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Spouse or Partner Caregiver Forum
Are there better alternatives to current treatments for Alzheimer's disease?
To a certain extent, acetylcholinesterase inhibitor such as Aricept and NMDA antagonists reduce oxidative stress and slow down the progression of Alzheimer's disease for awhile, but neither do so particularly well.
For those of you who disbelieve that herbs can be used to treat Alzheimer's disease or who like to pick apart the weaknesses in scientific studies, this might be a good place to stop as well. First, plant compounds can be used to treat Alzheimer's disease. Secondly, I am well aware of the limitation of the studies. But when you are continuously able to link the same mechanism to the same results, the individual weakness of each study begins to lose some of its bite.
So for those of you interested please read the following:
A formula (formula F) was prepared to counteract oxidative stress (OS) in the brain ((carnosine, coenzyme Q10, vitamin E, vitamin C, Beta-carotene, selenium, L-cysteine and ginkgo biloba)...The MMSE II score remained almost the same in the group treated with donepezil and placebo, whereas some significant improvements were found in the group treated with donepezil plus formula F.
A Case of Alzheimer’s Disease Was Kept Relative Stable with Sequential Therapy for Eight Years
The cognitive outcomes of the patient after receiving eight year’s sequential therapy was significantly better than the expected changes. The use of donepezil [Aricept] in this case also showed similar pinnacle effects around three months followed by a retreat to the baseline. However, with the support from our herbal formula, the beneficial effects sustained for a longer time and her cognition was steadily improved significantly thereafter. Therefore, this phenomena cannot be explained solely by the effects of donepezil, indicating that our herbal formula might work additively and independently to the cholinesterase inhibitor donepezil...A therapeutic approach characterized by programmatic, personalization, as well as dubbed metabolic enhancement for neurodegeneration (MEND protocol) was used. Authors reported that those patients had unprecedented symptom improvement. However, the time of those patients treated with this MEND protocol only ranges from five to 24 months. Our case was treated and observed for much longer time than this study. Meanwhile, a two year polite [pilot] study to check effects of the sequential therapy was conducted in more than two hundred patients recently. Primary results favor the sequential therapy than pure conventional medicine, which will be published soon.
The Chinese herbs used in this formula were similar to the following:
GAPT, also called as GEPT in our previous papers, is a combination of herbal extracts, including eight active components pro rata of Ginsenoside from ginseng 4.4 %, Cistanche 17.3 %, Radix Rehmanniae 17.3 %, Polygala tenuifolia 13 %, Acorus tatarinowii 13 %, Radix Curcumae 13 %, Poria cocos 13 %, Salvia officinalis 9 %.
A 24-week randomized open-label study with Korean red ginseng (KRG) showed cognitive benefits in patients with Alzheimer’s disease. To further determine long-term effect of KRG, the subjects were recruited to be followed up to 2 yr. Cognitive function was evaluated every 12 wk using the Alzheimer’s Disease Assessment Scale (ADAS) and the Korean version of the Mini Mental Status Examination (K-MMSE) with the maintaining dose of 4.5 g or 9.0 g KRG per d. At 24 wk, there had been a significant improvement in KRG-treated groups. In the long-term evaluation of the efficacy of KRG after 24 wk, the improved MMSE score remained without significant decline at the 48th and 96th wk. ADAS-cog showed similar findings. Maximum improvement was found around week 24. In conclusion, the effect of KRG on cognitive functions was sustained for 2 yr follow-up, indicating feasible efficacies of long-term follow-up for Alzheimer’s disease.
Nutritional interventions have shown varied efficacy on cognitive performance during Alzheimer's disease (AD). Twenty-four individuals diagnosed with AD received a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) under open-label conditions (ClinicalTrials.gov NCT01320527). Primary outcome was cognitive performance. Secondary outcomes were behavioral and psychological symptoms of dementia (BPSD) and activities of daily living. Participants maintained their baseline cognitive performance and BPSD over 12 months. These findings are consistent with improvement in cognitive performance and BPSD in prior placebo-controlled studies with NF, and contrast with the routine decline for participants receiving placebo.
