{"id":877,"date":"2019-09-16T12:25:12","date_gmt":"2019-09-16T12:25:12","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=877"},"modified":"2019-09-16T17:28:09","modified_gmt":"2019-09-16T17:28:09","slug":"scaling-the-alzheimers-cure","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2019\/09\/16\/scaling-the-alzheimers-cure\/","title":{"rendered":"Scaling the Alzheimer&rsquo;s Cure"},"content":{"rendered":"<p><i>This edition of Aging Matters is stolen from <\/i><a href=\"https:\/\/www.youtube.com\/watch?v=Sq7uVZ_0D3U\"><i>Rhonda Patrick\u2019s interview of Dale Bredesen<\/i><\/a><i>. That hour is so packed with actionable information and theoretical background that I found myself going through it slowly to understand and digest it. The result was an appreciation for the breadth of vision embodied in Bredesen\u2019s comprehensive program to combat Alzheimer\u2019s Disease, and also discovery of some gaps in which the story appears incoherent.<\/i><\/p>\n<p><i>For my own health and to learn more, I\u2019ve personally signed up for the RECODE program as a patient. After the video analysis I talk about my experience.<\/i><\/p>\n<hr \/>\n<p><b>The RECODE program in a nutshell<\/b><b><br \/>\n<\/b>from <a href=\"https:\/\/www.youtube.com\/watch?v=q80MXwXb7sA\">Deborah Gordon video<\/a><\/p>\n<ol>\n<li>Diet<\/li>\n<li>Lifestyle<\/li>\n<li>Hormone re-balancing<\/li>\n<li>Supplements<\/li>\n<\/ol>\n<ol>\n<li><b><i> Diet<\/i><\/b>: Low grains, low glycemic, high fats, quasi-ketogenic, anti-inflammatory. Intermittent fasting (e.g., 13 hours overnight fast every day). Eggs are good. Cilanthro is detoxifying. Ketones are good for the brain. Medium-chain triglycerides (MCTs) are a good shortcut to ketogenesis.<\/li>\n<li><b><i> Lifestyle<\/i><\/b>: Exercise 30-60 min each day, the more the better. Weights and interval training are particularly good. Sleep 8 hours each night. Challenge the mind with active learning and problem-solving.<\/li>\n<li><b><i> Hormones<\/i><\/b>: Estradiol, testosterone (DHEA), Pregnenolone, Thyroid hormones, Progesterone (but not progestins)<\/li>\n<li><b><i> Anti-diabetic supplements<\/i><\/b>: Magnesium, Chromium, Berberine, Vinegar, Cinnamon<br \/>\n<b><i>Nootropic supplements<\/i><\/b>: Ashwagandha, Gotu kola, Curcumin, Bacopa, NR, Mg Threonate<br \/>\nLion\u2019s Mane, ALCAR=Carnitine, Citicoline, DHA=Omega 3, PQQ,<\/li>\n<\/ol>\n<p>Blood targets:<\/p>\n<ul>\n<li>Homocysteine &lt;7 (!)<\/li>\n<li>Vit B12 &gt;500<\/li>\n<li>CRP &lt;1<\/li>\n<li>HbA1C &lt;5.5<\/li>\n<li>Insulin &lt; 5<\/li>\n<li>Vit D &gt;50, up to 100<\/li>\n<li>Zn\/Cu &gt;1 and Zn &gt;100<\/li>\n<\/ul>\n<p>Also from the <a href=\"https:\/\/www.youtube.com\/watch?v=q80MXwXb7sA\">Deborah Gordon video<\/a>: The APO\u03b54 allele is the biggest genetic risk factor for AD. It was the ancestral form of the gene, from early hominid history. In European populations, only 15% of genes are \u03b54, but there are tribes in Nigeria where the APO\u03b54 gene still predominates and, paradoxically, they have low rates of AD, <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/7668835\">even lower than Nigerians who don\u2019t have the APO\u03b54 allele<\/a>. (Maybe it\u2019s <a href=\"https:\/\/www.statnews.com\/2017\/08\/22\/alzheimers-apoe4-risk\/\">something they ate<\/a>.)<\/p>\n<p>A simple blood test or 23andMe can tell you if you have the APO\u03b54 risk factor, but many people don\u2019t want to know. Bredesen\u2019s program offers differential treatment for APO\u03b54 patients, and can greatly reduce the excess risk if started early.<\/p>\n<hr \/>\n<p><b>Notes from <\/b><a href=\"https:\/\/www.youtube.com\/watch?v=Sq7uVZ_0D3U\"><b>Rhonda Patrick\u2019s interview with Dale Bredesen<\/b><\/a><\/p>\n<p>AD is the 3rd leading cause of death in America, after cardiovascular disease and cancer, and it is rising as the population ages and as better treatments become available for the other two. 5.2 million Americans have been diagnosed with AD, and a substantial fraction remains undiagnosed.