You will recall from Beating the Dementia Monster that I auditioned for the Phase 3 trial for Aducanumab, but was rejected for failing to score low enough on their cognitive test. This turned out to be a good thing, because, although the small Phase 1 trial showed promise, the Phase 2 trial results were not fulfilling that promise. I had researched the history of the drug, and so I asked one of the researchers for the trial why they were going ahead with Phase 3. He said it had a lot to do with funding. The researcher doubted that the drug would fare better in the Phase 3 trial, and, well, he was right.
Aducanumab is a monoclonal antibody derived from the blood of elderly people free of AD. The antibodies effectively "eat up" the amyloids in the brain.
According to this week's ALZForum, Aducanumab has now been fully abandoned. A futility analysis found that it just wasn't worth the effort of completing the Phase 3 trial. The trial had engaged 3,200 participants from around the world to see what would happen if and when the drug actually removed amyloids from the brain.
This failure has produced profound disappointment in the research community, because huge hope had been placed on it. There was an expectation that this was THE key to breaking the back of AD. There has also now been a great deal of soul-searching, because (as I noted myself) there was strong early indication that the drug wasn't going anywhere. So why was so much false hope created? I know it created hope in me, because the buzz in 2015 was that an effective treatment would be available for me and people like me by 2019. This looked like it.
Aside from the matter of how to approach the unwarranted creation of expectations, there is thought going into what the results mean for our understanding of AD. The results reinforce recent thought that removing beta-amyloids after symptoms are evident is too late. This is one imperative for finding a biomarker test, perhaps a blood test for amyloids, that will detect the onset of AD before symptoms first appear.
Also interesting is the performance of Biogen's stock price. You will see here that it recently went into a tailspin, almost certainly due to this announcement. (It fell by about 1/3 on March 21.)
As a footnote, several authorities commented that it was not clear that Aducanumab actually removed amyloids from the brain. Scan results may have been incorrectly interpreted to indicate that it did.
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.
Monday, March 25, 2019
Saturday, March 23, 2019
More on the 2019 Facts and Figures Report
In my last post, we discussed a couple of new points of information in this year's report. But here are some more.
There is discussion of the number of Americans who have or will develop AD. This points generally to people over 65, and the oldest Baby Boomers turn 73 this year. The report estimates that 5.8 million Americans have Alzheimer's dementia. Of those, about 200,000 have the younger-onset form of the disease, and are likely in their 40s and 50s.
The report provides interesting charts and infographics for seeing the prevalence of Alzheimer's dementia among different populations and different American states. The study looks forward to better diagnostic tools that would also yield values for the incidence of MCI in the different segments of the population. Hope for better tools for assessing biomarkers appears throughout the report. (We discuss the prospects for new blood tests in a couple of posts.)
There is a discussion regarding how estimates of the number of cases of Alzheimer's dementia may be skewed high due erroneous diagnoses. Too often, diagnoses rely entirely on cognitive assessment, but it is accepted that a diagnosis should be based on a combination of cognitive assessment and biomarker evidence. Now autopsies sometimes fail to find evidence of AD in people who were diagnosed with AD. This may occur when cognitive assessment found cognitive decline, but there was a misdiagnosis, when biomarker evidence was not assessed.
(My first diagnoses of "possible early stage senile dementia of the Alzheimer's type" was based entirely on the results of a mini-mental state exam. This appears to be fairly common. When I was subsequently referred to Harborview in Seattle, they then performed in-depth cognitive testing and the brain MRIs that found biomarker evidence of the type associated with AD. )
The report discusses the incidence of AD by ethnicity. The best data indicated African Americans have the highest incidence, Latinos and whites are intermediate, and Asian Americans have the lowest incidence of Alzheimer's disease (based primarily on autopsy results in California).
Like last year, the report goes into our prospects for the future. They project a 27% increase in the number of persons over 65 with Alzheimer's dementia between 2019 and 2025. There are other bleak statistics, made even more bleak by the lack of progress in finding effective interventions.
