The End of Alzheimers the First Program to Prevent and Reverse Cognitive Decline Book Review

Overall score

61

Scientific accuracy

42

Reference accuracy

65

Healthfulness

75

How hard would information technology be to employ the volume's advice? Very difficult

In The End of Alzheimer'south , Dale Bredesen, Dr. argues that Alzheimer's disease is acquired by inflammation, toxins, insulin resistance, and a "shortage of brain-supporting molecules". According to the book, the affliction can be prevented and reversed by addressing these underlying causes using an array of diet and lifestyle changes, and occasionally medical treatments.

Key points from our review

• We independently evaluated three of the book's key claims and found them poorly to moderately well supported.
• Most of the nutrients the book claims have anti-Alzheimer'due south furnishings don't have compelling evidence behind them, although at that place may exist exceptions such equally vitamin D.
• The book makes many factual claims merely doesn't cite references to support nigh of them.
• The writer has conducted studies suggesting that the book's programme improves cognitive impairment. These studies are intriguing just far from definitive.
• We believe the volume's nutrition and lifestyle advice is generally good for you.

Bottom line: While the recommendations in The Stop of Alzheimer'southward seem by and large healthy, it remains unclear whether they tin preclude or contrary Alzheimer's disease.

Book published in 2017

Published by Avery

Get-go Edition, Hardcover

Review posted Feb 22, 2021

Primary reviewer: Morgan Pfiffner

Peer reviewer: Stephan Guyenet

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Table of contents

1. Introduction
2. Scientific accurateness
3. Reference accurateness
4. Healthfulness
5. Most unusual claim
6. Other
7. Determination
8. Updates

Introduction

There are limited treatment options for Alzheimer's disease. The numerous attempts to develop drugs targeting this debilitating affliction have resulted in far more failures than successes. The few medications which are approved for use seem to just amend symptoms, mostly to a limited extent. This frustrating situation appears to have been a significant goad in leading Dr. Dale Bredesen to develop the ReCODE protocol, a multifactorial lifestyle intervention intended to preclude and reverse cerebral turn down and Alzheimer'due south disease. The ReCODE protocol serves as the basis for Dr. Bredesen's book The Cease of Alzheimer's (TEOA), throughout which the author discusses the rationale behind ReCODE'southward various prescriptions, as well as anecdotes of patients who implemented the ReCODE protocol. I chose to review TEOA because of a growing involvement in Alzheimer's disease.

Scientific Accuracy

We evaluated iii key claims of TEOA:

1. The intake of diverse nutrients can influence cognitive decline and Alzheimer's disease.

2. Certain dietary factors promote Alzheimer's disease by causing inflammation.

3. Insulin resistance contributes to Alzheimer'southward illness.

The book received an overall scientific accurateness score of ane.7, indicating that the scientific claims are not well supported. The starting time claim received a score of ii, indicating that information technology'southward weakly supported by evidence. None of the nutrients claimed to exist important in cognitive pass up appeared to take stiff prove of benefit and many had almost none. Vitamin D, vitamin E, and sure B vitamins had some evidence of benefit, but there were serious limitations in this research.

The 2d merits received a score of ane, equally there was almost no evidence in back up. The available evidence did non show an inflammatory issue of nigh of the dietary factors claimed as such in the book. Furthermore, although at that place is some evidence inflammation in the encephalon may exist involved in the development of Alzheimer'south affliction, this does not mean inflammatory markers circulating in the blood are useful indicators of inflammation in the brain.

Finally, the third claim received a score of ii, indicating it'southward weakly supported by bear witness. There is some evidence to advise insulin resistance could play a role in Alzheimer's disease, but the exact nature of this relationship (and furthermore, how to treat information technology) has not been well established.

Claim 1

The intake of various nutrients tin can influence cognitive decline and Alzheimer's affliction.

Supporting quote(s) and folio number(s)

Page 121: "Keeping homocysteine optimally low requires sufficient levels of vitamins B6, B9 (folate), and B12, all in their active forms."

Page 126: "Reduced vitamin D activeness is associated with cognitive decline."

Page 132: "…aging is associated with lower zinc levels, and Alzheimer's illness with still lower zinc levels."

Page 134: "Magnesium is critical for brain part."

Page 135: "Selenium plays a key part in regenerating glutathione when it is used up scavenging costless radicals, so it is not surprising that reductions in selenium have been shown to exist associated with cognitive decline."

Page 142: "Vitamin E is an important protector of your cell membranes, an antioxidant with an anti-alzheimer'southward effect."

Criterion 1.1. How well is the claim supported by electric current prove?

2 out of 4

This claim received a score of two, indicating that the merits is weakly supported by current evidence. A number of nutrients, primarily vitamins and minerals, are emphasized in TEOA equally being important factors in the development of Alzheimer'due south illness and cognitive pass up. Maybe well-nigh emphasized is a sufficient intake of several B vitamins, primarily B6, folate, and B12, largely on the ground that these nutrients lower levels of homocysteine, loftier levels of which TEOA claims are "of import contributors to Alzheimer'due south affliction" (folio 119). There is some evidence to support this claim, equally these nutrients do play key roles in homocysteine metabolism and elevated homocysteine has been associated with an increased risk of Alzheimer-type dementia. Additionally, some testify suggests a astringent insufficiency or outright deficiency of vitamin B12 or folate can lead to (often reversible) cognitive impairment. Yet, the effect of B vitamin supplementation has been disappointing. A 2019 meta-analysis of multiple randomized trials reports that B vitamin supplementation lowers homocysteine levels but has no significant cognitive benefit in individuals with or without dementia, though a possibility of benefit was hinted at in subgroups (eastward.chiliad. those with elevated homocysteine). Information technology may be that these vitamins are helpful in some cases, simply more research is likely needed.

