.  You have to produce more through acetylcholine synthesis.  Alzheimer's sufferers need additional acetylcholine pumped into their neurotransmitter system and not just prevent the breakdown of what little acetylcholine is left.--Philoprof (talk) 14:09, 19 June 2008 (UTC)Philprof

Here is another study I thought you might find interesting on Galantamine efficacy:
 * --Philoprof (talk) 13:22, 19 June 2008 (UTC)Philoprof
 * It appears that you are ducking the question, so I'll put it to you directly: Do you have any citation that shows a phase three trial of the combination you call Memeron or not? LeadSongDog (talk) 15:24, 19 June 2008 (UTC)
 * If you want to know if I have paid for clinical trials in which I bias the results in favor of the product I developed, the answer is a simple no. I am not working on behalf of big-pharma. I do not have stock investors or venture capitalists pumping in money on my behalf.  There are sufficient studies conducted by independent institutions showing both the efficacy of Galantamine and Alpha GPC in treating Alzheimer's and other neurological conditions. There are additional studies as I have tried to lay out briefly refering to the synergy that ensues when you combine acetylcholinesterase inhibitors and choline precursors. I am a relatively independent researcher and developer of brain health supplements and neuropharmaceuticals.  Its a personal passion and I hope we do not confine ourselves merely to the products produced by big-pharma.  In fact, I do not feel that big-pharma has been particularly innovative at all in this field over the past ten years.  Most of the drugs on the market today were developed quite some time ago. They are just getting a new brand name and marketed anew with big-pharma backing.  I was personally excited about Namenda a few years ago and then I realized that memantine was developed back in the '60's.  I even invested in Neurobiological Technologies because they got FDA approval for Namenda (memantine) for mild to moderate Alzheimer's.  They didn't create anything new however.  This seems to be the modus operandi of big-pharma. I have tried to put together the best and highest quality pharmaceutical level treatment for Alzheimer's available.  The more research I do (including personal testimonials of individuals who have experience with the Memeron combination) the more I realize how effective it is.  Time will bear this out further, but I can only leave you with a few more studies for now: --Philoprof (talk) 17:42, 19 June 2008 (UTC)Philoprof
 * * --Philoprof (talk) 17:42, 19 June 2008 (UTC)Philoprof
 * All very interesting discussions of the individual constituents, which are already in the article. What we need is a citation that points us to a trial of the combination that you seem to think is somehow better than the individual constituents.  Not a personal testimonial.  Not a diatribe.  Just the relevant citation.  When you find one, Wikipedia will still be here.  Until then, we have to regard this as no more than an interesting hypothesis, as yet untested. LeadSongDog (talk) 18:10, 19 June 2008 (UTC)
 * I have referred you to 14 studies here to support the case for Memeron as an effective treatment for Alzheimer's. The personal testimonials are critically important to this whole discussion (much more so than the so-called clinical trials).  Either the product works or it doesn't and people know it from first-hand personal experience.  Clinical trials are highly dependent on personal testimonials for any efficacy claims.  Patient testimonials are absolutely essential.  A scientist cannot hardly write up a study without the testimony of patients.  How do they know what they know?  It becomes an epistemological issue.  Science is not an entirely objective affair.  Science requires subjective experience to validate her claims.  In my development of Memeron, I have relied first on personal subjective experience and second on the interpretations of the experiences from "scientists." The patient's personal experience will be the tell-tale sign and only secondarily the scientist's interpretation.  At some point, it becomes statistically significant and a repeatable experience is more likely than not.  At that point, we (as scientists and researchers) can make our recommendations and support our claims. --Philoprof (talk) 18:39, 19 June 2008 (UTC)Philoprof
 * No. You've referred us to studies to support the case for constituents in your product. I think you'll find that efforts to trash the use of science in medicine will not get you very far here.  In any case, the door remains open.  When you've got a usable paper to cite, let us know.LeadSongDog (talk) 18:49, 19 June 2008 (UTC)
 * I have no intention to trash science's epistemology and usefulness in medicine. The scientific method has been immensely helpful in contemporary medicine and should be utilized as much as possible. I simply wanted to state that its not just about papers and citations in the end, but real people with real problems.  This is especially true for Alzheimer's sufferers. --Philoprof (talk) 19:15, 19 June 2008 (UTC)Philoprof
 * I have referred you to 14 studies here to support the case for Memeron as an effective treatment for Alzheimer's. The personal testimonials are critically important to this whole discussion (much more so than the so-called clinical trials).  Either the product works or it doesn't and people know it from first-hand personal experience.  Clinical trials are highly dependent on personal testimonials for any efficacy claims.  Patient testimonials are absolutely essential.  A scientist cannot hardly write up a study without the testimony of patients.  How do they know what they know?  It becomes an epistemological issue.  Science is not an entirely objective affair.  Science requires subjective experience to validate her claims.  In my development of Memeron, I have relied first on personal subjective experience and second on the interpretations of the experiences from "scientists." The patient's personal experience will be the tell-tale sign and only secondarily the scientist's interpretation.  At some point, it becomes statistically significant and a repeatable experience is more likely than not.  At that point, we (as scientists and researchers) can make our recommendations and support our claims. --Philoprof (talk) 18:39, 19 June 2008 (UTC)Philoprof
 * No. You've referred us to studies to support the case for constituents in your product. I think you'll find that efforts to trash the use of science in medicine will not get you very far here.  In any case, the door remains open.  When you've got a usable paper to cite, let us know.LeadSongDog (talk) 18:49, 19 June 2008 (UTC)
 * I have no intention to trash science's epistemology and usefulness in medicine. The scientific method has been immensely helpful in contemporary medicine and should be utilized as much as possible. I simply wanted to state that its not just about papers and citations in the end, but real people with real problems.  This is especially true for Alzheimer's sufferers. --Philoprof (talk) 19:15, 19 June 2008 (UTC)Philoprof

To Do list
For reasons that should be obvious, I put this at the top of the talk page, but I'll add a note here to nudge attention up. The todo items captured from the recent FAC review are there. Please strike through them as they are completed.LeadSongDog (talk) 03:34, 16 June 2008 (UTC)


 * The pathophysiology/Disease mechanism section is clearly too techinical, underreferenced and underlinked. I don't know enough biology to modificate it but it has to be revised. Does anybody feel capable of doing it? --Garrondo (talk) 12:46, 17 June 2008 (UTC)


 * After recent archiving, the link to /ToDo is no longer at the top of the talk page. LeadSongDog (talk) 04:33, 17 July 2008 (UTC)

New metric for rate of AD progression
It seems MRIs showing enlargement of the ventricles can now be used to quantify the rate of disease progression during the mild cognitive impairment phase. See:

I'm not sure just how to fit this in.LeadSongDog (talk) 18:29, 14 July 2008 (UTC)

AD lasts for 5 and 20 years
But do we know if that's after diagnosis, as the intro currently states? It seems reasonable, but it also looks a bit like it could be an estimate that takes undiagnosed 'pre-dementia' into account. Unless I've missed anything? The refs don't seem to specify.