The report addresses routine screening for MCI and dementia. I've been asked to speak on this at a state advisory panel meeting in April. From age 65 on, all of us should be screened annually for emerging cognitive issues. This is paid for by Medicare and private insurance. But it's not done often enough, and there are two reasons for this.
First, primary care providers often don't feel comfortable administering either the Mini-Mental State Exam or the Montreal Cognitive Assessment. The report points out that there are lots of resources available to help primary care providers with this -- and it just ain't that hard. But people need to ask for it.
But there's another problem. A lot of us just don't want to know and won't submit to the test. I suppose this will change if and when we find better interventions. There would then be better reasons to know.
On the other hand, if someone is tested now and found to have MCI due to Alzheimer's disease, there is more motivation to apply the strategy we discuss in Beating the Dementia Monster.
There is discussion of the number of Americans who have or will develop AD. This points generally to people over 65, and the oldest Baby Boomers turn 73 this year. The report estimates that 5.8 million Americans have Alzheimer's dementia. Of those, about 200,000 have the younger-onset form of the disease, and are likely in their 40s and 50s.
The report provides interesting charts and infographics for seeing the prevalence of Alzheimer's dementia among different populations and different American states. The study looks forward to better diagnostic tools that would also yield values for the incidence of MCI in the different segments of the population. Hope for better tools for assessing biomarkers appears throughout the report. (We discuss the prospects for new blood tests in a couple of posts.)
There is a discussion regarding how estimates of the number of cases of Alzheimer's dementia may be skewed high due erroneous diagnoses. Too often, diagnoses rely entirely on cognitive assessment, but it is accepted that a diagnosis should be based on a combination of cognitive assessment and biomarker evidence. Now autopsies sometimes fail to find evidence of AD in people who were diagnosed with AD. This may occur when cognitive assessment found cognitive decline, but there was a misdiagnosis, when biomarker evidence was not assessed.
(My first diagnoses of "possible early stage senile dementia of the Alzheimer's type" was based entirely on the results of a mini-mental state exam. This appears to be fairly common. When I was subsequently referred to Harborview in Seattle, they then performed in-depth cognitive testing and the brain MRIs that found biomarker evidence of the type associated with AD. )
The report discusses the incidence of AD by ethnicity. The best data indicated African Americans have the highest incidence, Latinos and whites are intermediate, and Asian Americans have the lowest incidence of Alzheimer's disease (based primarily on autopsy results in California).
Like last year, the report goes into our prospects for the future. They project a 27% increase in the number of persons over 65 with Alzheimer's dementia between 2019 and 2025. There are other bleak statistics, made even more bleak by the lack of progress in finding effective interventions.
The report addresses routine screening for MCI and dementia. I've been asked to speak on this at a state advisory panel meeting in April. From age 65 on, all of us should be screened annually for emerging cognitive issues. This is paid for by Medicare and private insurance. But it's not done often enough, and there are two reasons for this.
First, primary care providers often don't feel comfortable administering either the Mini-Mental State Exam or the Montreal Cognitive Assessment. The report points out that there are lots of resources available to help primary care providers with this -- and it just ain't that hard. But people need to ask for it.
But there's another problem. A lot of us just don't want to know and won't submit to the test. I suppose this will change if and when we find better interventions. There would then be better reasons to know.
On the other hand, if someone is tested now and found to have MCI due to Alzheimer's disease, there is more motivation to apply the strategy we discuss in Beating the Dementia Monster.
2019 Alzheimer's Association Facts and Figures Report Is Now Out
The Alzheimer's Association publishes their Facts and Figures Report each March. This is my go-to source for where we stand in understanding the disease and the development of treatments. The 2019 edition is now out, and I've read it. (I skimmed the sections about care-giving, because isn't relevant to my current interest.) You can download it here. I always find it fascinating.
The first object of my fascination was the new section on brain changes. It's the best systematic description I've seen to date regarding how AD unfolds. The description draws on recent research that found the disease process beginning 22 years before the onset of symptoms, and atrophy beginning 13 years before symptoms appear. The research used people with the young onset variety of AD, which may or may not be representative of the timing for "sporadic" AD -- the most common type.