TEOA also regularly suggests vitamin D condition may benefit cognitive function. Perhaps the strongest evidence in favor of this proffer comes from Mendelian randomization studies, several of which take observed that genetically lower vitamin D levels are linked to an increased risk of Alzheimer'southward disease. Nonetheless, non all of these studies accept been supportive. One clinical trial also found daily supplementation of 400 IU of vitamin D for 12 months had some positive effects on some markers of cognitive function among elderly people with mild cognitive harm. While not conclusive, the residuum of the prove points to a possible benefit from vitamin D supplementation in the context of cerebral impairment.

Magnesium is cited as a benign nutrient, with magnesium 50-threonate cited as especially helpful for brain wellness. The testify for this comes largely from a randomized controlled trial in which supplementation of magnesium 50-threonate for 12 weeks improved performance on a composite of cerebral tests compared to a placebo. This study was conducted on people with mild-to-moderate anxiety, sleep bug, and self-reported cognitive issues, but with no cognitive harm on objective assessment. This study offers compelling testify for a beneficial effect of magnesium, though its relevance to Alzheimer's disease is uncertain, and given the brusk duration and inclusion criteria, additional research is warranted. It's also worth noting that iii of the five authors disclosed financial interests related to the supplement being tested.

Another food proposed past TEOA as potentially of import in the prevention and direction of dementia is zinc. However, while zinc levels are often plant to be lower in individuals with Alzheimer'southward disease, this does not necessarily mean lower zinc really contributes to the development of Alzheimer'due south disease. Meanwhile, one randomized controlled trial (the ZENITH study) failed to find disarming bear witness that zinc supplementation benefits cognitive role in older adults. However, considering this study did not examine individuals with Alzheimer's illness or established dementia a beneficial effect of zinc tin't be ruled out. A 2,166-person randomized controlled trial reports that supplementing with zinc and copper for 6.9 years did non significantly impact cognitive function relative to placebo in elderly people, although there was a non-meaning tendency toward lower risk of developing cognitive impairment. TEOA suggests that copper is harmful to cognitive office, and so that could be the book'due south counterargument, just we are uncertain if that is the case at the dose used in this study (2 mg of copper daily as cupric oxide).

Finally, TEOA recommends a number of nutrients partly on the ground that they tin increase antioxidant status. These nutrients include selenium, vitamin C, blastoff lipoic acid, CoQ10, and vitamin E. More often than not, most of these compounds have piddling to no disarming evidence of benefit in the context of dementia or Alzheimer's affliction. Interestingly, ane randomized trial on individuals with mild to moderate Alzheimer'south disease establish that subjects randomly assigned to have 500mg of vitamin C, 800IU of vitamin E, and 900mg of alpha lipoic acid for sixteen weeks saw a greater decline in cognitive function (every bit assessed using an MMSE test) than those taking a placebo. A second large randomized controlled trial reports that daily supplementation of the antioxidants vitamin C, vitamin E, and beta carotene for six.9 years did not touch cerebral function or the adventure of developing cognitive impairment among elderly people.

Vitamin E supplementation (in the class of a-tocopherol) has also been tested several times on its own and although some studies have reported benefits (eastward.g i 1997 trial reported a slowing of Alzheimer'southward disease progression), analysis of the entire torso of show does not appear to back up a clear do good of vitamin E on cognitive function related to dementia.

In virtually cases, at that place is not strong bear witness supporting the claims in TEOA regarding the ability of various nutrients to reduce risk and ho-hum progression of dementia and Alzheimer's disease. Two exceptions are that B vitamin supplementation may exist helpful in people with elevated homocysteine, and vitamin D supplementation may likewise be helpful. While nosotros don't accept enough evidence to judge whether the remaining claims are truthful or false, they appear to exist speculative.

Benchmark one.ii. Are the references cited in the book to support the claim convincing?

2 out of 4

The book received a score of 2, indicating the references are weakly disarming overall. In many cases, the volume does not provide references for these claims. For case, no references are provided to support the claimed beneficial furnishings of vitamin D, vitamin C, vitamin B1, among several other nutrients. When the book does cite research, the references are variable in how convincing they are. For instance, when discussing the benefits of magnesium and vitamin E, the book references clinical trials testing the effects of these nutrients on cognitive office. The trial of vitamin E cited suggests that it tin can modestly ho-hum cerebral decline in Alzheimer'south disease, although of note several secondary outcomes related to cognitive function in this trial showed no significant effect. The trial of magnesium did report a benefit to cognitive role.

At other points, references are not very disarming, albeit all the same consistent with the writer's claims. For example, the proposed benefits of selenium are based on a single observational written report looking at the association between selenium intake and cognitive impairment. Because this is an observational written report, it is unclear whether low selenium status causes cognitive impairment or is but along for the ride.

