According to a new article in ALZForum, some studies have shown that vitamin B-12 supplements can help with mild or moderate Alzheimer's disease, but other, more credible studies have failed to confirm the results. Some actively promote regular use of vitamin B-12 supplements to protect against developing dementia. Vitamin B12 deficiency has been shown to cause dementia, and taking supplements may counter that. But the article asks, "Is too much vitamin B12 a health hazard?"
Maybe it is. And maybe it's not. The article is based on research published on January 6 in JAMA Network Open. The article found that people with an abnormally high level of B12 in their blood had a significantly higher incidence of death over an 8-year period -- a 25% higher probability.
The objective of the research was to resolve two apparently conflicting findings in different research. One clinical trial reported less degeneration in
brain regions vulnerable to Alzheimer's disease in people with high levels of plasma
homocysteine and B vitamins, but other trials have
found higher mortality in elderly and hospitalized patients with high
blood levels of vitamin B12. Vitamin B12 helps metabolize the amino acid homocysteine, which is believed to contribute to the development of Alzheimer's disease.
If people with abnormal levels of vitamin B12 are dying at an abnormal rate, what are they dying from? Well, a number of causes that were difficult to correlate. (This is similar to studies finding that people taking vitamin E supplements had higher mortality, but not consistently from specific direct causes.) The authors concluded that they may be dying from underlying kidney and liver diseases aggravated by abnormally high levels of vitamin B12 in their blood.
On December 21 we posted about research showing generally that taking vitamin supplements actually raises mortality. Consistent with those findings, the B12 study authors caution against taking vitamin supplements when there is no identified deficiency.
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.
Friday, January 31, 2020
Tuesday, January 28, 2020
Does Herpes Cause Alzheimer's Disease?
In June, 2018 we posted about a possible connection between the herpes virus and Alzheimer's disease. (In February 2019 we posted about a bacterium that might also be implicated.) As we noted on January 15 of this year, 2019 saw new interest in the possible role of the herpes virus in the etiology of Alzheimer's disease.
So what are we to make of the role of pathogens in general and herpes in particular in what sparks Alzheimer's disease and what then drives its development?
The answer is that it depends on who you ask. This week's ALZForum carried an interesting article that attempted to assess where we're at with this question: "Herpes Viruses and Alzheimer's -- the Debate Continues." As we noted in the June 2018 article, the herpes virus can be found in the brains of people who died of Alzheimer's dementia, suggesting that it was part of the etiology -- although it noted that our brains begin accumulating viruses of many types from when we were children. But the new article points out that there are different ways of assessing the presence of viruses in an autopsy, and the different ways yield different conclusions.
A problem with the story that's been evolving since the important research in 2018 is that it's not clear that there are more herpes viruses in the brain of a person who died with Alzheimer's dementia than in that of a normal person. Some studies say there is, but other credible studies (using a different methodology) find that there isn't. On the other hand, there seems to be a consensus that viruses may well play a role in the development of Alzheimer's disease.
It's not so much about finding the viruses are still active, but rather finding the damage they caused.
Gene regulatory networks are systems that control how genes are expressed in proteins. (As a consequence, they control, for example, whether you are a human or a reptile.) Damaging them won't cause you to turn into a lizard, but damage in a gene regulatory network may cause a gene to express in a manner that promotes Alzheimer's disease. And damaged networks may focus their influence on the genes we have learned to associate with risk for Alzheimer's disease.
The evidence for a connection between herpes and Alzheimer's disease is strong, based on data used in the study we discussed in June 2018. Remember that Alzheimer's disease begins years, maybe decades before the first symptoms appear. So, while there may not be evidence of an unusual presence of herpes at death, it may have been much stronger long ago. The virus could have done its damage to the gene networks then, and the consequences were realized much later.
So what are we to make of the role of pathogens in general and herpes in particular in what sparks Alzheimer's disease and what then drives its development?
