Nothing slows progression
I started this thread because Beryette posted
We saw the neurologist yesterday for followup. He prescribed a patch to help slow progression.
My response is
If the physician said that it borders on malpractice. No medication stops the progression of this disease , What they do for a short period of time is help with symptoms
In particular for the prescribed Exelon patch
The effect of rivastigmine may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact.
There is no evidence that rivastigmine alters the course of the underlying dementing process.
Comments
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Crushed, I totally agree with you. Nothing slows the progression of this disease. The one medication my mom was on helped her until she declined and then we discontinued it. With DH, we were not told of anything like this but then, again, it may not be available in Canada. Drugs go through rigorous testing here in Canada.
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Crushed wrote:
What they do for a short period of time is help with symptoms
I would even go a step further, saying it MAY help with symptoms for some people.
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I would word it somewhat differently, the prescribed medications for Alzheimer's disease can slow the progression of early stage Alzheimer's disease for awhile in some people (somewhere between six months and a year). The number of studies on their long-term effect are sparse and the results vary considerably among the studies (see table one).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC419395/
Acetycholinesterase inhibitors are sigma-1 receptor agonists which by reducing the release of intracellular calcium reduce the breakdown of acetylcholine, the formation of amyloid, and oxidative stress all of which may have some limited impact on Alzheimer's disease early on. But as the disease continues, intracellular calcium release declines anyway. You cannot alter the course of the disease if you are only slowing down what is damaging the brain (oxidative stress and subsequent neuroinflammation) and if you don't at least reverse part of that damage. In mild Alzheimer's disease compounds that do all three have a chance to largely stabilize the disease and in the moderate stages may produce a sustained slow down in its advance.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729264/ (from figure one)
In mild Alzheimer's disease, MMSE change in groups with or without herbal medicine. a Patients with Alzheimer’s disease had a transient improvement in cognitive function with conventional therapy (CT), but declined to a level similar to no treatment after 18 months. CT supplemented with herbal medicine (CT + H) provided additional benefit. The effect from herbal medicines became more pronounced over time. Expected decline of MMSE were calculated by formula produced from previous data. b In subgroup analysis, patients with moderate AD (red lines) were initially more responsive to both CT + H and CT therapies than mild AD (blue lines) patients. Over the course of treatment, CT + H outperformed CT therapy, a substantial deceleration in cognitive decline being observed in patients with moderate AD, while a long-term stabilization effect being observed in the patients with mild AD. MMSE denotes mini-mental state examination.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729264/
One of the herbs used in the above study was panax ginseng. The following was from an open label trial which have the potential for rater bias. The results are however similar to the retrospective study above:
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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659550/
I follow closely a drug candidate called blarcamesine/Anavex 2-73. It is a sigma-1 receptor agonist like acetycholinesterase inhibitors. It too is more effective in mild that in moderate Alzheimer's disease patients. But its substantially bends the curve of decline much better than acetylcholinesterase inhibitors at 148 weeks (caveats again open label trial with small number of participants).
http://www.arianapharma.com/wp-content/uploads/2019/03/ANAVEX2-73_CTAD_2018_Presentation_v2.pdf
The evidence that blarcamesine is an effective antioxidant is somewhat circumstantial (it scavengers hydrogen peroxide and may scavenge peroxynitrite), but it seems clear that it is doing something other than inhibiting the release of intracellular calcium.
One observer once said the Alzheimer's field keeps trying things that have already failed, but won't pursue things that have already seemed to work.
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My husband's internist in NM jumped on top of his soapbox when he saw Dick was taking Alz meds. and told him to stop....0
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Crushed, I think you will change your mind when the results of the Emory montelukast Alzheimer's clinical trial come out, which is planned for December. Many researchers are beginning to see that reducing immune system induced inflammation is the way to go.0
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Crushed- I am glad I saw this thread you started. So taking the chance of sounding dumb- our family doc and this neurologist both have said there are no meds to reverse the disease, but the ones on the market slow progression. That is incorrect?? I am very impressed by all the posts on this thread- you all have truly done your research!! Somehow I am just trying to stay afloat right now and dont have the energy for doing the research I know I should. I am beginning month 2 of 4 month treatment of chronic lyme disease and it kind of kicks my behind!! Anyhoo- DH is minimum of 4 years into this. We closed our business 4 years ago and the reason was he couldnt remember whether customers had paid him or not. We owned a used car lot- so this was not a small thing!! He would call me at home and ask. I had to handle liquidation of the remaining inventory as DH could not keep his train of thought and the back and forth offers, etc. It was very hard to watch and sad. So I would say we are well into this journey. He is 80 yrs old. I have not put the patch on yet- for some reason I am nervous. I have decided to wait until Monday instead of beginning on the weekend. I worked in the ER for several years and I will feel better if the docs that know him are in their offices.