Benchmark 1.3. How well does the strength of the claim line upwards with the strength of the evidence?

two out of 4

The claims received a score of 2, indicating the merits is moderately overstated. In the majority of cases the claims about nutrients exceeded the strength of the bear witness. Associations, mechanisms, and case studies are often discussed to persuade the reader of the possible benefits. Shortcomings of this show are not typically addressed. In most of these cases, TEOA does non clearly merits a food will have a benign effect on Alzheimer'south, though it is strongly implied. Cases where causation is claimed more strongly include vitamin E, which is said to have an "anti-Alzheimer's effect" (page 142). In this example a clinical trial is cited which, despite some limitations, is in line with the claim However, as mentioned previously, not all clinical trials support a beneficial effect of vitamin E and such strong claims nigh its efficacy seem unjustified. On the other paw, the claim regarding vitamin D, namely that lower levels are "associated with cerebral decline" (folio 126), aligned well with the forcefulness of the prove.

Overall (average) score for claim 1

2 out of four

Claim 2

Certain dietary factors tin promote Alzheimer's disease by causing inflammation.

Supporting quote(south) and page number(south)

Page 124: "There is a directly mechanistic link between inflammation and Alzheimer'south disease"

Page 125: "Your hs-CRP should be below 0.9 mg/dL. If it is higher, you desire to determine the source of inflammation. This may exist from too much sugar and other unproblematic carbohydrates, or bad fats (for case, trans fats), a leaky gut (more than on this later), gluten sensitivity, poor oral hygiene, specific toxins, or any of many other sources"

Folio 145: "One of the almost important contributors to Alzheimer'southward disease is inflammation, and one of the nearly common means to create systemic inflammation is a leaky gut"

Page 199: "Inflammation is i of the most of import drivers of cerebral decline, and information technology feeds directly into the Alzheimer's affliction mechanisms"

Criterion 1.1. How well is the claim supported by current evidence?

1 out of 4

This claim received a score of 1, indicating that it is poorly supported by electric current bear witness overall.

TEOA repeatedly states that inflammation is an important driver of Alzheimer'due south disease and cognitive refuse. However, the bodily relationship betwixt inflammation and Alzheimer's disease may non be as simple equally described in TEOA. For example, while there is evidence suggesting inflammation occurs in Alzheimer'due south disease and may even contribute to the disease, information technology is non clear that inflammation markers in the blood (such as hsCRP) tell us much almost inflammation in the brain. This is apparent in observational studies, which have typically failed to find significant correlations between markers of systemic inflammation (many of which are touted as clinically important in TEOA) and the risk of developing Alzheimer's disease. Yet, information technology'due south worth noting that markers of systemic inflammation are correlated with dementia more than broadly, but not Alzheimer'due south disease specifically. Similar findings have besides been reported in genetic studies.

There is merely a limited amount of experimental testify testing the thought that suppressing inflammation reduces the take chances of Alzheimer's disease in humans, and results are non particularly compelling. One randomized controlled trial administered the anti-inflammatory drugs celecoxib or naproxen to individuals with a family history of dementia. This trial plant no effect of celecoxib on the development of Alzheimer's, but a possible benefit amongst those taking naproxen who had not yet developed symptoms. Unfortunately, a later trial appeared to contradict this latter finding. This testify does non necessarily discredit the thought that inflammation contributes to Alzheimer's illness, but information technology does propose that the connection is probably not every bit simple as laid out in the volume.

TEOA recommends avoiding a number of foods and dietary compounds on the basis that they are inflammatory. Setting aside the function of inflammation on Alzheimer's disease, the evidence appears mixed regarding whether the recommendations in TEOA will meaningfully impact inflammation. I proposed crusade of inflammation is dietary Advanced Glycation End Products, or AGEs, a chemical compound produced with dry heat cooking methods (e.1000. frying, barbecuing, roasting). A number of clinical trials accept indeed constitute show that a higher AGE intake may take an inflammatory upshot, typically indicated past an increase in the inflammatory mediator TNFa. Trans fats are also cited as inflammatory in TEOA and at least some evidence does seem to support this. On the other manus, many of the claims regarding inflammatory foods are not well supported by show. Dairy foods are said to exist inflammatory and should be avoided "equally much as possible" (folio 183), but a 2020 meta-analysis of various clinical trials testing the effect of dairy products on markers of inflammation reported no apparent pro-inflammatory effects from dairy foods (if anything, the opposite finding was indicated). While information technology's possible for an individual to have a dairy sensitivity, existing prove suggests this is not typical.

The claim is too made that omega-6 fat acids, particularly when consumed significantly in excess of omega-three fatty acids, are inflammatory. This is used equally a rationale to consume meat and eggs from pastured animals. However, a number of human experimental studies have failed to find articulate evidence to support the claim that an increased intake of omega-6 fat invariably leads to an increment in markers of inflammation, peculiarly in the amounts institute in brute foods.

TEOA also contends that carbohydrate and refined carbohydrates are inflammatory. In general, the prove to support this assertion is weak, although there may be certain contexts in which sugar and refined carbohydrates tin have inflammatory effects. For instance, some saccharide containing foods (e.thousand. sugary beverages like soda) seem to promote body fat proceeds. In these cases, carbohydrate could well be capable of promoting inflammation, though this is a less direct mechanism than described in TEOA.

