We know that controlling risk factors for type 2 diabetes reduces the risk for Alzheimer's disease, but why? Some interesting research from South Korea may provide new insight. The research was described in a recent article in the ALZForum, "Stress-Associated Protein Modulates γ-Secretase to Make More Aβ." What's that about?
In order to advance from the 10th to the 11th grade in Washington State public schools, you're required to know that the endoplasmic reticulum (ER) is a component part of most cells in the body, and it synthesizes lipids and cholesterol. The ER is an organelle (sort of like an organ of the cell) and is a structure made up of various proteins. This is one piece of the puzzle.
In diabetes there is excess glucose running around in the blood stream. The excess glucose is destructive and causes a form of stress for the cells. Another piece of the puzzle.
Beta amyloid is a malformed protein that is characteristic of Alzheimer's disease. It is formed when the "amyloid precursor protein" (APP) is cut by, among other things, the γ-secretase protein. (No one knows what the purpose of APP is, but it sure plays a big role when things go bad in the brain.) Apparently, changes in γ-secretase activity can vary the production of beta amyloid by doing more APP cutting. This implies that varying the amount of γ-secretase can affect the advance of Alzheimer's disease. Still another piece of the puzzle.
There is a protein called "the stress-associated ER protein 1" (SERP1) located on the surface of the ER. It promotes γ-secretase activity which results in more APP cutting and, therefore, more beta amyloid generation. Another puzzle piece.
SERP1 responds to stress from excess glucose -- a condition occurring in diabetes -- and prompts the generation of more γ-secretase and therefore more APP cutting and the generation of more beta amyloid. And so the excess blood glucose in diabetes can promote Alzheimer's disease. (This may be a serious over-simplification, but I think it's a reasonable overview.)
Well, anyway, that's the hypothesis. So how can this hypothesis be tested -- as we must inevitably do? For this, the researchers did a number of things, but one was to review the autopsy findings of normal brains and people who died with Alzheimer's disease. One finding was that the hippocampi in diseased brains contained ten times the SERP1 as in the normal brains. This was one of several confirmatory research findings.
The completed puzzle: Excess glucose in diabetes causes cellular stress. The stress stimulates the SERP1 protein, which encourages γ-secretase activity. γ-secretase activity results in more APP cutting and the generation of more beta amyloid. More beta amyloid means that Alzheimer's disease progresses.
The bottom line? Control your risk factors for type 2 diabetes! Eat right and get plenty of exercise! (Of course, you must always manage any type of diabetes in accordance with your physician's direction.)
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, March 26, 2020
Monday, March 23, 2020
For Primary Care Physicians: The Coming Tsunami of Dementia Cases
According to the 2020 Alzheimer's Association Facts and Figures Report, the number of Americans living with Alzheimer's disease will triple by 2050. How prepared are our primary care physicians to diagnose and manage a deluge of future cases? A survey of 1,000 primary care physicians found that three quarters said they had received little or no residency training in dementia, even though they regularly cared for patients with dementia. Half believed that their profession would be unable to meet future demands for care. So said an article in this week's ALZForum that echoed a report in the Facts and Figures Report.
Digging a little deeper in the survey, the researchers found that thirty-nine percent were uncomfortable making a diagnosis of dementia, and 27 percent were uncomfortable answering questions about dementia. Thirty-seven percent said most of their training comes from learning on the job while treating dementia patients.
The report drives toward a conclusion that this is inadequate, but what should be done? Increased federal funding for medical education programs to boost enrollment, forgiving federal and state education loans to inspire more doctors to choose primary care in rural areas, and training nurse practitioners in dementia care were suggested.
Digging a little deeper in the survey, the researchers found that thirty-nine percent were uncomfortable making a diagnosis of dementia, and 27 percent were uncomfortable answering questions about dementia. Thirty-seven percent said most of their training comes from learning on the job while treating dementia patients.
The report drives toward a conclusion that this is inadequate, but what should be done? Increased federal funding for medical education programs to boost enrollment, forgiving federal and state education loans to inspire more doctors to choose primary care in rural areas, and training nurse practitioners in dementia care were suggested.
Wednesday, March 18, 2020
The Alzheimer's Association Facts and Figures Report for 2020 Is Now Out
I'm hoping that all of our readers are well, both physically and emotionally. These are difficult times, but we will persevere.
