This is sort of illustrative of a prevalent failure mode in high level R&D strategy in medicine.
What they are doing is reasonable as an immediate extension of trying to map the disease process front to back, which is what pure research should be doing. The outcome of that, however, tends to be that people end up manipulating biochemistry to slow the disease process rather than fix it. You can get useful results out of this - see statins, for example. But you can't get cures. People who take statins will still end up in the same bad place in the end, just a little later. Also, it is very expensive to find safe new states for cellular operation that provide a decent benefit:harm ratio.
One right thing to do in Alzheimer's is map the whole thing end to end, them make a decision on what to do. An enormous task that is basically the same thing as understanding the human brain end to end - which is a good thing in and of itself, and if Alzheimer's provokes that work (in the same way that AIDS provoked analogous major efforts to understand viral biochemistry) then good. But in the short term that doesn't produce useful therapies.
The other right thing to do is to identify the fundamental differences between young, non-diseased tissue and aged, diseased tissue and work to revert them - even if you don't know how they are causing harm. Successful removal will tell you a great deal about the significance, and steer other research, and in the best case produce a useful therapy. Thus a focus on amyloid and tau, and immunotherapies to clear them, and dysfunctions in cerebrospinal fluid clearance mechanisms, with approaches ranging from simple mechanical adjustment of fluid drainage channels behind the nose to proposed stem cell therapies for the choroid plexus to addressing immunosenescence in the brain's immune system.
However, Alzheimer's is such a multifaceted condition that researchers tend to focus on reverting one of these items, then don't produce wondrous benefits because the other mechanisms are still in play, and then the people who prefer to slow disease progression instead arrive to argue that this means they shouldn't look at this direct approach of reverting differences. To fix Alzheimer's will likely require clearance of both amyloid and tau, and even then it is likely that since 60% of sufferers also have vascular dementia, it will be challenging to produce good trial outcomes under the present regulatory system.
If damage repair doesn't work, that means you're not repairing enough of the damage.
This falls under not repairing enough of the damage. If the view is that delaying Alzheimer's to let people die from heart disease a couple of years later is great, well, that's a problem. It isn't great. It isn't sufficient. It is taking an entirely too narrow a focus. It is deliberate aim at a worse outcome rather than a better outcome. Cures, not postponement, across the board must be the strategic goal - it is a shirking of responsibilities to shrug and say it is good enough to push off a disease for the year or two that would reduce its mortality rate if all other conditions kept happening at the same level as today, rather than aiming higher.
Delaying Alzheimers would be wonderful, even if death is not delayed. Having the last few years of your life stolen by Alzheimers is a living death in and of itself.
Having seen one or more family members suffer for years from Alzheimer's, I'm inclined to agree with you to an extent. Dementia is not a desirable end state. But I think the parent's point is also very important. Those family members also had other things killing them at the same time, so it was really a race between diseases.
We need to fix aging (and address the cultural belief that it's necessary), we need to cure cancer and heart disease, etc. Postponement, if it distracts researchers from the real goal rather than acting as a necessary stepping stone, is ultimately counterproductive.
Quality of life is just as important, or even more important, than length of life. AD destroys quality of life long before it kills you (and most AD sufferers are killed by something else anyway).
One right thing to do in Alzheimer's is map the whole thing end to end, them make a decision on what to do.
I think you're underestimating the difficulty of that task. Not only is current technology inadequate for mapping the brain, even if we did draw the lines, we would still be far from understanding it. Even C. Elegans took over a decade to map, and while it's true that our technology is better, it is still not up to the task of mapping the brain.
If we waited until the brain were mapped to make any progress would mean delaying much progress.
That's kind of the point. That is exactly what's happening in the research community, plus the inefficiency of people stepping off the mapping process as soon as they find some mechanism that might slightly slow disease progression, and then focusing on that rather than something that might clean up the damage instead of slowing it down.
Not enough of the research community is doing the other thing, the repair and reversion of differences between old and young tissues carried out in advance of full understanding, so as to aim at cures rather than delay.
Alzheimer's, funnily, is in a much better position than most other age-related diseases because a large chunk of the mainstream of the research effort is actually directed towards a repair-of-the-differences approach - removal of amyloid via immunotherapy in this case. That choice of strategy isn't true for heart disease, diabetes, dementia, etc, etc. If we want to see cures for age-related disease, there must be a sweeping change in the research community's high level strategy, towards repair of fundamental damage that distinguishes old tissues from young tissues, and away from tinkering with the disease state to slow it down or to compensate for some of its effects.
>People who take statins will still end up in the same bad place in the end, just a little later.
For many many people, this is enough. By the time we're 55 or 60, most of us have so many risk factors for various things that getting a delay of 20 years from statins means something else will most likely kill us before we have to worry about congestive heart failure.
If I'm going to die of cancer at 75, and I can use drugs to push Alzheimer's back to age ~80, then it might as well have been cured. Functionally there is no difference.
(aside:) The current fashion for people, like cattle, having to show they have nice strong teeth produces quite a few manic-looking photos ... (besides lots of income for dental cosmetology)
[W]e know there is little relationship between the amount of amyloid in one’s brain and your memory function. In fact, those “super-agers”—your 95-year-old great-great-aunt who finishes the crossword puzzle in 20 minutes, is president of the bridge club and has a better golf handicap than you—may have just as many amyloid plaques in her brain as AD patients.