People need to know how long they can plan (esp if diagnosed late), so this could need to be looked at further.--Matt Lewis (talk) 18:14, 17 July 2008 (UTC)


 * The second links says "some... have the disease for the last 5 years of their lives" (which suggests the full course of the disease) but I won't revert it at the moment as we need more information, anyway. People need to be aware of that 'pre-demntia' ambiguity, that no-one can put an exact timescale on - but they could also use some clear guidelines on 'average' timescales. --Matt Lewis (talk) 18:23, 17 July 2008 (UTC)


 * This reference says that the median survival is around 5 years after diagnosis. Because symptoms are nonspecific and misdiagnosed in early stages, I'm not sure there's a more accurate number out there.  I've been rereading the references AGAIN.  As a whiny aside, I wish we could stabilize this article.  I'm copy editing for what feels like the 25th time.   Orange Marlin  Talk• Contributions 18:33, 17 July 2008 (UTC)


 * Is anyone here to do anything else? The problem is that if it isn't perfect, things will get changed. And when it's right it's just a question of reverting! It's all really simple, didn't you know? We need to use that reference as a citation where it is mentioned in the Intro - it could be swapped for one of the two there (which are very similar). --Matt Lewis (talk) 19:25, 17 July 2008 (UTC)


 * I actually really like that reference--it really is easy to read, and supports what we are writing. There's one reference I found this morning that in combination with the one above, really is clear about prognosis and lifespan.  If you want to move them to the lead, please do so. Orange Marlin  Talk• Contributions 19:33, 17 July 2008 (UTC)

World Alzheimer's Day
I had the last line in the intro as "World Alzheimer's Day takes place annually on the 21st September." but it hasn't stuck.

What is the score with these? Can they be mentioned anywhere else other than the intro? They don't specifically have their own websites. At the moment it is not in the article at all. I notice world cancer day has it's own WP article, but it's not linked to by the main article. --Matt Lewis (talk) 18:31, 17 July 2008 (UTC)
 * I deleted, because I feel it's not really important to the article. I always ask myself, "does this information add to the general reader's knowledge of AD?".  Anyways, I wouldn't put it in the lead.  I guess we could put it in a cultural section.  Or a see also link?   Orange Marlin  Talk• Contributions 18:35, 17 July 2008 (UTC)
 * WP:MEDMOS would have it in a "Society and culture" section, under an "Awareness" subsection if appropriate. It's a recurring theme across many articles. LeadSongDog (talk) 18:58, 17 July 2008 (UTC)


 * It comes under 'general reader' to me, as I always see the articles as about the subjects it the fullest sense. I thought these 'world days' were used by fund raisers, awareness, drug companies, conventions, specialists etc - the whole thing? I'll look futher into it. If I give it it's own article, we can link to it somewhere I'm sure. I notice, btw, there are no 'Further links' on AD of any kind! Was that a decision, or have none ever come about? (I haven't looked through it for a while). --Matt Lewis (talk) 19:16, 17 July 2008 (UTC)


 * I think there is a real push for WP:MEDMOS to remove lists of trivia. I'm constantly reverting asthma because everyone wants to put in a blog about the disease, a new miracle cure, or frankly jokes.  I don't think anyone will mind having it, it's just that it's got to be watched carefully.   Orange Marlin  Talk• Contributions 19:31, 17 July 2008 (UTC)


 * See Further_reading. This article is already so extensively referenced there might be little point in adding a Further reading section.  BTW, it's good to have the Ghoti back. LeadSongDog (talk) 20:10, 17 July 2008 (UTC)

Aluminum
Why is aluminum not mentioned at all in the article? It's been in the news in connection with Alzheimer's disease for more than 15 years. Even if the link has been debunked, it should at least be mentioned. Badagnani (talk) 04:41, 26 June 2008 (UTC)
 * See discussion above at

As mentioned just above, aluminum should at least be mentioned in the article, due to the 15+ years of widespread public discussion of this issue. At present, the word doesn't appear in the text of the article even once. Badagnani (talk) 05:28, 26 June 2008 (UTC)


 * Well, it was in the article once, but it was "no link between AD and aluminum." We would spend paragraphs saying what isn't linked to it.  I don't think it belongs, but that's my opinion.   Orange Marlin  Talk• Contributions 22:43, 26 June 2008 (UTC)

Users will look for information at our supposedly encyclopedic article regarding aluminum, due to the 15+ years of news stories about this, yet not find a single mention of the metal in the supposedly encyclopedic article. I am one such user. Badagnani (talk) 23:48, 26 June 2008 (UTC)


 * But aluminum has no causal effect on AD. I'm not sure how encyclopedic it can be to mention that for everything that is out there.  And frankly, I haven't heard anything in the news for the past 10 years regarding aluminum and AD.   Orange Marlin  Talk• Contributions 00:39, 27 June 2008 (UTC)


 * I did a quick search of news articles on aluminum and AD over the past 20 years. The bulk of articles were written between 1989 and 1993.  The last article, in a regular news outlet, that discussed the link was in 1997, over 10 years ago.  The idea was debunked 15 years ago, at least.  An encyclopedia should not be a list of fringe ideas, even if they were debunked.  We should move on. Orange Marlin  Talk• Contributions 00:44, 27 June 2008 (UTC)

Our users will look for information about Alzheimer's disease and aluminum and expect to find information about this here. Omitting all mention of aluminum from the article does not do them a service. Badagnani (talk) 00:48, 27 June 2008 (UTC)

Which database did you scan? Lexis-Nexis gives 535 hits in the last 10 years alone, including the following:

The Alzheimer's riddle: Lone medical researcher insists aluminum must be the culprit The Gazette (Montreal, Quebec), October 30, 2000, Monday, FINAL, Living; E2, 1168 words, KATHERINE DEDYNA 2. HEALTH HELPLINE - YOURSELF; ALZHEIMER'S DISEASE. Sunday Express, February 11, 2001, FEATS; Pg. 56, 284 words, MARY SALMON 3. A QUESTION OF HEALTH The Independent (London), December 11, 2002, Thursday, FEATURES; Pg. 11, 668 words, Dr Fred Kavalier 4. Explore high-risk factors behind Alzheimer's disease USA TODAY, January 31, 2005, Monday,, 196 words 5. Alzheimer's patients absorb more dietary aluminium Pulse, March 25, 2000, Pg. 30, 176 words 6. Aluminum-Alzheimer's link is thin as tin The Gazette (Montreal, Quebec), May 18, 2002 Saturday Final Edition, Weekender; The Right Chemistry; Pg. F16, 1130 words, JOE SCHWARCZ 7. IS ALUMINIUM DANGEROUS? The Statesman (India), May 29, 2006 Monday, 441 words 8. IS ALUMINIUM DANGEROUS? The Statesman (India), May 29, 2006 Monday, 441 words 9. Why the great aluminium saucepan scare was rather overcooked SUNDAY TELEGRAPH(LONDON), November 23, 2003, Sunday, 615 words, ANSWER BY ROBERT MATTHEWS 10. SENILITY NOT THE RESULT OF ALUMINIUM Canberra Times (Australia), October 4, 1998, Sunday Edition, 664 words 11. The New York Times, April 26, 2005 Tuesday, Section F; Column 5; Health & Fitness; REALLY?; Pg. 6, 254 words, By ANAHAD O'CONNOR 12. CHOCOLATE PUDDING CAN ROT YOUR BRAIN Scotland on Sunday, June 20, 1999, Sunday, Pg. 8, 338 words, By Jackie Kemp 13. ALZHEIMER DISEASE; Recent studies from Johns Hopkins University, Department of Environmental Health Sciences add new data to Alzheimer disease Biotech Business Week, June 4, 2007, EXPANDED REPORTING; Pg. 719, 379 words 14. NOT FOREVER, The Boston Globe, March 20, 2005, Sunday, 242 words, PETER J. KELLY 15. Early-warning test that could combat Alzheimer's DAILY MAIL (London), April 16, 2003, Pg. 17, 671 words, James Chapman 16. CAREFUL what you use Housewares, November 1998, Pg. 37, 452 words 17. Alzheimer's research triggers call for new water poisoning inquiry: Camelford woman's death linked to aluminium level: Effects of incident were covered up, says husband The Guardian (London) - Final Edition, April 20, 2006 Thursday, GUARDIAN HOME PAGES; Pg. 7, 593 words, Sarah Hall, Health correspondent 18. Q & A Sydney Morning Herald (Australia), August 26, 2004 Thursday, HEALTH & SCIENCE; Pg. 4, 528 words, Dr Linda Calabresi Dr Calabresi is a practising Sydney GP and medical editor of Medical Observer. Email your questions to linda.calabresi@medobs.com.au 19. Is soup the only thing simmering in that pot? The Globe and Mail (Canada), March 13, 2001 Tuesday, HEALTH; LETTERS FROM ACADEMIA; Pg. R6, 1182 words 20. Fight the disease The Advertiser, February 1, 2005 Tuesday, FEATURES; Pg. 42, 871 words, James Duigan The Naked Trainer 21. Alzheimer's linked to aluminium pollution in tap water The Times (London), April 20, 2006, Thursday, HOME NEWS; Pg. 26, 734 words, Nigel Hawkes 22. Alzheimer's linked to aluminium pollution in tap water The Times (London), April 20, 2006, Thursday, HOME NEWS; Pg. 26, 734 words, Nigel Hawkes 23. Tin, Aluminum, Chromium The Washington Post, May 24, 2006 Wednesday, Food; F06, FOOD 101 Robert L. Wolke, 953 words, Robert L. Wolke 24. Rare Alzheimer death reignites aluminium fears The Times (London), April 20, 2006, Thursday, HOME NEWS; Pg. 31, 596 words, Nigel Hawkes, Health Editor 25. Rare Alzheimer death reignites aluminium fears The Times (London), April 20, 2006, Thursday, HOME NEWS; Pg. 31, 596 words, Nigel Hawkes, Health Editor

Badagnani (talk) 01:58, 27 June 2008 (UTC)

There were already some refs for aluminium when talking about the role of metals. I have specifically added aluminium with references both confirming and disconforming such link and other occupational exposures in the prevention section as a risk factors. I think that now all views are fairly represented.--Garrondo (talk) 10:30, 1 July 2008 (UTC)
 * I keep forgetting to look at this talk page. The above are fine repeats of the same urban myth over and over again, but nothing there impresses me that it's a current or newsworthy story.  I'm not opposed to information about aluminum.   Orange Marlin  Talk• Contributions 22:52, 9 July 2008 (UTC)

If it is a myth and has been fully debunked, like anything else at WP it should be presented (and debunked, with sources), since people will come looking for such information. However, the most recent Lexis-Nexis sources include ones that still include scientists who believe the metal has a relationship to the disease. Badagnani (talk) 23:06, 9 July 2008 (UTC)


 * Badagnani, would you mind removing all those news links? They are distracting and largely unciteable. Let's try to keep the page clean. Also, did you notice my review of the science above? I presented 6 recent scientific reviews positively inclined towards the aluminium hypothesis, and one 2001 Elsevier book. The Medline literature on aluminium/Alzheimer's largely supports the hypothesis. II  | (t - c) 03:52, 10 July 2008 (UTC)

Please don't edit in a threatening manner. It was necessary to place the links, as an editor claimed that his/her search proved that there were no such articles in the last ten years. Badagnani (talk) 03:54, 10 July 2008 (UTC)


 * I'm not trying to be threatening. When you cut out the noise, it is easier to see the signal (Signal-to-noise). You've already made your point, and I feel that. But now it would be nice to trim. Look at the abstracts of the reviews that I presented instead. Try to get ahold of the full-text. The aluminium section deserves more weight in this article. II  | (t - c) 03:57, 10 July 2008 (UTC)

I'm really not mistaken when I said that an editor (who seemed very sure of him/herself) stated that no article had appeared in any media source in the last ten years that mentioned aluminum vis-a-vis Alzheimer's disease. Badagnani (talk) 04:00, 10 July 2008 (UTC)


 * I know you're not mistaken. I said the exact opposite. You've proven him wrong ("You've already made your point"), and now it would be nice to trim. Check out RESOURCE if you want to get a hold of the full-text for some of those reviews. is free access.  II  | (t - c) 04:04, 10 July 2008 (UTC)

A review of the scientific reviews for Aluminium and Alzheimer's
Moving this down here since it seems to fit better. Garrondo, you gave me the wrong PMID. (2007 -- this is the one you gave me) has this to say on the issue: (2008), a systematic review of this particular issue, says this: It's not the most prestigious work, but along with the above review, there is obviously something going on which deserves a fair bit of attention. Perhaps you meant to point me to, which reviews 3 epidemiological studies and finds no relationship -- strangely, it doesn't include the 2000 epidemiological study referenced in this article. A 2001 book from Elsevier concludes that "we are far away from discounting the possibility that aluminium is a contributory factor in the aetiology of Alzheimer's disease." (2006),  (2006),  (2005), which PubMed count as reviews, also make the case for Al as a factor. I'm not just selecting either; click Related links on any of these, click Reviews, then sort by Pub date. These are the ones that come up. OM: I'm not really a "nice" or a "non-nice" person on Wikipedia -- but I'm certainly not trying to be mean. I'm here to promote good information. I'll admit that I'm disappointed that there's plenty of bad science flying around, and that it's clear that many people aren't really doing much research, just repeating things they've heard. I also don't think a Featured Article should present a biased view of the science. You say that proving a negative is difficult -- that's not true, especially when the supposed negative is actually a positive of "show me that scientists don't really think aluminium is really connected to Alzheimer's". ImpIn | (t - c) 02:18, 27 June 2008 (UTC)

Compare: and The hypothesis seems to still be fairly current.LeadSongDog (talk) 17:33, 17 July 2008 (UTC)

Definitely needs to covered before this becomes a featured article. II | (t - c) 06:08, 30 July 2008 (UTC)

MRI image


This was the comment for the image of a revisor in the FAC proccess:

''Image:Alzheimer's disease - MRI.jpg - the policy pages referenced in PD-USGov-NASA address only information hosted on JSC (Johnson Space Center) and JPL (Jet Propulsion Laboratory) websites. This image is from a GSFC (Goddard Space Flight Center) website (I didn't see an equivalent policy for this prefix). The notice page for this tutorial explicitly indicates that some images are not in the public domain. The tutorial does not appear to claim to be a work of NASA; indeed, the forward introduces the primary author as "a former NASA Goddard employee" (emphasis added). Where is the basis for the claim that this image was created by NASA? Why would the National Aeronautics and Space Administration be creating images pertaining to Alzheimer's?''

