5 ms·

The problem really lies with the fact that within the more than 100,000 published studies on Alzheimer's disease you are bound to find a random association betw

by pcrh 10y ago

The problem really lies with the fact that within the more than 100,000 published studies on Alzheimer's disease you are bound to find a random association between this disease and many other things. This is especially true for observational studies in people, and also true for low-powered studies in experimental animals. Experimental science, however, demands that one establishes a cause and effect relationship. There is no known cure of Alzheimer's disease, so one cannot refer to experimental medicine for an answer, with the exception of inherited dominant genetic mutations that impact only a small number of people. Unfortunately, of these mutations, those affecting the APP gene do not cause neuronal loss in mice; so the mouse models are inherently problematic. This editorial calls for a clinical trial for antimicrobials in this disease. While I doubt that Alzheimer's is caused by infectious agents, there really is no harm in trying (except perhaps to the pockets of the trial's sponsors). In fact a trial of the antibiotic minocycline was completed in 2014 [1], however the results do not appear to have been reported. [1] https://clinicaltrials.gov/ct2/show/NCT01463384 https://clinicaltrials.gov/ct2/show/NCT01463384

sc4th1s 10y ago
There is a cure for the mouse model of Alzheimers: http://www.fusfoundation.org/news/1535-new-pre-clinical-research-further-validates-potential-for-focused-ultrasound-in-alzheimer-s http://www.fusfoundation.org/news/1535-new-pre-clinical-rese...
davak 10y ago
Often negative results are never published. Great post.
randcraw 10y ago
Yes. I think few non-medical researchers realize how limited the value of a particular correlation generally proves to be. The more you work with biomedical data, the more you appreciate the limited value of big R values when no plausible mechanism of action accompanies it. Given enough metrics, it's common to find one with perfect correspondence to a disease's biomarkers or symptoms. Lab biologists and chemists have long ago lost interest in exploring all the miraculous sure-fire yet inexplicable signals found by data scientists. The solution in this case is for the paper's authors to spend THEIR OWN grant money underwriting the clinical trials to explore their 'discovery'.
- nonbel 10y ago
  >"how limited the value of a particular correlation generally proves to be" I would go further. In my medical research work I saw dozens, probably hundreds of "statistically significant" correlations between different variables in a rather small dataset. I found them just by taking different subsets or summarizing the same data in a few different ways. I didn't find any interesting and so published nothing about them, but I am sure others could build entire careers out of coming up with narratives to explain those correlations. I have to think that people who have trouble finding correlations are either clueless about exploring the data (eg have only ever looked at dynamite plots of their results) or are measuring something so swamped by instrumental noise it is meaningless.
- pge 10y ago
  Obligatory XKCD reference: https://www.xkcd.com/882/ https://www.xkcd.com/882/
klenwell 10y ago
While I doubt that Alzheimer's is caused by infectious agents, there really is no harm in trying (except perhaps to the pockets of the trial's sponsors). Or to taxpayers when some pharmaceutical company finds a specious statistical correlation between Alzheimer's and an infectious agent that one of their products happens to treat. A cynical view, yes. Borne out of my reading of Bad Pharma and coming across at least one startup whose business model was to do this with genetic tests.
