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MCI, new study on imaging
Mimi S.
Posted: Thursday, January 17, 2013 8:29 AM
Joined: 11/29/2011
Posts: 7029


From Biomed Central


Research
18F-florbetaben Abeta imaging in mild cognitive impairment
Ong K, Villemagne VL, Bahar-Fuchs A, Lamb F, Chetelat G, Raniga P, Mulligan RS, Salvado O, Putz B, Roth K, Masters CL, Reininger CB, Rowe CC
Alzheimer's Research & Therapy 2013, 5:4 (16 January 2013)
Abstract http://alzres.com/content/5/1/4/abstract
Provisional PDF http://alzres.com/content/pdf/alzrt158.pdf
As I read it, it may b e a means of telling which cases of MCI will progress to feull blown dementia. 
And is that the Pittsburg compound PEY that is being discussed.
Numbers involved in the study are low.

Lane Simonian
Posted: Thursday, January 17, 2013 9:59 AM
Joined: 12/12/2011
Posts: 4854


The measurement of amyloid plaque is a good, but not perfect indicator of the potential for Alzheimer's disease.  This is my favorite chart showing the pathway to Alzheimer's disease. 

 

          

It is the intracellular calcium release invoked by phospholipase C activity that leads to the formation of amyloid plaques.  The onset of Alzheimer's disease requires this and Protein Kinase C activation, MAPK activation, and the formation of peroxynitrites.  It is possible for the first operation to happen and not the second.  In other words, it is possible to have the accumulation of amyloid plaques and not get Alzheimer's disease (not likely but possible). 

 

Phospholipase C activity leads to high levels of acetylcholinesterase activity, and to the activity of the two enzymes which process the amyloid plaques (y-secretase and BACE1).  Phospholipase C gamma (y) activity can be inhibited by a diet high in polyphenols and the actions of both enzymes can be inhibited by a diet high in polyphenols and polyunsatured fats.   Thus a Mediterranean diet and an Indian diet would help someone with Mild Cognitive Impairment.  Latter these diets would help someone with Alzheimer's disease (as Mimi and many others on this board know) because these are diets full of antioxidants. 

 

http://www.ncbi.nlm.nih.gov/pubmed/16266772 

http://www.sciencedirect.com/science/article/pii/S0166432811008138 

 

Now here are the problems with the current and proposed treatments for Alzheimer's disease. 

 

Acetylcholinesterase inhibitors such as Aricept, Exelon, and Galantamine: 

 

They prevent the breakdown of acetycholine which is critical for short-term memory, but they do not stop the formation of amyloid plaques or peroxynitrites.  They thus provide sympomatic relief early in the disease.  Due to the near inactivation of phospholipase C as the disease progresses, acetylcholinesterase activity is decreased by 85%.  Acetylcholinesterases are weak antioxidants (Aricept and Exelon) or reach the brain in insufficient quantities to make much of a difference (Galantamine).  Combining these medications with other antioxidants such as various spices and essential oils may increase their efficacy. 

 

Y-secretase and BACE1 inhibitors 

 

They will somewhat slow down the formation of amyloid plaques and peroxynitrites, but they will at best slow down the progression of Alzheimer's disease.  These enzymes also have other functions and inhibiting them can lead to deleterious effects. 

 

Removing amyloid plaques 

 

Will only slow down the production of peroxynitrites and will likely slow down the progression of Alzheimer's disease early, but will not reverse the damage done by peroxynitrites and will not stop the formation of peroxynitrites. 

 

To partially reverse Alzheimer's disease one needs to use peroxynitrite scavengers.  To go along with my favorite chart, here is my favorite quote. 