The long incubation period points to one of the challenges of finding a therapy to treat the disease, because so much damage has already occurred before interventions are applied.
This year's report also updates information on the risk factors for AD. It's not that there are new risk factors, but the report provides more detail on the nature of each. The risk factors are:
I will address more elements of the report in subsequent post(s).
The first object of my fascination was the new section on brain changes. It's the best systematic description I've seen to date regarding how AD unfolds. The description draws on recent research that found the disease process beginning 22 years before the onset of symptoms, and atrophy beginning 13 years before symptoms appear. The research used people with the young onset variety of AD, which may or may not be representative of the timing for "sporadic" AD -- the most common type.
The long incubation period points to one of the challenges of finding a therapy to treat the disease, because so much damage has already occurred before interventions are applied.
This year's report also updates information on the risk factors for AD. It's not that there are new risk factors, but the report provides more detail on the nature of each. The risk factors are:
- Age -- 65 or older. 3% of people between 65 and 74 and 32% of people 85 and older have Alzheimer's dementia. They don't address statistics for people like me with MCI. I think this is due to the difficulty of assigning the cause of MCI to AD. Age, of course, does not cause AD, but it grants time and a fertile environment for the disease to develop.
- Presence of the ApoE4 gene variant in your genome. If you have one copy, you have elevated risk of developing AD, and if you have two copies your risk is elevated farther. Actual probability values vary with factors like ethnicity.
- Family history. Irrespective of the presence of the ApoE4 variant, a family history of AD suggests a higher risk factor. This is not necessarily a genetic phenomenon. Family members likely share lifestyle choices and environmental factors that increase or decrease the risk of developing AD.
- Cardiovascular disease risk factors. Heart disease can affect the flow of blood to the brain, and the brain consumes 20% of the body's oxygen and nutrients. Some factors, like a history of smoking and mid-life obesity, appear to affect both the heart and the brain through similar and differing mechanisms. Just remember, what's good for the heart is good for the brain. But, unexplained, is an association between a reduction of risk for AD for people over 85 with obesity and hypertension. Go figure.
- Diet in the context of cardiovascular disease factors. The study makes a connection between the elements of the heart-healthy diets (Mediterranean, DASH, MIND) and reduced risk for AD.
- Multi-domain lifestyle factors. This is where diet, exercise, social connectivity, and the other factors we discuss in Beating the Dementia Monster come into play. The discussion draws on the Finnish FINGER study that we discussed in a post on December 17.
- Education. There is a clear correlation between lesser educational attainment and AD. Some believe that they type of brain activity that occurs during learning somehow builds resistance to the AD disease process.
- Social and cognitive engagement. Maintaining social and cognitive activity may support brain health and possibly reduce risk of developing AD.
- Traumatic brain injury. There is a clear correlation between TBI and AD. One study found a two-fold increase in the occurrence of AD from mild TBI. The report did not clarify if this was a single TBI event or repeated events.
I will address more elements of the report in subsequent post(s).
Tuesday, March 12, 2019
Insulin Study Results Are Not Promising
I got a call today from a research coordinator at the VA hospital in Seattle, where we had participated in the SNIFF study. He said that the research results were beginning to come out, and they had not identified a significant difference in cognitive test results between subjects who were on actual insulin and those who were on the placebo. The SNIFF study evaluated the effect of insulin provided directly to the brain without raising insulin levels in other parts of the body. Since AD affects the metabolism of glucose in the brain, it was hoped that boosting insulin concentration in the brain at key times would improve uptake and utilization of glucose by the cells, thereby improving cognition.
Here is a discussion in the ALZ Forum that I missed regarding how things went on the SNIFF study. It's from November of last year.
You will recall that I was on the placebo during the one-year placebo-controlled phase of the study. During the subsequent six months, all of us were on the real insulin. The research coordinator said the results of the latter phase have not yet been released. I doubt they will change the conclusions as they are now emerging.
Here is a discussion in the ALZ Forum that I missed regarding how things went on the SNIFF study. It's from November of last year.