Each March I wait for publication of the Alzheimer's Association annual Facts and Figures Report. (I wrote about last year's report here.) This is my first go-to resource, and I cite it often in both editions of Beating the Dementia Monster. So they have now published the 2020 edition, and I have downloaded it. The report updates the statistics on the disease each year, but it also explains and updates what research is telling us about the disease. This year adds another increment to our understanding.
We covered most of what's new and (to me, at least) interesting in our regular blog posts since last March. As the news comes out, I try to write about it promptly.
One thing that struck me was their inclusion of a graphic in this year's report showing the progress of Alzheimer's disease from the pre-clinical stage through the third stage of Alzheimer's dementia. I made a similar graphic here, and I use it in presentations and in the (still forthcoming) second edition of Beating the Dementia Monster. In my presentations and in the book's discussion I break down Alzheimer's disease into its five stages (pre-clinical AD, MCI, mild dementia, moderate dementia, and severe dementia), but in my graphic I only show Alzheimer's dementia as a single, final stage of the disease -- so three stages. Their graphic breaks dementia down into its three stages, so their graphic shows five total stages of the disease (pre-clinical, MCI, and the three individual stages of dementia). Theirs may be more helpful.
Something that caught my attention was a discussion of the importance of an accurate diagnosis of the cause of a dementia case. Alzheimer's disease is responsible for 60 to 80 percent of dementia cases, but there are other causes, and their treatments will vary. This contradicts the too-common practice of diagnosing Alzheimer's disease purely on the basis of a single Mini-Mental Status Exam or a Montreal Cognitive Assessment. At Harborview in Seattle, they subjected me to a couple of hours of psychometric testing and a brain MRI. I've also had blood tests looking for vitamin deficiencies and other potential causes of my MCI. These are required for an accurate diagnosis and an appropriate course of treatment.
Something else they highlighted was a research finding that people who are concerned enough about deteriorating cognition to consult a heath professional often do have Alzheimer's disease or another cause of dementia. Everyone over about 60 begins to worry if they have Alzheimer's disease, but if they're not worried enough to see a medical professional about it, it's likely they are simply experiencing the result of normal aging.
They continue to promote annual screening for neurodegenerative disease, emphasizing that it's part of Medicare for everyone over 65. But doctors say they're too busy to do it, and a lot of their patients tell them they don't want to know if they have Alzheimer's disease. So we continue to not test enough. On the other hand, they (like us) noted that we are close to a very sensitive blood test for Alzheimer's disease, and I'd bet these tests will become routine soon enough for everyone over 65.
They have re-worded the discussion of the role of lifestyle changes in addressing Alzheimer's disease, but I didn't see anything new. The role of lifestyle changes is, of course, the thesis of Beating the Dementia Monster.
They simplified their discussion of brain changes over what they had last year, notably the roles of beta amyloid and tau tangles. I think it's helpful to read both of them -- this year's and last year's. The two articles overlap a lot, but each seems to have insight missing from the other.
They didn't focus quite so much this year on what to expect in the future, but their discussion is no less bleak than last year's.
If you're nerdy, you'll want to read the first three chapters, but we covered most of the material here our blog over the past 12 months. If your focus is on caregiving and the consequences of dementia, you'll want to read chapters four through six.
Each March I wait for publication of the Alzheimer's Association annual Facts and Figures Report. (I wrote about last year's report here.) This is my first go-to resource, and I cite it often in both editions of Beating the Dementia Monster. So they have now published the 2020 edition, and I have downloaded it. The report updates the statistics on the disease each year, but it also explains and updates what research is telling us about the disease. This year adds another increment to our understanding.
We covered most of what's new and (to me, at least) interesting in our regular blog posts since last March. As the news comes out, I try to write about it promptly.
One thing that struck me was their inclusion of a graphic in this year's report showing the progress of Alzheimer's disease from the pre-clinical stage through the third stage of Alzheimer's dementia. I made a similar graphic here, and I use it in presentations and in the (still forthcoming) second edition of Beating the Dementia Monster. In my presentations and in the book's discussion I break down Alzheimer's disease into its five stages (pre-clinical AD, MCI, mild dementia, moderate dementia, and severe dementia), but in my graphic I only show Alzheimer's dementia as a single, final stage of the disease -- so three stages. Their graphic breaks dementia down into its three stages, so their graphic shows five total stages of the disease (pre-clinical, MCI, and the three individual stages of dementia). Theirs may be more helpful.
