Alz

Alzheimer’s Diet, Microbiome, & Bio-marker Predictors

SUMMARY:  Learn the latest on Alzheimer’s Diet, Microbiome, & Bio-marker Predictors.  Such is welcome news as the latest Alzheimer’s Facts & Figures show that over 5 million Americans are living with Alzheimer’s, including an estimated 200,000 under the age of 65.  

By 2050, the number of people age 65 and older with Alzheimer’s disease may nearly triple, from 5 million to as many as 16 million.  Truly, Alzheimer’s is one of the diseases most feared in my talks; it is the sixth-leading cause of death in the United States.   The estimate is that by age 64, one in 8 will have Alzheimer’s.  That rate doubles every 5 years.  So by age 70, one in 4 will have Alzheimer’s.  And by age 75, one in 2 will have Alzheimer’s.  These stats are from a 2013  interview of Dr. Thomas Wisniewski, @ time 25:30: “Brains – The Latest Research 07/01/2013 – 08:04” (NYU Langone Medical Center Audiocast, SirusXM Dr. Radio programming), who’s lab, Dr. Thomas Wisniewski’s Lab, is one of the leading Alzheimer research labs.

Disease Epidemic_PNG file
Slide source: biomeonboardawareness.com

It certainly is challenging for caregivers to understand what goes on in the daily life of an Alzheimer’s patient to help explain behaviors. This ABC YouTube, “Experience 12 Minutes In Alzheimer’s Dementia,” opens our eyes and helps many to appreciate this world.

Understanding what may be biologically happening for Alzheimer’s

The study, The intricate association between gut microbiota and development of type 1, type 2 and type 3 diabetes,”  makes the connection between Diabetes Type 3 (a.k.a. Alzheimer’s) and connects the gut microbiome with increasing intestinal permeability:

“It has been proposed that changes in the composition of gut microbiota contribute to the development of diabetes Types 1, 2 and 3 (the latter known as Alzheimer’s disease). The onset of these diseases is affected by complex interactions of genetic and several environmental factors. Alterations in gut microbiota in combination with specific diets can result in increased intestinal permeability leading via a continuous state of low-grade inflammation to the development of insulin resistance. Since a change in composition of gut microbiota is also suggested to be the underlying factor for the development of obesity, it is obvious to link gut microbiota with the pathogenesis of diabetes. In addition, insulin resistance in the brain has been recently associated with Alzheimer’s disease. These new paradigms in combination with data from studies with prebiotics and probiotics may lead to a novel way to control and even prevent diabetes in general.”

I by no means am saying that pre- and probiotics is the only answer for Alzheimers.  I am just clarifying that long term dietary changes do alter the microbiome (see the post, OPTIMAL MICROBIOME DIET FROM AMERICAN GUT DATA is a start to understanding this) and the gut microbiome does rule beyond the gut walls, systemically, (see the post, THE SCIENCE BEHIND FOOD, DISEASE, MICROBIOME, and affects the blood brain barrier as discussed below.  Pre- and probiotics are only one dietary factor impacting the microbiome, as my readers well understand.

The paper, The Gastrointestinal Tract Microbiome and Potential Link to Alzheimer’s Disease,” focuses on emerging ideas concerning the contribution of the GI-tract microbiome to human neurological disease with emphasis on Alzheimer’s disease wherever possible:

“… dietary composition ultimately affects the structure, organization, function, and speciation of the human microbiome occupying the GI tract, in part by supplying multiple substrates for microbial metabolism. Typical Western diets containing high fat–cholesterol, low amounts of soluble and insoluble fiber, and sugar- and salt-enrichment not only impart deleterious nutrition but also dietary constraints on the human microbiome. This in turn impacts the supply of microbiome-generated molecules absorbed into the systemic circulation for transport into the extensive neurovasculature of the central nervous system.”

Parts II and III, Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part II – contemporary contextual research and Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part III – convergence toward clinical trials, respectively, goes into much microbiota specificity and functionality for those desiring such.

