The End of Alzheimer’s: reversing Cognitive Decline

Date aired: August 18, 2017


Episode Description

The global burden of dementia is staggering—it is a trillion dollar problem—and it is growing. Of the currently living Americans, about 45 million will die with Alzheimer’s disease (about 15% of the population). 75 million have the important genetic risk factor, ApoE4. Cognitive decline associated with Alzheimer’s disease and its precursors (MCI and SCI) can be prevented and reversed. The optimal approach for complex chronic illnesses such as Alzheimer’s disease is not a mono therapy but a personalized program that addresses all of the contributors. The many cases of Alzheimer’s disease are associated with metabolic and hormone abnormalities and exposures to pathogens including viruses, bacteria, metabolic and olds and mycotoxins, Dr. Bredesen has reversed cognitive decline in several hundred people on his personalized protocol, with unprecedented success. His book, The End of Alzheimer’s: the first program to prevent and reverse cognitive decline comes out on August 22,

Book :The End of Alzheimer’s : the first program to prevent and reverse cognitive decline, Random House


  • Alzheimer’s Disease (AD) is common, and is on the rise
  • AD is preventable and at the early stage is reversible
  • Alzheimer’s cognitive decline results from a protective response to various insults
  • Treatment goals are to identify and protect individuals from these various insults



  • AD is the third leading cause of death
  • Is increasing
  • Is more common that breast cancer in women
  • Two –thirds of Alzheimer’s disease is in women
  • Women represent 60 % of the care takers
  • 15 % of people will develop Alzheimer
  • Will have 45 million in US who will get Alzheimer’s
  • Cost over $200, billion in the US annually
  • By 2050, there will be 15 million people and 160 million people with AD around the world.


  • Cognitive decline has been on going for years
  • First patients have SCI (subjective cognitive impairment).
    • test normal but know there is a problem.
  • The next step is MCI (Mild Cognitive Impairment
    • test scores not normal
    • able to do activities of daily living. and care for self
  • Third step is AD –lose activities of daily living.


  • AD is a protective response to three fundamentally different classes of brain insults
    • Inflammation
    • Trophic Responses and
    • Toxins
    • Brain is trying to protect from classes


  • Centuries ago, people died of inflammatory diseases. Now people die of chronic diseases which have many contributing causes.

     APOe 4 Apo lipoprotein E

  • APOe lipoprotein is a fat bucket carrying fat around the body
  • Three different alleles 2, 3, 4
  • Get a copy from mother and one from the father
  • Most common allele is 3, 3
  • 75 million in the US (25 %) have at least one copy of the 4 allele
  • 7 million people in US who have two copies of allele 4
  • For people with no copies of the allele aPOe 4, the chance of getting Alzheimer’s Disease is nine percent.
  • With one copy of allele APOe4, the chance of getting Alzheimer’s Disease 30 %
  • With two copies of the allele APOe4 is between 50 – 90 %

     Genetic Alleles

  • 6 % of our evolution time, people had two APOe 4 alleles.
  • Millions of years ago, most people had the APOe4 allele.
  • 220,000 years ago, APO e3 appeared
  • 80, 000 yeas APO e2 appeared
  • Apo e 4 conveys an increased risk of activation inflammatory pathways
    • This helped in primitive societies where there where high risks of infections and exposure to microbes
    • These people have an increased risk factor for cardiovascular disease, Alzheimer’s disease and shorter life span
    • This is “Antagonistic pleotrophy” This helps protect you when you are young but puts you at an increased risk when older

     APOe 3 vs APOe 4

  • Bredesen draws the analogy of APOe 4 an aggressive society that puts its resources into preparation for war, arms and fighting off inflammation. (.e.g, North Korea).  It facilitates a pro-inflammatory , fight off intruders stance.
    • Involves NFKa related to Rel a
  • APOe3 is seen as akin to a society that puts its resources into longevity, research, and recycling (e.g, South Korea)
    • Involves SIRT 1 (which is in resevretol) which is associated with longevity, recycling and changes in metabolism
  • There is a mutual antagonism between these two pathways Rel A vs NFKa (inflammatory vs  preservation of stability)
  • Our life style choices can influence which pathway we go down
  • A prevention program would include diet, lifestyle choices, specific herbs and supplements to avoid triggering the proinflammatory trigger.
  • The status of the involvement in these opposing pathways can be measured and monitored.


  • Synaptoclastic vs synaptoblastic mechanisms
  • imbalance between enough of the synaptoblastic and synaptoclasticsignaling in the brain
  • There are a set of signals that are synaptoclastic and synaptoblastic (making synapse keeping memories)
    • Synaptoclastic build synapses/ construction
      • Eg, thyroid hormone, estradiol, testosterone, vitamin D, folate
    • Synaptoblastic tears down, destruction



  • Caused by inflammation and infection (such as chronic Lyme disease, fungi)
    • AD can be viewed as the neurosyphillis of 21st century
  • Presentation
    • present with common type which is amnestic
    • lose the ability to remember new things. With a loss of hippocampal volume, the brain cannot support the same network structure.
    • As an analogy, in a company, the first thing to shut down would be hiring new people (In a person’s life it is not crucial if one forgets last night’s friend.