Something that caught my attention was a discussion of the importance of an accurate diagnosis of the cause of a dementia case. Alzheimer's disease is responsible for 60 to 80 percent of dementia cases, but there are other causes, and their treatments will vary. This contradicts the too-common practice of diagnosing Alzheimer's disease purely on the basis of a single Mini-Mental Status Exam or a Montreal Cognitive Assessment. At Harborview in Seattle, they subjected me to a couple of hours of psychometric testing and a brain MRI. I've also had blood tests looking for vitamin deficiencies and other potential causes of my MCI. These are required for an accurate diagnosis and an appropriate course of treatment.
Something else they highlighted was a research finding that people who are concerned enough about deteriorating cognition to consult a heath professional often do have Alzheimer's disease or another cause of dementia. Everyone over about 60 begins to worry if they have Alzheimer's disease, but if they're not worried enough to see a medical professional about it, it's likely they are simply experiencing the result of normal aging.
They continue to promote annual screening for neurodegenerative disease, emphasizing that it's part of Medicare for everyone over 65. But doctors say they're too busy to do it, and a lot of their patients tell them they don't want to know if they have Alzheimer's disease. So we continue to not test enough. On the other hand, they (like us) noted that we are close to a very sensitive blood test for Alzheimer's disease, and I'd bet these tests will become routine soon enough for everyone over 65.
They have re-worded the discussion of the role of lifestyle changes in addressing Alzheimer's disease, but I didn't see anything new. The role of lifestyle changes is, of course, the thesis of Beating the Dementia Monster.
They simplified their discussion of brain changes over what they had last year, notably the roles of beta amyloid and tau tangles. I think it's helpful to read both of them -- this year's and last year's. The two articles overlap a lot, but each seems to have insight missing from the other.
They didn't focus quite so much this year on what to expect in the future, but their discussion is no less bleak than last year's.
If you're nerdy, you'll want to read the first three chapters, but we covered most of the material here our blog over the past 12 months. If your focus is on caregiving and the consequences of dementia, you'll want to read chapters four through six.
Monday, March 16, 2020
Are Different Personality Types More or Less Susceptible to Alzheimer's Disease?
An article in StudyFinds.org reported on some research at the University of Geneva, Switzerland on the relationship between personality and susceptibility to Alzheimer's disease. The researchers claim to have found that stubborn and argumentative people are less likely to develop Alzheimer's disease. My wife's question is, "Well, what happened to you?" (Maybe she never really said that, but she'd be justified if she did.)
The research was reported in the journal Neurology of Aging, and involved 65 subjects, 65 years of age and older. The research investigated whether there was a relationship between personality profiles and brain integrity in old age. The hypothesis was that brain structure might be involved in personality, and characteristics of varying brain structures might influence the advent and progress of Alzheimer's disease.
For slicing and dicing personality types, the researchers turned to the Big 5 model. (Nothing to do with the sporting goods chain.) The Big 5 model has largely displaced the Myers-Briggs type indicators as a tool for understanding (or misunderstanding) personality distinctions. The Big 5 personality traits are:
The researchers measured the volumes of the parts of the brain known to be affected by Alzheimer's disease at the beginning of the study and after 54 months. They conducted neuropsychological assessments at those times, but also at the 18-month mark. Results were evaluated in the context of the personality traits displayed by the test subjects.
This is similar to the testing I underwent for the insulin trial we discussed in Beating the Dementia Monster. In that case, my brain volumes were measured by MRI at the outset of the study and again at 18 months. I had neuropsychological assessment quarterly for 18 months.
So what did the new study find?
The research was reported in the journal Neurology of Aging, and involved 65 subjects, 65 years of age and older. The research investigated whether there was a relationship between personality profiles and brain integrity in old age. The hypothesis was that brain structure might be involved in personality, and characteristics of varying brain structures might influence the advent and progress of Alzheimer's disease.
