There has long been some thought that air pollution can contribute to or even cause Alzheimer's disease. You may have read that the pandemic shutdown has led to observable decreases in the concentration of airborne pollutants, and some researchers who otherwise might have been in their laboratories have been spending time at home reviewing the topic. And so, on May 22, the ALZForum published a two-part review which surveyed some of what we have learned.
To summarize, there is evidence of a link between air pollution and the accumulation of beta amyloid and other effects we associate with Alzheimer's disease. For example, people living near freeways are more likely to develop Alzheimer's disease, although early studies did not control for confounding factors. The culprits would be oxides of nitrogen and airborne particulates.
The oxides of nitrogen can enter the bloodstream through the lungs and cause damage to the cardiovascular system. What's bad for the heart is bad for the brain, and so we have discussed previously various connections between damage to blood vessels and damage to the hippocampus and other regions of the brain. We said this is especially a problem when the blood-brain barrier of the blood vessels is damaged, and the brain loses some protections.
Particulates, on the other hand, can enter the brain via the nose and the olfactory nerve. This is the same pathway they used to get insulin into my brain for the SNIFF study. You will recall from Beating the Dementia Monster that I was a study participant, although I was on the placebo. (The study failed to find that artificially manipulating the concentration of insulin in the brain could improve cognition.)
Depending on the results of studying the effects of air pollution on mice, researchers have constructed a hypothesis by which particulates enter the brain and activate the microglia. Since the blood-brain barrier prevents the entry of antibodies into the brain, the microglia serve to attack the invading particulate bodies in their place. But, just as with other infection, this attack involves inflammation, which gets out of control. And inflammation plays an important role in the development of Alzheimer's disease. There is then a cascade of events that lead to oxidative stress (so eat your blueberries!) and the accumulation of beta amyloid on the cells. This all results in cell death and atrophy of the brain.
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.
Thursday, May 28, 2020
Friday, May 22, 2020
Sleep Fragmentation and Alzheimer's Risk
I can no longer get a good night's sleep. My sleep doctor tells me that 7 hours is a good night for me, but getting to 7 hours has proven nearly impossible. I normally go to bed at 10, but awaken most nights at about 3. After laying in bed for a while I'll get up and do something for an hour or two, and then go back to bed. I can usually get enough total sleep time to get to that 7 hour threshold, but, from the standpoint of brain health, is that just as good as sleeping straight through? I wonder about that a lot.
In July 2018 we posted about why sleep is important in Alzheimer's disease prevention and treatment. One of the things we noted was that, in deep sleep, the brain cells shrink, causing circulation of cerebrospinal fluid (CSF). This allows the CSF to deliver the beta amyloid waste to the lymphatic system for removal from the brain. Accumulation of amyloid plaques in the brain is part of the Alzheimer's disease process, so removal is important. Varying levels of beta amyloid in the CSF are reflected in varying levels of beta amyloid in the blood.
The sleep cycle is generally about 90 minutes, and the cycle repeats throughout the night. Deep sleep is only one phase of the cycle, and it begins well into a new cycle. It is during deep sleep that researchers can measure falling concentrations of beta amyloid in mice and in humans. And so getting a good night's sleep, with plenty of deep sleep, is important to brain health.
The question that's been on my mind is, if I wake up repeatedly during the night but still get seven hours, is that as good as sleeping seven hours straight?
Probably not. There was some interesting research reported in the May 2020 issue of the journal Alzheimer's and Dementia that addressed this. The article was titled "The overnight reduction of amyloid β 1‐42 plasma levels is diminished by the extent of sleep fragmentation, sAPP‐β, and APOE ε4 in psychiatrists on call." Conclusion: sleep fragmentation diminishes the reduction of beta amyloid levels overnight, so fragmented sleep is probably not as good as uninterrupted sleep.
The research was interesting. The researchers studied psychiatrists in a hospital in Germany that were on call and thus experienced fairly frequent interruptions in their sleep. Blood samples were taken from subjects at the beginning and end of their shifts so that change in amyloid levels could be determined. This was then correlated with sleep interruptions. There were 17 participants, and they were studied over a total of 90 nights. Participants kept a log of sleep interruptions, but they also wore instruments to detect motion and corroborate their record. The subjects were sleeping at the hospital and not at home, and so researchers made an effort to control for varying sources of stress that could confound their results.
