In my book, "Beating the Dementia Monster," I describe what has occurred since 2015 when I first knew I had memory problems. (You can find it on Amazon.com.) I have experienced remarkable improvement, and I’m certain that I can share valuable information with many others. In this second edition I continue my story to 2020 and provide greater understanding of how Alzheimer's advances and why what I did worked.
Saturday, July 18, 2020
#1 in Amazon "Hot New Releases"
After one day, Amazon is showing the new edition of Beating the Dementia Monster as the #1 "hot new releases" in the Neurology browse category. Hopefully, this portends well for its future.
Thursday, July 16, 2020
The second edition is now out!
The second edition of Beating the Dementia Monster is now out! It's been almost two and a half years since I started on it, and it's been a lot of work. You can see it here.
If you read the first edition, I can tell you this is a major update and upgrade. I have also taken on a co-author, Dr. Vaishali Phatak. She is associate professor of neuropsychology at the University of Nebraska Medical School, and she brings a lot to the table. She was my attending neuropsychologist at Harborview in Seattle in 2015 and 2016.
For two weeks, I have set an introductory price of $0.99 for the Kindle edition and $5.50 for the paperback. After two weeks, both prices will rise to their consumer level. If you read it, you are invited to review it on Amazon and/or Goodreads.
If you read the first edition, I can tell you this is a major update and upgrade. I have also taken on a co-author, Dr. Vaishali Phatak. She is associate professor of neuropsychology at the University of Nebraska Medical School, and she brings a lot to the table. She was my attending neuropsychologist at Harborview in Seattle in 2015 and 2016.
For two weeks, I have set an introductory price of $0.99 for the Kindle edition and $5.50 for the paperback. After two weeks, both prices will rise to their consumer level. If you read it, you are invited to review it on Amazon and/or Goodreads.
Wednesday, July 15, 2020
Will Baby Einstein avoid Alzheimer's disease when she gets old?
Is a higher level of early-life cognitive enrichment (ELCE) associated with lower levels of late-life Alzheimer disease and other common dementia-related pathological changes? This was a question addressed by research published in the journal JAMA Neurology on June 29, 2020.
Their conclusion: "Early life cognitive enrichment was associated with better late-life cognitive health, in part through an association with fewer AD pathological changes."
So what did they do to get to this conclusion?
The research involved a longitudinal study of 813 elderly participants for seven years through to their deaths. Their cognition was measured throughout the seven years, and their autopsies looked for evidence of neurodegenerative disease -- notably amyloid plaques and tangles.
At the outset of the research, participants completed an extensive questionnaire to establish an index representing an individual's ELCE. The index was composed of four indicators of ELCE (early-life socioeconomic status, availability of cognitive resources at 12 years of age, frequency of participation in cognitively stimulating activities, and early-life foreign language instruction). These were established by evaluating education levels of the parents and the number of children in the family; availability of cognitive resources, such as a newspaper subscription, encyclopedias, or a globe, at 12 years of age; frequency of participation in cognitively stimulating activities such as reading; and years of foreign-language instruction by 18 years of age.
The researchers attempted to control for "recall bias" which might result from selective memories of the participants' childhoods. Most were in their 70s at enrollment.
The findings identified a clear correlation between greater ELCE and fewer plaques and tangles in the autopsy as well as better cognitive performance during the preceding seven years. In fact, an index one unit higher for a participant correlated with Alzheimer's pathology of someone eight years younger. It also correlated with a 25% slower rate of cognitive decline.
The researchers evaluated the effect of greater ELCE on eight other brain pathologies. Only Alzheimer's disease was found to be affected.
Some commentators noted that the cohort was more female, white, and highly educated than the general U.S. population. This creates some questions about how the the results should be interpreted, since we know that Alzheimer's disease unfolds differently in diverse populations. Are there confounding factors that should have been further considered?
I don't know how much providing children with cognitive stimulation makes them smarter, but I do know that it's a lot of fun!
Their conclusion: "Early life cognitive enrichment was associated with better late-life cognitive health, in part through an association with fewer AD pathological changes."
So what did they do to get to this conclusion?
The research involved a longitudinal study of 813 elderly participants for seven years through to their deaths. Their cognition was measured throughout the seven years, and their autopsies looked for evidence of neurodegenerative disease -- notably amyloid plaques and tangles.
