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Health Items from 2014:                                                  to enlarge a photo, click on it

A new look at the beginnings of Alzheimers   How safe are supplements?   Dyslexia upside   Further new on dyslexia   Too much of a good thing  DMS-5    Doctor doubting the need for gluten-free diets     Watch out for dietary advice   What causes fibromyalgia?     News on diabetes   New Chronic Fatigue Theory   New Alzheimer's testing system     Reversing memory loss    Shh don't tell anyone    The mechanism of red wine health effects   new 

A new look at the beginnings of Alzheimers
There is a recent paper that examines the very early stages of Alzheimers. They did very fine resolution scans of 96 healthy elderly people. After 3 1/2 years 12 of these people has mild Alzheimers. They could then compare the starting scans of those who remained healthy and those moving into Alzheimers. They could also compare the early and late scans of the Alzheimers sufferers. They found that Alzheimers starts in a small area called the lateral entorhinal cortex. It spreads from there along functional pathways – from neuron to neuron as they communicate directly with one another. The entorhinal cortex (both lateral and median) is extremely closely associated with the hippocampus, after that the parietal cortex. This is the stage these people were at when they were diagnosed.
This paper also looks at what make that particular area of the brain vulnerable. The lateral entorhinal cortex has a high level of tau protein accumulation compared to the rest of the brain. They found in separate studies on mice that high tau does not cause the disease, nor does high amyloid accumulation, but both together they cause damage that leads to cause Alzheimers. (So the argument between the tau and the amyloid research groups can stop – it takes both). And going back to the original baseline scans, it was found the 12 sufferers had a significant decrease in blood volume and therefore of metabolic activity in the lateral endorhinal cortex. This was when they were examined and no trace of Alzheimers was found. This decrease in activity was not seen in the people who remained healthy.
The early attack on the endorhinal cortex and the hippocampus fits with other studies and also with the symptoms. These are the areas that are associated most strongly with the episodic memory. The hippocampus with forming and recalling memories, the medial EC with navigation and the place component of memory, the lateral EC is involved in the placement of objects in space and the consolidation of memory. The EC is also how signals from the rest of the cortex tend to get to the hippocampus. So the picture of a person wandering lost and not remembering how to get home and not being able to recognize any familiar landmarks, is in keeping with the areas first compromised. So now the question is – what caused the slowing down of that particular area of the brain?

How safe are supplements?
Don't believe all that you read about supplements. Here is a report on a paper out of Oregon State University by B Frei: Most Clinical Studies On Vitamins Flawed by Poor Methodology
Most large, clinical trials of vitamin supplements, including some that have concluded they are of no value or even harmful, have a flawed methodology that renders them largely useless in determining the real value of these micronutrients, a new analysis suggests.
Many projects have tried to study nutrients that are naturally available in the human diet the same way they would a powerful prescription drug. This leads to conclusions that have little scientific meaning, even less accuracy and often defy a wealth of other evidence.
These flawed findings will persist until the approach to studying micronutrients is changed, Frei said. Such changes are needed to provide better, more scientifically valid information to consumers around the world who often have poor diets, do not meet intake recommendations for many vitamins and minerals, and might greatly benefit from something as simple as a daily multivitamin/mineral supplement.
Needed are new methodologies that accurately measure baseline nutrient levels, provide supplements or dietary changes only to subjects who clearly are inadequate or deficient, and then study the resulting changes in their health. Tests must be done with blood plasma or other measurements to verify that the intervention improved the subjects' micronutrient status along with biomarkers of health. And other approaches are also needed that better reflect the different ways in which nutrients behave in cell cultures, lab animals and the human body.
The new analysis specifically looked at problems with the historic study of vitamin C, but scientists say many of the observations are more broadly relevant to a wide range of vitamins, micro nutrients and studies.
"One of the obvious problems is that most large, clinical studies of vitamins have been done with groups such as doctors and nurses who are educated, informed, able to afford healthy food and routinely have better dietary standards than the public as a whole," said Frei, an international expert on vitamin C and antioxidants.
Vitamin or mineral supplements, or an improved diet, will primarily benefit people who are inadequate or deficient to begin with. But most modern clinical studies do not do baseline analysis to identify nutritional inadequacies and do not assess whether supplements have remedied those inadequacies. As a result, any clinical conclusion made with such methodology is pretty much useless, they said.
"More than 90 percent of U.S. adults don't get the required amounts of vitamins D and E for basic health," Frei said. "More than 40 percent don't get enough vitamin C, and half aren't getting enough vitamin A, calcium and magnesium. Smokers, the elderly, people who are obese, ill or injured often have elevated needs for vitamins and minerals.
"It's fine to tell people to eat better, but it's foolish to suggest that a multivitamin which costs a nickel a day is a bad idea."
Beyond that, many scientists studying these topics are unaware of ways in which nutrients may behave differently in something like a cell culture or lab animal, compared to the human body. This raises special challenges with vitamin C research in particular.
"In cell culture experiments that are commonly done in a high oxygen environment, vitamin C is unstable and can actually appear harmful," said Alexander Michels, an LPI research associate and lead author on this report. "And almost every animal in the world, unlike humans, is able to synthesize its own vitamin C and doesn't need to obtain it in the diet. That makes it difficult to do any lab animal tests with this vitamin that are relevant to humans."
Even though such studies often significantly understate the value of vitamin supplements, the largest and longest clinical trial of multivitamin/mineral supplements found a total reduction of cancer and cataract incidence in male physicians over the age of 50. It suggested that if every adult in the U.S. took such supplements it could prevent up to 130,000 cases of cancer each year, Frei said.
"The cancer reduction would be in addition to providing good basic health by supporting normal function of the body, metabolism and growth," he said. "If there's any drug out there that can do all this, it would be considered unethical to withhold it from the general public. But that's basically the same as recommending against multivitamin/mineral supplements."

