This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.
This is a press release about a primary research finding. We need to see whether or not this study, which even the press release calls "small," will replicate or not. I would be the first person here to cheer a genuine advance in preventing or treating Alzheimer disease (I am older than most of you are), but I have learned after 2145 days of participation on Hacker News that most press releases about medical breakthroughs kindly submitted for discussion on Hacker News never replicate and don't lead to any lasting productive paths in research.
As for the lifestyle recommendations numbered in another comment here, I
(1) eat some simple carbohydrates, but have avoided obesity;
(2) eat some (but not a lot) of gluten and processed food, but especially eat plenty of vegetables and fruits (and a little bit of fish);
(3) reduce stress through means other than yoga;
(4) do not meditate, having checked the evidence on this practice and found it wanting;
(5) do not take melatonin;
(6) usually attempt to sleep 7-8 hours per night;
(7) take vitamin B12, but not usually in the form of methylcobalamin;
(8) take vitamin D3 each day;
(9) take fish oil each day;
(10) never take CoQ10;
(11) optimize my oral hygiene using an electric flosser and electric toothbrush;
(12) don't take hormone replacement therapy (I'm not a woman, and I have plenty of testosterone);
(13) fast for a minimum of 9 hours between dinner and breakfast, and for a minimum of 1 hour between dinner and bedtime;
(14) and exercise for a minimum of 30 minutes three or four times a week.
I do the most of the things on the list that have the best evidence base. I check the evidence all the time about what the latest treatment-control studies say about healthy lifestyle.
Good luck to all of you desiring to keep healthy minds for a long life. That begins with being skeptical about press releases about preliminary research findings.
(4) do not meditate, having checked the evidence on this practice and found it wanting;
But have you personally tried it? The most important "evidence" may be how it affects you, personally.
In any case I'd be curious as to what your general assessment is on the body of studies claiming to show (apparently positive) impacts of sustained meditation practie, e.g. the following:
> But have you personally tried it? The most important "evidence" may be how it affects you, personally.
It sounds lame to say, but I agree here. I fairly consistently meditate. I don't spend more than five or ten minutes doing so, but regardless of whether or not it increases an objective measure of my health, I do feel that it's provided me with some positive mental tools for approaching certain situations.
As an example for me is that I used to be pretty anxious about falling asleep, and I think it caused it to be more difficult to fall asleep. Some of the insight meditation practices helped me deal with the anxiety feedback loop. It wasn't something crazy or mystical; I mostly just learned how to stop thinking about something, and was able to stop thinking about the anxiety. Honestly, I don't think I fall asleep any faster, but I do find that I just don't care anymore because the anxiety isn't there.
I continue with it because it's pretty easy to carve out five or ten minutes here and there. I have no idea if it's causing any long term health benefits. Subjectively I feel more relaxed right after I meditate, but that's about it. Honestly, I'd keep doing it just because it feels nice. I don't do any crazy postures or full lotus, or anything like that, so it seems like there's a low likelihood of it causing harm.
Maybe it's more important to maintain a state of mind where you could quickly relax into a period of no-thought, than to actually spend a lot of time in no-thought. Regular exposure makes you aware of when you're spending long periods in a stressful state of mind.
Yeah; I think I see what you're saying and I agree. Subjectively this seems to be the benefit for me. It seems to allow myself to reset to an almost default cognitive state when I recognize certain negative emotions/stress.
Wow, what an incredibly lame response. Everyone knows small studies may not be replicable, what else does this comment add?
Reversing effects of Alzheimer's is incredibly rare, so doing so in a scientific and carefully observed manner is newsworthy. I've previously known of only two individuals who've had the disease being reversed of the millions who suffer from it, anyone can correct me if they know of others.
This is a terrible disease, so all progress is welcome. If society was interested in discovering a means to reverse it, the answer is actually simple. Take a few thousand patents (there are millions, not a problem to come up with this many), and randomly divide them into groups of 200 and assign them to teams of researchers who can use any combination of nutrients, diet, approved drug, etc. Offer a prize of $100M to the team with the treatment that works best and smaller amounts to runners up. Then repeat every two years.
I was taking fish oil supplements daily until my Nephrologist suggested I don't. He pointed to some recent proper clinical trials that showed it not doing much of anything:
In addition to that, if you're taking liquid supplements (like gel caps, which I was), my doc told me that there is risk that it has oxidized and can actually cause cardiovascular damage. After that and a weekend of reading up on the internet, I decided to stop taking any fish oil supplements.