<\/p>\n<p>Diagnostic markers of AD are tau tangles and amyloid-\u03b2 placques in the brain. Amyloid-\u03b2 is a protein byproduct that aggregates into clumps about the size of a nerve cell. Tau is another protein that clogs microtubules, preventing chemical transmissions. Curiously, most AD patients have these markers, but some people have the markers without dementia symptoms, and others have dementia without the markers.<\/p>\n<figure id=\"attachment_878\" aria-describedby=\"caption-attachment-878\" style=\"width: 732px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-878 size-full\" src=\"https:\/\/scienceblog.com\/wp-content\/uploads\/sites\/2\/2019\/09\/Plaques-and-Tangles.png\" alt=\"\" width=\"742\" height=\"494\" srcset=\"https:\/\/scienceblog.com\/joshmitteldorf\/wp-content\/uploads\/sites\/2\/2019\/09\/Plaques-and-Tangles.png 742w, https:\/\/scienceblog.com\/joshmitteldorf\/wp-content\/uploads\/sites\/2\/2019\/09\/Plaques-and-Tangles-300x200.png 300w, https:\/\/scienceblog.com\/joshmitteldorf\/wp-content\/uploads\/sites\/2\/2019\/09\/Plaques-and-Tangles-451x300.png 451w\" sizes=\"auto, (max-width: 742px) 100vw, 742px\" \/><figcaption id=\"caption-attachment-878\" class=\"wp-caption-text\">Plaques are pink, Tau tangles black<\/figcaption><\/figure>\n<p>Spinal fluid taps can be assayed for presence of Amyloid-\u03b2, and this is the most sensitive test we have for AD, with an accuracy of 90%<\/p>\n<p>A-\u03b2 is both a neurotoxin and a neuro-protector, in different contexts. So the theory is that A-\u03b2 is produced by the brain in response to insults. A-\u03b2 can neutralize toxic metals and can kill invading microbes. Some people\u2019s brains produce A-\u03b2 and it successfully protects them, while others are producing A-\u03b2 though their brains are overwhelmed. One difference seems to be inflammation. Inflammation in combination with A-\u03b2 creates a strong dementia risk.<\/p>\n<p>Sirtuins and NF\u03baB are mutually inhibitory. The body flips between a pro-inflammatory state (NF\u03baB) and anti-inflammatory (sirtuins), and age almost always tips the balance toward more inflammation (NF\u03baB).<\/p>\n<p>Microglia are environmental brain cells, not neurons, but important to brain function. They are activated in two forms, called <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25598354\">M1 and M2<\/a><\/p>\n<figure style=\"width: 466px\" class=\"wp-caption alignnone\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.researchgate.net\/profile\/Weidong_Le2\/publication\/271139991\/figure\/fig1\/AS:295166482108420@1447384581881\/M1-and-M2-microglia-Microglia-possess-states-of-classical-activation-alternative_W640.jpg\" alt=\"\" width=\"476\" height=\"534\" \/><figcaption class=\"wp-caption-text\">There\u2019s an ideal ratio of M1:M2 = inflammation:resolution = 2.5<span style=\"text-align: center;background-color: #ffffff;color: #333333;font-family: 'Helvetica Neue', Helvetica, Arial, 'Nimbus Sans L', sans-serif;font-size: 15px\">\u00a0<\/span><\/figcaption><\/figure>\n<p>The amount of A-\u03b2 in the brain comes from a balance between A-\u03b2 production during glial metabolism and A-\u03b2 elimination through phagocytosis. That is to say, A-\u03b2 is constantly being consumed and eliminated by a class of white blood cells. A <a href=\"https:\/\/content.iospress.com\/articles\/journal-of-alzheimers-disease\/jad00426\">blood test by George Bernard<\/a> has shown that almost everyone diagnosed with AD is not eliminating enough A-\u03b2 via phagocytosis.<\/p>\n<p><a href=\"https:\/\/www.lipidhome.co.uk\/lipids\/fa-eic\/eicresol\/index.htm\">Maresins and resolvins<\/a> are members of a group of cell signaling molecules called SPMs or \u201cspecialized pro-resolving mediators.