Dyslexia Upside

A few things have accumulated in my dyslexia file so I'm putting some together here. They are some agreements on definitions and facts, some observations on an upside to dyslexia, and critics of Gladwell's treatment of dyslexia in his best-selling book.
The International Dyslexia Association definition of dyslexia adopted November 2002
Dyslexia is a specific learning disability that is neurological in origin. It is characterized by difficulties with accurate and/or fluent word recognition and by poor spelling and decoding abilities. These difficulties typically result from a deficit in the phonological component of language that is often unexpected in relation to other cognitive abilities and the provision of effective classroom instruction. Secondary consequences may include problems in reading comprehension and reduced reading experience that can impede the growth of vocabulary and background knowledge.”
In other words: one, dyslexia should no longer be classed as a psychological condition but a physical condition of the brain; two, the problem stems from a phonological deficit and not a visual of other deficit; three, it is not caused by particular methods of education. But it can be treated with special therapy. So we can forget those red-herrings.
Dyslexia pre-dates learning to read and could be diagnosed in pre-school children before they attempt to read. It is not caused by how a child is introduced to reading.
Another myth to dispose of is that dyslexia is caused by a lack of gray matter in the language areas of the brain. “In people with dyslexia, less gray matter in the brain has been linked to reading disabilities, but now new evidence suggests this is a consequence of poorer reading experiences and not the root cause of the disorder. It has been assumed that the difference in the amount of gray matter might, in part, explain why dyslexic children have difficulties correctly and fluently mapping the sounds in words to their written counterparts during reading. But this assumption of causality has now been turned on its head.”
Downs and Ups
Dyslexia should be recognized as a spectrum disorder, with symptoms ranging from mild to severe. It is a lifelong condition; people do not grow out of it (but can overcome some/most of its effects). In particular, people with dyslexia have difficulties with:
There are some up-sides to dyslexia if it is mild. People with dyslexia often: There have been a number of reports of very specific perception and learning tasks that dyslexics do faster and better than non-dyslexics. As yet there does not seem to be a pattern in the types of tasks for which this is true.
There was a program on dyslexic advantages. Here are the highlights:
Panel: Dr. Brock Eide- clinician and co-author with Dr. Fernette Eide of "The Dyslexic Advantage: Unlocking the Hidden Potential of the Dyslexic Brain", Laura Kaloi- National Center for Learning Disabilities, Jeffrey Gilger- professor, School of Social Sciences, Humanities and ArtsUniversity of California, Guinevere Eden- director, Center for the Study of Learning & professor, Department of Pediatrics Georgetown University Medical Center
What Is Dyslexia?
Dyslexia is a language-based learning disability that affects an individual's ability to read, write, and spell, as well as other activities that require our brain to process information. It affects nearly 2 million school age children in public schools in the U.S. It's estimated that up to 15 million people, including adults, are dyslexic. There are sometimes some very early warning signs that a child may be developing dyslexia, like when a toddler isn't gaining early speaking skills at the appropriate rate, Kaloi said. Intensive early intervention could help a child gain the speaking skills they need.
Is Dyslexia Heritable?
There are micro differences in the brains of dyslexic people, Eden said, and it is now known it is a heritable disorder. This doesn't mean that the environment isn't also important, Gilger said. But in families where any one individual has dyslexia, the odds that it will appear again in that family go up anywhere from four to ten times over the base rate, Gilger said. Researchers are beginning to be able to identify some of the genes that might be involved.
Advantages To The Dyslexic Brain
Eide and colleagues found four basic advantages that dyslexic people have in common, and they use the acronym "MIND" to represent them. "M" is for material, or spatial, reasoning; "I" is for interconnected reasoning, which allows the ability to see connections between objects and concepts and to fit these into a big picture; "N" stands for "narrative reasoning," the tendency to understand factual information as cases or examples rather than in the abstract; and "D" stands for "dynamic reasoning," or the ability to use remembered information to make predictions about processes that change over time. Kaloi believes that teachers need more resources to help them harness some of these strengths in dyslexic students. The dropout rate among dyslexics, she said, is currently about 20 percent.
A Caller's Perspective: "It's Not That You Can't Learn. You Just Learn Differently"
A caller named Ben talked about his own experiences as a dyslexic and said that people often think of dyslexia as a problem where people "reverse their letters." "It's not just about reversing letters. It's really about the acquisition of reading, which is something we created," he said. Kaloi responded by emphasizing again that teachers need to develop a better understanding of how dyslexic students learn. "You don't do what we call 'drill and kill' with kids with dyslexia," she said, "where they just get the worksheets and the same stuff over and over....we have to have a different approach for these students and how they learn," she said.
The Gladwell mess
Whether or not there are some advantages to dyslexia, they certainly do not offset the difficulties.
If you have read Malcolm Gladwell's 'David And Goliath', or if you are going to, or friends read it then be warned – it is not to be trusted on the subject of dyslexia. Many experts in the field have criticized his portrait of dyslexia. Steven Pinker, Christopher Chabris, Dorothy Bishop, David Runceman, Andrew Gellman were all critical. But probably the most thorough complaint came from Mark Seidenberg, psychology professor at the University of Wisconsin-Madison.
The Gladwell pivot
by Mark Siedenberg in LanguageLog
This piece is commentary on a chapter about dyslexia in Malcolm Gladwell’s latest book. I don’t follow his work closely, and the book is being reviewed and critiqued everywhere, but I thought the chapter merited a response from somebody, like me, who studies dyslexia and works with local advocacy groups for dyslexics and their families. The chapter deserves s a line-by-line analysis; what I’ve written only mentions the main issues. The document incorporates several key points that were handed to me by Maryellen MacDonald, for which I thank her, a lot.
Malcolm Gladwell, the immensely popular writer, has just released his latest best-selling book. Gladwell mainly writes about aspects of human behavior that are studied by researchers in psychology, neuroscience, sociology, and related fields. He has perfected a literary form that might be called the nonfiction short story (by analogy to Truman Capote’s “nonfiction novel”). Each chapter (or New Yorker article) explores an interesting, usually counterintuitive, idea by means of an engaging narrative, woven out of several types of cloth: personal biographies, telling anecdotes, research studies, expert opinions. The stories are exceptionally well told; it is a remarkable feat to turn an issue like the impact of practice on expertise (Outliers) into a page-turner.
The gripe about Gladwell is his selective use of such information—not letting facts get in the way of a good story. A different story, certainly a more nuanced one, would result if other studies, other personal narratives, other experts had been considered. The average reader is not aware of what has been left out and thus can be easily mislead. His selective use of the research literature turns scientific findings into another form of anecdote. This is particularly bothersome to scientists whose own first commandment is something like: thou shalt address all relevant evidence, not merely the findings that support the most interesting, attention-getting hypothesis.
But so what? The man is writing popular books for a general audience, not reviews of the scientific literature. He introduces people to fascinating topics they might not otherwise have known about or considered interesting enough to merit attention. He offers novel, surprising perspectives on topics that everybody wonders about, like the bases of extraordinary success. Gladwell is like a lot of journalists and public intellectuals whose greater commitment is to what is interesting, not necessarily true. Gladwell isn’t obligated to consider competing perspectives or contradictory findings. His only obligation is to engage his readers. It’s hard to build a compelling narrative out of “on the one hand this, on the other hand that,” even if that would be the most accurate characterization of what is known about a topic. Nothing is gained if people won’t pick up the book. Such books are valuable because they’re stimulating: readers are moved to think and talk about important questions, situations, and events. There are plenty of easily accessible sources for readers who want to know more. Besides, there is always some truth to what he is saying; the evidence may be circumstantial but he doesn’t just make it up. And the books are enjoyable: vivid characters, surprising findings, and anecdotes to share around the water cooler. It’s all benign.
Gladwell gets a lot of grief, but he does his job Damnwell. Reading is good. Knowledge is good. Enjoyment is good. Take the book for what it is and have fun. Or go read a novel.
But here’s something to consider. What if in telling one of these stories, the author inadvertently made life much harder for a large group of people who are disadvantaged in some way? What if it resulted in fewer people being able to overcome that disadvantage? What if it added to the considerable burdens that such individuals and their families already experience?
Could the Gladwell treatment be harmful to children?
There. That was my attempt to execute the famous Gladwell pivot, whereby he sets up an issue one way and then flips it around. You might have missed it because I’m an amateur, but here is the point:
Chapter 3 of the new book is about developmental dyslexia. It’s titled after David Boies, one of two dyslexic superachievers who are profiled. The chapter’s setup is this: Dyslexia is a serious disability. Lots of people struggle with it. Having a brain that’s wired to make it hard to read is a big liability.
The pivot is: [It being such a debilitating condition] “You wouldn’t wish dyslexia on your child. Or would you?”
Gladwell then develops the Idea that dyslexia might be a “desirable difficulty”, a condition that is usually a liability but can also be the engine for extraordinary personal success. He says that it’s hard to believe that the condition could be considered desirable given how many people struggle with it. But Gladwell is impressed by fact that “an extraordinarily high percentage of entrepreneurs are dyslexic”. And he is impressed by people like David Boies, the most successful, accomplished person at the top of a very high legal pyramid, who identifies as dyslexic. Boies is the dream-team litigator who worked on a slew of historic cases, including the IBM and Microsoft anti-trust cases, Gore vs. Bush, and the overturning of California Prop 8.
Gladwell’s idea isn’t just that such people manage to succeed despite their dyslexia. It’s that having dyslexia, and dealing with its consequences, played a causal role in their success. If dyslexia can boost people to stratospheric levels of success in professions like law and finance, and it can stimulate the creative, out-of-the-box thinking that contributes to entrepreneurial success, dyslexia might actually be a kind of “desirable difficulty.” Interesting!
Or disturbing. The answer to the question, “You wouldn’t wish dyslexia on your child. Or would you?” is, “No, you would not.” Gladwell seems oblivious to how deeply hurtful the “desirable difficulty” suggestion might be to people who have to deal with being dyslexic, and to the parents who struggle, against institutional resistance, to get their dyslexic children help. His light entertainment is likely to make it harder for many dyslexics to gain recognition of their condition from educators, or the early diagnosis and intervention that is effective for many. That would not be benign.
So here’s an irony: what if Gladwell’s chapter makes it harder for a dyslexic to achieve the levels of success he venerates?
Being dyslexic may or may not have contributed to the success of some very high achieving individuals. The truth of the matter is irrelevant for two reasons. First, it has no bearing on what to do about a dyslexic child. Withholding treatment would be unconscionable, and possibility that some dyslexics become superachievers doesn’t change that. Second, he’s created a meme whose existence doesn’t depend on being true. The meme is spreading through the culture at this very moment (move aside, “Overly Attached Girlfriend”). Gladwell has a vastly larger audience and far more influence on what people think than any scientist who studies dyslexia or advocacy organizations like the International Dyslexia Association. And so the idea that dyslexia can be a “desirable difficulty” will take hold, as will cruder versions than Gladwell intended, such as dyslexics being advantaged compared to ordinary folk.
Of course I’m talking about future consequences here rather than known outcomes, and there’s no Tardis time machine handy to let us see how much impact the book will have. It’s an ongoing experiment, the data aren’t in, and it may be possible to bias the outcome while the experiment is in progress. But given what we know about dyslexia and the very real difficulties parents currently experience in getting the deficit recognized, it’s rational to be concerned that Gladwell’s message of desirable difficulty will have undesirable consequences for the mass of individuals who are dyslexic.
Dyslexia places individuals at high risk for educational failure. It creates serious challenges to people fully participating in the workforce, managing their own health care, or advancing their children's education. Gladwell knows this; he just wants it also known that the condition apparently had remarkably positive effects for some people, and why. He’s not claiming that it works for all dyslexics, obviously; the theme of the book is that underdogs win more often than you might think, not always. The potential harm arises from the fact that dyslexics and their parents already face enormous obstacles. The condition is not highly visible and often goes undiagnosed. About 30% of the US population reads at the basic or below basic levels as defined by standard metrics. Many of these individuals are dyslexics whose condition was not diagnosed or treated. Dyslexia is poorly understood by teachers because their training doesn’t include exposure to modern research on developmental disorders, their behavioral characteristics, their neural and genetic bases, or effective interventions. Many educational theorists are skeptical that dyslexia exists. Pushed to acknowledge that it is a brain-based disorder with a genetic component, these educators respond that, if that is true, dyslexia is a medical disorder outside their purview. Whereas on the medical side, it is seen as an educational issue.