Two more general observations:
We suggest that oxidative stress mediated through NMDAR and their interaction with other molecules might be a driving force for tau hyperphosphorylation and synapse dysfunction. Thus, understanding the oxidative stress mechanism and degenerating synapses is crucial for the development of therapeutic strategies designed to prevent AD pathogenesis.
Oxidative stress has been implicated as a contributing factor to neurodegeneration in Alzheimer's disease. An endogenous, low molecular weight (LMW) inhibitor from Alzheimer's brain inactivates the human brain muscarinic acetylcholine receptor (mAChR). The inhibitor prevents agonist and antagonist binding to the mAChR as assessed by radioligand binding studies...Natural antioxidants and pyrophosphate analogs may improve the effectiveness of acetylcholinesterase inhibitors and prove useful in the treatment and prevention of Alzheimer's disease since the muscarinic acetylcholine receptor is required for memory, and decreased cholinergic function is a critical deficit in Alzheimer's disease.
It certainly appears that certain antioxidants provide a better treatment for Alzheimer's disease than the current standard of care (acetylcholinesterase inhibitors such as Aricept and the NMDA receptor antagonist Namenda)--although perhaps for some the improvement may be even greater when the antioxidants are used in conjunction with current medications (the reverse is almost certainly true).
There is a NOBEL prize awaiting anyone who actually shows a meaningful treatment for Alzheimer's or even an effective and meaningful statement of causation. No takers yet
Scientists don’t yet fully understand what causes Alzheimer’s disease
in most people. There is a genetic component to some cases of
early-onset Alzheimer’s disease. Late-onset Alzheimer's arises from a
complex series of brain changes that occur over decades. The causes
probably include a combination of genetic, environmental, and lifestyle
factors. The importance of any one of these factors in increasing or
decreasing the risk of developing Alzheimer’s may differ from person to
Scientists are conducting studies to learn more about plaques,
tangles, and other biological features of Alzheimer’s disease. Advances
in brain imaging techniques allow researchers to see the development and
spread of abnormal amyloid and tau proteins in the living brain, as
well as changes in brain structure and function. Scientists are also
exploring the very earliest steps in the disease process by studying
changes in the brain and body fluids that can be detected years before
Alzheimer’s symptoms appear. Findings from these studies will help in
understanding the causes of Alzheimer's and make diagnosis easier.
One of the great mysteries of Alzheimer’s disease is why it largely
strikes older adults. Research on normal brain aging is shedding light
on this question. For example, scientists are learning how age-related
changes in the brain may harm neurons and contribute to Alzheimer’s
damage. These age-related changes include atrophy (shrinking) of certain
parts of the brain, inflammation, production of unstable molecules
called free radicals, and mitochondrial dysfunction (a breakdown of
energy production within a cell).
I found an interesting link in your post.."what causes Alzheimers disease. As part of a clinical trial, my wife was genetically tested. Results showed no genetic cause for her EOAD.
Glad to read that your DW's placement is going relatively well.
Lane I have respect for your commitment and complete sympathy for you situation but you posted:
a certain extent, acetylcholinesterase inhibitor such as Aricept and
NMDA antagonists reduce oxidative stress and slow down the progression
of Alzheimer's disease for awhile,
This is , quite simply NONSENSE . Aricept affects certain detectable symptoms of Alzheimer's, not the underlying pathology . There is no evidence whatever that Aricept affects teh underlying pathology . It's not unlike giving painkillers to cancer patients. They may live better but it doesn't affect the course of the disease.
Because in vivo Alzheimers is only known by its symptoms and there is no underlying knowledge of the disease all Alzheimer's therapeutic testing is empirical. It is observational so it has all the problems of social science research.