For slicing and dicing personality types, the researchers turned to the Big 5 model. (Nothing to do with the sporting goods chain.) The Big 5 model has largely displaced the Myers-Briggs type indicators as a tool for understanding (or misunderstanding) personality distinctions. The Big 5 personality traits are:
- Openness to experience (inventive/curious vs. consistent/cautious)
- Conscientiousness (efficient/organized vs. easy-going/careless)
- Extraversion (outgoing/energetic vs. solitary/reserved)
- Agreeableness (friendly/compassionate vs. challenging/detached)
- Neuroticism (sensitive/nervous vs. secure/confident)
The researchers measured the volumes of the parts of the brain known to be affected by Alzheimer's disease at the beginning of the study and after 54 months. They conducted neuropsychological assessments at those times, but also at the 18-month mark. Results were evaluated in the context of the personality traits displayed by the test subjects.
This is similar to the testing I underwent for the insulin trial we discussed in Beating the Dementia Monster. In that case, my brain volumes were measured by MRI at the outset of the study and again at 18 months. I had neuropsychological assessment quarterly for 18 months.
So what did the new study find?
- Lower agreeableness is associated with better preservation of limbic areas. (Or could we call that higher disagreeableness?) The limbic system includes the hippocampus and is critical to emotions and the formation of memories, among other things.
- Personality impact on brain volume is independent of beta amyloid and presence of the APOE4 gene often associated with a higher risk of developing Alzheimer's disease.
Thursday, March 12, 2020
The Coronavirus Cancels My Trip
I was planning to travel to Washington DC next week to meet with our senators and congresspeople (likely staffers) to discuss funding for Alzheimer's research. I had my plane tickets and plans for visiting my Mom and other family members who live there. The meeting was sponsored by the Alzheimer's Association, where I've been doing volunteer work.
Not surprisingly, the meeting was cancelled due to the coronavirus outbreak. In fact, one of Maria Cantwell's staffers was found to be infected -- maybe someone that I'd have met with. I was already wondering who would listen to a request for increased funding for Alzheimer's research when there is so much need for coronavirus research. At first I was thinking to go anyway and make a few visits, but our sense of concern over the virus has escalated radically, and I decided that going would not be wise.
On another note, my Mom's reaction to our post of March 10 on THC and Alzheimer's disease was "Yippee!" I read my post again on March 11, and I wondered what I'd been smoking when I wrote it. Hopefully I've fixed the editorial problems...
Not surprisingly, the meeting was cancelled due to the coronavirus outbreak. In fact, one of Maria Cantwell's staffers was found to be infected -- maybe someone that I'd have met with. I was already wondering who would listen to a request for increased funding for Alzheimer's research when there is so much need for coronavirus research. At first I was thinking to go anyway and make a few visits, but our sense of concern over the virus has escalated radically, and I decided that going would not be wise.
On another note, my Mom's reaction to our post of March 10 on THC and Alzheimer's disease was "Yippee!" I read my post again on March 11, and I wondered what I'd been smoking when I wrote it. Hopefully I've fixed the editorial problems...
Tuesday, March 10, 2020
How about weed for Alzheimer's disease?
A few months ago during Q&A after a talk, someone asked me whether marijuana might be good for treating Alzheimer's disease. The question caught me cold, and I didn't go research what the person might have been talking about. The person asking the question seemed to be disappointed that I didn't have much of an answer for her. I had seen and heard nothing about this, and I probably didn't take the question seriously.
Then, two weeks ago, I got an email from my sister (the one who asked if I was following the research on intermittent fasting) asking me if I was following the research on THC as a treatment for Alzheimer's disease. Well ... no, I wasn't. So she sent me a link to this article in Discover magazine (and some others). It was very interesting.
I think everyone reading this knows that THC is the active ingredient in marijuana.
The first thing to note is that all of the research discussed in the article was done with mice. No people. So how transferable are the results? I suppose we'll need to wait for actual human tests to know for sure. But here's the upshot of what happened with the mice.
It's well established that long-term exposure to THC has a bad effect on the parts of the brain involved with memory. And so it was with the mice... at least the young ones. But the older mice? Exposure to THC seemed to actually improve the cognition of certain older mice.
The key to understanding what's going on are the "CB1" receptors on brain cells. According to the article, these receptors are activated by THC molecules, and that leads to humans feeling stoned. But there are CB1 receptors distributed throughout the brain, and their activation in some locations apparently leads to other results.