The truth is that there is hardly any way of knowing if this image is under public domain, and most probably it is not. I have searched other government pages to see if the picture appears and there is non, and right now even the tutorial where it was taken from has closed. It's a pity but I feel that the honest thing to do is to eliminate the picture from the article and probably from WP commons.

It is not by far as good as an MRI image but I have created a drawing comparing an AD brain and a normal brain. It is a beta version, and as I have created it with layers modifications could be easily be made. I hope people say what they think about it (Of course if anybody has an MRI image it would be most welcomed).

I am going to put it here with a possible comment to see what other editors think. Best regards to everybody.--Garrondo (talk) 09:02, 16 July 2008 (UTC)


 * I can only see the description. Does anybody know why?--Garrondo (talk) 09:07, 16 July 2008 (UTC)
 * I see it correctly now...Never mind --Garrondo (talk) 09:12, 16 July 2008 (UTC)
 * I liked the picture, but I'm concerned that policy around here is in lieu of explicit permission, we have to assume there is none. We could try to get someone familiar with images involved. Orange Marlin  Talk• Contributions 21:30, 16 July 2008 (UTC)


 * I've updated the MRI image metadata on the commons page to show the primary author and a current URL for the tutorial. He clearly thought the image was suitable for inclusion in a non-copyright NASA educational publication, the reasonable man would conclude that it is barring some counter-evidence.  I'm comfortable with using it, but if someone wants to email Dr Short about it, that should remove all doubt.  His address is in the metadata. LeadSongDog (talk) 16:50, 17 July 2008 (UTC)


 * Are we sure that even the tutorial is non-copyrighted? Even if it was, it may apply only to text, while images might be copyrighted. I really like the image, but we must be sure of the source. If it is not clearly stated that it is not copyrighted there might be a problem.--Garrondo (talk) 11:28, 18 July 2008 (UTC)
 * Given the nagging doubt, why not just email the guy?LeadSongDog (talk) 13:27, 18 July 2008 (UTC)
 * I doubt he answers but I'll try it. --Garrondo (talk) 13:42, 18 July 2008 (UTC)
 * The email does not work anymore. --Garrondo (talk) 13:58, 18 July 2008 (UTC)
 * I have also written to the goddard space center (creator of the tutorial where the image appeared) and the NASA office for copyrights issues... I don't think they would answer but nobody knows... :-) --Garrondo (talk) 14:17, 18 July 2008 (UTC)

LeadSongDog (talk) 20:03, 29 July 2008 (UTC)
 * Better alternatives are at the ADEAR Media room and they are declared there as being public domain. Woo-hoo! LeadSongDog (talk) 18:57, 29 July 2008 (UTC)
 * [[Image:PET_Alzheimer.jpg|left|thumb|PET scan of brain with AD - Image courtesy of US [[National Institute on Aging]] Alzheimer's Disease Education and Referral Center]] [[Image:PET_Normal_brain.jpg|right|thumb|PET scan of a healthy brain - Image courtesy of US [[National Institute on Aging]] Alzheimer's Disease Education and Referral Center]] Think these are suitable replacements?
 * They are PD, and there are many other interesting images we could use... Well Done. --Garrondo (talk) 08:30, 30 July 2008 (UTC)
 * I would not put the image exatcly where the MRI image is right now but in the diagnosis section since is where we talk about PET scan. In the neuropathology section I would put the diagram comparing the brain of a person with and without the disease from the same source. Finally just to be a little critic: I do not know much about PET, but I believe that to be able to compare the energy gradients of two images they have to be exactly in the same scale, and since the darkest point in both images is not the same colour I doubt they are in the same scale so it is not really fair to compare them (Even in the worsest state of AD there would not be such functional differences. Maybe it would be better to simply put the AD image and say that a temporal hipofunctionality is a characteristic of the disease which can be seen in the image.--Garrondo (talk) 10:52, 30 July 2008 (UTC)

Methylene blue
An exciting BBC report. See Talk:Alzheimer's disease clinical research LeadSongDog (talk) 22:58, 29 July 2008 (UTC)

Very early detection
It appears that successive volumetric MRI analyses of the basal forebrain can detect atrophy as much as 4.5 years before symptoms are detected. LeadSongDog (talk) 17:50, 30 July 2008 (UTC)
 * Basal forebrain atrophy is a presymptomatic marker for Alzheimer's disease DOI 10.1016/j.jalz.2008.04.005

Ambiguous statistic
The survival time after diagnosis is approximately 6 years

Is this a mean or a median figure? Presumably that information can be found in one of the seven citations given for it, but it should be in the article. --75.63.50.206 (talk) 23:21, 31 July 2008 (UTC)


 * The reason it's so non-specific is that diagnosis can be late or early in progress of the disease, because it's so nonspecific. Orange Marlin Talk• Contributions 23:48, 31 July 2008 (UTC)

FAC. Are we already there?
The article has changed very much in a year and the direction has always been FA. Two months ago it was presented as FAC. It was probably too early since a few sections had not been really revised. The FAC served its pourpouse since we had guides on what to improve. In these two months 3 sections have been fully rewritten, and most of the others improved. I believe content is good enough right now to pass the FA proccess, however there are a few issues that should be solved before the proccess begins. I think they are mainly three, but if anybody believes there are any others just say them.

Prognosis
I'll try to revise this section, since it is the smallest one of the article.

Lead
The lead should be a summary of the content of the article. Therefore I believe it should most likely follow the same order than the article give the same weight to article views and have same references. The lead of the AD article has evolved quite separated from the article, and there are importante differences between both of them. Could anybody with a good English take a look at it and rewritte some of it?

Citing style
Quite a lot of months ago this was alredy discussed. Consensus was reached to writte references vertically and using Diberris tool. Some sections and references do not use this style. Most importantly, I really do not like to put several references inside the same number since it is easy to repeat references without knowing it. Consensus has to be reached on whether to use such style and when (How many consecutive references are needed to combine them inside a single number?). Consensus should also be reached on which parameters from Diberris tool are the ones to be used in the references of the article.