So what does this mean for me? One more thing to worry about. My neurologist believes that sleep is likely my biggest challenge in dealing with my disease. Sleep needs vary between individuals, but all of the research I read suggests that I'm not getting enough. And I wonder if I can even get to an ideal amount of sleep regardless of what I do.
My cognition is to be tested at Harborview in about three weeks. I was not tested last year, but my subjective sense is that I experienced some unexpected decline then from which I rebounded. I further sense that I was doing better in the early part of 2020, but I have been declining again. This goes along with increased trouble with sleep.
But have I really been declining again? The upcoming testing should provide some clarity.
In July 2018 we posted about why sleep is important in Alzheimer's disease prevention and treatment. One of the things we noted was that, in deep sleep, the brain cells shrink, causing circulation of cerebrospinal fluid (CSF). This allows the CSF to deliver the beta amyloid waste to the lymphatic system for removal from the brain. Accumulation of amyloid plaques in the brain is part of the Alzheimer's disease process, so removal is important. Varying levels of beta amyloid in the CSF are reflected in varying levels of beta amyloid in the blood.
The sleep cycle is generally about 90 minutes, and the cycle repeats throughout the night. Deep sleep is only one phase of the cycle, and it begins well into a new cycle. It is during deep sleep that researchers can measure falling concentrations of beta amyloid in mice and in humans. And so getting a good night's sleep, with plenty of deep sleep, is important to brain health.
The question that's been on my mind is, if I wake up repeatedly during the night but still get seven hours, is that as good as sleeping seven hours straight?
Probably not. There was some interesting research reported in the May 2020 issue of the journal Alzheimer's and Dementia that addressed this. The article was titled "The overnight reduction of amyloid β 1‐42 plasma levels is diminished by the extent of sleep fragmentation, sAPP‐β, and APOE ε4 in psychiatrists on call." Conclusion: sleep fragmentation diminishes the reduction of beta amyloid levels overnight, so fragmented sleep is probably not as good as uninterrupted sleep.
The research was interesting. The researchers studied psychiatrists in a hospital in Germany that were on call and thus experienced fairly frequent interruptions in their sleep. Blood samples were taken from subjects at the beginning and end of their shifts so that change in amyloid levels could be determined. This was then correlated with sleep interruptions. There were 17 participants, and they were studied over a total of 90 nights. Participants kept a log of sleep interruptions, but they also wore instruments to detect motion and corroborate their record. The subjects were sleeping at the hospital and not at home, and so researchers made an effort to control for varying sources of stress that could confound their results.
So what does this mean for me? One more thing to worry about. My neurologist believes that sleep is likely my biggest challenge in dealing with my disease. Sleep needs vary between individuals, but all of the research I read suggests that I'm not getting enough. And I wonder if I can even get to an ideal amount of sleep regardless of what I do.
My cognition is to be tested at Harborview in about three weeks. I was not tested last year, but my subjective sense is that I experienced some unexpected decline then from which I rebounded. I further sense that I was doing better in the early part of 2020, but I have been declining again. This goes along with increased trouble with sleep.
But have I really been declining again? The upcoming testing should provide some clarity.
Saturday, May 16, 2020
A Covid-Related Death?
In September 2019, we posted regarding two friends living in elder care facilities. For reasons of privacy, I called them "Bill" and "Mike." In January 2020, I wrote that Bill had died. He was a WWII veteran who was usually quite lucid but occasionally hallucinated. He was almost 100.
Mike, on the other hand, was in a memory care facility where he lived largely in isolation. I visited him daily in the afternoon, and he was always happy to see me. But I know he didn't get out of his room much, and I believe he thought I was a different person each visit. His wife also visited him often, usually late in the morning. When I spoke with him, he could always tell me his first name but often could not recall his last name.
In January of this year we posted some observations (well, speculation) about people with neurodegenerative diseases living there in isolation. In the time that I had been visiting Mike he had not seemed to decline, although others around him did -- at least to my eye. I wondered if this wasn't a result of frequent visits and social interactions with his wife and me. In Beating the Dementia Monster we discussed the role of social interactions in slowing the progress of Alzheimer's disease.