And thank you all for the information and links. I will spend some time going thru all of it. Praying I make the right decision for him.
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Larrytherunner wrote:Crushed, I think you will change your mind when the results of the Emory montelukast Alzheimer's clinical trial come out, which is planned for December. Many researchers are beginning to see that reducing immune system induced inflammation is the way to go.
its good science but its a VERY small and limited trial with only one year treatment
and no further follow upStudy Type : Interventional (Clinical Trial) Actual Enrollment : 32 participants 32 participants is TINY
https://www.withpower.com/trial/phase-3-alzheimer-disease-8-2019-a9bfa#design
so only 16 subjects are getting the drug0 -
The Emory FDA montelukast Alzheimers trial started with 150 participants in 2019, half to be treated and half on placebos.The treated participants would take up to 20 mg twice a day for 12 months.
Intelgenx, a Canadian medical technology company, had already started its montelukast Alzheimers trial in 2018 under Health Canada supervision, with a planned 70 participants, half which were to be treated and half to be on placebos for 26 weeks. The approved dosage was 10 mg once a day, the same as the approved dosage for asthma. Intelgenx was having problems funding the trial and the trial was halted just before the Covid break.
During the Covid break, Intelgenx secured additional funds for its trial and also received authorization from Health Canada to treat participants with up to 30 mg twice a day.
Here is what I think happened next. With the resuming of trials approaching in late 2021, Emory realized that Integenx was now in a position to complete its trial using a more effective dosage and ahead of their own. In order to come out first, Emory reduced its participants to 32 with the approval of the FDA.
As it stands now, Intelgenx under the supervision of Health Canada has 70 participants in a double-blind placebo controlled study with treatments lasting 26 weeks and with dosages up to 30 mg twice a day.
Emory has 32 participants in its FDA double-blind placebo controlled study with treatments lasting 12 months and dosages up to 20 mg twice a day.
So the question is - who will announce results first. Both have announced that they expect to complete their respective trials in October with announcements planned in December.
It would be nice if they were to agree to announce their results on the same day, but so far, that has not been the case.
Emory montelukast Alzheimer trial https://clinicaltrials.gov/ct2/show/NCT03991988
Intelgenx montelukast Alzheimers trial https://clinicaltrials.gov/ct2/show/NCT03402503
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I have no idea what you mean by the FDA approved the smaller study
In order to come out first, Emory reduced its participants to 32 with the approval of the FDA.
The FDA does not approve the clinical trial as ADEQUATE only safe for the human subjects This is the INDA process
- An investigational new drug application (IND) outlines what the sponsor of a new drug proposes for human testing in clinical trials.
- Phase 1 studies (typically involve 20 to 80 people).
- Phase 2 studies (typically involve a few dozen to about 300 people).
- Phase 3 studies (typically involve several hundred to about 3,000 people).
- The pre-NDA period, just before a new drug application (NDA) is submitted. A common time for the FDA and drug sponsors to meet.
That has nothing to do with drug approval
With a smaller trial they have to show a much greater effect to prove it is not chance
Finally having served as an ethics advisor to to Data and Safety monitoring boards if a drug shows a clear and dramatic therapeutic effect it is unethical to continue the study
These are tiny studies
Canadian study is a phase IIa
This is a randomized Phase IIa, multi-center, double-blind, placebo-controlled study of a new buccal film of montelukast in patients with mild to moderate Alzheimer's Disease.
Separately, in September 2019, researchers at Emory began a university-sponsored Phase 2 trial of montelukast in tablet form for Alzheimer’s disease.
phase 2 trials are not enough for an NDA
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This is what pisses me of about the Alzheimers Association site. They have all these experts and they do absolutely nothing to help the people here but they delete others emails for stupid reasons. They do not realize the damage they are doing by leaving stupid post like this to go on without someone replying from AA to point out the benefits of these drugs.
I get it some of you did not befit by this drug but that does not meant others don’t. Your comments are hurting many who will benefit from them. I have said this before and many times. Don’t you folks care that you are hurting others in the proses of your comments????
Let me try another analogy since the one I always use does not seem to get your attention or make sense to you. Let’s say have a radio station that you listen to. You find that there is a lot of static. You get a bigger antenna to boost the signal. The radio station now comes in with much less static. Well that is what is happening in the brain. We can hear you better, focus on what you say or even figure thing out bettr are just a few things were it helps.