The net result is a lot of people who go undiagnosed and untreated, or whose condition is recognized very late when it is harder to address. People who study dyslexics and work with parents and support groups also have stories to tell. There is a parent I’ve worked with in an advocacy group for dyslexics and their families, a highly educated, upper middle class mother (a pediatrician) with a severely dyslexic child and an extended family history of dyslexia. At a meeting to discuss the child’s difficulties in school, the teacher asks, “Do you have any books in the home? Did you read to your child when he was younger? Is reading important in your family?” The child's difficulties are seen as arising from poor parenting rather than a heritable disorder.
Dyslexics and their parents are frequently challenged about the reality of the condition. In some states, like mine, even a diagnosis based on a full clinical neuropsych workup will not be accepted at face value. The child might get an IEP (individualized educational program) which stipulates that the classroom teacher will provide instruction tailored to the child’s needs. This is the same teacher who lacks any training about dyslexia or how to address it.
The other frequent response to parents is: He’ll catch up. Children learn to read at different rates. No need to worry. Or do anything. (I used “he” here because the condition occurs more often in males.)
Now parents may be faced with yet another response: dyslexia isn’t a developmental disability, it’s desirable. It can give a child an enormous advantage. Do you know that there are dyslexic superlawyers and Wall Street billionaires? You wouldn’t want to deprive your child of those possibilities, would you?
Is this Gladwell’s exact message? No. Will it be taken that way? Yes. Does his book promote shallow thinking about dyslexia? Absolutely. Was Chapter 3 such a compelling, rock-solid story that it had to be told, whatever the consequences? I don’t think so.
Which brings me to the actual substance of Gladwell’s argument about dyslexia being a desirable difficulty for even a few people. I found his idea utterly unconvincing, the evidence for key points either shallow, non-existent, or open to obvious alternative explanations. Here is a small sample of some of the howlers that in aggregate made me question whether Gladwell was paying attention to anything except maintaining his perfect narrative structure.
  1. The characterization of dyslexia.
The chapter starts with a brief description of dyslexia, supplying enough semi-accurate detail to establish that it a serious developmental disorder.
The howler was his discussion of the neuroimaging data, which generally have shown a pattern of underactivation in areas relevant to reading (e.g., the left occipital area where spellings are stored) and overactivation elsewhere (e.g., parts of the right hemisphere; the left inferior gyrus, part of Broca’s area). Gladwell’s glib summary of these findings: for dyslexics, “the [fMRI] scan looks like an aerial photo of a city during a blackout.” No, it doesn’t. The scans actually look like this...dyslexics and nondsylexics tend to activate the same neural structures during reading, with differences in degree of activation associated with degree of reading impairment. Differences between dyslexics and nondyslexics are seen in specific, limited regions, not throughout the brain.
Sometimes a contrastive analysis will yield no net activation in an area. This might occur in comparing dyslexics’ performance in a reading condition compared to a baseline condition (e.g. looking at meaningless squiggles). However, that result only indicates “no statistically reliable activation over and above that observed in the baseline condition,” not that the area had its lights out.
Dyslexics also tend to show overactivation in the right hemisphere, which Gladwell describes as the “conceptual side” of the brain, adding yet another entry to a long list of specious characterizations of hemispheric functions.
Gladwell’s goal is in this section is to establish that dyslexia is a serious condition, which doesn’t require the full DSM-IV treatment. He directs readers to Maryanne Wolf’s book on dyslexia for details. But the misstatements in what he does choose to cite raise questions about how much he understands about the condition, how closely he attends to the research, and his apparent willingness to exaggerate for rhetorical effect.
  1. Desirable difficulty?
The term was introduced by Robert Bjork, a UCLA psychologist. In his work the “difficulties” involve ways of structuring a student’s experience (e.g., spaced practice on math problems) that may produce a longer learning curve but better mastery. The idea that dyslexia could be a “desirable difficulty” is apparently Gladwell’s. The link he mentions is a study showing that making print harder to read (by using smaller letters in bad fonts at 60% grayscale) led to better learning by high school and college students compared to normal print. The print manipulation created a desirable difficulty, apparently forcing students to expend more effort, yielding better performance. Dyslexics also expend more effort reading texts because they are poor readers. Perhaps they too can attain the desirable benefits.
The comparison is risible. In one case skilled readers are able to expend additional effort in order to succeed in comprehending a degraded text. In the other case, dyslexics read normal texts laboriously because their abilities are so poor. The comparison is particularly inapt in light of research suggesting that dyslexia is caused by noisy (imprecise) neural processing. On this view the dyslexic brain processes stimuli as though they were degraded, to their misfortune, not benefit.
  1. David Boies.
The main biographical points here are that Boies became highly successful despite being dyslexic, because the condition forced him to develop work-arounds that turn out to be advantageous for a litigator. He read brief summaries of case studies rather than the entire casebook entries. He listened closely in class rather than taking notes, which helped him develop exceptional listening abilities and also gave him more time to think about what was being said. He worked at developing his memory skills. His spoken language is characterized as relatively sparse and employing limited vocabulary.
One question is whether David Boies is dyslexic by valid diagnostic criteria. People’s self-reports are not a reliable or sufficient basis for determining their reading abilities. An author such as Oliver Sacks does not just rely on patients’ characterizations of their conditions; indeed some of his most interesting patients are unaware of a dramatic impairment. I don’t know if Mr. Boies is or was dyslexic, but the behaviors that are described are not specific to dyslexics or strong clinical indicators. It’s said that he didn’t learn to read until third grade, which is common. Many people who aren’t dyslexic don’t like to read (as children they are often called “reluctant readers”). You don’t have to be dyslexic to prefer the Cliffs Notes/Sparknotes version to reading the whole text. Professors often struggle to get students to listen to what they are saying rather than merely take notes or copy slides.
Many people think they read abnormally slowly and with greater effort than normal. However, expectations about reading speeds and effort have been distorted by many years of fraudulent claims about speed reading techniques and the testimony of supposed super mega readers. As a consequence, people’s assessments of their own reading abilities are not accurate.
The suggestion that Mr. Boies succeeded by capitalizing on his listening and memory skills suggests a different causal argument and another narrative arc: People who have extraordinary memory and listening skills may be less dependent on acquiring information via text, requiring them to read less. Reading less works against gaining high levels of reading skill, which requires extended practice. Such persons might end up being relatively poor readers, though not because of a constitutional deficit.
The tendency to mistake normal behaviors for a reading deficiency is illustrated by another anecdote about Mr. Boies, who reports that his spelling was so poor that spell-checkers often could not come up with the correction. Has this ever happened to you? (In spell-checking this document, mine caught the typo “methology,” but did not list the obvious intended target, methodology.) This behavior is characteristic of spell-checkers, not diagnostic of a spelling impairment.
Finally, about Mr. Boies’ spoken language. First, if it is impaired, Mr. Gladwell contradicts himself by emphasizing elsewhere that dyslexia only affects reading. Second, it’s hard to detect any spoken language issues from YouTube videos of Mr. Boies speaking in various settings. Diagnosis cannot be accomplished by remote viewing. But perhaps Mr. Boies prefers to use a limited vocabulary in speaking to journalists.
  1. Dyslexic entrepreneurs.
In support of the idea that dyslexia might be a “desirable difficulty” Gladwell notes that “an extraordinarily high percentage of entrepreneurs are dyslexic”. He cites a study published by Julie Logan, City University of London, in the journal Dyslexia in 2009. Let’s dispense with this quickly. The study used an unnormed checklist for which I could find no evidence as to whether it differentiates dyslexics from nondyslexics. The checklist has 20 questions related to reading, spelling, memory, organizational skills, doing arithmetic in your head, and so on. For reasons that are not fully explained, the researcher chose to a focus on a subset of questions (difficulty with spelling, taking down and passing messages, and a couple of others). The questionnaire was sent to 2000 potential participants, “entrepreneurs” and corporate managers. The low 7% return rate yielded data from 102 entrepreneurs and 37 managers. The main data concern the “incidence of dyslexia,” even though the author had previously noted that the checklist can’t be used to diagnose dyslexia, only indicating “possible” dyslexia. Whereas only 3 of 37 corporate managers exhibited 4 or more dyslexic "traits", 36 of the 102 entrepreneurs did so. There were some other methodological problems and minor findings, which I’ll skip.
The howler for me was Gladwell’s leap from these results to the statement that “an extraordinarily high percentage of entrepreneurs are dyslexic.” Mr. Gladwell: show us the data.
  1. The personality angle.
If you are dyslexic, you might develop personality traits that are beneficial in big business. Gladwell talks about the “Big Five” personality traits, which are openness, conscientiousness, extraversion, agreeableness, and neuroticism. Dyslexia might make people disagreeable because they face so many daily frustrations and challenges. Being disagreeable might be helpful in some high-powered professions. Ergo, it is another desirable side effect of being dyslexic.
At this point I’m thinking: why stop with disagreeableness? What about the claim, popularized in another best seller, that corporate executives score high on tests of sociopathy? Let’s not deprive little sociopaths of their desirable difficulty either.
The howler, though, is that Gladwell’s discussion is entirely speculative, informed only by some personal testimony from some dyslexics who are, apparently, disagreeable. No empirical evidence.
This section provides the segue into the final act, a personal narrative from a Wall Street executive. This one is worth reading but not for the intended reason.
Relevant biographical details: the gentleman self-reports as being a dyslexic, describes a pattern of poor school performance, dislike of reading, life going nowhere. At some point he decides it would be a good idea to get a job on Wall Street. Long story short, he shares a cab with a banking executive who’s charged with starting a new options trading unit, bluffs the guy into giving him a job, lying that he knows a lot about options. He reports that he then picked up a copy of the Bible of options trading, McMillan’s Options as a Strategic Investment, which he proceeded to read, describing in detail the great effort it required. The cab ride was on a Friday, he was hired on Monday, and the options desk was running a week later. The book was read ““in that period of time””. The man so successful that he eventually became the CEO of Goldman Sachs. Dyslexia wins again.
The man seems disagreeable, to be sure, although perhaps more on the sociopathic side given the brazen way he lied his way into a job (and his firm’s deep, ethically indefensible, and obscenely lucrative participation in the subprime mortgage debacle).
But what about that bit about reading the Bible of the options trade in a few days? The man is dyslexic. He says it takes him about 6 hours to read 22 pages and that he won’t be reading Gladwell’s book because of the time and effort involved. The current edition of the McMillan Bible is 1072 pages. At 3.67 pages an hour, it would take approximately 292 hours to read the book. Say the guy picked up the book on Saturday and read straight through until the Monday the options unit opened. That’s 216 hours. To have completed the book reading at this rate the man would have had to read continuously about 32 hours a day.
Maybe he read an earlier edition of the book that was only 800 pages long: 218 hours. Maybe he didn’t have to read the whole book. Maybe he skipped around. Maybe he skimmed. Maybe he’s a genius. Maybe he’s not dyslexic. Maybe he's lying about completing the book in 9 days, just as he lied in his job interview. We don’t know. But something is not right.
The personal narratives in this chapter leave the following impression. Two rich and powerful Master of the Universe types relate self-invented, self-serving life stories to a close but credulous listener, a great writer who can embellish them even further in a book that will be read by millions. The writer either doesn’t have the curiosity to verify whether any of the key assertions are true or doesn’t want to ruin a great story.
It seems obvious that some professions tend to attract some types of people, and that different cognitive capacities and personality traits can be beneficial in different contexts. You could look it up. Some professions are surely better suited to people with impairments than others. For many years deaf people were overrepresented in the typesetting industry, for example. Some people’s impairments motivate them to excel and to do so by developing other skills. We admire people who succeed despite apparent handicaps.
Gladwell's novel contribution was to use superachievers to connect dyslexia with "desirable difficulty." With Boies and the Goldman Sachs guy, the role of their putative dyslexia in their professional success is unknown: the experiment can’t be run again with the relevant control conditions. Gladwell is still dealing with outliers, the subject of his last book. Outlier data can be highly informative but not the basis for generalizing, in this case to the mass of individuals who have to live with dyslexia and find ways to cope with it.
My great concern is that the desirable difficulty concept will combine in malevolent ways with the brush-offs that dyslexics already encounter, particularly “They grow out of it.” Both concepts encourage parents and educators to wait and see. That is dangerous advice, because with dyslexia, as with many other developmental disorders for which treatment is available, early identification and intervention offer the best hope of success. Though not at the level of David Boies, to be sure.
Other insightful commentaries on Gladwell’s new book, and the dyslexia chapter in particular, have begun to appear.

