Donepezil truth?

jaxmom

Does anyone know if Alzheimers patients used to die faster before late 1990s when donepezil started to be used? 

I have read several things that indicate Donepezil CAN extend life by something like 2.4 years on average. They don’t say it is in the early stages though... 

The biggest claim about it is how it makes care taking easier so patients can stay home longer thus saving caretaker money not having to spend thousands on memory care. I wonder if it extends life by 2.4 average years if any savings is blown anyway by longer life in the end severe stages. I don’t know if this has been honestly looked at. I get it that medical workers think in terms of extending life, they don’t look at it like a spouse of someone with AD might. It isn’t a blessing to extend life in end stages of 6 or 7 and I personally would add at least much of stage 5. If it were me I wouldn’t want that. Saving money on memory care homes is nice, but I don't really want 2.4 more years of caring for my spouse in or out of a home.

Are we all being taken by pharmaceutical companies and well meaning doctors who have no other tools?

Iris L.

Exelon and aricept are useful in the early stages to improve function and to prolong the early stages.  This is what I was told when I first joined, and I have found it to be true in my case.  Towards the end, the idea is to limit meds to comfort meds.  That's what I have to say on this matter.

Iris L.

tgeno

My DW was diagnosed with early stage AZ last November. She started talking 5mg of donepezil in mid December. Very quickly I noticed a significant improvement in her short term memory and in her awareness of time, which had been a real problem. We're both happy with the results. It's obviously too early to say how long this improvement will last.

Gig Harbor

I was told the damage to the brain progresses as it would without donepezil. The person is simply able to function better hence they may be able to stay home longer. Eventually it stops working.

Michael Ellenbogen

Why do you as this question?

Quilting brings calm

I agree with Gig.  It doesn’t extend life.  It just helps masks the symptoms in the early stages so that the person can spend more of what life span they have at home or in assisted living rather than memory care or a nursing home.  Which means the financial cost of care should be less. 

However it only works for a percentage of the people taking it and then only for  a couple years

And, yes, most of us don’t want to see our loved ones suffer for 2.4 additional years. 

Ed1937

I was under the same thoughts as Gig and Quilting.

Marta

The best predictor of longer survival in dementia patients is the quality of care that they receive. 

Donepezil does not prolong life. Its use may delay the need for institutional care, which can translate into substantial savings, but not into prolonging survival. 

Ed1937

Jaxmom, the  post above mine is from someone in the medical field, who is also a long time caregiver.

Bob in LW

Here is my personal experience.  My SO was diagnosed with early Dementia nearly four years ago.  Her main problem is that she has short term memory loss, and it has been getting slowly worse. Her doctor prescribed 10 mg of Donepezil to be taken at bedtime for memory loss.  She has NOT progressed to the other forms of dementia such as getting violent, not remembering her family, etc.  She is quite functional in many ways, for which I am thankful.  Her 88th birthday was last Saturday.

Ed1937

Bob, my wife never took anything for dementia. She never got violent, and had only two episodes where she didn't know her children. But those were one time things. She probably would have progressed to the point where she didn't know us, but she was well into stage 6 at death.

Kenzie56

My DH is in end-stage mixed dementia.  His doctor took him off Donepezil and Memantine after 4 years on the medication.  He remains on Seroquel and a couple anxiety meds to keep him calm. I was told that Donepezil and Memantine help in the early stages, but after about 1-2 years it can't keep up with the progressive nature of cell degeneration.  Like others have stated, the drugs help with memory, but only on the surface.  Brain degeneration continues at the same rate. I can attest to this.  When the drugs no longer work, it is very disheartening.  I'm sorry.

Beholden

I’m new to all of this. In Dec 2022, my DH was given a diagnosis of “Other Amnesia.”  He still has more cognitive testing to complete. In the meantime, he was prescribed 5mg of Donepezil, but he has chosen not to take it. Instead, he’s been going a more holistic route. He has read Dr. Dale Bredesen’s book, “The End of Alzheimer’s “ and is following his protocol. Dr. Bredesen is like the top guru when it comes to brain heath and reversing dementia and Alzheimer’s. He is a researcher, an MD, a professor at UCLA, and has reversed the disease of many patients through diet, lifestyle changes, etc. He is known internationally for his scientific and successful work.  So far, we’re seeing some good results.

Ed1937

Beholden, Dr. Bredesen has appeared many threads here. Most people seem to think he is a "snake oil" salesman. Do a search to see what has been said of him. Apparently he is becoming a very rich man by promoting his approach. 

" and has reversed the disease of many patients through diet, lifestyle changes, etc.". Who are these people who have had it reversed, and how can that be verified?