That's what Aricept and Razadyne (Namenda and Galatamine) do. They boost up the signals in the brain to help you process information better.
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Michael Ellenbogen wrote:
Let me try another analogy since the one I always use does not seem to get your attention or make sense to you. Let’s say have a radio station that you listen to. You find that there is a lot of static. You get a bigger antenna to boost the signal. The radio station now comes in with much less static. Well that is what is happening in the brain. We can hear you better, focus on what you say or even figure thing out bettr are just a few things were it helps. That's what Aricept and Razadyne (Namenda and Galatamine) do. They boost up the signals in the brain to help you process information better.
Better analogy
In old tube radios the tubes would be failing and reception poor
you could get temporary improvement with a better antenna but eventually the tubes give out completely and the antenna is useless0 -
This is a somewhat different analogy. Alzheimer's disease is like a sink filling up with water (oxidants). If you turn down the tap (inhibit the formation of oxidants) the water fills up more slowly and if you pull up a little on the stopper (remove oxidants) the water levels stabilize. For awhile, you can maintain people near baseline that way--maybe up to a year with acetylcholinesterase inhibitors. But eventually one faucet gets turned way down (the one that had initially led to high acetylcholinesterase activity), but the connected faucet gets turned up higher (via NMDA receptors), and the sink fills up almost at the same rate as if nothing had been done at all.
This is probably the key to the treament of Alzheimer's disease:
The inflammatory mediator peroxynitrite, when generated in excess, may damage cells by oxidizing and nitrating cellular components. Defense against this reactive species may be at the level of prevention of the formation of peroxynitrite, at the level of interception, or at the level of repair of damage caused by peroxynitrite.
Namenda partially inhibits the formation of peroxynitrite, acetylcholinesterase inhibitors partially inhibit the formation of peroxynitrite and intercept it (a peroxynitrite decomposition catalyst), panax ginseng, aromatherapy, and perhaps Anavex's blarcamesine inhibit the formation of peroxynitrite, scavenge peroxynitrite, and reverse part of the damage it does to the brain through oxidation and nitration.
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Crushed I love that analogy. That is spot on. But we don’t know when those tube will die and it can take 6 month or 10 years and we benefit most of that time. If we originally got benefit from the drug.
I use to fix TV's and all of electronics.
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Lane Simonian, thank you for your usual clear explanation and expertise.
Do you think aromatherapy produces measurable results?
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Even if they just slowed the symptoms for a few months, wouldn’t that alone be a good thing?
Yes I get the disease progresses, and the meds do nothing for many, but seems like slowing symptoms (which are often expressed as problem behaviors) would be good, even if just a short time.
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Alzheimer's disease is like a sink filling up with water (oxidants). If you turn down the tap (inhibit the formation of oxidants) the water fills up more slowly and if you pull up a little on the stopper (remove oxidants) the water levels stabilize.
you are confusing the symptoms of Alzheimers with the pathology of the disease itself
from NIHTreating the symptoms of Alzheimer’s can provide people with comfort, dignity, and independence for a longer period of time and can encourage and assist their caregivers as well. Galantamine, rivastigmine, and donepezil are cholinesterase inhibitors that are prescribed for mild to moderate Alzheimer’s symptoms. These drugs may help reduce or control some cognitive and behavioral symptoms.
Scientists do not yet fully understand how cholinesterase inhibitors work to treat Alzheimer’s disease, but research indicates that they prevent the breakdown of acetylcholine, a brain chemical believed to be important for memory and thinking. As Alzheimer’s progresses, the brain produces less and less acetylcholine, so these medicines may eventually lose their effect. Because cholinesterase inhibitors work in a similar way, switching from one to another may not produce significantly different results, but a person living with Alzheimer’s may respond better to one drug versus another.
https://www.nia.nih.gov/health/how-alzheimers-disease-treated
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For me I started to take two different kinds to get more benefit. But I have been on them for along time and they still work. I hope.
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No one is saying that the memory drugs or other drugs cure Alzheimer's Disease. In fact, the majority of drugs do not cure any chronic diseases. Improvement in symptoms is a plus for me. I'm glad my signals are coming in stronger! Why deny people something that might ease their issues for a while? My geriatrician told me the medication may work on the symptoms but the disease continues beneath the surface. That made sense.
Iris
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Thank you MaggieMae. There are a couple of small studies suggesting that aromatherapy can potentially improve both cognition and behavior.