Further news on dyslexia
There is a new development in understanding dyslexia. (Jamie Talan; A New Theory - and Brain Areas Implicated – to Explain Dyslexia (2014); Neurology Today, 14(3))
Adult dyslexics were compared to matched normal readers in scans while they were comparing phoneme sounds. They used the consonants that were most rapid (b d g p t k). I suppose that was in order to compare to the theory that dyslexics cannot deal with fast sounds. The two groups did not differ the the accuracy of phonetic representation but the dyslexics took much longer to response. This implied that the dyslexics did not have problems discriminating the sounds but did have problems processing the information.
Part of Broca's area accesses the auditory cortices for the information required for its phonological manipulations. The nerve track between these areas, the left arcuate fasciculus, was thinner in the dyslexics. Also the extent of difference in the track correlated with the extent of difficulties in the individuals.
As this gives us three theories: dyslexics cannot process short sounds and work orally with syllables so that learning phonetic symbols in order to read/spell is difficult; dyslexics lack communication between the left and right hemispheres in the area of auditory perception; and now, the auditory area is poorly connected to part of the language area (at least in adults). I assume that all these could be correct. First there is a fault in the area of auditory perception of short consonant sounds, this results in weak connections between the damaged area and the language center and between the two hemispheres during early development. When (if) the dyslexic learns to overcome the problem to the extent of being able to read and write, it is because other areas and pathways are being used to do the work of the damaged areas and non-existent connections. Phonological therapy remains the best help for dyslexic children just learning to read, even though dyslexic adults may appear to have normal-ish phoneme discrimination.
Here is a comment on the research by an authority, Dr. Tallal. “...brain differences assessed in adult samples likely reflect compensatory outcomes rather than the cause of dyslexia. It is important to understand that the neural mechanisms that are involved in developing a complex function such as reading are not the same as those needed to maintain that same function once developed. If we want to understand the causes of developmental disabilities we need to study development as it unfolds...
We need specialization for rapid processing. I am questioning whether the investigators looked at unilateral versus bilateral processing. Even though the dyslexics show more right hemisphere activity than normal readers they conclude that there is no difference in the interpretation of sound in the two groups — dyslexics and normal readers. Dyslexics may be getting there, but not the same way as normal readers. The brain is processing the acoustic information but through an alternate pathway that is not normal.... there is a disconnection in the pathway between the temporal parietal region and the inferior frontal gyrus (Broca's area) in the left hemisphere, but the disruption may occur because the acoustic information itself is represented more bilaterally by dyslexics and in different regions of the brain.”
picture: yellow – auditory cortex, green – Broca's area, blue – missing connection