You will recall that I was on the placebo during the one-year placebo-controlled phase of the study. During the subsequent six months, all of us were on the real insulin. The research coordinator said the results of the latter phase have not yet been released. I doubt they will change the conclusions as they are now emerging.
Monday, March 11, 2019
New Research on Iron and Dementia
There is a belief among some that ingestion of excessive iron may cause or contribute to AD. This week's issue of ALZ Forum carried an article that supported this idea. The article presented information from a study published in the journal Molecular Psychiatry that reviewed autopsy results for people who did and who did not have evidence of AD at death. The review found a very strong correlation between people who displayed evidence of AD and the presence of iron in the temporal cortices. The article stated, "Only people with clinical and pathological hallmarks of Alzheimer’s disease had more cortical iron."
The researchers did not come to a strong conclusion about the role of iron in AD pathology, although they suggested some possibilities. One limitation of the study was that it could only examine the brains of people who had already died. So their methodology couldn't correlate the progress of the disease with the amount of iron accumulating in the cortices. However it was evident to the researchers that the concentration of iron rises late in the AD pathology.
But what role might iron have in AD pathology? The ALZ Forum article stated that this question has been long debated, but there is no consensus. A researcher from the "Religious Orders Study and Memory and Aging Project" discussed autopsies where the presence of amyloid plaques and tau tangles did and did not correlate well with dementia prior to death. He said that elevated iron appeared in the brains of those who displayed dementia but not necessarily in the brains of those who did not. This recalls from the Nun study the apparent anomaly of nuns who displayed normal cognition prior to death, but their autopsies found their brains displayed significant damage of the type consistent with AD. (The Nun study and the Religious Orders study run cooperatively.)
The article pointed out that there is normally iron in the brain cells. However, free iron outside the cells may be the problem. The article discussed some studies that have tried to improve cognition by removing iron from the brain. So far, these have not produced positive results.
The researchers did not come to a strong conclusion about the role of iron in AD pathology, although they suggested some possibilities. One limitation of the study was that it could only examine the brains of people who had already died. So their methodology couldn't correlate the progress of the disease with the amount of iron accumulating in the cortices. However it was evident to the researchers that the concentration of iron rises late in the AD pathology.
But what role might iron have in AD pathology? The ALZ Forum article stated that this question has been long debated, but there is no consensus. A researcher from the "Religious Orders Study and Memory and Aging Project" discussed autopsies where the presence of amyloid plaques and tau tangles did and did not correlate well with dementia prior to death. He said that elevated iron appeared in the brains of those who displayed dementia but not necessarily in the brains of those who did not. This recalls from the Nun study the apparent anomaly of nuns who displayed normal cognition prior to death, but their autopsies found their brains displayed significant damage of the type consistent with AD. (The Nun study and the Religious Orders study run cooperatively.)
The article pointed out that there is normally iron in the brain cells. However, free iron outside the cells may be the problem. The article discussed some studies that have tried to improve cognition by removing iron from the brain. So far, these have not produced positive results.
The FDA Goes After Supplement Snake Oil
This week's issue of ALZ Forum carried several interesting articles, one of them on an FDA crackdown on the supplement industry. The FDA is moving against 17 companies it accuses of illegally marketing dietary supplements as dementia treatments. Some of these made explicit claims to treat AD.
The article quotes one researcher as saying “There is zero evidence from any reasonably rigorous study that any supplement or dietary aid has any benefit on cognitive function or decline in late life.” The article references analysis that reviewed many studies looking for evidence that some dietary supplements may help but found nothing.
In some cases, an early study of a supplement with seemingly positive results failed to fulfill its promise in a larger, statistically significant group of test subjects. When the larger study failed, the supplement companies sometimes marketed the supplement anyway. Presumably they cited the early results from small groups and didn't tell consumers the supplements failed when more thoroughly tested.
Consistent with what we said in Beating the Dementia Monster, researchers noted that in the case of a documented deficiency, such as Vitamin B12, supplements may in fact help with dementia caused by vitamin deficiency, but this is not AD.