We have almost 300 references in the article. It is really hard to follow them and very easy to repeat them or delete one... My proposal would be to use the full reference with the name parameter every time a reference is used. I know this increases the weight of the article, but it eases citing or deleting refences since you do not need to see if the ref is already used when including a new reference or if it is used in other sentences when deleting a reference. Anyway, if it is decided to only put the full reference the first time it is used there are many references (Probably most of them added by me) used several times with the full ref data.

--Garrondo (talk) 10:02, 1 August 2008 (UTC)


 * I have revised the prognosis and the lead. I have added info not present in the article from the lead and vice-versa.--Garrondo (talk) 12:45, 4 August 2008 (UTC)


 * See /Archive_4 re the combining of citations. SandyGeorgia said "three or more single-use citations", which strikes me as a pretty sensible threshold.LeadSongDog (talk) 19:27, 4 August 2008 (UTC)
 * Is there some reason for providing "convenience" urls to linkinghub etc where the citations already have a permalink (pmid, pmcid, doi, etc)?LeadSongDog (talk) 20:03, 4 August 2008 (UTC)
 * I'm removing them as I find them, because apparently pmcid is recently linkable within citations. This is going to be a fun cleanup.   Orange Marlin  Talk• Contributions 21:51, 4 August 2008 (UTC)
 * Can somebody exactly specify what should and should not appear in a ref so I can help to format all of them?--Garrondo (talk) 08:01, 5 August 2008 (UTC)
 * For cite journal, the DOI bot will check for and pare away redundant url and accessdate. The url is not needed where there is a correct pmid, pmcid, or doi provided. Accessdate is not needed for journals at all-they don't change. Every cite must have a title. Date, Journal, Volume, Issue, Pages are all good but not urgent to have. Author should normally list the first three authors and et al. where there are more than four. If a full date isn't available, using Year and Month fields is the alternative. LeadSongDog (talk) 14:33, 6 August 2008 (UTC)
 * I've been cleaning up the references. The DOI bot is not very efficient.  I've tried it, and it gets some stuff and not others, using some database that frequently adds URL's to journal locations that require paid logins.  I've been removing them.  I set up a macro on my computer to clean them up, which I've been doing.  Almost done.  So that the style is consistent, please let me finish (which i should do today).  Thanks.   Orange Marlin  Talk• Contributions 14:40, 6 August 2008 (UTC)
 * Yeah, it's not without its flaws. Its owner usually responds well to bug reports on User:DOI_bot/bugs, though he may not do so right away. Cases in point would be useful. Thanks.LeadSongDog (talk) 15:33, 6 August 2008 (UTC)
 * I use diberri's template for citations, and I notice that it pulls from a database that has url's on occasion. I don't think it's a bug, it's just that the database is a bit whacked.   Orange Marlin  Talk• Contributions 16:47, 6 August 2008 (UTC)

←I think it's close, but I think there are some style and grammar issues that need to be cleaned up. This is what I've seen in successful FAC's. To make the style clean and readable, one person should take the lead to clean it up. I can do that if I can have a couple of days without distraction. Also, we do have to clean up the citations per LDS' comments above. Orange Marlin Talk• Contributions 21:54, 4 August 2008 (UTC)
 * Wow! Have you been busy or what? Great job! I noted a couple of implicit choices you made (somebody had to choose...) to use the short form journal names and page ranges as per pubmed.  I really hate to quibble over this, but for a lay reader this can be rather confusing.  I suppose I should raise the subject at MEDMOS talk. If the journal name were linked it might be more palatable,  but as it is some are incomprehensible until you follow the permalink. Also noted that the short names were inconsistent about use of periods in the abbreviated words. I assume that's just what the tools did.LeadSongDog (talk) 20:54, 6 August 2008 (UTC)

Problems with outdated references in Prognosis section and a weak Prevention section
Based on my cursory glance over the references, there seems to be a reliance upon outdated primary articles when it comes to survival/prognosis. Ref 5., a 1986 primary article, is cited 5 times; it does not appear all that major, either. Ref 6., another primary article (1995) by the same author. Seems worth it to attempt to replace with up-to-date reviews, preferably freely accessible ones? Maybe I'm wrong; it is possible that those studies are the best, and that they were fairly conclusive on the causes of death/survival among Alzheimer patients. This plays into the prognosis section which you're thinking about revising. Also, it would be interesting to highlight seminal papers, although that might violate summary style. I also get the feeling that at least some of these references are superflous, and the best one should be chosen. A good review can cover a lot of information. "Best" can be decided by looking at how up-to-date the article is, how many citations it has, and how available it is (number of libraries with it, PMC availability, ect).

The article itself seems very well-written. It is hard for a layman to understand, but that's inevitable. The weakest section is, unfortunately, probably the most important section for the lay readers which Wikipedia attracts: prevention. I just read the first review referenced there to Alzheimer's/aluminium. It seems pretty good. The end of the prevention section presents a barrage of references which do not really support the "other studies have not confirmed this link" statement, especially because the two sentences bunch together EMF, solvents, and metals. That section needs work before this becomes a Featured Article. I've posted a review of scientific articles relating aluminium to Alzheimer's above on the talk section, which is widely considered to be the most closely related environmental contaminant. Disaggregating these different contaminants would be the first step. II | (t - c) 23:36, 4 August 2008 (UTC)


 * I think your points on the prognosis section deserve response (I'm still a holdout on discussing aluminum, because I have seen nothing that gives a biochemical reason for it inducing plaques or tangles, but I'll admit to not knowing everything about aluminum in neurons). The two articles mentioned are truly the best for the prognosis of the disease.  I used Pubmed's highly effective references that use references system.  One of the more modern articles   uses a Seattle base population (talk about self-selecting--maybe too much coffee), and its results aren't significantly different than the articles mentioned.  Sometimes there are just important studies that stand the test of time.  BTW, I don't think PMC availability is a useful indicator of the importance of articles.  It may have much more to do with arcane intellectual property ideals of various journals.   Orange Marlin  Talk• Contributions 00:05, 5 August 2008 (UTC)


 * Back to aluminum. The reason I don't buy into aluminum as a causal agent for AD is A) Post hoc ergo procter hoc, which weakens any argument, and B) I've yet to read a proposed mechanism.  I'd need convincing to put anything more about aluminum in this article.  And, I do not work for ALCOA.  In case you're wondering.  LOL.   Orange Marlin  Talk• Contributions 00:12, 5 August 2008 (UTC)