Too much of a good thing
Antioxidants can be too much of a good thing. Free radicals are very reactive substances – they can damage cells by reacting with important chemicals. Antioxidants are also reactive and prefer to react with free radicals and so making them harmless. In order to cut down on free radicals, many people take antioxidants in supplements. They also can be obtained in a good diet.
But this can be overdone. Free radicals are also signaling the condition of energy production in cells. They also act as signals that cause the heart to beat with the correct force. It is a myth that free radicals should be brought down – they only need to be lowered if they are exceptionally high. Under normal conditions, free radicals should be left alone to do their signaling.
When the body is subject to stress, the sympathetic nervous system stimulates beta-adrenergic receptors on the surface of heart muscle cells. The stimulation of the receptors leads to increased production of free radicals in the mitochondria, more energy, the contractions of the cells becoming stronger and the heart beating with greater force. Antioxidants interfere with this effect and so extra antioxidants are only needed to counteract prolonged high stress that might lead to heart failure.
The effect may be particularly important to the heart but the free radical levels also help regulate the production of energy in other (perhaps all) cells in the body. It is wise not to overdo the intake of antioxidants.

The American Psychiatric Association publishes the Diagnostic and Statistical Manual (DMS) which is used as the 'bible' in psychiatry. They have just published the fifth addition and it is not good. The quality of this book is important to all of us because in it is used by doctors in diagnosis and treatment, deciding who gets benefits and services, how resources are allocated, advice in legal judgments, the labeling and stigma of patients, special education provisions. It should be carefully written and command consensus among psychologists – it does not. It is accused of lack of testing, undue influence from big pharm, not following good established science, lack of consultation, and haste.
Here is Allen Frances' list of the 10 worst changes found in the new manual. He says doctors should ignore these 10.
1. Disruptive Mood Dysregulation Disorder is a new condition. In essence it is child temper tantrums. The condition is based on very slim research. This is likely to lead to more medication of young children.
2. Major Depressive Disorder is a new condition. This is what we have known as normal grief. So pills will take the place of the ways grief has been accepted in the past.
3. Minor Neurocognitive Disorder is a new condition. It covers the everyday forgetting that happens in old age. There isn't even a pill for this and it may be confusing to patients if they think they are being diagnosed with dementia.
4. Adult Attention Deficit Disorder is a new condition. There is a worry in the profession that this will contribute to drug misuse (recreational use of prescription drugs).
5. Binge Eating Disorder now has a definition of 12 occasions of excessive eating in 3 months (gluttony once a week qualifies).
6. Autism definition has been changed. This is probably to good change from the stand point of the doctors but it will needlessly affect many people who receive special services and education.
7. First time substance abusers will be lumped in definitionally in with hard core addicts despite their very different treatment needs and prognosis and the stigma this will cause.
8. Behavioral Addictions can be applied to most anything that people do a lot. It will lead to over-diagnosis of internet addiction, sex addiction etc.
9. Generalized Anxiety Disorder has a obscure boundary with the normal worries of everyday life. The reason for more pills.
10. The diagnosis of PTSD was a problem and the new manual has made it more of a problem in forensics.