Do the research yourself and make an educated guess.
Always worth it to bite down on a couple pills every so often and check. Use those rancid sensors built in by nature. It's oil after all. If it tastes bad, it's gone bad.
This sounds interesting, but before anyone starts changing their lifestyle based on this, you should be aware that not only isn't this a double-blind trial, there's no control group, and the results lump together subjective and objective improvement (in other words, 9 of the 10 either actually got better, or just thought they got better, possibly through the placebo effect).
Also, the article mentions neuropsychological testing done on one of the subjects, demonstrating his decline, but then there's no mention of whether he was retested after the treatment to see if there was any measurable improvement! And no mention of any objective testing of the other 9 subjects, either before or after the treatment. This strikes me as odd, given that neuropsychological testing is the most sensitive way of measuring cognitive decline.
My elderly aunt, who is 88 now, has Alzheimer's and while she's declining in cognitive ability now that her doctors have figured out her medications and dealt with some psychological issues her rate of decline has improved. The idea of somehow reversing her disease, or at least some of the major symptoms, is intriguing but there's got to a point where the treatment, however well-intentioned, isn't worth it.
But I can see the appeal for someone 30 years younger facing early-onset Alzheimers.
The argument against farmed fish is that they're fed corn, so you're getting high levels of omega-6, which causes inflammation and ultimately brain damage.
The argument against gluten is that it similarly causes inflammation, which causes brain damage.
For what it's worth, Andrew Weil has an anti-inflammatory diet on his website:
I've seen multiple studies that suggest a correlation between very high Omega-6 to Omega-3 ratios and various cancers, but I've never seen anything regarding brain damage.
Some casual googling just now suggests to me that this notion of generalized "inflammation" and it causing brain damage isn't rooted in an understanding of how pathology works and seems mostly talked about in rather quacky "woo" circles.[1][2]
That being said, it does seem like over-expression of inflammatory mediators like cyclooxygenase-2 (COX2) in the brain can cause brain inflammation[3], and Wikipedia says high Omega-6 to Omega-3 ratio can result in over-expression of COX2 in some parts of the body, so it's certainly possible that high Omega-6 levels could result in over-expression of COX2 in the brain, but I haven't yet seen anything supporting that.
Regarding Dr. Weil, he seems all over the lot with what he advocates. Sometimes he advocates quackery based on "some religious group somewhere says it works," but other times he points to a small body of positive evidence and rightly points out that there's an unfortunate lack of further higher quality research, and other times he espouses very logical or well-supported ideas. And unfortunately, he often doesn't make clear which category the current thing he's talking about falls under and often doesn't cite sources.
For what it's worth, his food pyramid doesn't ban gluten, and explicitly allows for occasional pasta. According to your link, his main criticism of glutenous foods has nothing to do with gluten but that such foods usually contain wheat flour, which has a high glycemic index, even in the form of whole wheat flour. In fact, he strongly recommends low-GI whole grains, including bulgur wheat.
The model of multiple targets and an imbalance in signaling runs contrary to the popular dogma that Alzheimer’s is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain – as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer’s disease shifts the memory-making vs. memory-breaking balance in favor of memory loss.
Given all this, Bredesen thought that rather than a single targeted agent, the solution might be a systems type approach, the kind that is in line with the approach taken with other chronic illnesses—a multiple-component system.
...
(1) eliminating all simple carbohydrates, leading to a weight loss of 20 pounds;
(2) eliminating gluten and processed food from her diet, with increased vegetables, fruits, and non-farmed fish;
(3) to reduce stress, she began yoga;
(4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day;
(5) she took melatonin each night;
(6) she increased her sleep from 4-5 hours per night to 7-8 hours per night; (7) she took methylcobalamin each day;
(8) she took vitamin D3 each day;
(9) fish oil each day;
(10) CoQ10 each day;
(11) she optimized her oral hygiene using an electric flosser and electric toothbrush;
(12) following discussion with her primary care provider, she reinstated hormone replacement therapy that had been discontinued;
(13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime;
(14) she exercised for a minimum of 30 minutes, 4-6 days per week.
The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results are anecdotal, and therefore a more extensive, controlled clinical trial is needed.