Finally, TEOA regularly implicates gluten every bit a source of inflammation, writing "Gluten can compromise the integrity of the gut barrier (and potentially the blood-brain barrier), leading to leaky gut, systemic inflammation, and increasing risk for cognitive refuse" (page 266). Still, outside of some in vitro research with questionable applicability to the human body (e.thousand. incubating abdominal cells with enzymatically treated gluten extracts), only a few experimental studies have examined the outcome of gluten consumption on biomarkers of inflammation and these have largely non supported the authors claims. A 2011 study, for example, randomly assigned people with irritable bowel syndrome (IBS) and suspected gluten sensitivity to a nutrition with or without gluten for half-dozen weeks, ultimately noting no credible rise in the inflammation marker CRP and no alter in intestinal permeability every bit a result of gluten consumption. A 2018 cross-over study on evidently salubrious adults also reported that a high gluten diet, compared with a low gluten diet, did not lead to higher markers of systemic inflammation (namely, circulating levels of CRP, TNF-a, IL-half-dozen) or increased intestinal permeability. This study did observe one possible marker of inflammatory potential was insufficiently college with more gluten intake (namely, IL-1b secretion from incubated claret exposed to lipopolysaccharide), but the applied and statistical significance of this finding is questionable. Past and large, there is footling evidence that eating gluten causes inflammation (excluding those with gluten allergies or Celiac disease).

Ultimately, the available prove provides express back up for the idea that avoidance of the aforementioned foods will decrease inflammation. Furthermore, the evidence is unclear whether focusing on the blood-borne markers of inflammation discussed in TEOA tin can modify the take chances of Alzheimer'southward disease.

Criterion i.2. Are the references cited in the book to support the claim disarming?

1 out of iv

The book's references received a score of one, as no references were provided to support this claim.

Criterion 1.3. How well does the force of the claim line upward with the strength of the show?

1 out of 4

The claim received a score of ane, indicating that the claim is greatly overstated.  As discussed previously, inflammation in the brain is linked to Alzheimer'south disease, only the human relationship between inflammation and Alzheimer's disease risk is far less straightforward than portrayed in the volume. Furthermore, there is little evidence that well-nigh of the factors said to exist inflammatory are in fact inflammatory.

Overall (average) score for claim 2

ane out of four

Claim 3

Insulin resistance contributes to Alzheimer'south disease.

Supporting quote(s) and folio number(southward)

Page 122: "High insulin and high glucose are ii of the most important risk factors for Alzheimer's disease."

Page 50: "Therefore, a disquisitional office of ReCODE is reducing insulin resistance, restoring insulin sensitivity, and reducing glucose levels, thereby restoring optimal metabolism."

Page 177: "If your fasting insulin is over 4.5 milli-international units per liter, your hemoglobin A1c over 5.v percent, or your fasting glucose over 93 milligrams per deciliter, you likely accept insulin resistance, arguably the single most important metabolic correspondent to Alzheimer'due south affliction development and progression."

Criterion 1.1. How well is the merits supported by electric current evidence?

3 out of 4

This claim received a score of iii, indicating that it is moderately well supported by current evidence.

A number of recommendations are made in TEOA based on the claim that insulin resistance is a central risk factor in the development of Alzheimer'southward disease. Several mechanisms are proposed to explicate this connection, including neuro-protective effects of insulin signaling in the brain and damage caused by elevated glucose.

Several lines of evidence have indicated a possible link between impaired insulin signaling in the brain and characteristics of Alzheimer's illness (e.g. cognitive harm), leading some researchers to refer to Alzheimer's illness every bit "type 3 diabetes". Though it'due south worth noting that the blazon of insulin resistance related to Alzheimer's disease is somewhat distinct from the systemic insulin resistance seen with type 2 diabetes. While insulin resistance underlying blazon 2 diabetes involves a reduced insulin sensitivity of major trunk tissues (due east.g. muscle, liver, and fat cells), in the case of Alzheimer's disease this reduction in insulin sensitivity is thought to exist brain specific. In other words, the insulin resistance in Alzheimer's disease and the insulin resistance discussed in TEOA are distinct entities. Still, there may be a correlation between systemic insulin resistance and brain insulin resistance. A 2006 study found insulin infusion stimulated brain glucose consumption to a lesser caste among people with systemic insulin resistance compared with those who were more insulin sensitive, suggesting brain insulin resistance and systemic insulin resistance may be associated.

Several studies have also noted a correlation between diabetes and Alzheimer's affliction, with one meta-analysis of prospective cohort studies reporting a 56% increased gamble of Alzheimer's disease amid people with type 2 diabetes. Additional studies have besides reported an association between both elevated fasting glucose and increased HbA1C (a marking of blood glucose levels) and a higher take a chance of Alzheimer's affliction, even amongst people without diabetes, consequent with the claims in TEOA that elevated glucose contributes to Alzheimer's. Unfortunately, this prove is observational (and thus causality is difficult to claim) and only a limited number of experimental trials have been washed examining how lowering blood glucose and/or improving insulin sensitivity impacts cognitive decline. Ane of the largest of these studies, the Accord Mind trial examined the effect of more intensive glucose lowering strategies versus standard therapy in 2,977 older people with blazon 2 diabetes. Despite lower glucose levels in the intensive group, tests of cognitive office over the course of the 40-month trial showed no benefit. This study therefore did not support the part of blood glucose in cerebral part. Even so, the finding is somewhat difficult to interpret because glucose lowering increased the risk of hypoglycemia. It's also not clear that lowering glucose through an intensive drug regimen that includes insulin injection, as in this trial, has the same issue as lowering glucose through diet.