Intestinal Permeability (a.ka. leaky gut) and autoimmunity

To simplify, the post, MICROBIOME RULES, WHAT IS IT? explains the many factors that contribute to intestinal permeability. Certain foods we ingest (gluten being one) always opens up tight junctions in our gut lining and what leaks through, stimulates our immune system.  A great portion of that post discusses this mechanism, as does Dr. Fasano, in the  YouTube, Cross Talk Between Gut & Brain – A Fasano, MD, published on Apr 23, 2014, where he links the intestinal permeability mechanism and the gut microbiome to the autism brain:

It is Dr. Fasano’s team discovery that “zonulin,” is the molecule which regulates intestinal permeability (also known as “leaky gut”) and their totally ground-breaking research that linked an overproduction of zonulin (gluten is a clear known trigger for such in celiacs) to the development of a series of autoimmune diseases, including Type 1 diabetes, celiac disease and multiple sclerosis (at least in animals at this point in time).

Just to back track for a moment, Celiac Disease & Gluten-Free Diets 06/04/2014 – 08:11 is an interview between Host: Dr. Samantha Heller and Guest: Dr. Alessio Fasano, Massachusetts General Hospital.  In summary:

Dr. Fasano explains that people can safely eat gluten for 30 or 40 years plus… and then develop autoimmune celiac due to the microbiome change to a state that caused autoimmunity. Over time, the microbiome has become less diverse and less dense.  The most influential factor that determines the makeup of the microbiome is nutrition since the microbiota feeds on what we consume.  And what is discussed for celiac applies for Type 1 Diabetes, MS, and beyond these autoimmunity, to dementia, Alzheimer’s… all are impacted by the microbiome.

Probiotics are not yet understood enough to customize which probiotic is helpful for which purpose.  Whole food probiotics is probably the safest way to go.  Cancer chemo or radiation trashes the microbiome and microbiome restoration is necessary, but we don’t yet understand how best to do this.  The agencies are still arguing if probiotics are drugs (FDA and NIH prefers therefore strict regulatory mandates) or classification as food additive (industry prefers so much less regulatory demands).  Those who can’t wait for the research (IBD, IBS, celiac, NCGS, autoimmunes, just to improve general health recognizing the need for microbiome…) should eat a more healthy, more plant based, more  fresh food diet, and if you want to add in probiotics, go with whole food sources yogurt and/or fermented vegetables. -Dr. Fasano and Samantha Heller

Dr.Fasano_Gluten Causes Leaky Gut In Everyone
https://www.youtube.com/watch?v=7c4QgDM6Zig#t=35
What Intestinal Permeability May Have to Do With Alzheimer’s:  Predictive Autoimmune Bio-Markers

To date, the autoimmunes: Type 1 Diabetes, celiac disease and multiple sclerosis (in animal models) have been positively associated with intestinal permeability.  Generally, when the gut becomes permeable, large molecules leak through the lining which should not and this stimulates our immune system.  We are designed to work this way, and it should be a way that “tunes up” our immune system.  When this leakage goes awry, inflammation ensues and chronic inflammation leads to disease.

The immune system performs molecular mimicry and can target our tissues and organs that look similar to that leaking.  This can lead to autoimmunity.  The work of Dr. Yehuda Shoenfeld, MD shows that bio-markers exist years preceding autoimmunity diagnosis.  He has highlighted the pertinent sections of this study below:

As Dr. Fasano explains in the YouTube mentioned above, Cross Talk Between Gut & Brain – A Fasano, MD,and in his presentation for the Autoimmune Summit, hosted by Dr. Amy Myers, MD, that aired a few weeks ago, “If you stop the leakage triggering the overstimulated immune reaction, we think you can stop the progression of this self attack by the immune system.”