Results: All patients showed significant improvement in personal orientation related to cognitive function on both the GBSS-J and TDAS after therapy. In particular, patients with AD showed significant improvement in total TDAS scores. Result of routine laboratory tests showed no significant changes, suggesting that there were no side-effects associated with the use of aromatherapy. Results from Zarit's score showed no significant changes, suggesting that caregivers had no effect on the improved patient scores seen in the other tests.
Conclusions: In conclusion, we found aromatherapy an efficacious non-pharmacological therapy for dementia. Aromatherapy may have some potential for improving cognitive function, especially in AD patients.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1479-8301.2009.00299.x
Conclusion: Aromatherapy can improve sleep, alleviate psychobehavioural symptoms and improve quality of life in patients with AD, which may be related to reducing the level of oxidative stress in patients and inhibiting inflammatory factors; it is a non-drug intervention that can be widely applied.
The more relaxing and calming essential oils such as lavender, rose, bergamont, and sweet orange seem to work well with a diffuser. The more cognitive enhancing essential oils such as rosemary, bay laurel, lemon, and clove seem to work better with direct inhalation for a few seconds each day.
The improvements I noticed using aromatherapy for my mother were fewer delusions, more alertness and awareness, and better memory in certain areas (object recognition, recognition of place, recognition of faces, for instance).
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The decline in acetylcholine levels is indeed one of the reasons why acetylcholinesterase inhibitors begin to lose their effectiveness in Alzheimer's disease, Crushed. The only factor is a decline in acetylcholinesterase activity in general.
I am not sure if the distinction between symptoms and causes is all that helpful. If the symptom is a decline in memory and you partially reverse that decline in memory by treating the cause of that memory loss you are modifying the disease. Acetylcholinesterase inhibitors temporarily reduce that cause; other treatments may reduce that cause over long periods of time.
Oxidation and nitration reduce both levels of acetylcholine and the regeneration of neurons in the hippocampus. If you reverse both oxidation and nitration, you partially restore certain types of memories (those connected to the hippocampus).
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I advise PWDs and caregivers to use this time for their bucket list and to get their affairs in order. Don't delay. This time won't last.
Iris
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Lane Simonian, thank younger the further info. The aromatherapy that you used for your mother that was helpful, how did you apply it? A diffuser, an inhaler, or just added to a cream, soap or lotion? I’ve tried adding lavender oil to a handsoap in a pump type bottle and it made the liquid soap too watery. I didn’t measure, but didn’t add that much. I frequently cook with fresh rosemary, adding it to chicken, turkey or salmon before cooking. We have been going through a very good period for the past couple of months (see my thread “A reprieve”) so I don’t know if the rosemary is helping or not, but it isn’t hurting anything and makes the kitchen smell good.
Specifically, which herbs did you find helped your mom the most? If you used oils, where did you get them? I’ve always sort of pooh pooed the idea of aromatherapy, but you’ve gotten my attention.Rescue Mom, I agree completely.
Michael Ellenbogen, my father used to repair radioes, and later TV’s. When he would babysit on Friday nights when mom went shopping or to a movie with her lady friends, he would show my sister and I how to build a radio with tubes and other electrical parts. There was always at least one disassembled tv in his workroom as well as a ham radio and years later, CB. He was the only dad in the neighborhood who knew Morse Code. I wish he would have lived to see computers and the internet.
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I love the smell og lavender. It makes me feel more relaxed.
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I forgot a point that is very important. We say that the memory meds and Best Practices may prolong the early stages, with the emphasis on early. Many PWDs who are given the memory meds are already in the middle stages by the time they are diagnosed. So, of course, the impact of the memory meds will be limited.
Iris
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Lane Simonian wrote:
I am not sure if the distinction between symptoms and causes is all that helpful. If the symptom is a decline in memory and you partially reverse that decline in memory by treating the cause of that memory loss you are modifying the disease.
OFGS the distinction between symptoms and causes has been the heart of medical science and advancement For over 150 years
Then you go on to say " If the symptom is a decline in memory and you partially reverse that decline in memory by treating the cause of that memory loss you are modifying the disease"
This is nonsense you are treating a Symptom
Headache may be a symptom of a brain tumor but treating the symptom is not treating the tumor
Memory loss is an effect of the underlying pathology
We know from strokes that the brain has the ability to rewire around the damaged tissue and restore functioning So short term increase in memory means nothing in terms of the Alzheimer's pathology
That is why QUACKS are so successful
Alzheimer's destroys brain function at the cellular level you are not modifying the disease unless and until you can demonstrate and effect on cellular degradation
From NIH How does Alzheimer’s disease affect the brain?The brain typically shrinks to some degree in healthy aging but, surprisingly, does not lose neurons in large numbers. In Alzheimer’s disease, however, damage is widespread, as many neurons stop functioning, lose connections with other neurons, and die. Alzheimer’s disrupts processes vital to neurons and their networks, including communication, metabolism, and repair.
