Comparisons Between Alzheimer's Treatments

Lane Simonian

It is hard to make exact comparisons between Alzheimer's treatments.  Each starts with a different baseline, different numbers of participants, and different trial protocols.  Nevertheless, one can somewhat glean what seems to largely stabilize the disease and what only slows it down a bit.  

Here are some numbers (note for ADAS-cog scores a lower number means improvement whereas for MMSE scores a higher number means improvement):

Drug or Natural Product                                                                               ADAS-cog

Aricept (at 24 weeks)                                                                                       -1.3

Simufilam (at 26 weeks)                                                                                   -1.6

GV-971 (a compound derived from brown seaweed) (at 24 weeks)            -2.19

Korean red ginseng/panax ginseng (at 24 weeks)                                        -4

A change in ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) scores of 4 points at six months (26 weeks) is considered to be clinically significant.

Placebo, Drug, or Natural Product                                      MMSE

Historical Placebo Decline (at 78 weeks)                                 -3.5

Conventional Therapy (primarily Aricept) (at 78 weeks)       -3.2

Aducanumab  (at 78 weeks)                                                      -2.7

Chinese Herbs plus Conventional Therapy (at 78 weeks)      -1.5

Anavex 2-73 (blarcamesine)  (at 70 weeks)                               3.0

Korean red ginseng/panax ginseng  (at 72 weeks)                   3.3

                                                

A change in two points in MMSE (Mini-Mental State Examination) at one year in mild Alzheimer's disease is considered to be clinically significant.  

Conventional drug treatments and aducanumab may achieve statistical significance but except for in a few individuals they do not achieve clinical significance.  In the case of aducanumab, the group that appears to receive the greatest benefit from the drug--those with two copies of the ApoE gene--also have the highest risk of side effects such as micro-bleeds and brain swelling.

The numbers for Anavex 2-73 (blarcamesine) go down to -2 MMSE at 148 weeks and the numbers for panax ginseng go down to 2.6 points at 96 weeks.  These numbers are clinically significant, but not statistically significant because of too few people in the trials.  

Take what you will from these trials, but what I take from it is that there is a distinct possibility that with the right treatments you can largely stabilize mild to moderate Alzheimer's disease.

 

Iris L.

Whatever treatment is chosen must begin in the EARLY stages. 

 Most often PWDs have been symptomatic for years before anyone thinks there might be a medical problem.  Even with clear signs and  symptoms, medical professionals often delay with alternative diagnoses or a belief that nothing can be done.  Some PWDs and families might be interested in a delay in progression, even if the outcome will eventually be unchanged.  

Thank you for the summary, Lane. 

Iris

Crushed

Better headline would be

COMPARISON OF SYMPTOMATIC MEDICATIONS FOR ALZHEIMER'S DISEASE

The MMSE  is an evaluation of an Alzheimer's SYMPTOM

medicating the symptom is not without benefit but you are not treating the disease. 

Think of painkillers and a terminal cancer patient.

  And note any studies of symptoms that are not double blind  are worthless

Please don't compare real science to quacks.

Lane Simonian

MMSE and ADAS-cog are measures of cognitive function.  ADAS-cog is considered to be a somewhat more accurate measure of this.  

Aricept temporarily improves cognitive function because for a time it maintains higher levels of acetylcholine which is needed to retrieve short-term memories.  Anti-amyloid drugs for awhile slow down cognitive decline (at least in those with the ApoE4 gene who have more amyloid to begin with) because they remove or block the formation of one of the many factors that likely cause Alzheimer's disease in the first place.  In addition to that amyloid is a secondary trigger.  Remove every single bit of amyloid oligomers and plaques from the brain and the other factors that put one at risk for Alzheimer's disease are still present.  All of these factors increase oxidative stress.

The key to getting beyond this is to not only limit the formation of oxidants but to remove them and reverse part of their damage.  This is why a drug like Anavex 2-73 or a natural product like panax ginseng staves off the progression of Alzheimer's disease for longer periods of time.  You then are treating the source of the disease not a triggering factor or a point in the pathway that leads to the disease.  

Iris is absolutely right, the earlier the treatment the better.  In the Chinese retrospective study, the use of Chinese herbs and conventional therapy stabilized mild Alzheimer's disease for two years, whereas in moderate Alzheimer's disease the drop was about 3 points in MMSE.  

The phase 2b/3 trial for Anavex 2-73 (blarcamesine) will be double-blinded randomized and placebo control.  I am not sure when or if a similar trial for panax ginseng will occur.  I don't understand, though, why we keep pursuing approaches that don't produce clinically significant results and ignore those which do.  

Crushed

The MMSE  is simply an empirical  screening test for symptoms of cognitive dysfunction

Note is it is not a test of cognitive FUNCTION  only dysfunction.   (see below)
 

and you never ever stabilize Alzheimers disease you stabilize  if anything the presentation of symptoms   if you stabilized the disease people would live longer.

 
MMSE IS NOT A DIRECT MEASURE OF ANYTHING  (it has fundamental mathematical limitations  since it is a summing of different tests that have never been separate validated so it is not a measurement.  (to give an example while each event in the decathalon can be a measurement  the sum of those measurements is simply arbitrary)  

MMSE is used because we know so little  about Alzheimer's that all we can do is look at the symptoms.