Another AD researcher, Rudolph Tanzi, recently made the same point, suggesting that it's the inflammation caused by these plaques in some patients that leads to dementia:
Ahh ye old biologist doing ye old refuctionist science.
Good luck on ye old calcium drug preventing more Alzheimer's then it does causing ye old bad something else.
I always find it interesting to figure out why work like this gets attention compared to the 87,000 other approaches for important disease X. This work seems particularly preliminary.
Silly humans distracting each other. It's like we are the Washington Generals and Disease is the Harlem Globetrotters.
The study shows that this diet may be sufficient for a better outcome for altheimers, but I'm skeptical that this in its entirety is necessary. Research on metabolic diseases is more and more pointing towards fats not being much of a factor, and sugar and too many total calories (from any sources) being large factors.
And ketogenic diets have shown some effect at fighting altheimers, other metabolic diseases, and even some cancers, which is why treating fat as the enemy doesn't make a whole lot of sense to me.
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[ 4.4 ms ] story [ 52.2 ms ] threadWhat they are doing is reasonable as an immediate extension of trying to map the disease process front to back, which is what pure research should be doing. The outcome of that, however, tends to be that people end up manipulating biochemistry to slow the disease process rather than fix it. You can get useful results out of this - see statins, for example. But you can't get cures. People who take statins will still end up in the same bad place in the end, just a little later. Also, it is very expensive to find safe new states for cellular operation that provide a decent benefit:harm ratio.
One right thing to do in Alzheimer's is map the whole thing end to end, them make a decision on what to do. An enormous task that is basically the same thing as understanding the human brain end to end - which is a good thing in and of itself, and if Alzheimer's provokes that work (in the same way that AIDS provoked analogous major efforts to understand viral biochemistry) then good. But in the short term that doesn't produce useful therapies.
The other right thing to do is to identify the fundamental differences between young, non-diseased tissue and aged, diseased tissue and work to revert them - even if you don't know how they are causing harm. Successful removal will tell you a great deal about the significance, and steer other research, and in the best case produce a useful therapy. Thus a focus on amyloid and tau, and immunotherapies to clear them, and dysfunctions in cerebrospinal fluid clearance mechanisms, with approaches ranging from simple mechanical adjustment of fluid drainage channels behind the nose to proposed stem cell therapies for the choroid plexus to addressing immunosenescence in the brain's immune system.
However, Alzheimer's is such a multifaceted condition that researchers tend to focus on reverting one of these items, then don't produce wondrous benefits because the other mechanisms are still in play, and then the people who prefer to slow disease progression instead arrive to argue that this means they shouldn't look at this direct approach of reverting differences. To fix Alzheimer's will likely require clearance of both amyloid and tau, and even then it is likely that since 60% of sufferers also have vascular dementia, it will be challenging to produce good trial outcomes under the present regulatory system.
If damage repair doesn't work, that means you're not repairing enough of the damage.
We need to fix aging (and address the cultural belief that it's necessary), we need to cure cancer and heart disease, etc. Postponement, if it distracts researchers from the real goal rather than acting as a necessary stepping stone, is ultimately counterproductive.
I think you're underestimating the difficulty of that task. Not only is current technology inadequate for mapping the brain, even if we did draw the lines, we would still be far from understanding it. Even C. Elegans took over a decade to map, and while it's true that our technology is better, it is still not up to the task of mapping the brain.
If we waited until the brain were mapped to make any progress would mean delaying much progress.
Not enough of the research community is doing the other thing, the repair and reversion of differences between old and young tissues carried out in advance of full understanding, so as to aim at cures rather than delay.
Alzheimer's, funnily, is in a much better position than most other age-related diseases because a large chunk of the mainstream of the research effort is actually directed towards a repair-of-the-differences approach - removal of amyloid via immunotherapy in this case. That choice of strategy isn't true for heart disease, diabetes, dementia, etc, etc. If we want to see cures for age-related disease, there must be a sweeping change in the research community's high level strategy, towards repair of fundamental damage that distinguishes old tissues from young tissues, and away from tinkering with the disease state to slow it down or to compensate for some of its effects.
For many many people, this is enough. By the time we're 55 or 60, most of us have so many risk factors for various things that getting a delay of 20 years from statins means something else will most likely kill us before we have to worry about congestive heart failure.
If I'm going to die of cancer at 75, and I can use drugs to push Alzheimer's back to age ~80, then it might as well have been cured. Functionally there is no difference.
Another AD researcher, Rudolph Tanzi, recently made the same point, suggesting that it's the inflammation caused by these plaques in some patients that leads to dementia:
http://www.aarp.org/health/brain-health/info-2016/alzheimers...
Good luck on ye old calcium drug preventing more Alzheimer's then it does causing ye old bad something else.
I always find it interesting to figure out why work like this gets attention compared to the 87,000 other approaches for important disease X. This work seems particularly preliminary.
Silly humans distracting each other. It's like we are the Washington Generals and Disease is the Harlem Globetrotters.
http://www.webmd.com/alzheimers/features/mind-diet-alzheimer...
• Green leafy vegetables
• Other vegetables
• Nuts
• Berries
• Beans
• Whole grains
• Fish
• Poultry
• Olive oil
You avoid:
• Red meat
• Butter and margarine
• Cheese
• Pastries and sweets
• Fried or fast food
And ketogenic diets have shown some effect at fighting altheimers, other metabolic diseases, and even some cancers, which is why treating fat as the enemy doesn't make a whole lot of sense to me.