At first, Alzheimer’s disease typically destroys neurons and their connections in parts of the brain involved in memory, including the entorhinal cortex and hippocampus. It later affects areas in the cerebral cortex responsible for language, reasoning, and social behavior. Eventually, many other areas of the brain are damaged. Over time, a person with Alzheimer’s gradually loses his or her ability to live and function independently. Ultimately, the disease is fatal.
https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease
That's it , you are just treating symptoms until you affect cell degradation and postpone death
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But if you are able to remove the tumor, the headaches may go away, Crushed. There are likely three main causes of memory loss in Alzheimer's disease: declining levels of acetylcholine, the lack of regeneration of neurons, and the death of neurons. If you can increase acetylcholine levels, regenerate neurons, and reduce the death of neurons you can partially offset memory loss.
The evidence for this is in mice, so not perfect by any means:
The study, to be published August 19 [2022] in the Journal of Experimental Medicine, shows that new neurons can incorporate into the neural circuits that store memories and restore their normal function, suggesting that boosting neuron production could be a viable strategy to treat AD patients.
New neurons are produced from neural stem cells via a process known as neurogenesis. Previous studies have shown that neurogenesis is impaired in both AD patients and laboratory mice carrying genetic mutations linked to AD, particularly in a region of the brain called the hippocampus that is crucial for memory acquisition and retrieval...
In the new study, Lazarov and colleagues boosted neurogenesis in AD mice by genetically enhancing the survival of neuronal stem cells. The researchers deleted Bax, a gene that plays a major role in neuronal stem cell death, ultimately leading to the maturation of more new neurons.
The route to the regeneration of neurons is via the phosphatidylinositol 3-kinase/Akt pathway which is inhibited by nitration in Alzheimer's disease (mediated by peroxynitrite). It is also peroxynitrite that leads to the death of neurons. By scavenging peroxynitrite, you partially reverse the nitration of the phosphatidyinositol 3-kinase (thus partially restoring neurogenesis) and reduce neuronal cell death caused by peroxynitrite. That is treating the cause of the disease.
Peroxynitrite induces inactivation of the Akt pathway. Furthermore, overexpression of constitutively active Akt inhibits both peroxynitrite-induced Bax translocation and cell death.
Two important caveats, regeneration of neurons likely does not makeup for all the neurons lost and neurons cannot be regenerated in the frontal cortex which is also damaged during Alzheimer's disease.
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MaggieMae, my sisters and I used a combination of essential oils which included rosemary, bay laurel, clove, sweet orange, oregano, and sage. We had her smell a couple of essential oils directly from the bottle for a few seconds each morning under each nostril.
The essential oil that I used first was rosemary essential oil. After about a month, my mother asked why I had been giving it to her to smell every day for a month. After about a year of using aromatherapy, she recognized her home again. Once she even said while coming down the street, we are almost home. She was able to remember her name again and spell it. She stopped having delusions.
There are a few accounts of beneficial responses to essential oils via massage, but in most cases a carrier oil does have to be used to avoid harming the skin.
I read an account by a son who had given his mother rosemary, but he did not say if it was as an herb or as an essential oil via aromatherapy. He and his mother's nurses and doctor were surprised that after a year of being non-verbal she was able to communicate in simple sentences.
I will try to find your thread. I missed it before.
There are quite a few case studies from memory care/nursing care facilites of aromatherapy creating more awareness and less fear among Alzheimer's patients. Aromatherapy does not cure the disease, but it does often give a person a better life with the disease.
I forgot to add we used to purchase several different brands of essential oils. I liked getting them from Dandelion Botanical Company near my sister's home in Seattle. They have since moved to Sequim but I think they still take order.
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Well, all I know is that DH has been on Aricept and Memantine for almost 2 years now. (since diagnosis (10/2020). I may have noticed some slight positive effect at the beginning, but there is definitely no benefit any more. This past Tuesday I took DH for his yearly check-in. Prior to the appointment, I sent the dr. information about the changes I've seen over the past year, and my most recent concerns. I felt like I was being proactive and laid out the information in a very clear format. One of the areas I addressed was these 2 medications, and also a request that he consider increasing the anti-depressant. The dr. thanked me for the information but did not reference any of the points I made. Instead of taking him off of the medications, he increased the Aricept, and switched it from night to morning.
I left the appointment feeling very unheard, and very frustrated.
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