The End of Alzheimer’s

Ray’s notes on The End of Alzheimer’s, by Dale E. Bredesen

 {Bought 11/19/18.

Started 11/19/18: 1.5 hours to p 30. 11/20/18: 3 hours to pg 92. 11/21/18 3 hours to pg 130}

Page 6-7 removing / stopping amyloid beta fails to improve Alzheimer’s Disease (AD) and can make it worse

Page 8 Aricept is a cholinesterase inhibitor that may alleviate some symptoms of AD, but does not treat it.

Page 9 AD is not a single disease: 3 subtypes that each need a different treatment.

Page 11 Genetic variants that increase AD risk: Apo E4 (1 copy increases risk to 30% , 2 copies to 50-90%) normal risk 9%.  Presenilin 1 and presenilin 2 also increase risk.

Page 12 Brain aging begins at 40

Page 12 -13 AD is result of normal brain activities gone bad

Page 13 ReCODE = reversal of cognitive decline, the protocol outlined in the book for helping with Alzheimer’s

Page 13-14 First ReCODE patient from 5 years ago before he wrote the book (2012?) is healthy

Page 16 Amyloid – beta is protective not harmful!  It i.s a defensive reaction by the brain trying to slow the disease

Page 17 most diseases have a 1- size fits all treatment.  For example measles, or a broken arm.

Page 19 more than 50,000 published papers on AD

Page 25 amyloid plaques and neuron tangles are not the cause of AD but the brain’s protective response

Page 26 AD results from brain defenses reacting to chronic (multiple) threats: 1 inflammation (from infection, diet or other).   2. Decline and shortage of supportive nutrients, hormones, etc.  3. Toxic substances such as metals

Page 28 “developing optimal treatment for complex chronic diseases like AD involves many contributors and fashioning the best program to target these contributors” = programmatics

Page 28 more than 36 factors contribute to cognitive decline

Page 31 with AD, you usually have it for 15-20 years before diagnosis.

Page 32-5 AD symptoms list (each one explained in the book):

·       Facial blindness

·       Decreasing mental clarity (especially later in the day)

·       Decreasing interest in reading, an inability to follow or engage in complex conversations, and an inability to follow movies with complicated plots

·       Decreasing ability to recall what was read or heard

·       Decreasing vocabulary

·       Mixing up words

·       Decreasing processing speed

·       Increasing anxiety about driving and finding the way

·       Difficulty remembering to-do list and appointments; often feeling “overwhelmed” by what needed to get done

·       Sleep disruption

·       No longer getting a mental boost from caffeine

·       Trouble speaking foreign languages that were once proficient in

Page 45 work with physician and Heath coach so you can get lab tests optimize your program and track response

Page 45 There are dozens of things cause cognitive decline–all fixable:

Page 45 1.  Prevent and reduce inflammation

Page 46 inflammation without infection from gluten, sugar, dairy, fat

Page 46 eating gluten or dairy or grains can cause leaky gut

Page 50 2.  Optimize hormones, trophic factors and nutrients

Page 51 3.  Eliminate toxins

Page 52 remove toxins with cruciferous vegies, water, saunas and increasing glutathione

Page 71 fig 3: APP production gives sAPPa or AB

Page 74 APP cleavage by netrin 1 prevents AB formation

Page 75 AB is a prion that cause APP cleavage -> more AB

Page 76 ReCODE shifts production away from AB production

Page 86 tropisetron encourages synapse formation

Page 88 new drug development costs $2.5 billion for each drug

Page 89 They (Dr. Bredesen’s team) were turned down on tropisetron trial

Page 90 treatment of complex problems like type 2 diabetes, lupus and obesity can be better treated by treating all contributing factors rather than targeting a single contributing factor.

Page 98 Type 1 AD: inflammatory (hot).

Page 100 evolution of Ap. E4

Page 102 type 1 lab results

Page 102 type 2 AD: is atrophic (cold).  Most frequent of these who carry 1 or 2 copies of Ap. E4 get this

Typically presents with loss of ability to make memories

Page 103 type 2 lab results

Page 103 type 2 responds more slowly than type 1 to treatment

Page 104 type 1.5 lab results. It is glycotoxic (sweet)

Page 104 type 3 is toxic (vile) people with this type often have difficulties with math, finding words and spelling and reading

Page 106 type 3 lab results

Page 108 dementogens – toxins that cause dementia

Page 110 Table 1. Chart of type 3 AD from Bredesen, Aging 2016,3

Page 116 AD asymptotic phase may last 1+ decades

Page 116 AD may be treated during mild & moderate AD

Page 119 Homocysteine comes from methionine that you eat

Page 119-20 Conversion of homocysteine requires vitamin B12, vitamin B6 folate and betaine (an amino acid)

Page 120 any homocysteine above 6 micromoles/l is bad

Page 120 take methycobalamin (active form of vitamin B12) not cyanocobalamin (inactive form of vitamin B12)