This is precisely what “gluten-free” does for many celiac, although there still is a large number of patients [I recall 1/3 although I need to dig for where that source is] need to go beyond only gluten-free for villi healing.  As a matter of fact, one of my favorite autism researchers, Paul Whiteley, just posted, Gut dysbiosis in treated coeliac disease: time for a probiotic or worse? which explores microbiome dysbiosis for participants diagnosed with celiac who hadfor several years [been gluten-free] and had restored small bowel mucosa and negative celiac autoantibodies.” Based on an analysis of bowel symptoms recorded using the Gastrointestinal Symptom Rating Scale, researchers reported that despite the use of a gluten free diet – universally indicated for coeliac disease (CD) – a proportion of their cohort still presented with “persistent symptoms” and it is within this cohort they were aiming to see whether: “abnormal intestinal microbiota may be associated with persisting gastrointestinal symptoms in treated celiac disease patients…  [found] higher relative abundance of Proteobacteria  and a lower abundance of Bacteroidetes and Firmicutes.” That and “their microbial richness was reduced.” All of this led authors to conclude that for some with CD, a gluten free diet might just be the start of a management schedule to alleviate symptoms and improve quality of life.”  

There is a lot more in Paul Whiteley’s post that addresses gut microbioime dysbiosis but I don’t want to digress any further than needed to make my point, and that is, that for some celiac, they need to increase dietary restrictions beyond gluten-free; some use the Specific Carbohydrate Diet which was the first celiac diet and which shows promise with other autoimmunes (see the post, FOOD MANAGING IBD & AUTISM: THE STUDIES).  Of course, as Rob Knight would stress, (see the post, OPTIMAL MICROBIOME DIET FROM AMERICAN GUT DATA), it is long term diet that will change a very stable microbiome so perhaps these folks simply need to be gluten-free even longer than “several years.”

Blood-Brain Barrier (BBB), Cerebrovascular Function and Neurodegenerative Diseases

-Directly from the paper:  Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy“:

“There is emerging evidence that BBB dysfunction is associated with the pathogenesis of a variety of neurodegenerative disorders such as Alzheimer’s (Bell and Zlokovic, 2009; Zlokovic, 2011), Parkinson disease (Chung et al., 2010; Bartels, 2011), multiple sclerosis (Lassmann et al., 2012; Prineas and Parratt, 2012; Tourdias and Dousset, 2013), and amyotrophic lateral sclerosis (Rodrigues et al., 2012; Garbuzova-Davis and Sanberg, 2014; Winkler et al., 2014), in addition to typical cerebrovascular disorders such as stroke and vascular dementia (Wardlaw et al., 2003; Iadecola, 2013).”  NOTE: This section details the BBB biology and the paper  should be read for better understanding, but if you skip that, in general, the BBB replicates that of the gut lining (so think about the intestinal permeability mechanism previously discussed as relevant too for the BBB).

“Summary:  A growing body of evidence links systemic inflammation and Alzheimer’s pathogenesis in the brain. Although the overall impact of the activated brain immune system on Alzheimer’s pathological features is complicated and still controversial, it is clear that it could be affected by the peripheral immune system. Direct or indirect modulation of the brain immune system from the periphery could be a new strategy to alter Alzheimer’s progression. The cerebral vasculature, especially the BBB, is an important interface linking peripheral inflammation and the Alzheimer brain (Figure 1). It remains unclear how exactly systemic inflammation could damage the integrity and function of the BBB and alter cognitive function, and the mechanisms need to be elucidated in order to develop new treatments for Alzheimer’s focusing on vascular and other interface pathology.”

Alzheimer's Frontier's In Aging Neuroscience Article
Figure 1: Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00171/full

Figure 1. Neuropathological features, inflammation, and cognitive/non-cognitive symptoms of Alzheimer disease. Cerebral accumulation of amyloid plaques and neurofibrillary tangles (NFT) leads to neurodegeneration in the Alzheimer brain, which causes progressive cognitive dysfunction such as memory loss and language problems. Non-cognitive symptoms, such as agitation, aggression and psychosis, are often observed in AD patients, besides cognitive deterioration. These symptoms can be triggered by an infection in peripheral organs such as pneumonia, suggesting a contribution of peripheral inflammation. BBB, blood-brain barrier.