Some German research discussed in the article used mice whose genome -- their DNA -- had been edited to omit the CB1 receptors. These are called "knockout mice," since some of their genes have been "knocked out" of their DNA. The mice would be born without the CB1 receptors. These mice, it turns out, were "dumber" than mice with normal receptors. They went into cognitive decline when they were about 35 in mouse years.
But a mystery emerged. Scientists in Brussels doing similar experiments found that their knockout mice were smarter than normal. What was the difference? The mice tested in Brussels were tested when they were teenagers -- in mouse years. So elimination of the CB1 receptors only negatively affected the cognition of the older mice. Therefore, it may be that stimulating the CB1 receptors with THC in older mice might impede cognitive decline. This is a great topic for future research.
Does this have implications for Alzheimer's disease? Or, if it turns out to be helpful for humans, would any benefit be restricted to memory loss from normal aging? More research is required. Currently, Europe seems to be where the most interest lies, but the article cites some regulatory hurdles there for work with marijuana.
American drug companies seem to be disinterested, perhaps because this may all flow from a drug that anyone can grow themselves. Not only that, drug trials have had trouble recruiting test subjects when they fear they could end up with the placebo. And my thought -- wouldn't any test subject perceive pretty quickly that they were or were not on the placebo?
Then, two weeks ago, I got an email from my sister (the one who asked if I was following the research on intermittent fasting) asking me if I was following the research on THC as a treatment for Alzheimer's disease. Well ... no, I wasn't. So she sent me a link to this article in Discover magazine (and some others). It was very interesting.
I think everyone reading this knows that THC is the active ingredient in marijuana.
The first thing to note is that all of the research discussed in the article was done with mice. No people. So how transferable are the results? I suppose we'll need to wait for actual human tests to know for sure. But here's the upshot of what happened with the mice.
It's well established that long-term exposure to THC has a bad effect on the parts of the brain involved with memory. And so it was with the mice... at least the young ones. But the older mice? Exposure to THC seemed to actually improve the cognition of certain older mice.
The key to understanding what's going on are the "CB1" receptors on brain cells. According to the article, these receptors are activated by THC molecules, and that leads to humans feeling stoned. But there are CB1 receptors distributed throughout the brain, and their activation in some locations apparently leads to other results.
Some German research discussed in the article used mice whose genome -- their DNA -- had been edited to omit the CB1 receptors. These are called "knockout mice," since some of their genes have been "knocked out" of their DNA. The mice would be born without the CB1 receptors. These mice, it turns out, were "dumber" than mice with normal receptors. They went into cognitive decline when they were about 35 in mouse years.
But a mystery emerged. Scientists in Brussels doing similar experiments found that their knockout mice were smarter than normal. What was the difference? The mice tested in Brussels were tested when they were teenagers -- in mouse years. So elimination of the CB1 receptors only negatively affected the cognition of the older mice. Therefore, it may be that stimulating the CB1 receptors with THC in older mice might impede cognitive decline. This is a great topic for future research.
Does this have implications for Alzheimer's disease? Or, if it turns out to be helpful for humans, would any benefit be restricted to memory loss from normal aging? More research is required. Currently, Europe seems to be where the most interest lies, but the article cites some regulatory hurdles there for work with marijuana.
American drug companies seem to be disinterested, perhaps because this may all flow from a drug that anyone can grow themselves. Not only that, drug trials have had trouble recruiting test subjects when they fear they could end up with the placebo. And my thought -- wouldn't any test subject perceive pretty quickly that they were or were not on the placebo?
Saturday, March 7, 2020
NOVA on Sleep
My friend Mike in Richmond, VA flagged for me a PBS NOVA episode on the importance of sleep. He brought it to my attention because they spent time discussing the role of sleep in both fighting and aggravating Alzheimer's disease. So I looked the episode up and found that it was the perfect length for one run on the treadmill at the gym.
I was well rewarded for the time I spent watching it. I had recently updated my video on sleep posted on my YouTube channel, and I covered what I believe are the main takeaways from the NOVA presentation with respect to Alzheimer's disease. But you will see that NOVA's production quality is a lot better than mine. (I'm still learning, and I need a better studio.)
I have been sleeping better recently, and I feel (a dangerous word) that my cognition is doing better. I don't know if it's cause and effect, coincidence, or the power of suggestion, but an improvement in sleep coincided with doing intermittent fasting for four or five weeks.