Phony claims about supplements helping with AD have been around for a long time. Claims made on internet web sites drive researchers and medical professionals nuts, so maybe this will bring more rigor to supplement company claims. But the authors of the article weren't that optimistic, since the industry is so large, and the internet is so hard to police for fraud.
The article quotes one researcher as saying “There is zero evidence from any reasonably rigorous study that any supplement or dietary aid has any benefit on cognitive function or decline in late life.” The article references analysis that reviewed many studies looking for evidence that some dietary supplements may help but found nothing.
In some cases, an early study of a supplement with seemingly positive results failed to fulfill its promise in a larger, statistically significant group of test subjects. When the larger study failed, the supplement companies sometimes marketed the supplement anyway. Presumably they cited the early results from small groups and didn't tell consumers the supplements failed when more thoroughly tested.
Consistent with what we said in Beating the Dementia Monster, researchers noted that in the case of a documented deficiency, such as Vitamin B12, supplements may in fact help with dementia caused by vitamin deficiency, but this is not AD.
Phony claims about supplements helping with AD have been around for a long time. Claims made on internet web sites drive researchers and medical professionals nuts, so maybe this will bring more rigor to supplement company claims. But the authors of the article weren't that optimistic, since the industry is so large, and the internet is so hard to police for fraud.
Wednesday, March 6, 2019
Uh oh ... MIND Diet Good, Mediterrnean Diet Maybe Not so Helpful?
In Beating the Dementia Monster we discussed the three favored diets for brain health: the DASH diet, the MIND diet, and their granddaddy, the Mediterranean diet. On December 17, 2018 I posted two articles about studies correlating diet with the development of AD -- one a Finnish study and the other a British study. The Finnish study failed to find cognitive improvement over a two year period from an improved diet that correlated with the Mediterranean diet and the DASH diet. The researchers discussed the MIND diet, but they did not evaluate the potential of the MIND diet in their study.
The British study found remarkable improvement in hippocampal volume that they correlated with improved diet over an eleven year period. It was difficult to understand from the methodology in the British study what their favored diet resembled -- Mediterranean, DASH, or MIND. They scored people's food intake based on the Alternative Healthy Eating Index, which favored green leafy vegetables over carbohydrate-rich foods -- among several other factors. I could not find a way to correlate the information in the report with any particular diet.
The British study found remarkable improvement in hippocampal volume that they correlated with improved diet over an eleven year period. It was difficult to understand from the methodology in the British study what their favored diet resembled -- Mediterranean, DASH, or MIND. They scored people's food intake based on the Alternative Healthy Eating Index, which favored green leafy vegetables over carbohydrate-rich foods -- among several other factors. I could not find a way to correlate the information in the report with any particular diet.
Now there's an interesting new study in the current issue of Alzheimer's and Dementia; the Journal of the Alzheimer's Association. The study is "MIND not Mediterranean diet related to 12-year incidence of cognitive impairment in an Australian longitudinal cohort study." It acknowledged studies in the US that correlated diet with brain health, but posited a need to determine if the results of American studies can be generalized outside of the US. For example, in Australia.
The conclusion was that they can, but ... the study failed to find a correlation between cognitive improvement and the Mediterranean diet after 12 years. On the other hand, it did find a substantial correlation for the MIND diet. Note that the Finnish study we discussed in one of my December 17 posts also found no correlation between cognitive improvement and the Mediterranean diet after two years. It did not evaluate the MIND diet.
I've always treated the three diets as essentially co-equal with respect to brain health because they all knock out the carbs and red meat while favoring green leafy vegetables, fish, and poultry. But maybe I should fashion my eating more after the MIND diet than the Mediterranean diet. I already do to a certain extent. I eat blueberries every day and one slice of whole grain bread that I would not otherwise be eating. But I do eat some plain cream cheese for snacks which is not on the MIND menu, even if it might be on the Mediterranean menu. And I don't eat beans, but maybe I should.
This article from the professional journal Today's Dietician compares the Mediterranean and MIND diets without finding much difference in comparative outcomes. (It does cite research that found favorable outcomes for both diets.)