 


[Clinical trials with over-the-counter supplements have concentrated either on
items which suppress inflammation, or on antioxidants which scavenge oxygen
derived free radicals. Most of these items have proved to be worthless in the
treatment of Alzheimer's disease. Similarly most drugs used to treat Alzheimer's
disease do little to slow the deterioration, but instead offer a mild temporary
symptom relief. However, evidence has been accumulating that the primary driver
of Alzheimer's disease is a nitrogen derived free radical called peroxynitrite,
which may mediate both amyloid and tau accumulation as well as their toxicity.
Excellent results have been obtained with peroxynitrite scavengers, with
reversals of Alzheimer's disease in human clinical trials being repeatedly
demonstrated. IMHO [in my honest opinion], the only thing which may be  preventing the abolition of  Alzheimer's disease is the mental inertia of scientists, as well as the bureaucrats who fund them. Unfortunately, most bureaucrats keep throwing money into repeatedly testing discredited interventions, while ignoring successful ones. Common sense is anything but...]

 

There are at least six clinical trials in which peroxynitrite scavengers have slowed the progression or partially reversed Alzheimer's disease: aromatherapy (with rosemary, lemon, orange, and lavender essential  

oils--the latter two for relaxation), heat-processed ginseng, tincture of lemon balm essential oil, tincture of sage essential oil, saffron, and Bacopa monnieri. 

 

http://onlinelibrary.wiley.com/doi/10.1111/j.1479-8301.2009.00299.x/abstract 

 

http://www.ncbi.nlm.nih.gov/pubmed/22780999 

 

http://www.ncbi.nlm.nih.gov/pubmed/12810768 

 

http://www.ncbi.nlm.nih.gov/pubmed/12605619 

 

http://www.ncbi.nlm.nih.gov/pubmed/20831681 

 

http://www.iomcworld.com/ijcrimph/ijcrimph-v03-n04-01.htm 

 

All of these were small studies and some had design flaws, but they all produced similar positive results in human beings. 

 

Effectively inhibit phospholipase C activity through diet and if necessary through supplementation and you delay the onset of Alzheimer's disease.  Effectively scavenge peroxynitrites and you can treat (not cure) Alzheimer's disease from the earliest to the latest stages.  That is the message which every Alzheimer's researcher and organization in the United States needs to hear. 


 


organicgreendoctor
Posted: Thursday, January 31, 2013 9:12 AM
Joined: 10/28/2012
Posts: 33


in the adni study that im in there are a large number of us with the early mci group that are having serial beta amyloid pet scans done along with serial neuropsych exams neurological exams spinal fluid analysis mri scans 

these results are being compiled by multple researchers who hopefully can answer some of the questions of the usefulness of these test early on

ive had one scan and will have another in april and if i get the results ever ill post them

the organicgreen doctor


Mimi S.
Posted: Thursday, January 31, 2013 9:14 AM
Joined: 11/29/2011
Posts: 7029


That's exactly what I've been looking for. How many in the study? How often are you tested?
organicgreendoctor
Posted: Thursday, January 31, 2013 9:26 AM
Joined: 10/28/2012
Posts: 33


there are i think 200+ in our group

we get a beta amyloid pet scan at start and at two years 

we get a lengthy neuropsychological exam at start and every 6 months year one

then yearly

we get spinal fluid analysis for beta amyloid and tau at start and year two 

we get mri at start and every 6 months year one then yearly 

we get the fdg glucose metabolism pet scan at start and year two

we also all get our human genome done which was done this fall 

we are followed up to five years and possibly longer based on funding

so some good results should come out of all of this 

in fact a lot of what you read about in alzheimers research is from 

this study 

as soon as the testing is reported each time its readily available 

for researchers over the world

the organicgreen doctor


Myriam
Posted: Thursday, January 31, 2013 12:32 PM
Joined: 12/6/2011
Posts: 3326


Here's the Alzheimer's Disease Neuroimaging Initiative (ADNI) website:


http://www.adni-info.org/


Mimi S.
Posted: Thursday, January 31, 2013 1:52 PM
Joined: 11/29/2011
Posts: 7029


For those interested in the science of choosing subjects do go to Myriam's link.

Again, usual complaint, not too many early onset. But not too many 90 year olds. Most in 70s and 80s. interesting thing to look at is education levels. Most by a long shot have post college education!

Doc, do keep us posted if you see any write-ups of results. 

It is a long term study.