jmichelz 10y ago
There is a known cure for early Alzheimer's. https://www.aging-us.com/article/9R5JsRe8k4Jq7uTXj/text https://www.aging-us.com/article/9R5JsRe8k4Jq7uTXj/text Bredesen DE. Reversal of cognitive decline in Alzheimer's disease. Aging (Albany NY). 2016 Jun;8(6):1250-8. doi: 10.18632/aging.100981. Bredesen DE. Reversal of cognitive decline: A novel therapeutic program. Aging (Albany NY). 2014; 6:707-17. doi: 10.18632/aging.100690.
- yourapostasy 10y ago
  Fascinating, thanks for the links. These findings might be preliminary, as this criticism of the claims lays out the case that it might be premature to make such assertions this early. https://www.sciencebasedmedicine.org/mend-protocol-for-alzheimers-disease/ https://www.sciencebasedmedicine.org/mend-protocol-for-alzhe... The commercialization of the MEND protocol might have run into some partnership issues between the original researcher and the first company he worked with dispensing the treatment: http://www.prnewswire.com/news-releases/dr-dale-bredesen-announces-termination-of-his-relationship-with-muses-labs-inc-300188947.html http://www.prnewswire.com/news-releases/dr-dale-bredesen-ann... Here is a more layman-friendly description of the MEND protocol. http://bottomlineinc.com/alzheimers-symptoms-reversed/ http://bottomlineinc.com/alzheimers-symptoms-reversed/
- pcrh 10y ago
  >Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4-, who were treated with the MEND protocol for 5-24 months. The number of patients studied is too few, i.e. is grossly underpowered statistically, and the results do not allow any general conclusion to be drawn.
- lazerpants 10y ago
  The reviews of this work conclude that it is dubious, example: https://www.sciencebasedmedicine.org/mend-protocol-for-alzheimers-disease/ https://www.sciencebasedmedicine.org/mend-protocol-for-alzhe...
deleted 10y ago
[deleted]
gmarx 10y ago
Why do you doubt that it is (or can be) caused by infectious agents, aside from the fact that in science doubt should be the default position. Is there evidence against it? My intuition is that it is more likely caused by an infection than that it is just a malfunction caused by random chance
- pcrh 10y ago
  I doubt it because if it were caused by an infection, one would expect infections to cause Alzheimer's disease-like conditions more generally. If it is caused by a specific infection, then one would expect such a specific infection to cause the disease in young as well as older people. Neither of these scenarios are known to occur. If you extend beyond these simple scenarios, then you have to assume that there is another (unknown) factor that induces Alzheimer's disease, and therefore that the theory of infectious disease causing this condition is not sufficient.
  - gmarx 10y ago
    Suppose it is a reaction to a viral infection you get when you are young which reactivates when you get older. It could even be that the initial infection is asymptomatic in many or most people and that only a small percentage of those infected ever get the later reaction. It could be one specific virus or it could be that several virus can do it. It could be dependent on some other factor such as how the virus integrates into the host genome or later immunosuppression.
kafkaesq 10y ago
From the wording of the article, it's pretty clear that the researchers that the authors are aware of the degree of circumspection that such findings typically raise -- and that this isn't just a matter of a single associational study; but rather, a retrospective finding over many studies. Which the researchers feel should forces to consider the fact that we may be close to a tipping point, with regard to the proposed etiology at hand. Hence statements like "We can't keep ignoring the evidence", "landmark editorial", etc.