Doctor doubting the need for gluten-free diets
I have just read an article on gluten-free diets by Brett Belchetz in Huffington Post. I have rarely read something so crazy. He actually states non-celiac gluten sensitivity is “a dietary condition that research suggests doesn't exist, for which there was no objective laboratory test, and for which treatment would cost your household thousands of dollars per year, while raising your fat and calorie intake with no measurable health benefits”. He claims that 28% of the population have self-diagnosed themselves with gluten sensitivity where as 1% of the population has celiac and they were all diagnosed as children. He has just left out a sizable group of people – those with adult onset celiac. For this group there are laboratory tests and biopsy tests. Some of the self-diagnosed people fall into this group. The nature and mechanism of celiac has been investigated for children and now for adults. It is not a condition that doesn't exist even though many subjects are self-diagnosed (why should anyone go though a biopsy just to prove that is obvious in dietary testing). So lets remove them from the 28%. Then we have people with a straight forward allergy to wheat. This is not unknown and can be tested for. But again as with many allergies (dairy, seafood etc. many people self-diagnose the obvious). They can remove them from the 28%. There are people who feel better on less carbohydrate – almost always self diagnosed. That leaves a remainder that are fooling themselves or are food fad junkies. It is probably fair to criticize this last group but what harm are they doing to anyone else. Criticizing adult celiac and wheat allergy sufferers is another matter. Next point, treatment does not cost thousands a year. It costs nothing to not eat bread; what costs is buying fake bread. You do not put on weight by cutting bread; you put on diet by eating fake bread. It has been 8 years since I tasted real bread. I have had gluten-free bread on two occasions and for about a week while travelling – it was not worth buying at any price because it did not taste of bread or much else for that matter. It also made me nervous about what was in it. I had gluten-free pasta once and that was enough. The only gluten-free product we buy regularly is a corn based thickener for gravies and sauces. It is easy to manage a gluten-free diet with very little additional expense. It does not add to fat or carb intake, it is not unhealthy. I am self-diagnosed. I went to the doctors repeatedly when my symptoms started. I was checked, scoped and Xrayed etc. - a complete diagnostic workout for GI problems. And I was told there was no reason for my diarrhea. I decided it might be an allergy. I cut dairy products and then challenged with a high dairy meal after about 3 weeks. There was no improvement or reaction to the challenge. I did the same with lentils and so on through the common allergies. It did not occur to me to try cutting gluten until I heard about adult celiac. I felt slightly better cuting and worse with a challenge. I continued to improve without gluten and after a second challenge, I went permanently off gluten. But I was challenged twice more later accidentally because I was not aware of the amount of gluten in some flavouring cubes and in soy sauce. I continued to improve for more than 2 years and also noticed improvement in a skin condition and in my rhummy joints. The reason for going through all this is that I am getting very tired of doctors tell people that their illnesses are their imagination. I remember how much the people in pain from their ulcers were told that if they just relaxed their personality type, they would get better. They had an infection in their stomach (you would have an uptight personality if you were in pain all the time too). But doctors were very reluctant to accept this idea even when the proof was coming in. Doctors are prone to say there is nothing they can do to help the obese because it is just an overeating problem. Many doctors still do not accept chronic fatigue or ME. I am sick of those doctors who are telling people who are actually suffering that they are not ill, that they have been taken in by a fraud or fad, or that they have a psychological problem. This kind of doctor is arrogant and cruel, besides practicing bad medicine. Belchetz has given inaccurate ammunition to those who want to talk (or even trick) someone out of their gluten-free diet.

Watch out for dietary advice
graph I have written before about bad advice on nutrition. The belief now is that fats are not bad (except trans fats), some unsaturated fats are extra good, carbohydrates are good in moderation and if they are not too refined, dairy is OK, fibre is good, avoid too much salt. Good is fresh fruit and vegetable, fish, nuts, chocolate. Meat is OK in moderation. Avoid sweet sodas, highly processed foods (especially meats), empty calories. The advice is exercise, eat real food, not too much, mostly plants, with variety. If possible cook at home and avoid 'food' made in factories. Many spices and herbs are good in moderation. Vitamin D may be need but if you eat well you should not need other vitamin and mineral supplements. And do not believe every new announcement – they are often wrong. Do not trust the big food company ads.
“According to Katz, Americans did not gain weight by increasing carbohydrate consumption during the 'fat scare'; they simply ate more low-fat junk. In 1977, the advice to cut down fat was intended to direct Americans to naturally low-fat foods that made up the bulk of supermarket products at the time, including vegetables, fruits, beans and whole grains. Instead, the food industry perverted the guidelines by creating highly palatable reduced-fat food. It is big business: according to the Hudson Institute, low-fat, light or diet better-for-you products drove roughly 70% of food company sales growth from 2007-2011. The result? We began to over-consume fat-free, sugar-laden foods. Every year, the food industry spends billions of dollars selling the low-fat-is-good-health message, insinuating that we can eat limitless 'healthy' low-fat junk foods with impunity.” The food industry has fought the 'fat is not bad' message with all that they have. There is a lot of money to be made and its a jungle out there.
Tens of thousands of papers on nutrition are published each year. Many contradict each other, many are too small a sampling, many use bad methodology. If one followed every announcement, every fad, every new food product, one would lose one's mind. You simply cannot believe every article you read. To protect yourself, you have to avoid going overboard with any nutritional idea.


What causes fibromyalgia?
shunts There is a new, credible, explanation of the pain and fatigue of fibromyalgia. It is faulty AV shunts. What are AV shunts?
The body has to regulate temperature very closely to protect the core internal organs. Heat is produced primarily by muscles and lost primarily by skin. The loss through the skin is regulated by how much of the blood flows through the little capillaries in the skin surface. (We flush pink when hot and have white skin when cold – indications of the amount of blood in the capillaries.) The mechanism for controlling the amount of blood that goes through the skin is the opening or closing of bypasses or shunts between the little arteries that take blood to the skin's capillaries and the little veins that take it away. The AV shunts are surrounded by tiny muscles that contracts to close the paths to the capillaries and relax to open the paths. These muscles are controlled by two sets of nerves to fine tune the amount of blood going to the capillaries and thus keeping the core temperature constant. The fibromyalgia fault is in one of these sets of nerves – there is way too many of them at the AV shunts and they do not act correctly.
Not only do the extra nerves themselves give painful signals but they do not allow enough blood to flow to the large muscles of the body during exertion. The muscles then form lactic acid and suffer fatigue. Between the AV shunt nerves and the fatigued muscles, pain and fatigue is felt throughout the body.