Then came the Covid-19 lockdown, and I have not seen him since. On April 26, we posted about my concerns with respect to the impact of the lockdown's loneliness and isolation on people with Alzheimer's disease. I didn't say as much, but I worried that the lockdown might accelerate Mike's disease. I don't know if it did or not, but he died a few days ago.
Mike, on the other hand, was in a memory care facility where he lived largely in isolation. I visited him daily in the afternoon, and he was always happy to see me. But I know he didn't get out of his room much, and I believe he thought I was a different person each visit. His wife also visited him often, usually late in the morning. When I spoke with him, he could always tell me his first name but often could not recall his last name.
In January of this year we posted some observations (well, speculation) about people with neurodegenerative diseases living there in isolation. In the time that I had been visiting Mike he had not seemed to decline, although others around him did -- at least to my eye. I wondered if this wasn't a result of frequent visits and social interactions with his wife and me. In Beating the Dementia Monster we discussed the role of social interactions in slowing the progress of Alzheimer's disease.
Then came the Covid-19 lockdown, and I have not seen him since. On April 26, we posted about my concerns with respect to the impact of the lockdown's loneliness and isolation on people with Alzheimer's disease. I didn't say as much, but I worried that the lockdown might accelerate Mike's disease. I don't know if it did or not, but he died a few days ago.
ApoE4 and Dementia Without Alzheimer's Disease
The gene referred to as apolipoprotein E4 (ApoE4) is a recognized risk factor for Alzheimer's disease. If you carry this gene, it doesn't guarantee that you'll get Alzheimer's disease, but the odds are greater. Therefore, genetic testing companies like 23andMe and Ancestry.com will test for the #4 variant of ApoE. If they find that you carry this gene, the companies are required by law to explain to you that this does not guarantee you will get Alzheimer's disease, but they must recommend that you to seek counseling on your path forward.
So what does ApoE4 do that's so bad? About a year ago, we posted a list offenses, noting that each offense played its own role in a very complex disease.
Recall that, like all genes, ApoE4 is the design description for a protein. In this case, it's a protein that helps transport cholesterol through the blood. But what's wrong with variant #4? Two things we noted have come up again in recent research published in the journal Nature ("APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline"): promoting inflammation and damaging the blood-brain barrier. We have been discussing both of these in recent posts.
The more we learn about inflammation, the more we realize how pervasive its effects are on many of the body's maintenance mechanisms -- and on many diseases. But what I found interesting in the recent research linked above was how the ApoE4 protein is associated with damage to the blood-brain barrier -- most notably in the hippocampus and temporal regions.
We discussed the blood-brain barrier in the post on dietary salt. The blood-brain barrier is part of the brain's own immune system, and it blocks the entry of pathogens into the brain. Breakdown of the blood-brain barrier has been associated with Alzheimer's disease.
The research reported in Nature brought something new to the table. While a correlation between breakdown in the blood-brain barrier and Alzheimer's disease seems to be established, it may be that there can also be cognitive decline here without Alzheimer's disease.
In their study population, the researchers conducted brain scans for beta amyloid and abnormal tau proteins among subjects carrying the ApoE4 gene. (Beta amyloid plaques and accumulation of tau-related tangles are important biomarkers for Alzheimer's disease.) They identified those individuals who did not have Alzheimer's disease. Nevertheless, there were cases of cognitive decline in this population, suggesting that there are more ways in which this problem gene can cause dementia than just through Alzheimer's disease.
So what does ApoE4 do that's so bad? About a year ago, we posted a list offenses, noting that each offense played its own role in a very complex disease.
Recall that, like all genes, ApoE4 is the design description for a protein. In this case, it's a protein that helps transport cholesterol through the blood. But what's wrong with variant #4? Two things we noted have come up again in recent research published in the journal Nature ("APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline"): promoting inflammation and damaging the blood-brain barrier. We have been discussing both of these in recent posts.