>6) she increased her sleep from 4-5 hours per night to 7-8 hours per night;
This alone probably accounts for everything. My god, even a healthy person at 4 hours of sleep is a mess. Doubling that is a major, major difference. The difference for me between 6 and 8 is like night and day, especially from a memory point of view. I can't imagine 4-5 for a long stretch, let alone as my regular sleeping pattern.
I wonder if caffeine abuse is a factor here. I meet a lot of older folk who can drink 10+ cups of coffee a day. I really don't think they have that strong of a tolerance. I think it just props them for a while due to poor sleep and they get used to be being stimulated and cranky instead of addressing their sleep issues.
I don't know how to interpret this. The fact that better diet, exercise, and sleep can improve cognitive function is well-known, right? Is there any reason to believe that this isn't just yielding short-term benefits that seem to counteract the decline rather than reversing the memory loss associated with Alzheimer's?
It's a study using 10 people. So the best way to interpret it is to ignore it.
However, "One potentially important outcome is that all six of the patients whose cognitive decline had a major impact on job performance were able to return to work or continue working without difficulty." which suggests a significant improvement even if it was simply temporary.
Indeed, couldn't that type of sleep deprivation alone account for the memory issues? I know it would for me. That and the hormone therapy seem like huge red flags. I know that the diagnostics for dementia-type illnesses are usually rather imprecise, but it seems ominous for the study that one of the few patients had such an abnormal lifestyle to begin with.
As for #11, Non-flossed teeth are a material source of inflammation in the body. Inflammation has been shown to be a significant driver of several health conditions [1] including arterial clogging (ie, that cholesterol itself only starts to "stick" in the presence of inflammation). Arterial clogging is an issue in the brain as well as the heart. Poor dental hygeine is correlated with heart attacks, for example.
Avoiding simple carbohydrates (#1) is primarily important to control blood sugar (elevated blood sugar has many detrimental effects, both short term and long term [2]). But fructose and alcohol, also simple carbs, are metabolized by the liver and the metabolic by-products are shown to cause inflammation as well [3]
Basically, people with poor oral hygiene are more likely to develop Alzheimer's than people with good teeth.
You might have heard about a similar study that found a link between oral hygiene and heart disease. The theory, at least in that case, is that bad oral hygiene causes chronic long-term inflammation throughout the body, not just in your gums. This might increase risk of heart disease. Without looking at the data, I would guess that the same theory applies to Alzheimer's and maybe other diseases. The usual caveat about correlation != causation applies of course.
?? If Alzheimer's is related to memory & executive functioning(probably is) then the people who are likely to develop Alzheimer's are likely to have poor oral hygiene.
Oral hygiene is a good proxy for people who know it's important, but somehow still forget. A solid proxy for executive functioning decline, executive functioning in general, working memory, and a cluster of other things.
There is a link between dental hygiene and cognitive function. This is caused because bad dental hygiene leads to a bacterial infection in the mouth which in turn leads to large amounts of inflammation which damages the brain in addition to the cardiovascular system.
His laboratory has found evidence that Alzheimer’s disease stems from an imbalance in nerve cell signaling: in the normal brain, specific signals foster nerve connections and memory making, while balancing signals support memory loss, allowing irrelevant information to be forgotten. But in Alzheimer’s disease, the balance of these opposing signals is disturbed, nerve connections are suppressed, and memories are lost.
This is a theory that I hadn't heard before, but it makes sense. I'm wondering if this signaling imbalance is something that could discovered in a test or scan, and if so, how early?
At what karma level does one gain the ability to downvote stories? Anyone know?
No one has enough karma to downvote stories. Hacker News isn't set up to allow downvoting stories. Some users can flag stories, which has the partial effect of making stories slide down the front page a little faster (and autokilling the stories if enough users flag them).
I don't want to flag stories like this when they don't actually violate the terms of use. But IMHO, there should be some way for users to express the popular "Why is this on Hacker News?" sentiment without cluttering up the comment thread.
Otherwise, we'll just end up with upvoting cabals, and I'd argue that this story is likely to be a prime example of such.
That's one of the functions of flagging. I learned from some veteran participants on Hacker News to flag more stories about politics--even if they relate to startup industry--than I used to. That doesn't always work, but it seems to help.
http://www.impactaging.com/papers/v6/n9/full/100690.html
Abstract
This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system.