News on Diabetes
There is a new development in understanding diabetes. The very serious disease Type1 Diabetes which can only be treated with insulin injections and is otherwise fatal, and the more gradual onset Type2 Diabetes which can be treated with diet and pills (also called Juvenile and Adult onset) have until now been treated as diseases with different causes. Now there is a theory that they are both caused by the build up of toxic accumulations of amylin.
Amylin and insulin are both hormones produced by the pancreas. They work together to control the level of glucose in the blood. Without this control the glucose rises to levels that are harmful to many organs. Insulin controls the removal of glucose from the blood by muscle and other tissues. Amylin slows the entrance of glucose into the blood by inhibiting over eating and slowing the emptying of the stomach.
Amylin can clump (like amyloid in Alzheimer's) and this poisons the cells that produce the two hormones. The scientists working on this believe that it will only be a couple of years before they have drugs to test.

New Chronic Fatigue theory
Two Japanese researchers, Tanaka and Watanabe, think they have cracked the fatigue part of CF/ME (new pain part theory was reviewed above). This is a fault in the way the central nervous system fails to deal with the need for increased effort.
Normal fatigue happens like this:
We want to do a physical task so the primary motor cortex activates the motor neurons in the spinal cord which send signals to some individual muscle fibers to contract. If those fibers start to fatigue then more effort is need, the motor cortex increases its activation of the spinal cord and more fibers join the contraction. We feel this as more effort but not as fatigue. But when all the fibers are contracting and there are no more to recruit, we start to feel fatigue as resources are used up in the muscle and lactic acid is produced. We can stop the effort or increase it to work through the fatigue for a little while but in the end we have to stop due to fatigue. This increase in effort after fatigue has started is called 'facilitation', and it seems to supply some extra energy to the muscles. The facilitation system includes: the limbic system, basal ganglia, thalamus, orbitofrontal cortex, prefrontal cortex, anterior cingulate cortex. They allow the premotor area, supplementary motor area and primary motor cortex to signal for the extra effort. There is another system (a sort of safety valve), the fatigue inhibition system, that can override the facilitation system and stop signals from the motor cortex to increase muscle effort. Working through the fatigue stops; you have hit the wall as they say.
What happens in chronic fatigue:
First there is a problem in recruiting fibers even when there are fresh fibers to be recruited. This seems to be a fault of the motor part of the cortex or basal gangia inputs to the cortex. It causes fatigue to set in very quickly, 'central fatigue'. This early, constant fatigue activates the fatigue inhibition system to stop any signals to the muscles. Overuse of the facilitation system simply locks down the commands to muscles. The researchers think that the dorsal lateral prefrontal cortex is the key at this stage. It seems to decide between energy enhancement or chronic fatigue.
“Here in a nutshell is how it appears to work: Once you begin feeling mentally fatigued you, without knowing it, activate something called the facilitation system to enhance your mental performance. This system consists of a neural loop connecting the limbic system, basal ganglia, thalamus, and frontal cortex. It’s thrown into action mainly through dopaminergic inputs into the striatal-thalamic-frontal loop, but studies suggest those are inhibited in ME/CFS. Cranking up this facilitation system too often (something that will surely occur in ME/CFS) causes an inhibition system (consisting of the thalamus, somatosensory cortex, insular cortex, posterior cingulate cortex, and frontal cortex) to become activated to suppress performance – to induce rest and avoid more fatigue. The more you try to punch through your fatigue, the more the inhibition system (via classical conditioning) induces fatigue. At this point you’re in a state of ongoing chronic fatigue. Damage to the prefrontal cortex likely pushes the brain to increase activity in the fatigue-inducing circuit. ” There is probably a fault in the signals going from the muscles to the brain as well as faults in the other direction, and there is some evidence for this.

New Alzheimer's testing system
There has been an argument on the cause of Alzheimer's between the amyloid school and the tau school. The tau people point out that it is the tau tangles that kill neurons. The amyloid people point out that the genetic form of Alzheimer's is caused by the enzyme that produces beta-amyloid plaques. Some researchers say that it takes both problems. The mice strains that are used for testing drugs are either amyloid faulty or tau faulty but not both, which would mean that in mice, either fault can cause the Alzheimer's mimic.
Now a group has developed a human test setup. Human cell systems have not worked well in the past. The researchers add a gel and made the human neural stem cell culture system 3 dimensional. This made it work better. In fact it will probably mean faster, simpler, cheaper and actually human rather than mouse screening of new drugs prospects. The system shows both beta-amyloid and tau production with particular genetic types of stem cells.

Hopefully, this will encourage universities and drug companies to return to the search for treatments/cures for Alzheimer's. There was great disappointment in the failures of almost all of the long trials for Alzheimer's drugs and little interest in starting more such expensive dead-ends. A faster and cheaper method should change the atmosphere.