The answer is that it depends on who you ask. This week's ALZForum carried an interesting article that attempted to assess where we're at with this question: "Herpes Viruses and Alzheimer's -- the Debate Continues." As we noted in the June 2018 article, the herpes virus can be found in the brains of people who died of Alzheimer's dementia, suggesting that it was part of the etiology -- although it noted that our brains begin accumulating viruses of many types from when we were children. But the new article points out that there are different ways of assessing the presence of viruses in an autopsy, and the different ways yield different conclusions.
A problem with the story that's been evolving since the important research in 2018 is that it's not clear that there are more herpes viruses in the brain of a person who died with Alzheimer's dementia than in that of a normal person. Some studies say there is, but other credible studies (using a different methodology) find that there isn't. On the other hand, there seems to be a consensus that viruses may well play a role in the development of Alzheimer's disease.
It's not so much about finding the viruses are still active, but rather finding the damage they caused.
Gene regulatory networks are systems that control how genes are expressed in proteins. (As a consequence, they control, for example, whether you are a human or a reptile.) Damaging them won't cause you to turn into a lizard, but damage in a gene regulatory network may cause a gene to express in a manner that promotes Alzheimer's disease. And damaged networks may focus their influence on the genes we have learned to associate with risk for Alzheimer's disease.
The evidence for a connection between herpes and Alzheimer's disease is strong, based on data used in the study we discussed in June 2018. Remember that Alzheimer's disease begins years, maybe decades before the first symptoms appear. So, while there may not be evidence of an unusual presence of herpes at death, it may have been much stronger long ago. The virus could have done its damage to the gene networks then, and the consequences were realized much later.
Saturday, January 25, 2020
A Device to Improve Cognition in Alzheimer's Disease
The January 16 issue of the journal Alzheimer's and Dementia carried a likely interesting article about research on a device that improves cognition by simultaneously applying magnetic and cognitive stimuli to the brain.
Why do I say "likely?" Because the article is behind the paywall, and I could only read the abstract. But the abstract indicated positive results from the research, and it identified the company behind the device and its protocol.
The device is called the neuroADTM Therapy System by Neuronix. The protocol for treatment is to first use MRI scans to identify areas of the brain affected by Alzheimer's disease and then stimulate those areas with focused magnetic fields. While these areas are being stimulated, the patient participates in cognitive training exercises. Neuronix claims that the magnetic fields "strengthen the signal transmission and chemical bonds between the neurons in the brain." Not sure I'd have phrased it that way, assuming I understand what they're trying to say.
No one claims that this treatment stops or slows the progress of Alzheimer's disease. However, like donepezil (Aricept) and the other acetylcholinesterase inhibitors, it temporarily improves cognition in people suffering from Alzheimer's disease. The research seems to indicate that improvement from this treatment is superior to that from the medications. For me, that's good, because I had unpleasant side effects when I tried to take donepezil. And I wasn't alone.
Why do I say "likely?" Because the article is behind the paywall, and I could only read the abstract. But the abstract indicated positive results from the research, and it identified the company behind the device and its protocol.
The device is called the neuroADTM Therapy System by Neuronix. The protocol for treatment is to first use MRI scans to identify areas of the brain affected by Alzheimer's disease and then stimulate those areas with focused magnetic fields. While these areas are being stimulated, the patient participates in cognitive training exercises. Neuronix claims that the magnetic fields "strengthen the signal transmission and chemical bonds between the neurons in the brain." Not sure I'd have phrased it that way, assuming I understand what they're trying to say.
No one claims that this treatment stops or slows the progress of Alzheimer's disease. However, like donepezil (Aricept) and the other acetylcholinesterase inhibitors, it temporarily improves cognition in people suffering from Alzheimer's disease. The research seems to indicate that improvement from this treatment is superior to that from the medications. For me, that's good, because I had unpleasant side effects when I tried to take donepezil. And I wasn't alone.