 * You're probably right about the prognosis section; it looks like most of the major articles are mentioned on this page, and the most recent review was in 2000. PMC availability is not an indicator of the importance of the article, it is an indicator of the availability to the reader only, which should be considered. I've actually noticed that this article will sometimes put up a real strong review followed by an older primary article available at PMC, which is appreciated. As far as the mechanism: since studies have found that aluminium is present in much higher concentrations in the brains of AD patients, that entirely presupposes a mechanism. The question is not whether there is a mechanism, then, but the consistency of these findings, because if these findings are consistent, then the mechanism question is moot. Sorry, misread what you meant by induce. Yes, how the aluminium translates into brain damage is a question, but plenty of research has gone into the mechanism. The 2007 Journal of Alzheimer's Disease article discusses mechanisms and epidemiological findings, and it concludes that "metals, particularly aluminium, are clearly involved, but it is unclear whether they play a minor or a major role in the etiology of the disease". If you don't have it available I can email it to you. II  | (t - c) 00:41, 5 August 2008 (UTC)
 * There are reviews which conclude there is a relationship and others which conclude the opposite so I believe we maintain a neutral point of view as both views are shown and the same weight is given to both of them. Maybe in the future the role of Aluminium is more clear but for the moment there is no scientific consensus on its function and the only thing clear is that it has appeared related in some epidemiological articles. I do not believe the link needs to be more in depht covered in the main article.--Garrondo (talk) 08:14, 5 August 2008 (UTC)


 * Giving both sides equal weight because "there is a dispute" seems like rather poor reasoning. A 2007 review by Carpenter in a highly specialized journal says there is clearly a relationship. The papers cited which "dispute this claim" have some problems. The most recent 2007 one takes a scattershot approach and looks at all hypothesized risk factors. Because its approach is so wide, it looked at only 3 aluminium epidemiological studies. It apparently selectively picked out ones which were negative. The 2007 J. Alzheimer's Dis. lists 20 aluminium epidemiological studies in table 1, page 4. Of those 20, 15 are positive. The rest of the studies used against the aluminium link are primary/outdated. Clearly some sloppy work in this section, and it casts some doubt on the other sections, unfortunately. Understandably, it is impossible to read all these papers, but the error here could have been gathered from looking at the most relevant paper (2007 focused review) rather than trying to use outdated/primary studies to contradict it. In addition, the 2007 review discusses the mechanisms, so the information is out there if OrangeMarlin feels like exploring past mistaken conventional wisdom. My proposal is that we cut some of the primary studies. The Santibanez paper appears, prima facie, to be strikingly biased, selectively picking 3/20 studies and managing to pick the 3/5 negative ones. It could maybe be used for inconsistency in other risk factors, but the bias makes it a suspicious source IMO. If someone could send it over I would appreciate it; it would be interesting to see how they justify their selection. II  | (t - c) 09:24, 6 August 2008 (UTC)


 * Well: if there is a dispute between primary sources and no scientific consensus in a matter, wikipedia should only state such debate since reaching a conclussion or giving more weight to a view would be original research. I don't feel that a single recent review means there is scientific consensus. On the other hand most articles on prevention, and not specifically centred in aluminium state that there are not enough facts to clearly propose preventive measures.--Garrondo (talk) 11:50, 6 August 2008 (UTC)


 * Back to Post hoc ergo procter hoc. Just because it's there, I'm not sure there is a cause.  By the way, undue weight doesn't quite work the way as described above.  Remember, science rarely tries to prove a negative, hence all the alternative medicine crap out there where someone will say, hey there are no references that dispute it.  I think most researchers dispute any relationship, precisely because no one has elucidated a mechanism of action, which means it's ultimately not falsifiable.  Aluminum is not quite a fringe theory, but it is nearly so.   Orange Marlin  Talk• Contributions 14:45, 6 August 2008 (UTC)
 * OTOH, Occam leads us to hold that the association indicates causality, albeit not what the cause is. If both the metal and the plaques are present because of a mutual causative process, I haven't seen any suggestions what that common cause might be.  If the plaques are causing the metal to concentrate that too would need a mechanism.  Hence I continue to hold that we just don't know why they're associated.  Time will tell but the article needn't wait on it. We should outright say that they're correlated but we don't know why.LeadSongDog (talk) 15:23, 6 August 2008 (UTC)
 * That's why I'm not totally dismissive as I might be if someone was pushing "Vitamin C prevents AD". There is enough research to make it seem like there is a link, but not quite enough to say it's verified.  It's moved from fringe theory to almost interesting.  I'm on the fence, but I don't want to give much weight to it.   Orange Marlin  Talk• Contributions 16:50, 6 August 2008 (UTC)

Review of Causes section
I just copyedited (or at least tried to do so) this section. And I'm still confused. The first paragraph says that there are three hypotheses. Yet it reads like there are four, but then the last hypothesis seems to be a slight revision to #3. I'm confused. Can someone clarify or rewrite. Orange Marlin Talk• Contributions 23:51, 4 August 2008 (UTC)


 * And one more issue: there doesn't appear to be any information about what might cause these things to happen.  Down's syndrome and a genetic anomaly seem to be it.  Which negates writing anything in prevention except maybe, "hey you're either going to get this or not, it's a matter of genes."  is that true?  Because that's what I would conclude from reading the section.   Orange Marlin  Talk• Contributions 23:54, 4 August 2008 (UTC)


 * I'm not following. Did you look at the genetics section? Certain genes will strongly predispose you to AD, but if you don't have those, it seems less genetically determined. II  | (t - c) 00:51, 5 August 2008 (UTC)


 * We might have a lack of knowledge to review this section and the pathophisiology section (I am sure I have). It is very specific and an important amount of biochemistry is needed. Could it be a good idea to ask at project medicine for some help?--Garrondo (talk) 07:00, 5 August 2008 (UTC)


 * Probably even better to try to go outside of Wikipedia and try to tap one of the real experts.


 * I have written to one of the Alzheimer's genetics specialist of the research center I work at. I have asked him if he will consider reviewing the causes and pathophisiology sections. I do not have a strong relationship with him so he may or may not help us. Does anybody know if his name can appear in something like an aknowledgements box or something like that if he does an external review? I seem to remember to have seen it in some other page, but I am not sure. As soon as he answers I will communicate it. --Garrondo (talk) 13:51, 7 August 2008 (UTC)


 * You're possibly thinking of Template:External peer review, which goes in the top matter of the article talk page and links it in to External peer review. It is quite distinct from WP:Peer review.LeadSongDog (talk) 19:33, 7 August 2008 (UTC)


 * He has decided not to review the article since he does not have time.I could maybe ask some of his doctorate biologists but I suppose they will have similar problems and secondly most of them are right now on holidays. A pity. Any ideas? --Garrondo (talk) 07:32, 11 August 2008 (UTC)


 * Considering the July 2008 results, we need to ask if the beta-amyloid hypothesis is still tenable. First the 19 July Lancet autopsy results on the AN-1792 recipients showed clearing the AB didn't affect the dementia, then the Chicago ICAD methylene blue results showed attacking the tau did. It seems at least to some that the question is pretty much decided.LeadSongDog (talk) 20:33, 13 August 2008 (UTC)


 * IMO, we should make a statement that it is pretty much decided. But we have to keep in the prior hypotheses, just in case someone is reading this article and says, "hey what about AB."  Eventually, if the tau hypothesis becomes the consensus, we reduce the other two hypotheses to mentions per WP:WEIGHT.  Remember, in science, it takes repeatability of results to make good science, and I don't think we're quite there yet.  The methylene blue results are preliminary, and pharmaceutical companies can make things appear more than they are.  Orange Marlin  Talk• Contributions 21:15, 13 August 2008 (UTC)

Let's do it
I believe its ready now. We should present it as a FAC.--Garrondo (talk) 07:41, 13 August 2008 (UTC)

Image change proposal for FAC
First of all I wanted to remark the hard-wonderful job of OrangeMarlin and LeadSongDog. The article would not be nearly as good without all your editions...