At the outset of the research, participants completed an extensive questionnaire to establish an index representing an individual's ELCE. The index was composed of four indicators of ELCE (early-life socioeconomic status, availability of cognitive resources at 12 years of age, frequency of participation in cognitively stimulating activities, and early-life foreign language instruction). These were established by evaluating education levels of the parents and the number of children in the family; availability of cognitive resources, such as a newspaper subscription, encyclopedias, or a globe, at 12 years of age; frequency of participation in cognitively stimulating activities such as reading; and years of foreign-language instruction by 18 years of age.
The researchers attempted to control for "recall bias" which might result from selective memories of the participants' childhoods. Most were in their 70s at enrollment.
The findings identified a clear correlation between greater ELCE and fewer plaques and tangles in the autopsy as well as better cognitive performance during the preceding seven years. In fact, an index one unit higher for a participant correlated with Alzheimer's pathology of someone eight years younger. It also correlated with a 25% slower rate of cognitive decline.
The researchers evaluated the effect of greater ELCE on eight other brain pathologies. Only Alzheimer's disease was found to be affected.
Some commentators noted that the cohort was more female, white, and highly educated than the general U.S. population. This creates some questions about how the the results should be interpreted, since we know that Alzheimer's disease unfolds differently in diverse populations. Are there confounding factors that should have been further considered?
I don't know how much providing children with cognitive stimulation makes them smarter, but I do know that it's a lot of fun!
Monday, July 13, 2020
Exercise stimulates the genesis of new brain cells ... via the liver?
As we discussed in Beating the Dementia Monster, exercise stimulates production of the the BDNF protein, the brain derived neurotrophic factor. BDNF plays a role in neurogenesis, prompting stem cells in the hippocampus to form new neurons. It may also have a healing function for cells damaged by Alzheimer's disease. How this works remains kind of mysterious. But according the this week's ALZForum, some researchers at UC San Francisco found that, during exercise, the liver produces an enzyme that plays a role in the production of BDNF and may have other positive effects. At least in mice. They were able to link this with improved cognition in older mice.
Some suggest this points to a "liver-brain axis."
What's also interesting is that serum taken from exercising, older mice and delivered to sedentary mice appears to convey a positive effect to the sedentary mice, perhaps by carrying over the enzyme.
The enzyme is glycosylphosphatidylinositol-specific phospholipase D1. We’ll just call it Gpld1.
Gpld1 removes certain proteins from the surfaces of cells, but also suppresses the complement system, which is part of the body's immune response. Isn't that bad? But part of the immune response is inflammation, and, as we have discussed before, too much inflammation is bad. Therefore, much of our effort to treat Alzheimer's disease is through reducing inflammation. Diet, exercise, intermittent fasting, and getting good sleep can all contribute to reducing inflammation. Apparently the production of Gpld1 is part of the story regarding how exercise can be associated with reducing inflammation in the brain, even though injury to the body during exercise has its own inflammatory response.
According to the article, there is a connection between neuroinflammation (inflammation in the brain) and peripheral inflammation (inflammation in the rest of the body). But it's not well understood. Gpld1 is a large molecule, and so it is blocked from involvement with brain chemistry by the blood-brain barrier. The blood-brain barrier blocks pathogens from getting into the brain, but it also blocks antibodies and other large proteins. So it's not clear how this Gpld1 is able to act on the brain, but it does appear to stimulate the production of BDNF, which is the main factor in my success in battling my disease. In mice, at least, overproduction of Gpld1 in exercising mice increased production of BDNF by 40% and tripled the generation of new neurons.
There two things worthy of further consideration. The first is the open question of whether what has been observed in mice reflects what occurs in the human body. The second is whether the increased expression of Gpld1 from the liver can be stimulated pharmacologically in people too frail to exercise. If so, that would be great.
Some suggest this points to a "liver-brain axis."
What's also interesting is that serum taken from exercising, older mice and delivered to sedentary mice appears to convey a positive effect to the sedentary mice, perhaps by carrying over the enzyme.
The enzyme is glycosylphosphatidylinositol-specific phospholipase D1. We’ll just call it Gpld1.
Gpld1 removes certain proteins from the surfaces of cells, but also suppresses the complement system, which is part of the body's immune response. Isn't that bad? But part of the immune response is inflammation, and, as we have discussed before, too much inflammation is bad. Therefore, much of our effort to treat Alzheimer's disease is through reducing inflammation. Diet, exercise, intermittent fasting, and getting good sleep can all contribute to reducing inflammation. Apparently the production of Gpld1 is part of the story regarding how exercise can be associated with reducing inflammation in the brain, even though injury to the body during exercise has its own inflammatory response.