by pcrh 10y ago

sc4th1s 10y ago

There is a cure for the mouse model of Alzheimers: http://www.fusfoundation.org/news/1535-new-pre-clinical-research-further-validates-potential-for-focused-ultrasound-in-alzheimer-s http://www.fusfoundation.org/news/1535-new-pre-clinical-rese...

davak 10y ago

Often negative results are never published. Great post.

randcraw 10y ago

Yes. I think few non-medical researchers realize how limited the value of a particular correlation generally proves to be. The more you work with biomedical data, the more you appreciate the limited value of big R values when no plausible mechanism of action accompanies it. Given enough metrics, it's common to find one with perfect correspondence to a disease's biomarkers or symptoms. Lab biologists and chemists have long ago lost interest in exploring all the miraculous sure-fire yet inexplicable signals found by data scientists. The solution in this case is for the paper's authors to spend THEIR OWN grant money underwriting the clinical trials to explore their 'discovery'.

nonbel 10y ago
>"how limited the value of a particular correlation generally proves to be" I would go further. In my medical research work I saw dozens, probably hundreds of "statistically significant" correlations between different variables in a rather small dataset. I found them just by taking different subsets or summarizing the same data in a few different ways. I didn't find any interesting and so published nothing about them, but I am sure others could build entire careers out of coming up with narratives to explain those correlations. I have to think that people who have trouble finding correlations are either clueless about exploring the data (eg have only ever looked at dynamite plots of their results) or are measuring something so swamped by instrumental noise it is meaningless.
pge 10y ago
Obligatory XKCD reference: https://www.xkcd.com/882/ https://www.xkcd.com/882/

klenwell 10y ago

While I doubt that Alzheimer's is caused by infectious agents, there really is no harm in trying (except perhaps to the pockets of the trial's sponsors). Or to taxpayers when some pharmaceutical company finds a specious statistical correlation between Alzheimer's and an infectious agent that one of their products happens to treat. A cynical view, yes. Borne out of my reading of Bad Pharma and coming across at least one startup whose business model was to do this with genetic tests.

jmichelz 10y ago

There is a known cure for early Alzheimer's. https://www.aging-us.com/article/9R5JsRe8k4Jq7uTXj/text https://www.aging-us.com/article/9R5JsRe8k4Jq7uTXj/text Bredesen DE. Reversal of cognitive decline in Alzheimer's disease. Aging (Albany NY). 2016 Jun;8(6):1250-8. doi: 10.18632/aging.100981. Bredesen DE. Reversal of cognitive decline: A novel therapeutic program. Aging (Albany NY). 2014; 6:707-17. doi: 10.18632/aging.100690.

yourapostasy 10y ago
Fascinating, thanks for the links. These findings might be preliminary, as this criticism of the claims lays out the case that it might be premature to make such assertions this early. https://www.sciencebasedmedicine.org/mend-protocol-for-alzheimers-disease/ https://www.sciencebasedmedicine.org/mend-protocol-for-alzhe... The commercialization of the MEND protocol might have run into some partnership issues between the original researcher and the first company he worked with dispensing the treatment: http://www.prnewswire.com/news-releases/dr-dale-bredesen-announces-termination-of-his-relationship-with-muses-labs-inc-300188947.html http://www.prnewswire.com/news-releases/dr-dale-bredesen-ann... Here is a more layman-friendly description of the MEND protocol. http://bottomlineinc.com/alzheimers-symptoms-reversed/ http://bottomlineinc.com/alzheimers-symptoms-reversed/
pcrh 10y ago
>Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4-, who were treated with the MEND protocol for 5-24 months. The number of patients studied is too few, i.e. is grossly underpowered statistically, and the results do not allow any general conclusion to be drawn.
lazerpants 10y ago
The reviews of this work conclude that it is dubious, example: https://www.sciencebasedmedicine.org/mend-protocol-for-alzheimers-disease/ https://www.sciencebasedmedicine.org/mend-protocol-for-alzhe...

deleted 10y ago

[deleted]

gmarx 10y ago

Why do you doubt that it is (or can be) caused by infectious agents, aside from the fact that in science doubt should be the default position. Is there evidence against it? My intuition is that it is more likely caused by an infection than that it is just a malfunction caused by random chance

pcrh 10y ago
I doubt it because if it were caused by an infection, one would expect infections to cause Alzheimer's disease-like conditions more generally. If it is caused by a specific infection, then one would expect such a specific infection to cause the disease in young as well as older people. Neither of these scenarios are known to occur. If you extend beyond these simple scenarios, then you have to assume that there is another (unknown) factor that induces Alzheimer's disease, and therefore that the theory of infectious disease causing this condition is not sufficient.
- gmarx 10y ago
  Suppose it is a reaction to a viral infection you get when you are young which reactivates when you get older. It could even be that the initial infection is asymptomatic in many or most people and that only a small percentage of those infected ever get the later reaction. It could be one specific virus or it could be that several virus can do it. It could be dependent on some other factor such as how the virus integrates into the host genome or later immunosuppression.

kafkaesq 10y ago

From the wording of the article, it's pretty clear that the researchers that the authors are aware of the degree of circumspection that such findings typically raise -- and that this isn't just a matter of a single associational study; but rather, a retrospective finding over many studies. Which the researchers feel should forces to consider the fact that we may be close to a tipping point, with regard to the proposed etiology at hand. Hence statements like "We can't keep ignoring the evidence", "landmark editorial", etc.