  • Due to a change in trophic support: an excess of synaptoclastic activity over synaptoblastic activity in the brain.
  • Includes changes in substances such as
  • thyroid, estradiol, pregnenolone, progesterone, testosterone, vitamin D, vitamin B 12, nerve growth factor, BDNF
  • As these are withdrawn, brain activates production of amyloid and synaptoclastic pathways
  • Presentation
    • present with common type which is amnestic
    • lose the ability to remember new things. With a loss of hippocampal volume, the brain cannot support the same network structure.
    • As an analogy, in a company, the first thing to shut down would be hiring new people (In a person’s life it is not crucial if one forgets last night’s friend.


  • Exposures to toxins including
    • biotoxins
      • can be measure in urine
    • micotoxin made from mould
    • metallotoxins
  • Examples
    • penicillium, apsergillus, ocrha toxin A,
    • Copper
    • Mercury
      • Fish
        • tuna fish, long lived fish with large mouth
        • eat small fish (salmon mackerel, sardines, herring)
        • Eat wild, caught fish
        • Farmed fish i
          • introduces pollutants high in other pollutants
          • Will be low in omega 3 to omega 6
        • Mercury in fillings (Amalgams)
          • If you replace mercury in fillings, take appropriate precautions
        • The brain makes amyloid to bind to these toxins
        • Cortical presentations. Can manifest as
          • Parietal lobe problem
          • Difficulty in calculation organization (frontal or parietal lobe
          • Praxis learned programs dressing
          • Prosopagnosia can’t  remember faces
          • Difficulties in word finding and speaking.
          • Problems with visual perception
        • Patients tend to be younger in fifties
        • At least 500, 000 Americans with this problem
        • Always associated toxins
        • These people tend to be APOe 4 negative with a negative family history.
        • They tend to respond more slowly to inflammation, but respond more readily to toxins

D. TYPE 1.5

  • Insulin resistant type 1.5
    • Some of the features of type 1 and some of the features of type 2 Alzheimer’s Disease
    • Body does not respond as well to insulin
    • Don’t get trophic response to insulin
    • Get high glucose get high AGE, à inflammation
  • due to a combination of inflammatory factors such as trans fatty acids, too much AGE from simple carbs and trophic factors


  • Chronic diseases such as cancer, heart disease, AD are complex with many causes
  • determine all the contributors from which brain is protecting it self
    • remove these things
    • remove the inducers, then
    • remove the amyloid
    • Removing the amyloid (akin to an electric protective fence) does not help if the assaultive insults are not removed.


  • Treatment is not just one simple drug
  • There can be up to 50 contributing causes in an individual.
    • Need to identify the contributing factors for the individual.
      • There are 10 – 25 contributors for each person
    • Address the causes that are having the largest impact
      • Bredesen likens treatment to addressing a structure that has a roof with 50 holes. Each hole is a different size,
      • Patching up the largest holes has an effect.
      • Don’t have to patch all the holes
      • Giving one medication, patches only one hole
      • For each person, the holes are different sizes
        • For example low vitamin D 3
        • Eg, early oophorectomy without hormone replacement therapy
      • So the treatment must be personalized/ individualized
      • He has an algorithm for assessing appropriate individualized treatment for an individual.
    • Need to live the program
    • Need to live the program for 3 – 6 months
    • Stopping treatment typically results in symptoms returning within ten days.
    • Need to reduce insulin resistance and inflammation
    • Need to reduce exposure to toxins and drain toxins from the body
      • One person went to 17th to 71st percentile in a cognitive test
      • One person went from the 3rd to 84th and from the 13th to the 79th percentile in two different cognitive tests


  • PET scan with FDG (glucose measurements) or amyloid
  • Spinal tap
  • Neuroexosomes
    • In each milliliter of blood have 1.2 billion of exosomes are fragments of cells that are expelled by cells of body
    • Are 1/70th diameter of a red blood cell
    • Are looking at garbage
    • About 10 % of these come from brain cells
    • These have markers so they can be evaluated
    • This is good for monitoring treatment
    • Phagocytosis index: eat bacteria and eat amyloid
      • When have AD have poor ability for WBC to snap up amyloid


  • For Inflammation- Type 1 Alzheimer’s Disease
    • Hs crp high sensitivity c reactive protein Is ist > 1
    • Homocysteine
  • Trophic Withdrawal- Type II Alzheimer’s Disease
    • estradial, testosterone, vitamin D
    • BDNF from exercise
    • Homocysteine methylation, vitamin B
    • Inflammatory state
  • Exposure to specific toxins
    • copper / zinc
    • mercury


  • Earlier start better
  • Diet
    • Mild ketosis
    • Mainly plant based mild ketogenic diet
    • Grass fed meats
    • 12 hour fast
    • if 4 14 hours, 16 hours
    • three hour fast before dinner
  • Exercise
    • At least five times per week
      • Aerobic exercise
      • Strength training helps insulin sensitivity
    • Sleep
      • Poor sleep is pro Alzheimer’s
      • 7- 8hours per night
      • check sleep apnea
      • check UARS upper airway resistant syndrome
      • While sleeping are getting rid of amyloid
      • Sleeping 4- 5 hours per night is a dementogen
  • Stress
    • Affect hormones
    • Affect inflammatory state
    • High cortisol can decrease hippocampal volume
    • Affect gut microbiome
      • Leaky gut is important contributor
    • Cognoscopy
      • A colonoscopy is recommended starting at age 50
      • Over age, 45 a cognoscopy is recommended
    • must know where stand
    • can be addressed
    • can be prevented
    • we can decrease global burden of dementia
    • Address inflammatory
    • Address atrophic and toxins