According to the article, there is a connection between neuroinflammation (inflammation in the brain) and peripheral inflammation (inflammation in the rest of the body). But it's not well understood. Gpld1 is a large molecule, and so it is blocked from involvement with brain chemistry by the blood-brain barrier. The blood-brain barrier blocks pathogens from getting into the brain, but it also blocks antibodies and other large proteins. So it's not clear how this Gpld1 is able to act on the brain, but it does appear to stimulate the production of BDNF, which is the main factor in my success in battling my disease. In mice, at least, overproduction of Gpld1 in exercising mice increased production of BDNF by 40% and tripled the generation of new neurons.
There two things worthy of further consideration. The first is the open question of whether what has been observed in mice reflects what occurs in the human body. The second is whether the increased expression of Gpld1 from the liver can be stimulated pharmacologically in people too frail to exercise. If so, that would be great.
Thursday, July 9, 2020
The aducanumab drama continues to continue
As we discussed back in December 2019, Biogen has now filed with the FDA their application for approval of aducanumab. You will recall that the monoclonal antibody treatment initially failed its phase three trial, but Biogen reevaluated the test data and concluded the drug was effective. You will also recall from Beating the Dementia Monster that I had auditioned for the phase three trial but was screened out.
Out of fear of adverse effects on test subjects (brain micro-hemorrhages), Biogen reduced the dose part way through the trial. After first concluding that the drug had failed the trial, they later re-evaluated the data with a focus on only results unaffected by the dose change. They claim that these results confirm that the drug is actually effective. Will the FDA agree? We shall see.
The biggest obstacle for Biogen will be to convince everyone that they don't need to start over with the phase three trial. The argument for a do-over is that they didn't complete the trial, and the evidence for the drug's effectiveness is weak. My perception is that the argument for going straight to market is that the safety risks are reasonably well understood, and that the need for something ... anything ... that will actually address the disease mechanisms is more significant than any call for caution.
Aducanumab is one of several drugs that have been shown to actually remove amyloid plaques from the brain. These plaques are a consequence of the progression of Alzheimer's disease. They appear to inhibit the flow of information in the brain which affects memory and cognition. They also appear to kill brain cells. But it's not clear that removing the plaques improves cognition or slows progress of the disease.
Biogen claims that their data shows aducanumab slows progress of the disease and improves cognition. (They don't claim that it "cures" Alzheimer's disease.) We'll see if the FDA agrees.
Out of fear of adverse effects on test subjects (brain micro-hemorrhages), Biogen reduced the dose part way through the trial. After first concluding that the drug had failed the trial, they later re-evaluated the data with a focus on only results unaffected by the dose change. They claim that these results confirm that the drug is actually effective. Will the FDA agree? We shall see.
The biggest obstacle for Biogen will be to convince everyone that they don't need to start over with the phase three trial. The argument for a do-over is that they didn't complete the trial, and the evidence for the drug's effectiveness is weak. My perception is that the argument for going straight to market is that the safety risks are reasonably well understood, and that the need for something ... anything ... that will actually address the disease mechanisms is more significant than any call for caution.
Aducanumab is one of several drugs that have been shown to actually remove amyloid plaques from the brain. These plaques are a consequence of the progression of Alzheimer's disease. They appear to inhibit the flow of information in the brain which affects memory and cognition. They also appear to kill brain cells. But it's not clear that removing the plaques improves cognition or slows progress of the disease.
Biogen claims that their data shows aducanumab slows progress of the disease and improves cognition. (They don't claim that it "cures" Alzheimer's disease.) We'll see if the FDA agrees.
More Etcetera
Consistent with my last post, I did get the written results of my tests of June 15. They were, of course, what my neurologist said they would be. They compared my 2020 results with 2018, and I could see the areas where I had weakened. However, I then compared the 2020 results to my results of 2015, and I am still doing a lot better!
And so far, declining test results have not been reflected in declining abilities. I'm still able to do everything I set out to do, although I'm being more cautious about what I choose to do. Managing the complexity of getting the new book out is an example of what I'm fully able to do. A role I'd begun to take on with the Alzheimer's Association (point man with our congressional representative) is an example of a source of stress I needed to shed.
Getting the new edition to Beating the Dementia Monster continues to be an important focus right now. I got an author proof copy the other day, and I found several things that needed correction. I found one badly misspelled word, and a number of formatting oversights. Also, there's a graphic with poor contrast. So I've corrected these, but I really need to see anther author's proof copy to make sure that I fixed everything well. Too often, it looks great on the computer, but in real life ... not so much.