On the other hand, I did experience some improvement in sleep last fall. This coincided with the longer nights we have here in the Pacific Northwest in the fall and winter. After moving here from Hawaii, I have always slept better in those seasons, and it was April of last year when I seemed to lose ground on cognition. April is the month when the suddenly longer days have always hit me.
The one day of the year I hate the most is when we start Daylight Saving Time, and that's tonight. The governor said he was going to get rid of it in Washington, but he hasn't kept his promise. (Or rather, he was going to put us on permanent DST.) Statistically, we have a national jump in heart attacks and car accidents on that day, when we lose that hour of sleep. I wonder what they would find if they measured everyone's cognition on that day.
I was well rewarded for the time I spent watching it. I had recently updated my video on sleep posted on my YouTube channel, and I covered what I believe are the main takeaways from the NOVA presentation with respect to Alzheimer's disease. But you will see that NOVA's production quality is a lot better than mine. (I'm still learning, and I need a better studio.)
I have been sleeping better recently, and I feel (a dangerous word) that my cognition is doing better. I don't know if it's cause and effect, coincidence, or the power of suggestion, but an improvement in sleep coincided with doing intermittent fasting for four or five weeks.
On the other hand, I did experience some improvement in sleep last fall. This coincided with the longer nights we have here in the Pacific Northwest in the fall and winter. After moving here from Hawaii, I have always slept better in those seasons, and it was April of last year when I seemed to lose ground on cognition. April is the month when the suddenly longer days have always hit me.
The one day of the year I hate the most is when we start Daylight Saving Time, and that's tonight. The governor said he was going to get rid of it in Washington, but he hasn't kept his promise. (Or rather, he was going to put us on permanent DST.) Statistically, we have a national jump in heart attacks and car accidents on that day, when we lose that hour of sleep. I wonder what they would find if they measured everyone's cognition on that day.
Wednesday, March 4, 2020
News for Nerds -- New Insights from PET Scans
The science of using positron emission tomography (PET) scans to study how Alzheimer's disease progresses is advancing. In my case, they used MRIs to produce images showing the progressive atrophy of my brain, but PET scans can show a lot more about what's actually going on in different cases. My doctors would have wanted to do a PET scan, but it would not have led to any change in my treatment, and the cost couldn't be justified. PET scans are more expensive than MRIs and would only yield interesting information of no practical value. PET scans are, of course, used extensively in research on Alzheimer's disease.
In a PET scan, the subject is injected with a dye (tracer) containing atoms that radioactively emit positrons -- anti-matter electrons. The anti-matter electrons quickly find regular electrons with which they undergo "annihilation." (The physics teacher in me can't resist...) This is where E=mc^2 comes in. Both particles are converted to pure energy in the form of gamma rays following Albert Einstein's famous formula.
Instruments around the brain measure these gamma rays and can map where the dye is accumulating. The tracer can be formulated to accumulate in amyloid plaques or in the tau tangles. These are characteristic of Alzheimer's disease, although they could result from other causes at lower quantities. An important way that PET scans are used is to see how and where glucose is being used in the brain. Changes in how glucose is used in the brain may indicate Alzheimer's disease.
Each case of Alzheimer's disease unfolds a little differently, and PET scans can be used to examine how the brain is being affected in different cases. For example, I believe that my most significant initial symptom was Benson's syndrome (or the visual syndrome) that affected how my brain processed visual information. I began to notice this at about the same time I began having cognitive issues, but I'm not sure which was first. Perhaps a PET scan at the time would have found more tau buildup in the occipital lobe of my brain where visual images are processed.
One of the findings of the Nun Study was that some women whose brains showed, during autopsy, significant damage along with the plaques and tangles characteristic of Alzheimer's disease nevertheless had normal cognitive function before they died. I read one of the autopsy reports which noted the distribution of the plaques could have influenced how the disease was expressed. (I did not see any effort to correlate lifestyle behaviors, such as physical exercise, with an apparent disparity between disease and cognition.) So PET scans can be a valuable too in studying the different ways that Alzheimer's disease progresses.
What prompted me to write all of this was an article in this week's ALZForum, "Can PET Match Up Areas of Protein Deposit With Alzheimer’s Symptoms?" The article reported on The Human Amyloid Imaging Conference, held in Miami January, 15-17. The article was kind of dense, but it made some interesting points.