My whole career had been devoted to technical safety in innovative technologies. Some safety analysis is fundamental where we understand the epistemic aleatory and teleological uncertainties in the problem . Other safety analysis is purely empirical, where we know what works, but not why. Advances are made by scientifically testing suitable hypotheses developed by abductive inference. Scientific testing of empirical hypotheses is very difficult.
We simply do not know where this disease comes form, why and how it progresses or know reliably who has it except in very late stages. All that makes reliable research very hard. samples sizes have to be very large.
Thank you, Crushed. You remind me to try to stay level-headed and to try to work harder to find higher quality information and to provide better explanations. I know that I sometimes get more excited than I should based on limited evidence.
Scientists are often very tentative as perhaps they should be. I think the following statement that you posted is largely correct:
"The causes probably include a combination of genetic, environmental, and lifestyle factors."
Other factors that don't quite fit into these categories are likely sleep apnea, pysychological stress, and traumatic brain injuries. Some risk factors are more established than others and it is possible that some potential risk factors for Alzheimer's disease will not turn out to be (some medications for example may or may not increase the risk for Alzheimer's disease). I also think, Mike, raises a very important point regarding a largely ignored area of research: cases of early onset Alzheimer's disease that are not due to genetics. This is the sad case more often than people realize. Trying to identify the reasons why may lead to a better understanding of Alzheimer's disease in general.
I largely agree with you regarding Aricept and Namenda, Crushed. The studies on Aricept are all over the place. Some of the better ones suggest that there is a temporary improvement in cognition when given early and that there is then a retreat to baseline (maybe around six months) but at three years there is no difference between Aricept and placebo. The statement then that Aricept provides temporary symptomatic relief is likely accurate but the statement that it is effective for all stages of Alzheimer's disease likely is not.
Namenda may temporarily help some people with activities of daily living as the disease progresses.
So perhaps some people benefit from the drugs at certain stages, but neither alters the ultimate course of the disease.
Aricept inhibits intracellular calcium release and by doing so it inhibit the formation of amyloid beta, the breakdown of acetylchline, and oxidative stress via protein kinase C and Namenda receptors. It may also be a mild antioxidant. But neither of these actions does more than temporarily slow down the disease early on.
Amyloid beta also contributes to oxidative stress (as do many other factors) via protein kinase C early in Alzheimer's disease. Indeed without this early activation there is likely no Alzheimer's disease.
"Malinow's team found that when mice are missing the PKC alpha gene, neurons functioned normally, even when amyloid beta was present. Then, when restored PKC alpha, amyloid beta once again impaired neuronal function. In other words, amyloid beta does not inhibit brain function unless PKC is active."
Namenda/memantine as even its chief researcher (Stuart Lipton) admits is not a very good NMDA receptor antagonist:
"Lipton's lab had previously discovered how a drug called memantine can be targeted to eNMDA receptors to slow the hyperactivity seen in Alzheimer's. This patented work contributed to the FDA approval of memantine in 2003 for the treatment of moderate to severe Alzheimer's disease. However, memantine's effectiveness has been limited. The reason, the researchers found, was that memantine—a positively charged molecule—is repelled by a similar charge inside diseased neurons; therefore, memantine gets repelled from its intended eNMDA receptor target on the neuronal surface."
A number of polyphenols are better protein kinase C inhibitors than Aricept and better NMDA antagonists than Namenda.
Thank you for all your great responses.
Compared to Alzheimer's in terms of research HIV/Aids is a kindergarten project. Bigotry slowed the research but it is an infectious disease so it obeys modified Koch's postulates. HIV appeared in 1981 and the causative agent was isolated by 1984. We have known about Alzheimers's for over a hundred years.
There are some drugs available now that could be effective in treating alzheimer's. However they are off patent and therefore drug companies don't want to pay for clinical trials for those drugs. However putting together a combination off patent drugs together could get them a patent, even if one of the drugs is not really effective.