There is limited information looking at whether changes in insulin sensitivity accomplished via dietary strategies can atomic number 82 to beneficial furnishings on cognitive function. A 3 calendar month trial on older people reported that a calorie restricted nutrition improved retention testing scores and this improvement in memory score was correlated with reduction fasting insulin, consistent with the idea that improving insulin signaling may benefit cognition. In a year long weight loss trial participants randomly assigned to either a low fat or a low carbohydrate diet improved their score on a working retentiveness examination to a like extent and this change was also correlated with decreasing fasting insulin. On the other hand, one study found that a reduced calorie DASH diet, combined with aerobic exercise, improved insulin sensitivity likewise as tests of neuro-cognitive performance, just there was no apparent human relationship between the two; changes in insulin and glucose regulation did not correlate with improvements in cerebral office. Unfortunately, none of these diet studies were conducted on subjects experiencing dementia or age related cognitive decline, maybe limiting their relevance to these weather. For this we expect to a 2016 trial report on older people with obesity and mild cognitive impairment. Subjects were randomly assigned to standard care or a diet "rich in fiber, fruits, vegetables, and whole grains and included at least 1 g/kg of weight of protein per 24-hour interval, with a recommended calorie deficit of approximately 500 kcal/d". This nutrition led to weight loss, improvements in an insulin resistance marker HOMA-IR (among other changes), and benefits to tests of cognitive function. Some, simply not all cerebral improvements were correlated with the credible improvements in insulin resistance.

Several studies have also administered insulin sensitizing agents (i.e. metformin, pioglitazone, and rosiglitazone) to individuals with cognitive impairment and Alzheimer'southward disease. Some of these trials, particularly smaller trials, have shown positive furnishings on markers of cognitive function. However, in several trials no clear benefit was plant. One six month report constitute that the diabetes drug Liraglutide increased glucose metabolism in the encephalon (indicating improved cognitive insulin sensitivity), just this did not correspond to cerebral benefits. These mixed results provide only express support to the claims that insulin sensitivity is an important modifiable risk gene in Alzheimer'due south affliction. Ultimately, the evidence appears compelling just not conclusive that insulin resistance is an important contributor to Alzheimer's disease and the interventional data is currently limited.

Criterion 1.2. Are the references cited in the book to support the merits convincing?

1 out of four

The book's references received a score of one, equally no references were provided to support this claim.

Criterion 1.iii. How well does the strength of the claim line up with the force of the evidence?

ii out of 4

The claim received a score of ii, indicating that the claim is moderately overstated. The role of impaired insulin signaling in the development of Alzheimer's disease does appear compelling, but whether this procedure is equally important every bit indicated in TEOA remains uncertain, given that the current torso of show remains somewhat preliminary and occasionally contradictory.

Overall (average) score for merits 3

two out of four

Overall (average) score for scientific accuracy

1.vii out of 4

Reference Accurateness

We randomly selected 10 references in TEOA and scored how well they support the passages associated with them. TEOA received a score of 2.7, indicating its references provide weak to moderate back up for its claims. References appeared to be less supportive when applied to claims relating to diet (eastward.k. about diet and micronutrients) versus those relating to physiology. This may be considering the writer has a background in medicine rather than nutrition.

Reference 1

Reference

Chapter 7, reference iv.  Chausmer, A. B. Zinc, insulin and diabetes. Journal of the American College of Nutrition 17: 109-115 (1998)

Associated quote(s) and page number(s)

[Page 133: "…zinc is critical for insulin synthesis, storage, and release"

Criterion 2.1. Does the reference back up the claim?

four out of four

This reference received a score of iv, indicating that it offers strong support for the claim.  This review covers the physiological role of zinc in the product of insulin, which is mostly well established. It's perhaps worth noting that this review cites research where zinc supplementation had conflicting effects on insulin dynamics.

Reference 2

Reference

Appendix D, reference v.  Lu, D. C., et al. A second cytotoxic peptide derived from amyloid-beta-protein precursor. Nature Medicine 6: 397-404. (2000)

Associated quote(southward) and folio number(s)

Page 285: "APP is a dependence receptor" (reference 7 was besides associated with the merits)

Criterion two.ane. Does the reference support the claim?

four out of iv

This reference received a score of iv, indicating that it offers strong support for the claim.

Reference iii

Reference

Affiliate 8, reference 4. https://articles.mercola.com/sites/articles/annal/2014/09/21/hilary-boynton-mary-brackett-gaps-cookbook-interview.aspx

Associated quote(due south) and page number(due south)

Page 201: "…at that place are complementary methods for gut healing. One method is bone goop"

Benchmark 2.1. Does the reference support the claim?

1 out of iv

This reference received a score of 1, indicating that the reference does not convincingly support the claim.  The reference is to a video interview with 2 authors who merits os broth is beneficial to gut health, but no apparent scientific testify is mentioned.

Reference 4

Reference

Chapter 7, reference 8.  Basha, One thousand. R., et al. The fetal basis of amyloidogenesis: exposure to lead and latent expression of amyloid precursor poly peptide and beta-amyloid in the aging brain. Journal of Neuroscience 25: 823-829 (2005)

Associated quote(southward) and page number(s)

Page 138: "Exposure to lead–typically through old paint and dust in cities–also increases amyloid formation later on in life, rodent studies have shown"

Benchmark 2.1. Does the reference support the claim?

3 out of four

This reference received a score of iii, indicating information technology offers moderate support for the merits. This study did find that the addition of lead to drinking water of pregnant mice resulted in offspring that adult elevated brain expression of APP and amyloid beta later in life. However, the suggestion that this mouse study therefore demonstrates that such a miracle will occur in humans is peradventure overstated.