I also wanted to propose an image change. The lead image is anything but friendly, and would not encourage anybody to read the article except pathologists, which are not very common. I think a possible solution is to put the image of the comparison between the two brains as the lead image and put the pathology one in the place left by the first. Texts fit perfectly so nothing would have to be rewritten and I feel the image of the brains is much more attractive. --Garrondo (talk) 13:16, 7 August 2008 (UTC)


 * I think we need to get someone to do a copyedit--someone who hasn't worked on this article like the three of us. I'll ask a couple of individuals.   Orange Marlin  Talk• Contributions 07:45, 13 August 2008 (UTC)


 * good idea. I will do the same.--Garrondo (talk) 09:53, 13 August 2008 (UTC)

The lead image change is good. Colin°Talk 12:42, 13 August 2008 (UTC)

I've tweaked the first paragraph a bit. Two changes affect the meaning and I want to check with you guys: Colin°Talk 13:38, 13 August 2008 (UTC)
 * I've added "often" to the "terminal disease" bit as later the text says AD is "the underlying cause" for 70% of deaths. I'm not sure if this means that some folk can have AD for a very long time (and so die of an unrelated illness -- they lived with AD rather than dying of it) or merely that AD will kill you unless something else gets there first. Any thoughts?
 * I've removed the "although estimates vary greatly" from the lead. The discussion of estimate quality is probably best left out of the lead and if this is our best guess then let's just present as such. Also, the citation for that clause didn't support it as it only had figures up to 2030 rather than 2050.


 * I agree with the second change, but not with the first: from my point of view it is always terminal, which has nothing to do with the fact that for example an old person can die of a heart attack or a car accident before AD kills him. I change it again--Garrondo (talk) 14:42, 13 August 2008 (UTC)

Last minute issues from Casliber
Hang on folks, just going through - these longer articles are a real pain in the neck if issues crop up and the FAC page becomes a morass of text...Cheers, Casliber (talk · contribs) 10:06, 17 August 2008 (UTC)


 * the physician or healthcare specialist.. - do we need 'healthcare specialist' here? Aren't internal medicine specialists and geriatricians physicians?
 * The disease course is divided into four stages, with a progressive pattern of cognitive and functional impairment expressed from one stage to the next and during each stage. -erm, this sentence has 3 'stages' in it...may wanna try and mix it up a little...
 * I simply eliminated the second part of the sentence leaving it as: The disease course is divided into four stages, with a progressive pattern of cognitive and functional impairment.


 * noncritical - I have never heard this word used in a medical context, and never seen it non-hyphenated (or is that nonhyphenated) either. Could probably replace with normal aging or somesuch.

*Any particular reason under Characteristics section why Advanced doesn't have 'dementia' after it like the others?
 * Added dementia for the advanced section


 * PS:Any edits you think I screwed up in by losing meaning or just ugliness of prose, please revert


 * .. and the tangles are located in areas of the brain that cause deterioration of mental function - areas of the brain which cause this??
 * I have said which area is where Ad patients have more tangles and eliminated the part of the sentence of the cause of deteriorioration of mental function (Almost any brain damage supposes deterioration of mental function).

US/UK English
This article is predominantly US English and has been since the start. Despite my personal preference for UK spelling, I attempted to fix the few non-US spellings in this edit according to WP:ENGVAR. Adherence to guidelines is part of the FA criteria. This was undone by. I queried this with Matt but we're at a stalemate. All I desire is consistency within the article; the choice of US or UK English is up to the major contributors IMO. Could someone else decide either way. Thanks, Colin°Talk 21:26, 20 August 2008 (UTC)


 * I addressed the "has been from the start" in response on my talk.. I think the US-lead appraisal is unnecessarily unfair (as it goes..). And AD is not area specific (or not in 'the West' at least - hard to say elsewhere). If FA's demand one type only, how about International English? The American editors have been more than amenable so far. It's not all about Ronald Reagan - its about AD. It's a bugger for us all. I'm happy with both (I don't even notice the variation), but it looks like we must make a choice...--Matt Lewis (talk) 21:55, 20 August 2008 (UTC)


 * I don't care which one to use (I don't even know the difference between both of them), but WP policies say that one should be chosen.--Garrondo (talk) 09:24, 21 August 2008 (UTC)
 * I prefer UK English, because it is used by more English speaking countries and in countries (such as India) where English is the second language. I am comfortable with both, but I suggest we use the UK version.  Bugger is a bit difficult to understand.  LOL.   Orange Marlin  Talk• Contributions 14:43, 21 August 2008 (UTC)


 * It looks we have consensus leaning towards UK English. It would be my pleasure to make the change to consistent UK spelling. I'll have a go later, unless anyone shouts in the meantime. Colin°Talk 15:15, 21 August 2008 (UTC)
 * No objection either way, but yes, we need consistency. International's fine with me.  Go for it.LeadSongDog (talk) 15:19, 21 August 2008 (UTC)

Done. Unfortunately, the templates and categories are US English. Colin°Talk 17:07, 21 August 2008 (UTC)
 * No flies on you! Bravo.LeadSongDog (talk) 17:42, 21 August 2008 (UTC)

neuroimaging
The text days "SPECT and PET neuroimaging are used to diagnose Alzheimer's in conjunction with methods involving mental status examination." Earlier it said "Alzheimer's disease is usually diagnosed clinically". This paragraph may give the (contradictory) impression that such scans are routine, which I suspect they are not. Can someone clarify the text (insert the word "occasionally", or say "under research for the diagnosis", etc) or whatever is appropriate. What may be available for rich patients in the top US teaching hospitals isn't necessarily so elsewhere. Colin°Talk 12:44, 21 August 2008 (UTC)
 * I believe that SPECT and PET are used for confirmatory diagnosis, but the initial diagnosis does not require it. Let me reread and add some appropriate words.  I'm not sure what happened, but this came up in the first FAC, and we added some language about availability of procedures.   Orange Marlin  Talk• Contributions 14:40, 21 August 2008 (UTC)
 * At least in Spain they are very rarely used in public health (which comprises 99 per cent of medical care). Only in private hospitals as the hospital I work at it is clinically used routinously. It is probably the same over the world: A pet is expensive but a spect is VERY expensive.--Garrondo (talk) 06:47, 22 August 2008 (UTC)
 * Here in America, I think it's more common than elsewhere, but not a standard medical tool. I would say that most major medical centers have one.  And of course, there are independent for-profit institutions that have them. Orange Marlin  Talk• Contributions 18:45, 22 August 2008 (UTC)