We have HIV combination drugs, but I believe each drug back then was first clinical trialed separately. Now drugs companies want combination drugs to go through trials from the beginning. They have a better chance of getting a patent because they don't have to prove both drugs are effective.
You might say that at least you have a better treatment available, but it is not the best. When you add an ineffective drug to the treatment, you also add unnecessary side effects, but then, that is part of the drug business.
Yes you can get a patent for a new use of an old drug NIH specifically supports such research since teh safety of the drug has already been established
I have been an ethics advisor at NIH
Beyond this the career boost for scientists who can demonstrate any effect in this area is enormous . Please dont repeat this nonsense
Just from some one who's worried
I know what you're saying, but technically ALZ won't become an epidemic, since it has not been shown to be contageous and "caught" from one person to another. Will the number of people who get it (from whatever cause) rise in coming years? Most assuredly yes, especially since medical advances lead to more people living longer. Kind of astonishing that more advances in our knowledge of ALZ have not been made. Whatever advances or breakthroughs are in the future, It won't help my own situation (too late for that), but maybe our kids and grandkids?
Lane - I enjoy your thoughts on the subject. Your threads always cause me to think.
I know what you're saying, but technically ALZ won't become an epidemic, since it has not been shown to be contageous and "caught" from one person to another.
this is actually an out of date concept as CDC says
The previous description of epidemics presumes only infectious agents,
but non-infectious diseases such as diabetes and obesity exist in
epidemic proportion in the U.S.(51, 52)
The follow up study on Chinese herbs plus Aricept.
Conventional therapy (CT), such as donepezil and memantine are well-known short-term treatments for the symptoms of Alzheimer’s disease (AD). They, however, have little disease-modifying effects after 18 months. In a two-year study, combined CT with Chinese herbal medicines (CT+H) significantly ameliorated cognitive decline in patients with mild to moderate AD.
I was afraid the image would shrink: red is conventional treatment plus Chinese herbs, blue is conventional treatment, and the black line is the expected decline in the Mini-mental state examination. So these particular herbs lead to some improvements at nine months and then a slower decline compared to conventional treatment at two years. Hopefully that is not the best outcome possible utilizing other plant compounds, but at this point I don't know if that is the case or not. At least it tells me a lot more than I knew before.
NB NOTHING in the study Lane quotes says
1) the patients were randomly assigned
2) the study was double blind
3) the differences observed were clinically important
4) the "herbs" were not identified.
5) no conflict of interest statement
This is not science. Its not even a school kids science fair project
Yet, the article is printed in what appears to be a
very reputable scientific publication, Alzheimer’s & Dementia: The Journal of the
Alzheimer’s Association. Go figure?
Debating about what is "technically" an epidemic is silly. Its an "epidemic" by shear numbers in laymen's terms, thus the term epidemic proportions.
In scientific terms, epidemic is something contagious. But can we all agree we have an "epidemic" of drug addiction, of diabites, of breast cancer, and of ALZ and its cousins?
I for one want answers, and I am all for holistic methods in addition to medical treatments, I hate the pills, so many side affects. But how does one treat for causes that aren't there in someone like my mom? She can't live any healthier and couldn't before diagnosis. Glad research is happening, just wish this was taken more seriously and more help for us caregivers along the way...(i won't get political here though its very tempting!!)
NO it is a reprinted poster presentation from the 2017 London meeting. Poster presentations never meet the Journals scientific standard.go to the original publication http://www.alzheimersanddementia.com/article/S1552-5260(17)30355-2/pdf
Adding some more to the study above:
A cohort of outpatients (n=344) meeting criteria for clinical diagnosis of AD were treated with either CT+H (n=243) or CT alone (n=101) for two years. All participants underwent standardized neuropsychological assessments. Coronary MRI scans were used to assess the age-adjusted medial temporal lobe atrophy. Cognitive function was assessed by the mini–mental state examination (MMSE) every 3 months.