\u201d Many SPMs are metabolites of omega-3 fatty acids and have been proposed to be responsible for the anti-inflammatory benefits of omega-3 in the diet. Patrick says that in her own research she has found that people who are APO\u03b54 positive benefit from fish in the diet, but not from omega-3 supplements. Bredesen speculates that this might be true generally, and that there are anti-oxidants in fish flesh that we haven\u2019t yet catalogued.<\/p>\n<p><b>How RECODE Works<\/b><\/p>\n<p>Bredesen has identified 36 risk factors for AD, and different patients suffer from different combinations of these. The factors break down into just six categories:<\/p>\n<p><b>Type 1 AD is primarily caused by Inflammation.<\/b><\/p>\n<p>The inflammation may come from a variety of causes, for example<\/p>\n<ul>\n<li>leaky gut (which also contributes to arthritis)<\/li>\n<li><i>P gingivalis<\/i> (a periodontal infection that can spread to the brain)<\/li>\n<li><i>Borrelia burgdorferi is the Lyme bacillus<\/i><\/li>\n<li>Mold and other fungi in the environment<\/li>\n<\/ul>\n<p><b>Type 2 AD is atrophic<\/b><\/p>\n<p>Some of the nutrients or hormones necessary for nerve growth and synaptic connection are missing. Examples include<\/p>\n<ul>\n<li>Estradiol<\/li>\n<li>Vitamin D<\/li>\n<li>Progesterone<\/li>\n<li>Testosterone<\/li>\n<li>Pregnenolone<\/li>\n<li>Thyroid hormones<\/li>\n<\/ul>\n<p>In a healthy brain, there is a balance between learning and forgetting, of growing new synapses and recycling old ones. We can think of Type 1 as too much destruction of synapses, and Type 2 as failure to grow new synapses.<\/p>\n<p><b>Type 1.5 AD is glycotoxicity=too much sugar<\/b><\/p>\n<p>Diabetes has two components: depressed response to insulin (insulin resistance) and excess sugar in the blood (because the insulin signal is not being heeded). The excess blood sugar causes Type 1 symptoms, while the insulin resistance causes Type 2 symptoms. There is both too little creation of new neural connections and also too much loss of existing neural connections. Type 1.5 really means a combination of Type 1 and Type 2, and it is associated with metabolic syndrome or diabetes.<\/p>\n<p>Edward Goetzl of UCSF <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25342129\">has shown<\/a> that AD is characterized by insulin resistance in brain neurons even when the rest of the body is not insulin resistant.<\/p>\n<p>Sugars can bind to proteins, gumming them up, creating <b>A<\/b>dvanced <b>G<\/b>lycation <b>E<\/b>ndproducts, or AGEs. When this happens because of sugar levels that are too high, it\u2019s called glycotoxicity. Hemoglobin A1c is glycated hemoglobin, and it is commonly measured blood tests to assess the extent to which glycation is a problem more generally.<\/p>\n<p>Note: Symptoms for all Types 1, 1.5, and 2 are memory loss, particularly short-term memory.<\/p>\n<p>If your fasting insulin is &gt;4.5 <b>or<\/b> your A1c &gt;5.5 <b>or<\/b> your fasting glucose &gt;93, you have insulin resistance, which is the most common, most important, and most treatable condition leading to AD.<\/p>\n<p><b>\u201cKetoflex 12\/3\u201d <\/b>is a mnemonic for Bredesen\u2019s basic diet program: (1) mild ketosis, ongoing (2) flexible vegetarian diet, treating meat as a condiment (3) 12 hours of fasting every night, beginning 3 hours before bedtime.<\/p>\n<p>Vegetarian is fine. If adding meat, it should be grass-fed beef or free-range fowl. If fish, the best fish are Salmon, Mackerel, Anchovies, Sardines, Herring (mnemonic: \u201cSMASH\u201d) to maximize omega-3s and minimize mercury.<\/p>\n<p><b>Beta hydroxybutyrate (BHB)<\/b> When the body is fasting or deprived of carbohydrates, it switches over to ketones for fuel. BHB is one of the ketones the body burns, and it also signals the body to alter gene expression in a beneficial way.<\/p>\n<p><b>Bredesen recommends 70% of calories from fat.<\/b> This is really on the edge of an extreme keto diet, best achieved with a nut-based diet supplemented by salad oil.