Reference 5

Reference

Chapter 7, reference 1.  den Heijer, T., et al. Homocysteine and encephalon atrophy on MRI of non-demented elderly. Brain 126 (Pt. 1): 170-175 (2003)

Associated quote(due south) and page number(s)

Page 119: "High levels of homocysteine are important contributors to Alzheimer's disease"

Criterion 2.1. Does the reference support the claim?

ii out of 4

This reference received a score of ii, indicating that it offers weak support for the claim. Information technology is an observational study examining blood levels of homocysteine and brain cloudburst in older individuals without dementia. This study establish that higher homocysteine levels was associated with lower cortical volume. However, while this study seems consequent with the hypothesis that homocysteine contributes to Alzheimer'south illness, several problems limit its utilise for inferring causation. Perhaps most importantly, other factors could pb to both higher homocysteine and lower brain volume (due east.g. certain nutrient deficiencies and health conditions), pregnant homocysteine could be associated with simply not necessarily contribute to Alzheimer's disease.

Reference six

Reference

Chapter 8, reference five. http://draxe.com/scd-diet/

Associated quote(southward) and folio number(southward)

Page 202: "Another arroyo is to follow a diet that uses specific carbohydrates to allow gut healing, called the SCD diet"

Benchmark 2.1. Does the reference support the claim?

2 out of 4

This reference received a score of two, indicating that it offers weak back up for the merits.  Information technology is a popular health website commodity discussing the Specific Carbohydrate Diet (SCD). This article does brand some references to scientific enquiry on the possible gut benefits of the SCD, simply these appeared to be entirely case studies, which are not a specially stiff form of bear witness, and all were on individuals with IBD, meaning that the findings may not be relevant to people with normal gut function.

Reference 7

Reference

Appendix D, reference 4.  Lourenco, F. C., et al. Netrin-1 interacts with amyloid precursor poly peptide and regulates amyloid-beta production. Jail cell Death and Differentiation 16: 655-663 (2009)

Associated quote(s) and page number(south)

Page 285: "APP is a dependence receptor" (reference 2 was also associated with this claim)

Criterion 2.1. Does the reference support the merits?

4 out of 4

This reference received a score of 4, indicating that it offers stiff back up for the claim.

Reference 8

Reference

Chapter 7, reference 3.  Brewer, G. J. Copper excess, zinc deficiency, and noesis loss in Alzheimer'south Disease. Biofactors 38: 107-113 (2012)

Associated quote(due south) and folio number(due south)

Folio 133: "…zinc supplements raise cognition"

Criterion ii.one. Does the reference support the claim?

1 out of 4

This reference received a score of 1, indicating that the reference does not convincingly support the claim.  The article discusses the hypothesis that inadequate zinc promotes Alzheimer's disease. The review covers results of several trials examining the effect of zinc on cognition, most of which failed to detect improvements in markers of cognition. In fact, contrary to the claim in the book the summary section from the newspaper states "our data so far indicate zinc therapy does not improve cognition, but rather stabilizes it and at least partially prevents cognition loss occurring otherwise. We should know within ane-2 years, when our definitive report is completed…" While this may seem somewhat persuasive at commencement glance, the findings were only meaning in a subgroup analysis of participants over 70. Such unplanned subgroup analyses ofttimes render unreliable results, so the finding should be interpreted with caution.

Reference 9

Reference

Chapter 7, reference 9.  Bakulski KM, Rozek LS, Dolinoy DC, Paulson HL, Hu H. Alzheimer'south affliction and environmental exposure to lead: the epidemiologic prove and potential function of epigenetics. Current Alzheimer Research Jun;9(5):563-73 (2012)

Associated quote(s) and folio number(s)

Page 138: "In people, there is both epidemiological and toxicological evidence that lead raises the risk of historic period-related cognitive decline"

Benchmark 2.1. Does the reference support the merits?

4 out of 4

This reference received a score of iv, indicating that information technology offers strong support for the claim. The review cited provides diverse lines of evidence suggesting lead increases cognitive decline.

Reference 10

Reference

Affiliate 5, reference vi.  Clarkson TW, Magos 50, Myers GJ. The toxicology of mercury–current exposures and clinical manifestations. New England Periodical of Medicine Oct thirty;349(18):1731-7 (2003)

Associated quote(due south) and folio number(s)

Folio 87: "Tropisetron blocks four of the thirty-six contributors we knew almost at the time"

Benchmark 2.ane. Does the reference back up the claim?

1 out of 4

This reference received a score of i, indicating that the reference does not support the claim. The reference is to a review commodity on mercury. Meanwhile, the statement referencing this paper is nearly the possible anti-Alzheimer'south drug tropisetron. After checking several times to make sure the claim and the reference did in fact stand for we conclude this reference was likely placed erroneously.

Overall (average) score for reference accurateness

2.6 out of 4

Healthfulness

The End of Alzheimer's recommends numerous diet and lifestyle changes. This includes a mildly ketogenic diet primarily based on whole plant foods, such as non-starchy vegetables and nuts/seeds, with moderate amounts of meat, limitations on refined carbohydrates/carbohydrate and saturated fat, and no gluten or dairy products. Gentle cooking methods are recommended. The volume recommends about 20 supplements, including a variety of vitamins, minerals, non-essential nutrients, phytochemicals, and herbs, with more than suggested in specific cases. Other recommendations include obtaining adequate sleep, physical activity, a daily fasting period, and social back up. Finally, certain medical treatments (due east.g. hormone replacement therapy) are advised when applicative.