The other thing hanging out there in my mind is how well the studies supporting these diets have been controlled for exercise. From what I can see, only the research supporting the MIND diet claims to have controlled for exercise, and some have criticized how well that was done. Do people in Australia who follow the MIND diet get more exercise than people who follow the Mediterranean diet? It may seem like a silly question, but when questions like these are probed we sometimes get surprising answers.
Can a Pattern of Sleep Disturbance Predict the Onset of Alzheimer's Disease?
The current issue of Alzheimer's and Dementia; the Journal of the Alzheimer's Association, carried an interesting article about a study of disturbed sleep preceding the onset of the AD disease pathology. The article was "Alteration in sleep architecture and electroencephalogram as an early sign of Alzheimer's disease preceding the disease pathology and cognitive decline."
The study began by noting that there is an established correlation between disturbed sleep and AD. It also recalled earlier research the investigators had conducted that found a relationship between sleep and AD in humans. Apparently the studies focused on people in the later stages of AD. What has not been established is whether sleep disturbance could be a feature of the early stages of AD. Also, it was not clear how valuable electroencephalograms (EEGs) may be in studying sleep disturbances in people who have or may develop AD.
This study relied on EEG studies of mice. (In the conclusions the authors discussed the need for future studies with human subjects.) Mice have been used for many AD studies, because the genes of some mice have been edited to promote the development of AD. Findings from studies in mice must, of course, be confirmed in similar studies in humans. Sometimes findings can be confirmed, but other times there is doubt regarding how valid an analog mice are for humans in these cases.
What did they find this time? Young mice that were genetically predisposed to develop AD but which had not begun to develop amyloid plaques displayed a different sleep "architecture." In other words, disturbed sleep preceded the development of AD pathology -- at least the AD pathology we know how to observe.
The authors discussed the need to perform similar studies on humans. But they also noted that this will be very difficult. The main challenge will be finding and obtaining the cooperation of a large population of presymptomatic elderly people with AD as well as people with only the earliest symptoms. Conducting large numbers of EEGs is difficult and time-consuming.
We have discussed before the imperative for developing diagnostic tools to identify presymptomatic AD. While a lot of people want to know whether they are developing AD (while a lot don't...), an equally important need for such tools is to identify large numbers of potential human research subjects who have begun to develop AD but have not advanced to MCI. These are people who, in the past, would not have known they were developing AD.
The researchers believe that further study of the relationship between sleep and the development of AD may shed important light on AD pathology and progression.
The study began by noting that there is an established correlation between disturbed sleep and AD. It also recalled earlier research the investigators had conducted that found a relationship between sleep and AD in humans. Apparently the studies focused on people in the later stages of AD. What has not been established is whether sleep disturbance could be a feature of the early stages of AD. Also, it was not clear how valuable electroencephalograms (EEGs) may be in studying sleep disturbances in people who have or may develop AD.
This study relied on EEG studies of mice. (In the conclusions the authors discussed the need for future studies with human subjects.) Mice have been used for many AD studies, because the genes of some mice have been edited to promote the development of AD. Findings from studies in mice must, of course, be confirmed in similar studies in humans. Sometimes findings can be confirmed, but other times there is doubt regarding how valid an analog mice are for humans in these cases.
What did they find this time? Young mice that were genetically predisposed to develop AD but which had not begun to develop amyloid plaques displayed a different sleep "architecture." In other words, disturbed sleep preceded the development of AD pathology -- at least the AD pathology we know how to observe.
The authors discussed the need to perform similar studies on humans. But they also noted that this will be very difficult. The main challenge will be finding and obtaining the cooperation of a large population of presymptomatic elderly people with AD as well as people with only the earliest symptoms. Conducting large numbers of EEGs is difficult and time-consuming.
We have discussed before the imperative for developing diagnostic tools to identify presymptomatic AD. While a lot of people want to know whether they are developing AD (while a lot don't...), an equally important need for such tools is to identify large numbers of potential human research subjects who have begun to develop AD but have not advanced to MCI. These are people who, in the past, would not have known they were developing AD.
The researchers believe that further study of the relationship between sleep and the development of AD may shed important light on AD pathology and progression.