<\/p>\n<table style=\"height: 776px\" width=\"583\">\n<tbody>\n<tr>\n<td><\/td>\n<td><strong>% calories from fat<\/strong><\/td>\n<\/tr>\n<tr>\n<td>Walnuts<\/td>\n<td>83%<\/td>\n<\/tr>\n<tr>\n<td>Sesame Tahini<\/td>\n<td>77%<\/td>\n<\/tr>\n<tr>\n<td>Avocado<\/td>\n<td>77%<\/td>\n<\/tr>\n<tr>\n<td>Chocolate unsweetened<\/td>\n<td>74%<\/td>\n<\/tr>\n<tr>\n<td>Peanuts<\/td>\n<td>72%<\/td>\n<\/tr>\n<tr>\n<td>Almonds<\/td>\n<td>72%<\/td>\n<\/tr>\n<tr>\n<td>Sunflower seeds<\/td>\n<td>72%<\/td>\n<\/tr>\n<tr>\n<td>Egg<\/td>\n<td>64%<\/td>\n<\/tr>\n<tr>\n<td>Tofu<\/td>\n<td>57%<\/td>\n<\/tr>\n<tr>\n<td>Chicken drumstick<\/td>\n<td>53%<\/td>\n<\/tr>\n<tr>\n<td>Salmon<\/td>\n<td>49%<\/td>\n<\/tr>\n<tr>\n<td>Milk, whole<\/td>\n<td>47%<\/td>\n<\/tr>\n<tr>\n<td>Ground Beef<\/td>\n<td>44%<\/td>\n<\/tr>\n<tr>\n<td>High-fat yoghurt<\/td>\n<td>31%<\/td>\n<\/tr>\n<tr>\n<td>Kale<\/td>\n<td>30%<\/td>\n<\/tr>\n<tr>\n<td>Brown Rice<\/td>\n<td>15%<\/td>\n<\/tr>\n<tr>\n<td>Broccoli<\/td>\n<td>8%<\/td>\n<\/tr>\n<tr>\n<td>Whole Wheat<\/td>\n<td>5%<\/td>\n<\/tr>\n<tr>\n<td>Oranges<\/td>\n<td>4%<\/td>\n<\/tr>\n<tr>\n<td>Lentils<\/td>\n<td>3%<\/td>\n<\/tr>\n<tr>\n<td>Apples<\/td>\n<td>0%<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>The chart gives you a rough idea of what Keto-flex looks like in practice.\u00a0 Salads with oily dressing are a good staple, since the greens provide fiber and phytonutrients but few calories, and most of the calories are from the oil in the dressing. Nuts are a tasty protein source that keeps the fat intake high. Fruits are bad news. If you eat an apple (0% of calories from fat), you have to expiate the sin with 1\u00bd Tablespoons of salad oil.<\/p>\n<p>It takes a few weeks to switch over from a sugar-burning metabolism to a ketone-burning metabolism. If you try to do it too quickly, you end up with the \u201cketo flu\u201d, headaches, nausea and low energy.<\/p>\n<p>MCT=Medium-chain triglycerides, such as coconut oil, are the best oils for inducing ketosis. They are good for APO\u03b54 negative people, but with APO\u03b54 positive they pose a long-term risk of \u201cbad cholesterol\u201d in the blood. APO\u03b54 positive people should jump-start a ketogenic diet with MCTs, then switch to olive, sunflower, or walnut oil.<\/p>\n<p>During fasting, the body clears out waste outside cells (<a href=\"https:\/\/en.wikipedia.org\/wiki\/Glymphatic_system\">glymphatic system<\/a>) and digests waste within cells (<a href=\"https:\/\/en.wikipedia.org\/wiki\/Autophagy\">autophagy<\/a>). For people who are APO\u03b54 negative, 12-14 hours fasting each day is sufficient, APO\u03b54 positive 15-16 hours is better.<\/p>\n<p><b>Type 3 AD is cortical\/toxicity<\/b><\/p>\n<p>Derives from toxic build-up, heavy metals, pesticides, environmental toxins. Type 3 tends to present with high ratio of copper to zinc in the blood (generally a bad thing) and low triglycerides (generally a good thing).<\/p>\n<p>Copper and zinc compete in the body, and many factors contribute to an excess of copper in modern Western environments (copper water pipes, low stomach acidity). This is one more reason not to take PPIs for common gastric distress or GERD*.<\/p>\n<p>* PPIs include Prilosec and Nexium. Never take PPIs. If you must take PPIs, get off them after a few weeks.\u00a0 This advice is from Mitteldorf, not from Bredesen.<\/p>\n<p>Zinc is a component of many enzymes and hormones in the body, and contributes to neurogenesis and to a healthy immune system. Low zinc is also a risk factor for type 2 diabetes. High copper:zinc ratio increases inflammation. There are many good reasons to keep your zinc levels high, from male sexual function to enhanced immune response.<\/p>\n<p>Note: Presenting symptoms for Type 3 are more often problems with disorientation, calculations, visual perception, reasoning and word-finding. Type 3 is more common in younger patients, in females, and in people without the APO\u03b54 allele.<\/p>\n<p>Look up more information about Type 3 under <a href=\"https:\/\/scholar.google.com\/scholar?hl=en&amp;as_sdt=0%2C39&amp;q=posterior+cortical+atrophy+%28PCA%29&amp;btnG=\">Posterior Cortical Atrophy (PCA)<\/a>.