TEOA received a healthfulness score of 3 out of iv. This score came from an cess of the program's nutritional capability, general healthfulness, and whether the plan would do good its target condition, namely Alzheimer's. Overall, the programme is likely nutritionally adequate due to its generally unprocessed, somewhat varied nutrition and numerous nutritional supplements. The dietary recommendations seem generally healthy, given the components and dietary pattern tend to be associated with positive health outcomes, though there was some uncertainty regarding the risks of certain understudied supplements. But it is unknown if the plan benefits the target condition.

There has been some research on ketogenic (often very-low-carbohydrate) diets on Alzheimer'southward disease, based largely on the idea that cerebral deficits in Alzheimer'south disease are driven by a reduced ability of neurons to produce energy from glucose (related to the insulin resistance discussed in merits 2) and supplying ketones could assistance address this energy arrears. A scattering of studies on ketogenic diets have observed possible benefits on some cerebral tests in people with Alzheimer'south disease, though these trials have limitations, including lack of control groups, small sample sizes, and variability in outcome.

In general, at that place is very picayune experimental evidence examining the outcome of any blazon of dietary changes on Alzheimer'south illness, meaning it was unclear whether the overall diet in TEOA would provide do good. Amidst the supplements, most appeared to have very little or even no evidence supporting the contention that they reduce the risk of Alzheimer's disease, or improve existing disease. Some evidence exists for vitamin D and maybe context-specific utilize of sure B vitamins, though this evidence had limitations (encounter claim 1, criterion one.one). Still, practise and physical activity exercise bear witness compelling, albeit preliminary evidence of benefit and observational evidence too suggests adequate sleep may be benign, at least for prevention. Patient case studies described in TEOA tested the event of the complete plan, but this is low-quality prove. The writer has published some of these case studies, only for reasons detailed in the scoring section, we do non find these studies very disarming.

Overall, there was not enough evidence to say whether the program reduces the risk of Alzheimer's disease or improves established affliction. Withal, we notation that this does not necessarily mean the plan is ineffective.

Summary of the health-related intervention promoted in the book

TEOA recommends an extensive number of possible interventions. This includes do, adequate slumber, minimizing stress, taking various supplements, and eating a plant-based, mildly ketogenic diet. The book makes the post-obit dietary recommendations:

• Bulk of diet volume composed of various non-starchy vegetables
• Include fat from avocado, basics, seeds, olive oil, and MCT oil (to help achieve ketosis)
• Aim to swallow fermented foods and/or take probiotics
• Moderate amounts of meat (a few ounces per 24-hour interval) with preference to grass-fed/pastured meat
• Limited amounts of refined carbohydrates and saturated fat
• Avoidance of gluten and dairy
• Daily fasting (at to the lowest degree 12 hours, including slumber)
• Gentle cooking of food

The book besides recommends a large number of supplements, some of which are only recommended in specific contexts.

Condition targeted by the volume, if applicable

Alzheimer's disease and age-related cognitive decline.

Apparent target audience of the volume

This book is written for individuals, caregivers, and medical professionals interested in preventing, managing, or treating Alzheimer'due south illness and age-related cerebral decline.

Criterion 3.ane. Is the intervention likely to improve the target condition?

2 out of 4

The intervention received a score of 2, indicating that its effect on Alzheimer's disease appears very uncertain. With respect to the treatment of cognitive harm and probable Alzheimer'due south affliction (mayhap the main focus of the book), the large majority of recommendations made in TEOA appeared to lack prove of their do good individually. There did appear to be evidence for a few parts of the plan (e.thou. concrete action, vitamin D, ketogenic diet), but these nigh all came from preliminary research that seems promising merely requires farther study.

The book's writer has published papers claiming to show testify of the effectiveness of the program on cognitive decline. This research is cited as evidence of effectiveness of the plan. The about comprehensive paper covers 100 patients, all of whom are claimed to have benefited from treatment with the protocol outlined in TEOA. However, this paper has major limitations.

First, this article is published in a very-low-bear upon journal and is not available on the widely-used biomedical database PubMed. In and of itself, this doesn't necessarily mean information technology'due south not rigorous, just it'due south a bad sign and it suggests that the Alzheimer'south illness inquiry customs is not convinced past the finding.

Second, this was a instance serial, considered a weak form of evidence. This type of study is usually viewed as a starting bespeak for research rather than an endpoint. In this particular example, we don't know how many patients were included in the paper, and how many were excluded. 100 patients improving sounds like a lot, only how many patients didn't improve and were excluded from the paper? None? 100? ane,000? This has a large impact on how we translate the findings. Second, this type of written report doesn't have a command grouping and doesn't randomize people to different groups (as in a gold-standard randomized controlled trial), which makes information technology harder to come to firm conclusions based on its findings.

Third, given the lack of randomization and a control group to compare with, nosotros tin can't rule out the possibility that some cases would take improved without intervention. This may seem unlikely given the typical blueprint of decline in Alzheimer'south disease, however many patients didn't have an actual diagnosis of Alzheimer's disease, just rather mild cerebral harm. This means that health conditions other than brain degeneration could have been responsible for their condition, and these may be more probable to wax and wane. Furthermore, if a person is given a detail cognitive examination repeatedly, they're likely to improve on it simply due to do, and then an increase in score may not reflect an actual comeback in cerebral ability. Control groups are typically used to rule out effects like this.