 

 It is always adjusted for education level even as a screen 

 Alert Level: In general participant scoring below education-adjusted cut-off scores* on the MMSE may be cognitively impaired.
 
 MMSE-EDUCATION ADJUSTED CUT-OFF SCORES
 
 a. Subjects whose education levels are 7th grade or lower, a score on the MMSE of 22 or below
 b. Subjects whose education attainment level is sth grade or some high school (but not a graduate of), a score on the MMSE of 24 or below
 c. Subjects whose education attainment level is high school graduate, a score on the MMSE of 25 or below
 d. Subjects whose education attainment level is some college or higher, a score on the MMSE of 26 or below.

 

Laurention

Thank you "Crushed" you're  much better equipped respond  to these claims than  than I am

..Not something I'm proud of, but I'm a High School drop out ..So I'll ask you folks  to forgive my atrocious grammar, sentence structure, and all.  

My late DW was just lucky ( if you want to call it that ?) ..Diagnosed  by a world renown Neurologist.at Sunnybrook Hospital Toronto .. in November of 2011 . 3 months shy of her 54th birthday ..she was literally the Poster girl for Suunybrook Neurology dept. They used her interviews, photos and her story ..for fund raising.

At the age of 54 .DW was a great communicator, and had excelled at many Post secondary level courses. She worked her way from Bank Teller to senior Manager in charge of six branches by the time she was 50.

  Pfizer and in conjunction with another big pharma company were running world wide clinical trials with a treatment  of   Babineuzumab ..I think I spelt that right ? 

We were ecstatic when DW was chosen to participate .  Pfizer spared no expense ( I'm in Canada just a little different system ) ..We were treated like Royalty, premo parking, free lunch ..MRI's ...P.E.T scans Genetic testing. Pfizer was picking the bills up , they didn't care . This miracle drug looked very promising. The Pfizer CEO actually put her retirement on hold. This was going to be the first med that could stop or considerably slow down Alzheimers!!!!!

In early June 2012 Pfizer wanted a second Genetic test to rule out APOE 4 ? DW did not carry that Gene . Once again we were relieved ..We even started to make future plans !!

 I'm going to guess July 20 th ..2012 ?? DW received her first dose. Was it the placebo ? or was it the real thing ??? We'll never know ...July 24 -25. 2012 Pfizer announced the med and trial was deemed a failure, and cut the funding!

Within 2 yearsMMSE  had dropped 7 points .  When it gets down to below 11 the results are insignificant .

I lost my wife on January 8 2021. I typed this through the tears !!!!

 We all due respect Mr Simonian ...I know your intentions are noble ..But I'll stand with "Crushed " on this one .

   Michael  

Donr

Thank you for posting Lane

Lane Simonian

Thank you, Don.  Always good to see you here.

1962ART

Dear Crushed:

Thank you for being the voice of reason and science.

Both are so important to us as we navigate caregiving.

Crushed

I respect Lane and his efforts . His heart and mind are in the right place and with us.

My wife was a brilliant physician .  My field is science based safety regulation.  I was offered the job at FDA  in 1978 to develop what was called at the time the "science court" 

I have examined all kinds of scientific evidence from a variety of agencies and hazards.

Of common diseases Alzheimer's  may be the most difficult for researchers. It is also a fertile field for quacks,  both well meaning and  charlatans.   

I would have done ANYTHING that I thought would help my wife.  I had resources and contacts.  I consulted people all over the world.   NIH is a mile away and I have contacts there.   My wife used to be on staff at Johns Hopkins and our older daughter did her PhD there in public health/microbiology. She is now with FDA  My late mother in law was a pioneer in bioinformatics.  I had every resource at my finger tips

I just tear my hair out when I hear "Dr" so and so has the secret of Alzheimers and all you need is some garbage that they are promoting.   I don't care if they are deluded or crooks. There is a well known process for doing Alzheimer's research which at least can tell if  its clearly worthless.   Once you get past that stage we have the more complex problem of saying if it works  for some people or some time etc.    

 There is a NOBEL prize awaiting anyone who can show a useful positive treatment for teh underlying Alzheimers pathology.   So far, no takers.
  

Iris L.

Not every patient has classic Alzheimer's pathology.  There are many factors that might contribute to dementia and cognitive impairment.  I don't have Alzheimer's Disease although I have a lot of the signs and symptomatology and I'm positive for APOE4.  Anything that I have learned to do that could possibly help me, I have done.  So far, so good.

I'm grateful for the efforts of all the researchers.  But they don't know everything.  Look at how Covid-19 has been handled over the past year.  I have taken steps to protect myself based on my own research.  I don't just rely on what comes out of the "official" voices.  

Iris

Crushed

Iris L. wrote:

I'm grateful for the efforts of all the researchers.  But they don't know everything.  Look at how Covid-19 has been handled over the past year.  I have taken steps to protect myself based on my own research.  I don't just rely on what comes out of the "official" voices.  

 The actual vaccine researchers were brilliant.  The epidemiologists were solid and viral transmission folks were doing their best with a novel virus.  Public health physicians had a nightmare to deal with of lack of preparation

 

The further you got away from the politicians and their medical sycophants the better the medical effort.

 

You might take a look at Premonition by Michael Lewis

https://www.nytimes.com/2021/05/06/books/review/the-premonition-michael-lewis.html