Tuesday, January 21, 2020
In the Memory Care Facility
Back in September, I posted about visiting two friends living in elder care facilities, Bill and Mike. Since then, Bill has died. I'd known him for 30 years, and he was pushing 100 years of age. (So he was my father's age.) Bill did not have Alzheimer's disease, but he did have days when he hallucinated about where he was and what part of his life he was living. Other days, he was quite lucid, and he offered very coherent prayers to his God.
Mike, on the other hand, appears to me to be in the middle stage of Alzheimer's dementia. In this stage you are usually still ambulatory, but you need a lot of help to get through your day. (In the final stage, you are bedridden.) He lives in a memory care facility which is quite near our home. I've been visiting Mike almost every day for four months. Most days he's pleasant to talk to, but he mostly talks gibberish. He seems to recognize me and is happy to see me. He usually knows his own first name but often can't recall his last name.
In visiting Mike, I've also come to know some of the others living there. They come up and talk to me. Some at first seem coherent, but I soon realize that they don't know where they are. One man who used to work on the railroad wanted me to help him solve some issue that was keeping the trains from moving. Yesterday, a man who was once a construction manager for a large company building power plants and oil refineries asked me for help with tools for a job. I'm repeatedly approached by people, including Bill and Mike, saying that they are broke, and they don't know how they will pay their rent. Among other things, they want to know how they can get a job. Few of these people ever have visitors.
One thing that has surprised me is how quickly most of these people are declining. In just four months I've seen remarkable deterioration in the cognition of several of these people -- but not Mike. At least to me, Mike seems to be about where he was when he first entered the facility back in September. While Alzheimer's disease progresses differently in different people, it still strikes me as odd that Mike seems to declining so much more slowly than some others there.
So, I wonder. Mike is the only one for whom there's someone who sits with him daily and talks with him. It may be nonsense talk, but there is still human interaction.
In Beating the Dementia Monster, we discussed the role of human interaction in staving off cognitive impairment. I wrote that a neurologist once told me that, in his experience of 22 years, social connection was more important than exercise. At Harborview, they told me not to quit my job, the idea being that working along side other people and interacting with them resists the advance of the disease. I did cease my employment, but I now volunteer at the food bank, and getting to the 2nd edition of Beating the Dementia Monster seem to serve the same purpose.
Mike, on the other hand, appears to me to be in the middle stage of Alzheimer's dementia. In this stage you are usually still ambulatory, but you need a lot of help to get through your day. (In the final stage, you are bedridden.) He lives in a memory care facility which is quite near our home. I've been visiting Mike almost every day for four months. Most days he's pleasant to talk to, but he mostly talks gibberish. He seems to recognize me and is happy to see me. He usually knows his own first name but often can't recall his last name.
In visiting Mike, I've also come to know some of the others living there. They come up and talk to me. Some at first seem coherent, but I soon realize that they don't know where they are. One man who used to work on the railroad wanted me to help him solve some issue that was keeping the trains from moving. Yesterday, a man who was once a construction manager for a large company building power plants and oil refineries asked me for help with tools for a job. I'm repeatedly approached by people, including Bill and Mike, saying that they are broke, and they don't know how they will pay their rent. Among other things, they want to know how they can get a job. Few of these people ever have visitors.
One thing that has surprised me is how quickly most of these people are declining. In just four months I've seen remarkable deterioration in the cognition of several of these people -- but not Mike. At least to me, Mike seems to be about where he was when he first entered the facility back in September. While Alzheimer's disease progresses differently in different people, it still strikes me as odd that Mike seems to declining so much more slowly than some others there.
So, I wonder. Mike is the only one for whom there's someone who sits with him daily and talks with him. It may be nonsense talk, but there is still human interaction.