<\/p>\n<p>Damp or water-damaged buildings can lead to toxic mold exposure. Aflatoxin is common in our diet.\u00a0 It comes from grains or nuts that have been improperly stored, and especially from peanuts. Different people can have very different sensititivies to aflatoxin.<\/p>\n<p>Mold contributes to both inflammation and toxicity. You can <a href=\"https:\/\/www.mycometrics.com\/index.html\">test your home<\/a> for mold spores, or <a href=\"https:\/\/www.greatplainslaboratory.com\/gplmycotox\">test your urine<\/a> for mold toxins in the body.<\/p>\n<p><b>Type 4 AD is vascular<\/b><\/p>\n<p>The causes and risk factors are the same as for cardiovascular disease, but arterial blockage can affect the brain as well as the heart.\u00a0 Multiple small strokes lead to loss of function in specific brain areas, inducing idiopathic forms of dementia.<\/p>\n<p><b>Type 5 AD Traumatic<\/b><\/p>\n<p>The same kinds of cognitive symptoms can derive from trauma to the brain, most often from a car accident or sports injury.<\/p>\n<p>&nbsp;<\/p>\n<p><b>From the Discussion between Patrick and Bredesen<\/b><\/p>\n<p>Herpes virus is a risk factor for AD, possibly because of its inflammatory effect.<\/p>\n<p>Saunas are protective against AD. This is because of heat shock protein, but also because sweating helps the body to eliminate heavy metals. Wash immediately after sweating with a non-oily soap to assure that the toxins are not re-absorbed.<\/p>\n<p>Homocysteine is a risk factor for faster brain atrophy and worsening cognitive decline. The old standard was &lt;13, but Bredesen likes to see &lt;7. How to lower your homocysteine? Eat raw vegetables, take folate supplements = vitamin B9. Caffeine, metformin, and niacin=vitamin B3 can all <b><i>raise<\/i><\/b> homocysteine levels. The MTHFR gene variant increases homocysteine levels. The amino acid methionine tends to raise homocysteine, but (the chemical relationship) there is <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19422296?dopt=Abstract\">no evidence<\/a> that supplementing with SAMe increases homocysteine.\u00a0 <a href=\"https:\/\/www.webmd.com\/vitamins\/ai\/ingredientmono-1008\/betaine-anhydrous\">Betaine<\/a> is a supplement that decreases homocysteine directly.\u00a0 (Betaine also increases stomach acid, so it\u2019s appropriate for some stomachs and not others.)<\/p>\n<p>&nbsp;<\/p>\n<p><b>RECODE in My Experience<\/b><\/p>\n<p>For a new drug or a specific diagnostic test, translation from the laboratory to the field is straightforward. What Bredesen has is something else.\u00a0 It is a program of diagnostics, leading (through expert analysis and personal counseling) to an individualized program tailored to the patient. Though in principle it should be scalable, it\u2019s a system that resists mass production. This year, Bredesen has partnered with <a href=\"https:\/\/www.ahnphealth.com\/\">Apollo Health<\/a> to train a diaspora of specialized doctors, and begin to offer his program for Alzheimer\u2019s nationwide. The program is called RECODE, for REversal of COgnitive DEcline.<\/p>\n<p>Last fall, I enrolled in the RECODE program to learn more about it, and to help formulate an Alzheimer\u2019s prevention program for myself (age then=69). I was frustrated by the unresponsiveness of the Apollo team. They seemed well-intentioned, but overwhelmed by expansion that was faster than they could keep up with. This summer, I tried again, and I also enrolled Ben (85), a relative who has recently moved with his wife to a Continuing Care facility because of early stage AD.<\/p>\n<p>I found that the dysfunctional system had become functional, and that there is now a network of doctors trained in RECODE, including several near my home in Philadelphia. My personal experience has been good. Dr Reina Marino, who worked with me, was attentive and knowledgable and patient with the technical details that I imagine I was the only patient to ask about. In the months that she has been practicing RECODE, she has already seen some patients significantly improved, though no dramatic recoveries to report yet. She hinted that some patients didn\u2019t follow through with the multi-faceted protocols for changes in life syle, diet, and environment. Indeed, I was disappointed to learn that Ben decided that his memory was \u201cnot that bad\u201d, and he couldn\u2019t be bothered with the program. On the other end, Dr Marino has been too busy to follow through with me.