Fourth, the paper doesn't provide much evidence that the program improves objective markers of Alzheimer's disease. A number of patients did accept tests indicative of Alzheimer's (east.g. PET scans) and in such cases cognitive tests appeared to be the most mutual method of assessing improvement (e.g. MoCA, MMSE, and SLUMS). Many of the improvements did appear impressive in the context of Alzheimer's disease, but it remains to exist seen if this represents a true and sustained reversal. Only 4 of 100 cases were noted to have experienced improvements in objective measures of affliction pathology. 3 cases experienced some degree of comeback in an EEG reading of their encephalon. However, none of these cases had a positive Alzheimer's disease diagnosis. I instance which did have evidence of Alzheimer'due south disease experienced an increase in hippocampus volume, merely at 1 case out of 100 patients, and an unknown number of additional patients non included in the paper, this result is of unclear significance.

Overall, the findings in this newspaper are intriguing, simply until a randomized controlled trial is published in a reputable journal supporting the TEOA program, the evidence of its effectiveness remains uncertain.

It's of import to distinguish between two different claims the book makes. The first is that the protocol tin can improve knowledge in the context of cognitive impairment–this seems inside the realm of possibility, though overall the evidence is weak. The 2d is that the protocol tin opposite the brain harm underlying Alzheimer's illness. This is a college bar and seems poorly supported by electric current evidence.

Criterion 3.ii. Is the intervention likely to improve general health in the target audience?

three out of four

The intervention received a score of three, indicating that it is probable to moderately ameliorate general health. Many characteristics of the diet (low carbohydrate, express refined carbohydrates, emphasis on vegetable intake) seem likely to benefit cardiometabolic health based on results from clinical trials. Additionally, some of the major components of the diet (leafy greens, crucifers, nuts and seeds) are oft associated with various positive wellness outcomes.

Yet, a diet is arguably simply beneficial if it can be followed and some may find adherence to the diet difficult. Beyond its restrictions on various processed foods, the diet too advocates consummate avoidance of dairy products, wheat (both refined and whole grain), tropical fruits (due east.yard. mango and pineapple) and limits grains, starchy vegetables, and meat (the latter to 2-3 ounces per twenty-four hours). A daily 12-16 hour fast is besides part of the dietary plan. While some may find this all easy to adhere to, others, perchance particularly those experiencing cognitive impairment, may struggle to adopt the diet.

Finally, numerous supplements are recommended and a few seem uncertain in their prophylactic. As an example, TEOA recommends supplementing vitamin Eastward at a dose of 400-800 IU's per day, though testify from clinical trials suggests this may increase the risk of dying (albeit modestly). And while TEOA recommends vitamin Due east as mixed tocopherols and tocotrienols rather than the a-tocopherol course used in all long term clinical trials, whether this removes the risk is uncertain. Another supplement recommended in TEOA comes from a constitute known as skullcap. Several case studies take noted a possible (though not definitive) connection between skullcap supplementation and liver toxicity. It'south likewise worth mentioning that the toll of all these supplements may be substantial, and that Bredesen's company Apollo Health sells some of them.

Criterion 3.three. Does the diet portion of the intervention promote an acceptable nutrient intake for general health in the target audience?

4 out of 4

The nutrition received a score of 4, indicating information technology is likely essentially more than nutritionally acceptable. Upon exam, someone following the diet recommended in TEOA seems probable to achieve an adequate intake of most vitamins and minerals and any shortcomings would probable exist met by the various supplements recommended. Additionally, intake of various not-essential nutrients would also be notable, either from foods or supplements.

Overall (average) score for healthfulness

three out of 4

Most unusual claim

During a Q&A section of sorts, the book states "a expert mode to squelch carbohydrate cravings is to take MCT oil, 1000 mg or even a teaspoon" (page 251). The thought that cravings for sugar or sweet foods can be altered is not entirely without merit. A 2018 meta-analysis on decreased calorie diets found, at least over the long term, sugariness cravings ofttimes decrease as a effect of such diets. One such study (known as The POUNDS Lost written report) reported that cravings for sure types of foods (including sugariness foods) appeared related to how frequently dieters consumed said foods. In other words, reducing how oftentimes you swallow sugary foods may, at least eventually, reduce your cravings for sugary foods. Nonetheless, the evidence that saccharide cravings tin be reduced by adding whatever detail food or supplement is currently lacking. Although some inquiry suggests large amounts (due east.chiliad. 25 grams) of MCT oil might be fairly satiating (although evidence is mixed), we were unable to detect show that consuming MCT oil, particularly in the small amounts suggested, can reduce ane's desire to eat carbohydrate.

Conclusion

TEOA claims to contain the solution to Alzheimer's affliction; a multifactorial lifestyle intervention said to non only prevent the disease but reverse it once started. Given the extraordinary nature of this claim, one might expect the volume to provide extraordinary evidence. Unfortunately, the show is far from convincing. Although some specific aspects of the plan were supported by compelling prove, much of the research was very weak, and the only direct scientific evaluation of the program was a depression-quality study. Overall, whether the plan contained in TEOA can prevent or treat Alzheimer's disease remains uncertain. And while the general communication does seem healthy, it would likely be difficult and expensive to implement.

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Source: https://www.redpenreviews.org/reviews/the-end-of-alzheimers-the-first-program-to-prevent-and-reverse-cognitive-decline/

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