The more we learn about inflammation, the more we realize how pervasive its effects are on many of the body's maintenance mechanisms -- and on many diseases. But what I found interesting in the recent research linked above was how the ApoE4 protein is associated with damage to the blood-brain barrier -- most notably in the hippocampus and temporal regions.
We discussed the blood-brain barrier in the post on dietary salt. The blood-brain barrier is part of the brain's own immune system, and it blocks the entry of pathogens into the brain. Breakdown of the blood-brain barrier has been associated with Alzheimer's disease.
The research reported in Nature brought something new to the table. While a correlation between breakdown in the blood-brain barrier and Alzheimer's disease seems to be established, it may be that there can also be cognitive decline here without Alzheimer's disease.
In their study population, the researchers conducted brain scans for beta amyloid and abnormal tau proteins among subjects carrying the ApoE4 gene. (Beta amyloid plaques and accumulation of tau-related tangles are important biomarkers for Alzheimer's disease.) They identified those individuals who did not have Alzheimer's disease. Nevertheless, there were cases of cognitive decline in this population, suggesting that there are more ways in which this problem gene can cause dementia than just through Alzheimer's disease.
Wednesday, May 13, 2020
Inflammation, Depression, and Alzheimer's Disease - A Deadly Triad
Inflammation is the body's response to just about any insult, from physical injury to infection. It exists to serve a protective function, but quickly begins causing serious damage of its own. In recent years, inflammation has been found to play a role in exacerbating just about anything that goes wrong in the human body, including in Alzheimer's disease. Therefore, an important dietary target for treating Alzheimer's disease is reduction of inflammatory foods, especially refined flour and refined sugar.
Recent research increasingly associates depression with inflammation, and, according to the Alzheimer's Association Facts and Figures Report, depression is an early symptom of Alzheimer's disease. As I wrote in Beating the Dementia Monster, one of my first symptoms was frequent, brief occurrences of mild depression. It's not surprising that we find inflammation, depression, and Alzheimer's disease together.
Professor Edward Bullmore chairs the department of psychiatry at Cambridge University and writes on the flood of new research on inflammation. In a recent article in The Guardian ("From Depression to Dementia, Inflammation is Medicine's New Frontier"), he discussed the link between autoimmune diseases, neurological diseases, and inflammation.
In our recent post on salt and dementia, we discussed the blood-brain barrier and the immune system in the brain that is separate from the immune system protecting the rest of the body. Professor Bullmore contends medical science is learning that the the two immune systems communicate with each other far more than we had believed. And so, inflammation plagues them both. He further believes that focusing research on inflammation will lead to breakthroughs in treatment of many other diseases, because inflammation is involved in so many of them.
In February 2019 we posted regarding a link between gum disease and the advent of Alzheimer's disease. Professor Bullmore sees an important link between gum disease and inflammation, and he believes inflammation is then the link from gum disease to Alzheimer's disease. He cites ongoing research that may lead to improvement in how we treat Alzheimer's disease by treating gum disease.
Recent research increasingly associates depression with inflammation, and, according to the Alzheimer's Association Facts and Figures Report, depression is an early symptom of Alzheimer's disease. As I wrote in Beating the Dementia Monster, one of my first symptoms was frequent, brief occurrences of mild depression. It's not surprising that we find inflammation, depression, and Alzheimer's disease together.
Professor Edward Bullmore chairs the department of psychiatry at Cambridge University and writes on the flood of new research on inflammation. In a recent article in The Guardian ("From Depression to Dementia, Inflammation is Medicine's New Frontier"), he discussed the link between autoimmune diseases, neurological diseases, and inflammation.
In our recent post on salt and dementia, we discussed the blood-brain barrier and the immune system in the brain that is separate from the immune system protecting the rest of the body. Professor Bullmore contends medical science is learning that the the two immune systems communicate with each other far more than we had believed. And so, inflammation plagues them both. He further believes that focusing research on inflammation will lead to breakthroughs in treatment of many other diseases, because inflammation is involved in so many of them.
In February 2019 we posted regarding a link between gum disease and the advent of Alzheimer's disease. Professor Bullmore sees an important link between gum disease and inflammation, and he believes inflammation is then the link from gum disease to Alzheimer's disease. He cites ongoing research that may lead to improvement in how we treat Alzheimer's disease by treating gum disease.