In Beating the Dementia Monster, we discussed the role of human interaction in staving off cognitive impairment. I wrote that a neurologist once told me that, in his experience of 22 years, social connection was more important than exercise. At Harborview, they told me not to quit my job, the idea being that working along side other people and interacting with them resists the advance of the disease. I did cease my employment, but I now volunteer at the food bank, and getting to the 2nd edition of Beating the Dementia Monster seem to serve the same purpose.
Saturday, January 18, 2020
More on Intermittent Fasting
In my post of January 10, I wrote about a coincidence in which I'd gotten an email from my sister asking for my thoughts on intermittent fasting, and the same day Amy's nephew shared with us his success with intermittent fasting. This prompted me to spend more time investigating it, since there was evidence that intermittent fasting is helpful with Alzheimer's disease. (In Beating the Dementia Monster, we promote a daily 12-hour intermittent fast.)
But the coincidences keep on coming.
We returned home from spending Christmas with Amy's family in Hawaii, and I returned to my gym here. My routine is to spend 50 minutes a day on the treadmill watching YouTube videos on various subjects. These often relate to my interest in how to deal with Alzheimer's disease. I often rely on YouTube to serve up what it thinks I'll like, and it seemed to perceive that I was interested in Intermittent fasting.
The other day, I was presented with a video on intermittent fasting that cited a recent article in The New England Journal of Medicine about intermittent fasting, "Effects of Intermittent Fasting on Health, Aging, and Disease." I made a note to find the article when I got home.
Well, I got home and I was piddling around the house when the doorbell rang. It was my neighbor, a retired physician (and reviewer for Beating the Dementia Monster). He had in his hand a paper copy of the NEJM article that he had torn from his paper copy of the journal. Quite a coincidence, but this article seems to be getting a lot of attention.
I am continuing work on the second edition of Beating the Dementia Monster, and I thought it well to address intermittent fasting. Here is a preview of what I intend to say:
Intermittent fasting can take several forms. A daily fast of 12, 16, or 20 hours every day is one possibility. For the 16 and 20-hour fasts, this means forgetting breakfast and perhaps delaying lunch. (Don't worry -- medical research has totally destroyed the idea that breakfast is the most important meal of the day.) Some see the 16-hour fast as a stepping stone to the 20-hour fast. With the 20-hour fast, you will then do all of your eating during a four-hour window every day. Another approach is to eat normally five days a week but to only consume 500 calories each of two days per week. For example, you might eat normally on Sunday, Tuesday, Wednesday, Friday and Saturday, but eat only 500 calories of food on Monday and Thursday. Sound hard? People I know who do this tell me that it gets easy after a couple of weeks.
But what’s this about? An article appeared in the December 2019 issue of The New England Journal of Medicine that described intermittent fasting and what is being learned about it. The article was entitled “Effects of Intermittent Fasting on Health, Aging, and Disease.” It says that the practice of intermittent fasting improves glucose regulation, increases resistance to oxidative and metabolic stress, and suppresses inflammation. Inflammation and oxidation are major factors in the development of Alzheimer’s disease. Fasting elicits these effects as responses from cells in the body.
Intermittent fasting shares some traits with the increasingly popular (fad?) keto diet, about which I have no comment. Both strategies lead to a condition called ketosis. The article notes that glucose and fatty acids are the main sources of energy for the cells. It goes on to say that, after meals, glucose is used for energy, and fat is stored as triglycerides. During fasting, triglycerides are broken down to fatty acids and glycerol. The liver converts fatty acids to “ketone bodies,” which, in the absence of glucose, provide a major source of energy for many tissues, especially the brain. This is ketosis. The ketone bodies also give you bad breath.
In the keto diet (if faithfully adhered to—a challenge), the body remains in ketosis. However, during intermittent fasting, the body undergoes “metabolic switching” in which the body shifts in and out of ketosis. It shifts back and forth between relying on glucose and fat for energy.