Specific to Alzheimer’s Predictive Autoimmune Biomarkers:

Alzheimer’s research is now beginning to report on what can be termed “Predictive Autoimmune Bio-markers” specifically for early diagnosis of Alzheimer’s.  See UTILITY OF AUTOANTIBODY BIOMARKERS FOR DETECTION OF ALZHEIMER’S DISEASE (Parkinson’s was looked at as well) and Neuronal PAD4 expression and protein citrullination: possible role in production of autoantibodies associated with neurodegenerative disease.  Also see here  and the study, Biomarkers could predict Alzheimer’s before it starts. which in summary:

“[The] preliminary study involving 525 people aged over 70. The work identified a set of ten lipid metabolites in blood plasma that distinguished with 90% accuracy between people who would remain cognitively healthy from those who would go on to show signs of cognitive impairment.

“Neurologist Howard Federoff of Georgetown University Medical Center in Washington DC,  and his colleagues tested the participants’ cognitive and memory skills, and took blood samples from them, around once a year for five years. They used mass spectrometry to analyse the blood plasma of 53 participants with mild cognitive impairment or Alzheimer’s disease, including 18 who developed symptoms during the study, and 53 who remained cognitively healthy. They found ten phospholipids that were present at consistently lower levels in the blood of most people who had, or went on to develop, cognitive impairment. The team validated the results in a set of 41 further participants.”

We don’t really know the source of the ten molecules, though we know they are generally present in cell membranes,” says Federoff. But he proposes that concentrations of the phospholipids might somehow reflect the breakdown of neural-cell membranes.”

“The exact mechanisms of the cell breakdown are still under investigation, Mapstone says.”

“We didn’t set out to find specific metabolites,” he says. “We looked at about 4,600 metabolites and discovered that 10 lipids were significantly altered in the plasma of cognitively normal older adults who would go on to develop the clinical symptoms of Alzheimer’s disease. We believe that this 10-lipid phospholipid biomarker panel reflects the breakdown of neural cell membranes in those individuals destined to develop advanced moderate cognitive impairment or Alzheimer’s disease and may mark the transition between preclinical states where synaptic dysfunction and early neurodegeneration give rise to subtle cognitive changes.”

“These findings are potentially very exciting,” says Simon Lovestone, a neuroscientist at the University of Oxford, UK, and a coordinator of a major European public-private partnership seeking biomarkers for Alzheimer’s. But he points out that only 28 participants developed symptoms similar to those of Alzheimer’s disease during the latest work. “So the findings need to be confirmed in independent and larger studies.”

The post, MICROBIOME RULES, WHAT IS IT? discussed how far we’ve come in establishing that autoimmune bio-markers exist pre-disease. An example was this study, which focused on RA and systemic lupus erythematosus autoimmune biomarkers, and the discussion occured within the section titled:  AUTOIMMUNE BIO-MARKERS EXIST YEARS BEFORE DIAGNOSIS, with a focus on RA and systemic lupus erythematosus, but its insights applies to all autoimmunes).” 

Implications and Awareness

How will people react to learning, years in advance of noticeable symptoms, that they will likely develop Alzheimer’s disease (or any other autoimmune disease really), especially if the news arrives before definitive treatment options are developed?  In the case of Alzheimer’s,  this article discusses the emerging “Predictive Test” from the ethical and notes:

“…how will people respond to knowing years in advance of a 90 percent chance of dementia type of concerns?  …People who abhor the prospect of living with dementia would have an interval of lucidity in which to act, writes Dena S. Davis, JD, PhD, Presidential Endowed Chair and Professor of Religion Studies at Lehigh University, on The Hastings Center’s Bioethics Forum. The blog’s editors conclude cautiously: “The big advantages of the blood test over the other biomarker tests are that it is easy to use and minimally invasive. These advantages … increase the necessity for society to examine the ethical implications for [such tests] and develop guidelines for their responsible use.”