Saturday, March 2, 2019
More Insight on Inflammation and Alzheimer's Disease
This weeks edition of ALZForum reported on an interesting study correlating mid-life peripheral inflammation with subsequent cognitive decline. We discuss the (incompletely) understood role of inflammation in the development of AD in Beating the Dementia Monster. Consistent with what we said, the article said that diet and exercise are some of the best ways for controlling inflammation. (Especially, stay away from fast food!)
The study has been following a cohort of more than 12,000 people for 30 years, testing their blood for proteins associated with inflammatory processes and correlating the findings with cognitive test results. The upshot is that people who displayed evidence of inflammation in mid-life were significantly more likely to experience cognitive decline 20 years later. The discussion in the article correlated the cognitive decline with the development of AD. Tests also found increased presence of the beta-amyloid and tau proteins that are markers for AD.
The study warns to be careful about confusing correlation with causation. They could not rule out the possibility that the inflammation was actually a reaction to the disease process, not a result of it. They also said that measuring these proteins would be a poor way to predict AD risk, since there are many proteins involved, and they tend to have non-specific origins.
Not discussed but worth thinking about is the tie in with the ApoE4 gene variant. This is what genetic testing services look for when predicting your risk for developing AD. Some believe that enzymes (proteins) synthesized from the design specified by the ApoE gene play a role in controlling inflammation in the brain. Enzymes synthesized from the ApoE4 variant may do a poor job in aiding the body's ability to control inflammation. There is no evidence from the article that they controlled for the presence of the ApoE4 gene variant, but I'm left wondering if poor performance of the enzyme from this gene in fighting inflammation could be why they detected the inflammation byproducts.
So my take:
ApoE4 gene variant results in enzyme -> enzyme does a poor job of controlling inflammation -> inflammation results in the presence of marker proteins in midlife -> inflammation triggers AD -> AD disease process causes cognitive decline -> disease process generates more beta-amyloid and tau proteins
The study was The Atherosclerosis Risk in Communities (ARIC) cohort study. It began with a cohort of 15,000 adults aged 45 to 65 from cities around the U.S. More than half the participants are women, and almost a third are black. The cohort was whittled down to 12,336 based on health and other factors that might confound the study.
The study has been following a cohort of more than 12,000 people for 30 years, testing their blood for proteins associated with inflammatory processes and correlating the findings with cognitive test results. The upshot is that people who displayed evidence of inflammation in mid-life were significantly more likely to experience cognitive decline 20 years later. The discussion in the article correlated the cognitive decline with the development of AD. Tests also found increased presence of the beta-amyloid and tau proteins that are markers for AD.
The study warns to be careful about confusing correlation with causation. They could not rule out the possibility that the inflammation was actually a reaction to the disease process, not a result of it. They also said that measuring these proteins would be a poor way to predict AD risk, since there are many proteins involved, and they tend to have non-specific origins.
Not discussed but worth thinking about is the tie in with the ApoE4 gene variant. This is what genetic testing services look for when predicting your risk for developing AD. Some believe that enzymes (proteins) synthesized from the design specified by the ApoE gene play a role in controlling inflammation in the brain. Enzymes synthesized from the ApoE4 variant may do a poor job in aiding the body's ability to control inflammation. There is no evidence from the article that they controlled for the presence of the ApoE4 gene variant, but I'm left wondering if poor performance of the enzyme from this gene in fighting inflammation could be why they detected the inflammation byproducts.
So my take:
ApoE4 gene variant results in enzyme -> enzyme does a poor job of controlling inflammation -> inflammation results in the presence of marker proteins in midlife -> inflammation triggers AD -> AD disease process causes cognitive decline -> disease process generates more beta-amyloid and tau proteins
The study was The Atherosclerosis Risk in Communities (ARIC) cohort study. It began with a cohort of 15,000 adults aged 45 to 65 from cities around the U.S. More than half the participants are women, and almost a third are black. The cohort was whittled down to 12,336 based on health and other factors that might confound the study.
Subscribe to:
Posts (Atom)