\u00a0 My sample of one may or may not indicate that individualized medicine is time-consuming and expensive. On the subject of \u201cexpensive\u201d, Medicare won\u2019t pay for RECODE treatment, and my Medicare Advantage plan only covers a small part of the cost.<\/p>\n<p>The <a href=\"http:\/\/drbredesen.com\">RECODE web site<\/a> for patients is not as friendly as it ought to be. I\u2019m a computer professional, and I still had to get a RECODE staff person on the phone to tell me what needed to be filled out before I could download my test results and find a practitioner. The interface should be re-designed as soon as is practical to be navigated easily by older people who may be uncomfortable with computer systems.<\/p>\n<p><b>Two more causes for concern<\/b><\/p>\n<p>Ben scored 11 out of 30 on the standard MOCA paper-and-pencil test for cognitive impairment. That\u2019s low even for an Alzheimer\u2019s patient (though, to speak with him, one might have the impression that he was functioning at a high level). I was surprised to see that Ben\u2019s blood test scores were better than mine in most areas. Comparing our two test results, it was not at all obvious why Ben should be impaired while I am not. If these tests are designed to pinpoint an individual cause for individual symptoms, then it seemed to me that they did not distinguish well between Ben\u2019s condition and mine.<\/p>\n<p><a href=\"https:\/\/drive.google.com\/file\/d\/1lTBkGBiaOM7Xpg-d9ArRxbxcQU9r47SA\/view?usp=sharing\" target=\"_blank\" rel=\"noopener noreferrer\">Link to my personal RECODE report<\/a><\/p>\n<p>The initial report scores patients in five areas:<\/p>\n<ul>\n<li>Toxicity&#8211;mercury, lead, arsenic, mold, pesticides, toxins that build up in the body<\/li>\n<li>Glycotoxicity&#8211;accumulated damage from too much sugar in the blood<\/li>\n<li>Trophic loss&#8211;micronutrients and minerals insufficient in the bloodstream<\/li>\n<li>Inflammation&#8211;from leaky gut or chornic disease burden or autoimmunity or just aging<\/li>\n<li>Vasculature&#8211;stiff or clogged arteries depriving the brain of sufficient oxygen<\/li>\n<\/ul>\n<p>In four of these areas, Ben\u2019s score was better than mine (meaning lower risk); only in glycotoxicity did I do a bit better than Ben. The risks are individually ranked for each patient, and both Ben and I were found to be at highest risk for toxicity, associated with Type 3 AD. But Ben\u2019s toxicity was well below my own.<\/p>\n<p><b>\u201cThis is not a one-size-fits-all program. Everyone\u2019s version of RECODE is personalized, based on their test results.\u201d<\/b><\/p>\n<p>This has been a hallmark of the Bredesen protocol from the beginning, based on the premise that AD has very different causes in different individuals. It is, of course, the most difficult thing to achieve while the program is moving from the laboratory into the health care system. Differential diagnosis depends on, first, a computer algorithm, and then, the human intelligence of a doctor or other practitioner who has been trained by the RECODE core team.<\/p>\n<p>Despite our very different profiles and different diagnoses (Type 3 for me, Type 1.5 for Ben), the first three steps in our computer-generated recommendations were identical. The section labeled \u201cYour Suggested Plan\u201d was identical for Ben and myself. The greatest risk factor identified for both of us was toxicity, yet the #1 recommendation for both of us was the keto-flex diet. This is congruent with the paradigm promoted by <a href=\"https:\/\/newsnetwork.mayoclinic.org\/discussion\/researchers-link-alzheimers-gene-to-type-iii-diabetes\/\">Mayo Clinic<\/a> and elsewhere that AD is a kind of \u201ctype 3 diabetes\u201d. Bredesen endorses this as one piece of a more complex story, so I had hoped for a more nuanced prescription from RECODE.