What are the benefits of being in ketosis? According to the article, ketone bodies serve not only as fuel for the cells, but they also signal cells and organs to perform a variety of functions involved in health and aging. Earlier theories about fasting focused on restricting calories for weight loss, but recent research points to a whole suite of other positive effects from not eating. The article discussed positive effects for obesity and diabetes, cardiovascular disease, cancer, neurodegenerative disorders (like Alzheimer’s disease), asthma, multiple sclerosis, arthritis, and healing from traumatic injury.
Too good to be true? I don’t know, but the 12-hour fast has been part of my regimen from the beginning. I am currently experimenting with more aggressive fasts, and the research seems compelling.
But the coincidences keep on coming.
We returned home from spending Christmas with Amy's family in Hawaii, and I returned to my gym here. My routine is to spend 50 minutes a day on the treadmill watching YouTube videos on various subjects. These often relate to my interest in how to deal with Alzheimer's disease. I often rely on YouTube to serve up what it thinks I'll like, and it seemed to perceive that I was interested in Intermittent fasting.
The other day, I was presented with a video on intermittent fasting that cited a recent article in The New England Journal of Medicine about intermittent fasting, "Effects of Intermittent Fasting on Health, Aging, and Disease." I made a note to find the article when I got home.
Well, I got home and I was piddling around the house when the doorbell rang. It was my neighbor, a retired physician (and reviewer for Beating the Dementia Monster). He had in his hand a paper copy of the NEJM article that he had torn from his paper copy of the journal. Quite a coincidence, but this article seems to be getting a lot of attention.
I am continuing work on the second edition of Beating the Dementia Monster, and I thought it well to address intermittent fasting. Here is a preview of what I intend to say:
Intermittent fasting can take several forms. A daily fast of 12, 16, or 20 hours every day is one possibility. For the 16 and 20-hour fasts, this means forgetting breakfast and perhaps delaying lunch. (Don't worry -- medical research has totally destroyed the idea that breakfast is the most important meal of the day.) Some see the 16-hour fast as a stepping stone to the 20-hour fast. With the 20-hour fast, you will then do all of your eating during a four-hour window every day. Another approach is to eat normally five days a week but to only consume 500 calories each of two days per week. For example, you might eat normally on Sunday, Tuesday, Wednesday, Friday and Saturday, but eat only 500 calories of food on Monday and Thursday. Sound hard? People I know who do this tell me that it gets easy after a couple of weeks.
But what’s this about? An article appeared in the December 2019 issue of The New England Journal of Medicine that described intermittent fasting and what is being learned about it. The article was entitled “Effects of Intermittent Fasting on Health, Aging, and Disease.” It says that the practice of intermittent fasting improves glucose regulation, increases resistance to oxidative and metabolic stress, and suppresses inflammation. Inflammation and oxidation are major factors in the development of Alzheimer’s disease. Fasting elicits these effects as responses from cells in the body.
Intermittent fasting shares some traits with the increasingly popular (fad?) keto diet, about which I have no comment. Both strategies lead to a condition called ketosis. The article notes that glucose and fatty acids are the main sources of energy for the cells. It goes on to say that, after meals, glucose is used for energy, and fat is stored as triglycerides. During fasting, triglycerides are broken down to fatty acids and glycerol. The liver converts fatty acids to “ketone bodies,” which, in the absence of glucose, provide a major source of energy for many tissues, especially the brain. This is ketosis. The ketone bodies also give you bad breath.
In the keto diet (if faithfully adhered to—a challenge), the body remains in ketosis. However, during intermittent fasting, the body undergoes “metabolic switching” in which the body shifts in and out of ketosis. It shifts back and forth between relying on glucose and fat for energy.
What are the benefits of being in ketosis? According to the article, ketone bodies serve not only as fuel for the cells, but they also signal cells and organs to perform a variety of functions involved in health and aging. Earlier theories about fasting focused on restricting calories for weight loss, but recent research points to a whole suite of other positive effects from not eating. The article discussed positive effects for obesity and diabetes, cardiovascular disease, cancer, neurodegenerative disorders (like Alzheimer’s disease), asthma, multiple sclerosis, arthritis, and healing from traumatic injury.