Saturday, May 9, 2020
Dietary Salt Causes Cognitive Impairment
For several years, researchers have been studying "the gut-brain axis." Essentially, there is a form of communication between gut microbes and the brain, and when things go wrong in the gut they can go wrong in the brain. Also, it's easy to make the case that excess salt intake will have a negative effect on cognition because it raises blood pressure. High blood pressure is bad for the heart and is a risk factor for Alzheimer's disease. What's good for the heart is good for the brain.
But a December 2018 article in Scientific American (reproduce here by Pocket) discussed a separate gut-brain axis involving salt but that does not involve blood pressure. The article's author cited research published in Nature Neuroscience about work with mice. It found "excess dietary salt suppresses resting cerebral blood flow and endothelial function, leading to cognitive impairment. The effect depends on [certain cells] in the small intestine." "Endothelial function" refers to the work of endothelial cells lining the blood vessels that control contraction and relaxation of the blood vessels, among other things. Its failure contributes to a number of bad consequences for both the heart and the brain.
The research with mice points to a pathway between the gut and the brain via the immune system. Then excessive intake of salt can impact the immune function in the small intestine with a negative effect reflected back to the brain. A very important consequence is that blood flow may be restricted to the hippocampus and the cortex -- ground zero for Alzheimer's disease.
Prior the research on salt, there was research studying other contributions that issues in the gut can make to Alzheimer's disease. One idea is that microbes may leak from the gut when the spectrum of gut microbes is disturbed. The leaked microbes can promote inflammation throughout the body, including in the brain. Inflammation in the brain plays a role in Alzheimer's disease.
The inflammation can cause impairment of the blood-brain barrier. The blood-brain barrier protects the brain from pathogens by only allowing small molecules and ions to pass in and out of the blood vessels in the brain. This is another work of the endothelial cells lining the blood vessels in the brain. (Special proteins regulate the passage of certain specific molecule that must pass in and out.) Some studies suggest that impairment of the blood-brain barrier allows beta amyloid molecules to enter the bloodstream and then be more widely distributed in the brain, thus propagating Alzheimer's disease.
Speaking for myself, I have always had fairly low blood pressure. During periods when it seems too low my cardiologist suggested raising my intake of salt. Maybe that's good advice, but I'm wondering what it means for neurodegeneration in light of this research.
But a December 2018 article in Scientific American (reproduce here by Pocket) discussed a separate gut-brain axis involving salt but that does not involve blood pressure. The article's author cited research published in Nature Neuroscience about work with mice. It found "excess dietary salt suppresses resting cerebral blood flow and endothelial function, leading to cognitive impairment. The effect depends on [certain cells] in the small intestine." "Endothelial function" refers to the work of endothelial cells lining the blood vessels that control contraction and relaxation of the blood vessels, among other things. Its failure contributes to a number of bad consequences for both the heart and the brain.
The research with mice points to a pathway between the gut and the brain via the immune system. Then excessive intake of salt can impact the immune function in the small intestine with a negative effect reflected back to the brain. A very important consequence is that blood flow may be restricted to the hippocampus and the cortex -- ground zero for Alzheimer's disease.
Prior the research on salt, there was research studying other contributions that issues in the gut can make to Alzheimer's disease. One idea is that microbes may leak from the gut when the spectrum of gut microbes is disturbed. The leaked microbes can promote inflammation throughout the body, including in the brain. Inflammation in the brain plays a role in Alzheimer's disease.
The inflammation can cause impairment of the blood-brain barrier. The blood-brain barrier protects the brain from pathogens by only allowing small molecules and ions to pass in and out of the blood vessels in the brain. This is another work of the endothelial cells lining the blood vessels in the brain. (Special proteins regulate the passage of certain specific molecule that must pass in and out.) Some studies suggest that impairment of the blood-brain barrier allows beta amyloid molecules to enter the bloodstream and then be more widely distributed in the brain, thus propagating Alzheimer's disease.
Speaking for myself, I have always had fairly low blood pressure. During periods when it seems too low my cardiologist suggested raising my intake of salt. Maybe that's good advice, but I'm wondering what it means for neurodegeneration in light of this research.
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