Beholden

Hi Ed. I realize some people think Dr. Bredesen is a fake.  However, in the back of his book are pages filled with published scientific papers supporting his research. I have listened to numerous MD’s who reference his work and are also implementing his protocols with great success. I respect your opinion, and also your choices for treatment. We need to seek help wherever, and try whatever we can for our loved ones.

storycrafter

Several things can help various people for a short time. I have a friend who saw amazing results in her spouse, from diet and supplement changes. It lasted perhaps a year in their case. Then he declined rapidly regardless of diet and exercise.

My dh can only tolerate a half dose of Donepezil. It seems to help him function a smidgen better in his thought processes. He can't see it, but I do. Any improvement makes a difference in both our qualities of life.

dayn2nite2

Beholden wrote:

I’m new to all of this. In Dec 2022, my DH was given a diagnosis of “Other Amnesia.”  He still has more cognitive testing to complete. In the meantime, he was prescribed 5mg of Donepezil, but he has chosen not to take it. Instead, he’s been going a more holistic route. He has read Dr. Dale Bredesen’s book, “The End of Alzheimer’s “ and is following his protocol. Dr. Bredesen is like the top guru when it comes to brain heath and reversing dementia and Alzheimer’s. He is a researcher, an MD, a professor at UCLA, and has reversed the disease of many patients through diet, lifestyle changes, etc. He is known internationally for his scientific and successful work.  So far, we’re seeing some good results.

No.  You are one of dozens of people who come here, post about how wonderful this "protocol" is and never come back.

That book is a bunch of bull, mostly for the claims that he is a guru and that he has been able to "reverse" dementia.

Lane Simonian

Dr. Dale Bredesen is probably correct in that there are at least 36 different causes/triggers for Alzheimer's disease.  He describes it as thirty-six different leaks in a roof.

Identifying each and every cause in each and every individual, though, can be a herculean (and expensive) task.  Some triggers may be easy to identify; others not.  Some risk factors can be easily mitigated; others not.

If you cannot find and patch every leak from above, there are several other options.  You can put down several sublayers.  The first sublayer is between the receptors whose overactivation lead to the disease and the overactivation of NMDA receptors.  Aricept/donepezil is one part of that sublayer.  In addition to inhibitng the breakdown of acetylcholine which is needed for the retrieval of short-term memories, it inhibits intracellular calcium release.  The first mechanism of action provides symptomatic relief for awhile, but then the problem becomes the depletion of acetylcholine rather than its breakdown.  The second mechanism of action (reducing intracellular calcium release) inhibits the activation of protein kinase C which for awhile (about a year) delays the progression of mild 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 they restored PKC alpha, amyloid beta once again impaired neuronal function. In other words, amyloid beta doesn’t inhibit brain function unless PKC alpha is active." [what is true for amyloid which is a secondary trigger for Alzheimer's disease in those with the APOE4 gene is true for most other primary triggers for Alzheimer's disease].

Two problems with this, though, some protein Kinase C activity is needed for memory and learning, and secondly protein kinase C activity declines as Alzheimer's disease progresses.  So the sublayer of protection that Aricept provides no longer works once you progress past the early stages, and it only slows down the progression of the early stages for awhile.

The second sublayer involves intervening between the activation of NMDA receptors and the formation of the nitro-oxidant peroxynitrite.  One point in this pathway is inducible nitric oxide synthase (the combination of inducible nitric oxide and superoxide anions produces peroxynitrite).

"Deficiency of iNOS substantially protected the AD-like mice from premature mortality, cerebral plaque formation, increased beta-amyloid levels, protein tyrosine nitration, astrocytosis, and microgliosis. Thus, iNOS seems to be a major instigator of beta-amyloid deposition and disease progression. Inhibition of iNOS may be a therapeutic option in AD."

https://pubmed.ncbi.nlm.nih.gov/16260491/

But this sublayer begins to give way as well.

The third sublayer involves the scavenging of peroxynitrite and the partial reversal of the damage that it does to the brain via oxidation and nitration.  The Bredesen protocol does include dietary and supplement recommendations that partially does this, but more effective antioxidants exist then the ones he proposes.  

If you patch some of the leaks and add all three sublayers early in Alzheimer's disease you have the possibility of stabilizing the disease for at least two years and possibly longer.  If you add the second and third sublayers for moderate and perhaps severe Alzheimer's disease you can maybe stabilize the disease for about a year with a slower progression after that.  

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729264/

The following much more succinctly sums up this approach:

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. 

https://pubmed.ncbi.nlm.nih.gov/12676458/

 

 

 

Donr

Thank you for the lesson, Lane.