Too good to be true? I don’t know, but the 12-hour fast has been part of my regimen from the beginning. I am currently experimenting with more aggressive fasts, and the research seems compelling.
Wednesday, January 15, 2020
Aaaak!
The original version of the post "Looking back, looking ahead" was loaded with editorial errors. Some of them confused points in the post. I've corrected them. Sorry about that.
Looking back, looking ahead
This week's issue of the ALZForum carried a long but very interesting article on the state of affairs in Alzheimer's research. It reviewed important things that happened during 2019 with implications for what's ahead in 2020. A few highlights:
- In the United States, government funding for Alzheimer's research was increased to $2.8 billion. This is close to what the National Institute of Health believes is required to find an effective cure for the disease. (The US is spending more than any other country on Alzheimer's research, but someone at a conference I attended said that China is #2. I haven't been able to corroborate that because information on Alzheimer's funding internationally seems to be pretty scant.)
- The article reviewed the aducanumab drama. Excitement around aducanumab raised hope that it and several other drugs will clean the brain of amyloid plaques and in so doing may improve cognition and slow the progress of Alzheimer's disease -- if administered in large enough doses. Will the FDA approve it? Do we really understand how well it works? What additional trials will be required? Stay tuned.
- The article sought to dispel the common belief that Alzheimer's research is focused on the amyloid hypothesis we discussed in Beating the Dementia Monster. The article listed several other strategies that researchers are pursuing. It thus emphasized the broad fronts in this war.
- The article discussed new insights in the role of genetics in identifying those susceptible to Alzheimer's disease. When we think of the role of genetics in the disease pathology, we first look for genes, like Apoe4, that can be directly linked and implicated. But there is a whole host of other genes for which Alzheimer's may be a secondary consequence. For example, genes that predispose to heart disease or diabetes can indirectly lead to Alzheimer's disease through these other diseases. Researchers are finding ways to more accurately profile someone's risk by analyzing a person's whole genome.
- The relationship between beta amyloid and pathological tau protein was clarified. For a long time it was thought that an important cause of cognitive impairment was amyloid plaques interfering with the flow on information between neurons. However, after several years of steady buildup of the plaques, there is a sudden explosion of amyloid which appears to prompt the appearance of the famous tau tangles. It is now thought that it may be the tau tangles that are impairing cognition.
- Microglia got a lot of attention this year. The brain exists largely outside the body's immune system, so microglia are the brain's own immune system. One idea pursued this year and into 2020 is that a role of properly functioning microglia is to rid the brain of both amyloid plaques and tau tangles. So some kind of failure of the microglia may be part of the Alzheimer's pathology.
- There was a lot of progress in finding new biomarkers for Alzheimer's disease, such as by using blood tests. We discussed this several times, including September 2018 and February 2019. These blood tests measured traces of amyloid in the blood, but new research last year explored blood tests for pathologic tau protein. This might give evidence of Alzheimer's disease well before there's any evidence amyloid.
- There were some breakthroughs in brain imaging in which PET scans could more clearly identify buildup of tau protein and beta amyloid -- and distinguish between them.
- There was new interest in the role that infection might play in the genesis of Alzheimer's disease, notably with the herpes virus. We discussed this in June 2018.
- Exercise. Yes, the idea that vigorous physical exercise protects against and treats Alzheimer's disease got new momentum.
- As we discussed in November 2019, there is a new understanding developing about the role of sleep, especially deep sleep, in Alzheimer's disease. Apparently the type of brain waves seen in deep sleep can cause rhythmic pulses in the brain that prompt the movement of cerebrospinal fluid (CSF). The movement of the CSF likely sweeps beta amyloid and tau tangles out of the brain. This may be why poor sleep plays a prominent role in Alzheimer's pathology.
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