If all goes according to plan, I'll find the book ready to go by, say, next Tuesday. At that point I can submit it for final publication. Up to now, Amazon's robot has been ensuring that the book conforms to all of their requirements. But prior to actual publication, a human must look at it. This usually takes a couple of days. So, who knows, maybe we can go to press over the weekend of June 18? Readers of this blog will be the first to know.
I anticipate that the introductory price will be $0.99 for the eBook and $5.50 for the paperback. After two weeks, this will rise to the regular consumer price.
And so far, declining test results have not been reflected in declining abilities. I'm still able to do everything I set out to do, although I'm being more cautious about what I choose to do. Managing the complexity of getting the new book out is an example of what I'm fully able to do. A role I'd begun to take on with the Alzheimer's Association (point man with our congressional representative) is an example of a source of stress I needed to shed.
Getting the new edition to Beating the Dementia Monster continues to be an important focus right now. I got an author proof copy the other day, and I found several things that needed correction. I found one badly misspelled word, and a number of formatting oversights. Also, there's a graphic with poor contrast. So I've corrected these, but I really need to see anther author's proof copy to make sure that I fixed everything well. Too often, it looks great on the computer, but in real life ... not so much.
If all goes according to plan, I'll find the book ready to go by, say, next Tuesday. At that point I can submit it for final publication. Up to now, Amazon's robot has been ensuring that the book conforms to all of their requirements. But prior to actual publication, a human must look at it. This usually takes a couple of days. So, who knows, maybe we can go to press over the weekend of June 18? Readers of this blog will be the first to know.
I anticipate that the introductory price will be $0.99 for the eBook and $5.50 for the paperback. After two weeks, this will rise to the regular consumer price.
Wednesday, July 1, 2020
Test Results, etc.
I "saw" my neurologist yesterday for my annual assessment. (I "saw" her by Zoom conference.) The neuropsychologist had tested me two weeks before, and yesterday I received the results. They weren't great -- which wasn't a surprise.
As I said before, I've been on kind of a cognitive roller coaster since April 2019, and I had two terrible nights of insomnia before the test. So I was expecting disappointing results. They didn't quantify the results, but they said they were concerned. I should receive the report in the mail with all of the numbers in a few days. She said they would compare the results over the past few years.
One thing the neurologist noted is that I have been steadily taking on more responsibilities which raises stress levels. The stress hormone, cortisol, has been known to be hard on the hippocampus of people with Alzheimer's disease. She also suggested that I speak with my primary care provider about the possibility of a vitamin D3 deficiency. So I sent him an email asking about the blood test she suggested.
We also talked a little bit about the SNIFF study with insulin. She said that it may not be dead yet. As noted here, there may have been a problem with the delivery system, and so the research may not have been valid.
After meeting with her, I attended an on-line webinar about progress with Alzheimer's research in the Pacific Northwest. Most research is at a standstill, and some research has been abandoned due to the pandemic. Most of the research they discussed was promising work showing how much can be gained through exercise and other lifestyle improvements.
We have finalized the new book (Beating the Dementia Monster, 2nd edition) and the cover -- I hope. My co-author and I should receive proof copies on Tuesday. If they're good, we go to press next week! There will be a two-week window with a low introductory price, and you will be told when that starts.
As I said before, I've been on kind of a cognitive roller coaster since April 2019, and I had two terrible nights of insomnia before the test. So I was expecting disappointing results. They didn't quantify the results, but they said they were concerned. I should receive the report in the mail with all of the numbers in a few days. She said they would compare the results over the past few years.
One thing the neurologist noted is that I have been steadily taking on more responsibilities which raises stress levels. The stress hormone, cortisol, has been known to be hard on the hippocampus of people with Alzheimer's disease. She also suggested that I speak with my primary care provider about the possibility of a vitamin D3 deficiency. So I sent him an email asking about the blood test she suggested.
We also talked a little bit about the SNIFF study with insulin. She said that it may not be dead yet. As noted here, there may have been a problem with the delivery system, and so the research may not have been valid.
After meeting with her, I attended an on-line webinar about progress with Alzheimer's research in the Pacific Northwest. Most research is at a standstill, and some research has been abandoned due to the pandemic. Most of the research they discussed was promising work showing how much can be gained through exercise and other lifestyle improvements.
We have finalized the new book (Beating the Dementia Monster, 2nd edition) and the cover -- I hope. My co-author and I should receive proof copies on Tuesday. If they're good, we go to press next week! There will be a two-week window with a low introductory price, and you will be told when that starts.
Subscribe to:
Posts (Atom)