<\/p>\n<p>Reducing homocysteine was the #2 recommendation for both Ben and myself. The medical establishment recommends keeping homocysteine levels under 15, but Bredesen wants us to cut that in half. I have read the section on homocysteine from Bredesen\u2019s book, and it is not clear whether homocysteine is important because of its direct neurotoxicity or because it is a marker of inflammation. After my RECODE interview, I left the Marcus Institute for Integrative Health with a bottle of a supplement formula designed to lower my homocysteine levels by direct and indirect action. Principal ingredients are B vitamins, N-Acetyl Cysteine (NAC) and (this one was new to me) <a href=\"https:\/\/en.wikipedia.org\/wiki\/Betaine\">betaine-HCl<\/a>=trimethyl glycine (TMG). TMG reacts directly with homocysteine, pulling it out of the bloodstream. Are we fooling ourselves if we pull homocysteine out of the blood without reducing inflammation? <a href=\"https:\/\/www.drkarafitzgerald.com\/2019\/04\/30\/episode-62-methionine-metabolism-and-methylation-with-dr-david-quig\/\">David Quig<\/a> says that betaine works great in the liver, but it doesn\u2019t affect homocysteine levels on the other side of the blood-brain barrier. A better alternative for the brain is <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20608755\">5-methyl tetrahydrofolate<\/a>, a fancier folate supplement than the common and cheap synthetic folic acid. (Note also that folic acid is toxic to people with the MTHFR allele.)<\/p>\n<p><b>The bottom line<\/b><\/p>\n<p>Last year, Bredesen <a href=\"https:\/\/www.coastalmedicine.com\/assets\/silver_websites\/coastal-neurotherapy\/pdf\/Bredesen_Hagedorn_et_al_2018_J_of_Alz_Disease.pdf\">published an account<\/a> of replicated success in 100 patients that was, if anything, more impressive than the original. Under his close supervision, the Bredesen lab is able to reverse AD with a rate of success well beyond any treatments in the past. The Bredesen system depends on individualized diagnosis and individualized treatment plans, so scaling his methodology for wide application presents daunting challenges.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>This edition of Aging Matters is stolen from Rhonda Patrick\u2019s interview of Dale Bredesen. That hour is so packed with actionable information and theoretical background that I found myself going through it slowly to understand and digest it. The result was an appreciation for the breadth of vision embodied in Bredesen\u2019s comprehensive program to combat &#8230; <a title=\"Scaling the Alzheimer&rsquo;s Cure\" class=\"read-more\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2019\/09\/16\/scaling-the-alzheimers-cure\/\" aria-label=\"Read more about Scaling the Alzheimer&rsquo;s Cure\">Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":878,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-877","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"yoast_head":"<!-- This site is optimized with the Yoast SEO Premium plugin v27.4 (Yoast SEO v27.4) - https:\/\/yoast.com\/product\/yoast-seo-premium-wordpress\/ -->\n<title>Scaling the Alzheimer&rsquo;s Cure - Josh Mitteldorf<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2019\/09\/16\/scaling-the-alzheimers-cure\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Scaling the Alzheimer&rsquo;s Cure\" \/>\n<meta property=\"og:description\" content=\"This edition of Aging Matters is stolen from Rhonda Patrick\u2019s interview of Dale Bredesen. 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. 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Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. 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