Kraepelin
Text mentions 8th edition, ISBN is broken. I only find seventh. I suspect that the content is in volume 4: Dementia praecox and paraphrenia but someone should verify this.LeadSongDog (talk) 16:36, 22 August 2008 (UTC)


 * You are right: I copy the following text from an article :


 * Secondly, a new nosological entity relevant to and accepted by clinical practitioners can only be developed in relation to a diagnostic and therapeutic system. This step was taken by Emil Kraepelin in the 8th edition of his famous textbook published in 1909. He, but not Aloys Alzheimer, really created Alzheimer's disease. In the 7th chapter of the 2nd volume on senile and presenile psychiatric disorders Kraepetin mentions Alzheimer at least three times and then goes on to define an "Alzheimer's disease" that is characterized by a severe dementia, beginning at about the age of 50 with its typical neuropathological alterations, especially tangles of fibrils, but without signs of cerebral arteriosclerosis. Then Kraepelin discussed the clinical and nosological meaning of Alzheimer's disease:


 * ... The clinical interpretation of this Alzheimer's disease is still confused. While the anatomic findings suggest that we are dealing with a particularly serious fon~a of senile dementia, the fact that this disease sometimes starts already around the age of 50 does not allow this supposition. In such cases we should at least assume a "senium praecox'" if not perhaps a more or less age-independent unique disease process...(Kraepelin, 1909, p. 627)


 * The citation for his 1909 book is: Kraepelin, E. (1909). Psychiatric. Ein Lehrbuch far Studierende und °rzte. 8. Auft., Band II/l. Leipzig: Barth. (Engl. trans. (1987): Senile and pre-senile dementias). In K. L. Bick, L. Amaducci & G. Pepeu (Eds) The Early Story of Alzheimer's Disease (pp. 32-81). Padova: Liviana Editrice].


 * I do not have time right now to look for the isbn and correct citation but I will do it tomorrow or at last on monday if nobody does it before.
 * --Garrondo (talk) 17:53, 22 August 2008 (UTC)


 * I'm a bit confused. The isbn # works, and I can even buy the reprint on Amazon.com.  I'm not sure if there's any reason to use the original reference, since it might be difficult to find.  Since the reprint is exactly the same, and is available to find at a library or for purchase, that's the reference we should use.   Orange Marlin  Talk• Contributions 18:43, 22 August 2008 (UTC)
 * The question comes down to which edition introduced the pioneering content. It's a rather fine point, but if we're putting it in, we should try to get it right.LeadSongDog (talk) 19:39, 22 August 2008 (UTC)
 * I see now that the isbn works on A9 and on Google Shopping, but not WorldCat, Ottobib, or Google Books. Very strange. Presumably the reprint of 2007 just hasn't percolated through the indices yet, but it may be the book hasn't actually been reprinted pending sufficient orders.LeadSongDog (talk) 19:50, 22 August 2008 (UTC)
 * Ok, this is just too funny. I hate to think what Babelfish would do...LeadSongDog (talk) 20:14, 22 August 2008 (UTC)
 * The truth comes out in the end. It's a print-on-demand book. LeadSongDog (talk) 20:32, 22 August 2008 (UTC)
 * You can't handle the truth. Oh. Sorry.  I digress.  :)   Orange Marlin  Talk• Contributions 22:31, 25 August 2008 (UTC)
 * "Now that I do know it I shall do my best to forget it." - Doyle AC. A Study in Scarlet: The science of deduction LeadSongDog (talk) 16:16, 26 August 2008 (UTC)

Early onset Alzheimer's
I think the Intro is misleading in the second line. It used to mention the "early-onset form" of AD, but now just mentions Familial Alzheimer disease (in the line "although a less prevalent inherited form strikes earlier") as the 'other form' of AD. But are they strictly the same thing? I can't find any proof that 'early onset' AD is always genetically inherited. Surely we need to mention 'early onset' AD? I'll re-include the term, and will make an article for it too - I'll retain the link in the Intro it to Familial AD (as it was 'piped' before) until it's done.

This line has proved hard to write as we simply can't say how many 'forms' of AD there are. A way around this is to use the word "Alzheimer's" instead of 'form'. I'm trying this:

"Initial onset typically occurs in people over 65 years of age, although the less-prevalent early-onset Alzheimer's can occur much earlier".

I'm a bit worried about the finalisation of the FA process being a bit of a train - we need to get matters like this right, rather than 'edit around' them, which I suspect may have happened here.--Matt Lewis (talk) 18:25, 18 August 2008 (UTC)


 * I think your rewrite is fine. As for the "train", I'm not sure you should be too worried about it.  The FA process seems to be thorough (as opposed to years ago--I read some FA articles that are just plain bad).  I agree with not editing around concerns.   Orange Marlin  Talk• Contributions 18:35, 18 August 2008 (UTC)

Onset
Incidentally, does the actual "onset" occur after 65? Maybe the start of this line can be addressed too.--Matt Lewis (talk) 18:33, 18 August 2008 (UTC)

I will try "Generally it is diagnosed in people over 65 years of age..." --Matt Lewis (talk) 18:36, 18 August 2008 (UTC)


 * The problem with words like "commonly" is that they seems to allude the prevalence of the disease across society, rather than over age. --Matt Lewis (talk) 18:46, 18 August 2008 (UTC)


 * I looked over 3 or 4 articles (I used one to reference the statement), and Alzheimer's appears to almost never happen before 65. The article from Brookmeyer, seems to indicate it's less than 0.05%.  I guess in a population of 5 million over that age, that's still a big number.   Orange Marlin  Talk• Contributions 18:55, 18 August 2008 (UTC)
 * BTW, there's really no good articles that make a definitive statement about when it does occur. The 65 number is used because I think the epidemiological studies indicate that it becomes a significant (though very small) number at that point.  One day, when we know what actually predisposes someone to Alzheimer's, we can determine the exact onset age.  Also, I think there's a delay in diagnosis, which may make the date later than usual. Orange Marlin  Talk• Contributions 18:58, 18 August 2008 (UTC)

Early-onset Alzheimer's disease created
I intitally created the article and introduction, then was 'bold' and merged in the text from Familial Alzheimer's disease below the intro (FAD accounts for about half of early onset AD). It's easy to delete the text I've inserted, and I haven't 'redirected' the FAD article to the new article yet. I've asked for comments in Talk:Early-onset Alzheimer's disease. If it is OK, we can link the second line in the Introduction straight to Early-onset, instead of pipe-linking it to FAD, which is only half the story. --Matt Lewis (talk) 02:17, 19 August 2008 (UTC)

Dementia before age 65
Frontotemporal dementia usually is diagnosed before age 65. Mention of this might be helpful, in a section of the article about differential diagnosis. --Una Smith (talk) 04:57, 27 August 2008 (UTC)