Clearly, the science is moving towards identifying predictive bio-markers and one would hope, lifestyle modifications can be taught and implemented soon enough to preclude permanent tissue autoimmune damage.

“Pearls” from the Autoimmune Summit, hosted by Dr. Amy Myers, MD

Regarding the Autoimmune Summit, Dr. Amy Myers, MD recently posted, “What I Learned From Interviewing 39 Experts in Autoimmunity,  which summarizes her “Pearls” of the Autoimmune Summit, which I copied below.  Time and again, people are seeing dramatic improvement and even reversal of symptoms with attention to the factors listed below. Read her article for more specifics (and resources) pertaining to each factor.
1. Clean up your diet by removing toxic and inflammatory foods.
2. Eat a variety of organic whole foods.
3. Take care of your microbiome.
4. Reduce your stress.
5. Sleep.
6. Exercise (but don’t overdo it!).
7. Clean up your environment.
8. Be your own advocate.

These are all consistent with the Whole Health Pillars that I teach. You can tweak where is most comfortable, and then move onto your NEXT…

Whole Foods1_meats,vegs,fruit,fat,dairy
Slide source http://biomeonboardawareness.com/
Grain Brain and Coconut Oil for Alzheimer’s?

I want to point out the work of Dr. David Perlmutter, MD, who’s been tirelessly vocal in getting information out to the public regarding diet and Alzheimer’s.  His book, “Grain Brain,” is a wealth of dietary resource as is his website.  Also, just goggle for his many presentations.

Grain Brain, by Dr. David Perlmutter, MD, Neurologist
Source: http://www.drperlmutter.com/about/grain-brain-by-david-perlmutter/
Lastly, research (active recruiting clinical trial) addressing coconut oil (medium chain triglyceride) for Alzheimer’s  does exist, see Coconut Oil for Alzheimer’s Disease:
ClinicalTrials.gov ID 
Official Title: 
A Randomized, Double-Blind, Placebo-Controlled, 6 Month Cross-Over Study to Evaluate the Efficacy of Coconut Oil (Fuel for Thought™) Treatment for Subjects With Mild to Moderate Alzheimer’s Disease
Study Start Date: June 2013
Study End Date: September 2015
Disease Stage: EarlyMiddle
Enrollment: 65

Detailed Description: 

This randomized, double-blind, placebo-controlled trial is designed to determine the effect of taking coconut oil on the cognition, functioning, and behavior of older adults with mild to moderate Alzheimer’s. Participants will take a proprietary blend of coconut and medium-chain triglyceride oils, administered as a 1-ounce drink three times daily, for either Months 1-3 or Months 4-6 of the study; a placebo will be taken during the other 3-month period. The study medication formula is Cognate Nutritionals’ Fuel for Thought™

Many YouTube Alzheimer/medium chain triglyceride links can be googled such as this with Dr. Mary Newport, who’s website is: What If There Was A Cure For Alzheimer’s and Nobody Knew?


Last updated: March 23, 2016 at 4:50 am for SEO optimization.

In health through awareness,

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4 thoughts on “Alzheimer’s Diet, Microbiome, & Bio-marker Predictors”