In my mind, one thing it reinforced was our understanding that beta amyloids build up slowly over the years until some sort of tipping point. Suddenly, there's a virtual explosion of tau protein in the brain that corresponds with the first appearance of cognitive problems. One study underscored an emerging understanding that initial buildup of beta amyloid may correspond with early indications of cognitive problems, but tangles appear to be implicated in the later stages of the disease.
One study discussed at the meeting analyzed the uptake of tracers indicating that more tau deposition occurred in the medial temporal lobes, the hippocampus, and the amygdala of people showing evidence of cognitive decline. The researchers said, “data suggest that tangle accumulation in these regions can precipitate cognitive decline.”
Recall from Beating the Dementia Monster that microtubules form a sort of skeleton for the cell, and these are given their strength by tau protein. In Alzheimer's disease, an abnormal form of tau protein appears that fails to provide sufficient strength for the microtubules, and they collapse into a "tangle." These tangles were first observed by Alois Alzheimer when, in 1906, he performed an autopsy on the brain of Auguste Deter. (This was but a few months after Albert Einstein published his very famous series of papers, including one that gave us E=mc^2.)
In a PET scan, the subject is injected with a dye (tracer) containing atoms that radioactively emit positrons -- anti-matter electrons. The anti-matter electrons quickly find regular electrons with which they undergo "annihilation." (The physics teacher in me can't resist...) This is where E=mc^2 comes in. Both particles are converted to pure energy in the form of gamma rays following Albert Einstein's famous formula.
Instruments around the brain measure these gamma rays and can map where the dye is accumulating. The tracer can be formulated to accumulate in amyloid plaques or in the tau tangles. These are characteristic of Alzheimer's disease, although they could result from other causes at lower quantities. An important way that PET scans are used is to see how and where glucose is being used in the brain. Changes in how glucose is used in the brain may indicate Alzheimer's disease.
Each case of Alzheimer's disease unfolds a little differently, and PET scans can be used to examine how the brain is being affected in different cases. For example, I believe that my most significant initial symptom was Benson's syndrome (or the visual syndrome) that affected how my brain processed visual information. I began to notice this at about the same time I began having cognitive issues, but I'm not sure which was first. Perhaps a PET scan at the time would have found more tau buildup in the occipital lobe of my brain where visual images are processed.
One of the findings of the Nun Study was that some women whose brains showed, during autopsy, significant damage along with the plaques and tangles characteristic of Alzheimer's disease nevertheless had normal cognitive function before they died. I read one of the autopsy reports which noted the distribution of the plaques could have influenced how the disease was expressed. (I did not see any effort to correlate lifestyle behaviors, such as physical exercise, with an apparent disparity between disease and cognition.) So PET scans can be a valuable too in studying the different ways that Alzheimer's disease progresses.
What prompted me to write all of this was an article in this week's ALZForum, "Can PET Match Up Areas of Protein Deposit With Alzheimer’s Symptoms?" The article reported on The Human Amyloid Imaging Conference, held in Miami January, 15-17. The article was kind of dense, but it made some interesting points.
In my mind, one thing it reinforced was our understanding that beta amyloids build up slowly over the years until some sort of tipping point. Suddenly, there's a virtual explosion of tau protein in the brain that corresponds with the first appearance of cognitive problems. One study underscored an emerging understanding that initial buildup of beta amyloid may correspond with early indications of cognitive problems, but tangles appear to be implicated in the later stages of the disease.
One study discussed at the meeting analyzed the uptake of tracers indicating that more tau deposition occurred in the medial temporal lobes, the hippocampus, and the amygdala of people showing evidence of cognitive decline. The researchers said, “data suggest that tangle accumulation in these regions can precipitate cognitive decline.”
Recall from Beating the Dementia Monster that microtubules form a sort of skeleton for the cell, and these are given their strength by tau protein. In Alzheimer's disease, an abnormal form of tau protein appears that fails to provide sufficient strength for the microtubules, and they collapse into a "tangle." These tangles were first observed by Alois Alzheimer when, in 1906, he performed an autopsy on the brain of Auguste Deter. (This was but a few months after Albert Einstein published his very famous series of papers, including one that gave us E=mc^2.)
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