Most of the patients were initially diagnosed with mild (MMSE=21-26, n=177) and moderate (MMSE=10-20, n=137) dementia. At 18 months, CT+ H patients scored on average 1.76 (P=0.002) better than CT patients, and at 24 months, patients scored on average 2.52 (P<0.001) better (Figure 1). Patients with mild AD received the most robust benefit from CT+H therapy. The deterioration of the cognitive function was largely prevented at 24 months (ΔMMSE=-0.06), a significant improvement from CT alone (ΔMMSE=-2.66, P=0.005). Overall number of patients with improved (ΔMMSE≥0) or deteriorated (ΔMMSE≥-4) were showed over time (Table 1).
The herbs are not stated but in a previous part of the study where Alzheimer's disease appeared to be relatively stabilized in one person for eight years, the authors stated they used a similar herb combination that they labelled GAPT.
The results from the Korean red ginseng for Alzheimer's disease for two years basically matched this one.
No more information is available to me at this time. This is, however, the largest study over the longest period of time that suggests (does not prove) that Alzheimer's disease can be kept relatively stable. Unfortunately, maybe at this point in time that is the most that can potentially be achieved.
I can see
that the article is listed in the supplemental section of the July 2017 issue,
pages P257-P258. But in the online
version there no mention of the study as being from a questionable source; that
the study is NOT subject to the same scrutiny as those that appear in the journal
proper; or any sort of disclaimer at all.
As a layman, this seems like very shoddy
reporting and makes me think less of the Alzheimer’s Association in general.
My main concern regarding this study is that it may not have been double-blinded. Omitting that information was a mistake by the authors. If it is not double-blinded, bias can enter the study.
I just quickly looked at the chemical constituents of the herbs likely used in this study--it is an impressive array of antioxidant compounds. But even that only appears to significantly slow down the progression of the disease. So I have very conflicting emotions regarding the results. If true, it means that you can slow down the progression of the disease for long periods of time, but may be no more than that with antioxidants at least.
My DW was prescribed Aricept at DX..6 months later the Dr's added Memantine. My DW was 55 years old at that time.
Did these meds work ? I have no idea. What I do know, is that she declined and a very rapid rate. I placed her into Long Term Care 8 days after her 61'st birthday.
Today, while the decline has slowed somewhat, my DW is in early stage 7..My DW still takes both meds ? The facility Dr. and senior nursing staff have experienced mixed results with discontinuing Aricept and Memantine ? They recommended not to discontinue the use of such meds? Medical staff went as far as "going to bat for me" with two insurance companies that were questioning the effectiveness at this stage.
On this one, I have to agree with Lane..There is no consensus on the effectiveness of these meds.
As I prepare for my visit today, I will keep your poignant comment in mind.
Best of luck to you sir.
I, too, greatly appreciated the thoughts that you expressed in your posts, Bill. I did better when I started treating my mother as the person she was instead of the person that I wanted her to be. It did not really make the pain and sadness any less on my end, but maybe it made her feel better. That does not mean I am any less sympathetic to all who are suffering as caregivers.
You are a gentleman, Bill. You wife, Doc, and all who surround you will bring you some happiness on the journey ahead. Your realism and intuition will serve you well, also
Dear Bill I have never suggested this in the slightest. I have a multitply handicapped grand niece who is the poster child for computer assisted communication
Its much worse than that even on its face . They had 243 people in the herb plus CT group and only 101 in the CT group. This screams that people were not randomly assigned but in fact CHOSE which group to be in or it was chosen for them. This simply makes the results Worthless.
The MMSE has also never been validated for this purpose. it is a screening test potentially useful for showing the decline of a specific individual. It has no absolute score validity. The scores are essentially ordinal, not ratio numbers. The poster compares average scores, which are useless. What you have to compare are changes in individual scores over time. Tehy don't do that