  1. More studies on autoimmune autoantibioties years in advance of disease diagnosis (these on lupus): Dr. Melissa Arbuckle studied 132 veteran patients with lupus researching their frozen blood vials stored at the VA from the prior 30 years, including blood from prior to the patients’ illnesses. Elevated levels of autobodies were present in half of the patients many years before they were diagnosed with lupus. The levels slowly rose until it plateaued when their lupus symptoms began appearing, 2-3 years thereafter they were diagnosed with lupus, according to a study published in The New England Journal of Medicine, 2003. The Prevalence, Onset, and Clinical Significance of
    Antiphospholipid Antibodies Prior to Diagnosis of
    Systemic Lupus Erythematosus http://onlinelibrary.wiley.com/doi/10.1002/art.20120/pdf
    Also Study discussed here:
    Oklahoma Researchers Show Autoantibodies Occur before Lupus in New England Journal of Medicine Study, October 15, 2003
    http://omrf.org/2003/10/15/the-oklahoma-medical-research-foundation-announced-today-that-it-has-received-a-10-million-grant-from-the-national-institutes-of-health-new-england-journal-of-medicine-study/
    In conducting this new study, the researchers used the Department of Defense Serum Repository in Washington, D.C., which contains approximately 30 million blood samples collected from more than five million U.S. Armed Forces personnel.  From the military’s medical records, the scientists were able to identify 130 servicemen and women who were initially healthy but later developed lupus.  The scientists then analyzed blood samples collected from the lupus patients prior to their diagnosis and compared them with samples from matched service personnel without the disease.
    “In patients with lupus, we found that their natural defense system just continued to produce more and more abnormal responses – autoantibodies – up until the time they were diagnosed with the disease,” said Judith James, M.D., Ph.D., of OMRF and OUHSC, one of the study’s co-authors.  “Unaffected military personnel might occasionally make an abnormal immune response, but those normally resolve spontaneously, and no additional antibodies develop.”

    Another confirmatory study: Clinical Criteria for Systemic Lupus Erythematosus Precede
    Diagnosis, and Associated Autoantibodies Are Present Before
    Clinical Symptoms http://onlinelibrary.wiley.com/doi/10.1002/art.22665/pdf Conclusion. Symptoms associated with the ACR
    criteria for classification of SLE are commonly present
    before the diagnosis of SLE, and development of organassociated
    autoantibodies generally precedes the appearance
    of their associated clinical features.

  2. More autoimmune marker papers:
    From Questioning Answers blog: “Autoantibodies by the way, refers to antibodies against self tissue as per what has been noted in various autoimmune conditions/diseases,” and Paul Whiteley cites to: Plasma Autoantibodies (Disease Associations) located at: http://www.patient.co.uk/doctor/plasma-autoantibodies-disease-associations.

    Already on this post is the work of Dr. Yehuda Shoenfeld, MD, “The Mosaic of Autoimmunity: Prediction, Autoantibodies, and Therapy
    in Autoimmune Diseases – 2008” located at http://www.ima.org.il/FilesUpload/IMAJ/0/42/21035.pdf paper (from the Gluten Summit) and which is already cited on some of my tagged “microbiome” posts and the most recent “ALZHEIMER’S, DIET-MICROBIOME, & BIO-MARKER PREDICTORS” posting, http://biomeonboardawareness.com/alzheimers-diet-microbiome-bio-marker-predictors/

  3. More connections between the brain and the gut revealed: The Braniste paper: http://stm.sciencemag.org/content/6/263/263ra158 THE GUT MICROBIOTA INFLUENCES BLOOD-BRAIN BARRIER PERMEABILITY IN MICE

    Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to regulate barrier function in endothelial tissues. Exposure of germ-free adult mice to a pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. Our results suggest that gut microbiota–BBB communication is initiated during gestation and propagated throughout life.

    Sci Transl Med 19 November 2014:
    Vol. 6 no. 263 pp. 263ra158
    DOI:10.1126/scitranslmed.3009759

    Citation: V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Tóth, A. Korecka, N. Bakocevic, N. L. Guan, P. Kundu, B. Gulyás, C. Halldin, K. Hultenby, H. Nilsson, H. Hebert, B. T. Volpe, B. Diamond, S. Pettersson, The gut microbiota influences blood-brain barrier permeability in mice. Sci. Transl. Med. 6, 263ra158 (2014).

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