Reversing memory loss
I learned from first hand experience that high blood pressure really hurts the memory, and a change of hypertension drug strength can return it to normal. Bladder infections, I learned second hand, do likewise and the memory returns when the infection is cured. I have never associated these memory loses with Alzheimer's. But here is an interesting paper:
Review of paper by Bredesen in the journal Aging Sept 2014 “Reveral of cognitive decline: a novel therapeutic program.
In the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants displayed subjective or objective improvement in their memories beginning within three to six months after the program’s start.
Patient one had two years of progressive memory loss. She was considering quitting her job, which involved analyzing data and writing reports, she got disoriented driving, and mixed up the names of her pets. Patient two kept forgetting once familiar faces at work, forgot his gym locker combination, and had to have his assistants constantly remind him of his work schedule. Patient three's memory was so bad she used an iPad to record everything, then forgot her password. Her children noticed she commonly lost her train of thought in mid-sentence, and often asked them if they had carried out the tasks that she mistakenly thought she had asked them to do.
Since its first description over 100 years ago, Alzheimer's disease has been without effective treatment. That may finally be about to change: in the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants, including the ones above, displayed subjective or objective improvement in their memories beginning within three to six months after the program's start. Of the six patients who had to discontinue working or were struggling with their jobs at the time they joined the study, all were able to return to work or continue working with improved performance. Improvements have been sustained, and as of this writing the longest patient follow-up is two and one-half years from initial treatment. These first ten included patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI; when a patient reports cognitive problems). One patient, diagnosed with late stage Alzheimer's, did not improve.
The study, which comes jointly from the UCLA Mary S. Easton Center for Alzheimer's Disease Research and the Buck Institute for Research on Aging, is the first to suggest that memory loss in patients may be reversed, and improvement sustained, using a complex, 36-point therapeutic program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.
The findings, published in the current online edition of the journal Aging, "are very encouraging. However, at the current time the results are anecdotal, and therefore a more extensive, controlled clinical trial is warranted," said Dale Bredesen, the Augustus Rose Professor of Neurology and Director of the Easton Center at UCLA, a professor at the Buck Institute, and the author of the paper.
In the case of Alzheimer's disease, Bredesen notes, there is not one drug that has been developed that stops or even slows the disease's progression, and drugs have only had modest effects on symptoms. "In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer's at an aggregate cost of over a billion dollars, without success," he said.
Other chronic illnesses such as cardiovascular disease, cancer, and HIV, have been improved through the use of combination therapies, he noted. Yet in the case of Alzheimer's and other memory disorders, comprehensive combination therapies have not been explored. Yet over the past few decades, genetic and biochemical research has revealed an extensive network of molecular interactions involved in AD pathogenesis. "That suggested that a broader-based therapeutics approach, rather than a single drug that aims at a single target, may be feasible and potentially more effective for the treatment of cognitive decline due to Alzheimer's," said Bredesen.
While extensive preclinical studies from numerous laboratories have identified single pathogenetic targets for potential intervention, in human studies, such single target therapeutic approaches have not borne out. But, said Bredesen, it's possible addressing multiple targets within the network underlying AD may be successful even when each target is affected in a relatively modest way. "In other words," he said, "the effects of the various targets may be additive, or even synergistic."
The uniform failure of drug trials in Alzheimer's influenced Bredesen's research to get a better understanding of the fundamental nature of the disease. His laboratory has found evidence that Alzheimer's disease stems from an imbalance in nerve cell signaling: in the normal brain, specific signals foster nerve connections and memory making, while balancing signals support memory loss, allowing irrelevant information to be forgotten. But in Alzheimer's disease, the balance of these opposing signals is disturbed, nerve connections are suppressed, and memories are lost.
The model of multiple targets and an imbalance in signaling runs contrary to the popular dogma that Alzheimer's is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain -- as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer's disease shifts the memory-making vs. memory-breaking balance in favor of memory loss.
Given all this, Bredesen thought that rather than a single targeted agent, the solution might be a systems type approach, the kind that is in line with the approach taken with other chronic illnesses -- a multiple-component system.
"The existing Alzheimer's drugs affect a single target, but Alzheimer's disease is more complex. Imagine having a roof with 36 holes in it, and your drug patched one hole very well -- the drug may have worked, a single "hole" may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much."
Bredesen's approach is personalized to the patient, based on extensive testing to determine what is affecting the plasticity signaling network of the brain. As one example, in the case of the patient with the demanding job who was forgetting her way home, her therapeutic program consisted of some, but not all of the components involved with Bredesen's therapeutic program, and included:
(1) eliminating all simple carbohydrates, leading to a weight loss of 20 pounds;
(2) eliminating gluten and processed food from her diet, with increased vegetables, fruits, and non-farmed fish;
(3) to reduce stress, she began yoga;
(4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day;
(5) she took melatonin each night;
(6) she increased her sleep from 4-5 hours per night to 7-8 hours per night;
(7) she took methylcobalamin each day;
(8) she took vitamin D3 each day;
(9) fish oil each day;
(10) CoQ10 each day;
(11) she optimized her oral hygiene using an electric flosser and electric toothbrush;
(12) following discussion with her primary care provider, she reinstated hormone replacement therapy that had been discontinued;
(13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime;
(14) she exercised for a minimum of 30 minutes, 4-6 days per week.
The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. "This is the first successful demonstration," he noted, but he cautioned that the results are anecdotal, and therefore a more extensive, controlled clinical trial is needed.
The downside to this program is its complexity. It is not easy to follow, with the burden falling on the patients and caregivers, and none of the patients were able to stick to the entire protocol. The significant diet and lifestyle changes, and multiple pills required each day, were the two most common complaints. The good news, though, said Bredesen, are the side effects: "It is noteworthy that the major side effect of this therapeutic system is improved health and an optimal body mass index, a stark contrast to the side effects of many drugs."
The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. "This is the first successful demonstration," he noted, but he cautioned that the results need to be replicated. "The current, anecdotal results require a larger trial, not only to confirm or refute the results reported here, but also to address key questions raised, such as the degree of improvement that can be achieved routinely, how late in the course of cognitive decline reversal can be effected, whether such an approach may be effective in patients with familial Alzheimer's disease, and last, how long improvement can be sustained," he said.
Cognitive decline is a major concern of the aging population. Already, Alzheimer's disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it's estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer's disease is on the rise--recent estimates suggest that AD has become the third leading cause of death in the United States behind cardiovascular disease and cancer.

Shh don't tell anyone
graph This is a graph of what is called the obesity paradox. It is not true that the more you weigh the shorter your life. Being both way too thin or way too fat cuts your life expectancy. Also the older you get the more heavy is the optimal weight. This is in spite of over weight being a risk factor for diabetes, heart disease, cancer and other chronic diseases. (But the risk of getting diabetes is higher but the life expectancy once diabetes is diagnosis is longer.) This somewhat odd situation is why it is a paradox. At first it was not accepted and more studies were done. Meetings were held to discuss what could be wrong with the data. That fight is over and scientists accept the data – there is a paradox, and a number of possible explanations.
Now the discussions are over whether this information shown be reported in the press. People might stop trying to keep a good weight, doctors might stop encouraging weight loss in over-weight patients, but particularly the public might stop trusting science. “Some public-health experts fear, however, that people could take that message as a general endorsement of weight gain. Willett says that he is also concerned that obesity-paradox studies could undermine people’s trust in science. “You hear it so often, people say: ‘I read something one month and then a couple of months later I hear the opposite. Scientists just can’t get it right’,” he says. “We see that time and time again being exploited, by the soda industry, in the case of obesity, or by the oil industry, in the case of global warming.”
The other side says, the data is the data, it should be published and people can make of it what they will. “I work for a federal statistical agency. Our job is not to make policy, it’s to provide accurate information to guide policy-makers and other people who are interested in these topics.” Data is “not intended to have a message”.
This problem is showing up in reports on diet (fat vs carbs, Vit D, gluten etc.) - some want to, in effect, suppress information so that the public doesn't have to follow back and forth disagreements. Some climate researchers are criticized for publishing reports that conflict with other reports. Neuroscientist are told by philosophers not to keep reporting results that contradict folk psychology. This is dangerous for science – it depends on honest reporting and open discussion. The general public will have to learn that nothing is written in stone and newspapers are not the best place to get scientific information.

The mechanism of red wine health effects
The compound that is the supposed source of red wine's health benefits is resveratrol. (Also found in red grapes, peanuts, mulberries, cacao and some other plants.) There has been some “yes it is – no it isn't” back and forth on whether resveratrol is really effective at the amounts found in red wine. It is said to prevent cancer, protect the heart, and prevent metabolic syndrome/diabetes.
Researchers have now found a possible mechanism for resveratrol to have these effects. Resveratrol interacts with tyrosyl tRNA synthetase (TyrRS) which the body produces in response to stress. This interaction activates one compound and increases the levels of three compounds in the body: p53 which is known to inhibit tumor growth, AMPK which is known to promote cell survival under stress, and SIRT6 which is known to reduce blood glucose. It activates PARP-1 which is a DNA repair factor. Human clinical trials are planned.
Why would resveratrol be produced in plants but be so potent in humans? Plants also must deal with stressful situations and they to use tyrosyl tRNA synthetase to respond to stress. TyrRS is a protein with other functions and is fundamental to life. It is essential to make the transfer RNA to deliver an amino acid, tyrosine, during the making of any protein. It is ancient and has not changed since before plants and animals separated in evolution. "We believe that TyrRS has evolved to act as a top-level switch or activator of a fundamental cell-protecting mechanism that works in virtually all forms of life," said one of the researchers, Sajish.
In the meantime, we do know that the Mediterranean diet is good for health. It includes: more fish and vegetables and less red meat, olive oil, red wine.