Page 120 take methytetrahydrofolate, not folate because it is the more active form

Page 120 take pyridoxal -5- phosphate, not pyridoxine

Page 121 keeping homoeystein low means having enough B6, B9 (folate) and B12

Page 121 test B12, not MMA

Page 122 Goals:  B12 = 500-1500 pg/ml; folate 10-25 ng/ml; B6 60-100 mcg/L

Page 122 human body not designed for more than 15 g/day sugar

Page 123 IDE = insulin degrading enzyme. Also degrades AB

Page 123 discussion of AGE (Advanced Glycation End products) and the damage it does

Page 123 Keep fasting insulin < 4.5; glucose <90; hemoglobin Alc < 5.6%

Page 125 6 key measure of inflammation:

1. C-reactive protein (use a high sensitivity (hs) CRP test) : < 0.9 mg/dL

2. ratio of albumin to globulin (A/G ratio)  1.8+

3. ratio of omega 6 to omega 3 in your red blood  cells : less than 3 but greater than 0.5

4. Interleukin 6 and tumor necrosis factor alpha (cytokines) : IL – 6 < 3 pg/ml; TNF alpha < 6 pg/ml

Page 126 vitamin D3 turns on over 900 genes!

Page 126 aim for 50-80 ng/ml vitamin D

Page 126 use 100x rule to determine D3 dosage :

  • Example:
    • subtract current (say 30) from goal (60?) = 30
    • and ×100 = 3000 IUs for your daily dose
  • For me, from 2008 (the last time I had it tested–yes, almost 11 years ago):
    • (was about) 15
    •    60-15 = 45
    • 45*100 = 4500 IU per day !

Page 127 thyroid function: measure armpit temp b-4 get dosage up.  Ir ahould be 97.8 and 98.2 F. If your temperature is lower then you may have low thyroid function

Page 127 when thyroid function is low, reflexes slow. Thyroflex can measure how fast your reflexes are and gives an indication of thyroid function.

Page 128 sub optimal thyroid function: need to measure free T3 (3.2-4.2 pg/ml) free T4: (1.3-1.8); TSH< 2.0 micro IU/ml reverse T3<20ng/dL; {[free T3 × 100] / [reverse T3] }  > 20

Page 129 women ovaries removed inceases (by 2x) the risk of AB due to decreased estrogen

Page 129 high estradiol to progesterone ratio results in brain fog

Page 130 estradiol 50-250 pg/ml; progesterone 1-20 ng/ml; estradiol / progesterone ratio = 10-100

Page 130 testosterone 500-1000 mg/dL; free testosterone 6.5-15 mg/dL

Page 132 stress hormones–cortisol (morning) 10-18 mg/do; pregnenolone=50-100 ng/dL; DHEA sulfate = 350-430 Mcg/dL women, in men 400-500 Mcg/dL

Page 132 to Cu:Zn ratio. Prof George Brewer from U of Michigan expert.

Page 133 zinc supplements enhance cognition

Page 133 zinc deficiency especially prevalent in old

Page 134 copper: zinc ratio 0.8-1.2; 90-110mcg (each) / dL (or red blood cell zinc = 12-14 mg/dL)

Page 135 magnesium in RBC = 5.2 – 6.5 mg/dL

Page 136 serum selenium = 110-150 ng/ml; glutathione (GSH) = 5.0-5.5 micromolar

Page 137 note for checking arsenic: do not eat seafood for 3 days before the test

Page 139 metals: Hg, Pb, As, Cd < 50th percentile (by Quicksilver) or if by blood levels Hg<5mcg /dL; Pb<2 mcg?dL; As<7 mcg/L; Cd<2.5 mcg/L

Page 139-40 sleep affects on cognition (5 points)

Page 140 75% of patients with sleep apnea not diagnosed

Page 141 AHI = apnea – hyponea index (=times/hour stop breathing)

Page 141 AHI goal = <5/hour, but prefer 0

Page 142 when total cholesterol is <150, brain shrinks

Page 142-3 Vitamin E (measured as alpha-tocopherol) = 12-20

Page 143 B1 (serum thiamine) 20-30 nmol/L (OR red blood cell thiamine pyrophosphate (TPP) =100-150 ng/ml (packed cells)

Page 145 (in block “Vicky”) integrative physician (see https://www.dukeintegrativemedicine.org/about/what-is-integrative-medicine/ which says it puts the patient at the center of care which “puts the patient at the center and addresses the full range of physical, emotional, mental, social, spiritual and environmental influences that affect a person’s health”)

Page 145 leaky gut test: give lactulose and mannitol if find both in urine = leaky gut.  Because lactulose not absorbed unless gut is leaky

Page 146 other ways to determine leaky gut

Page 146 do not want leaky gut. (Cyrex Array 2 = neg.)

Page 148 There are abnormalities in the blood brain barrier in AD.  Cyrex Array 20 tests for leaked brain proteins

Page 149 Book Grain Brain about gluten sensitivity

Page 149 glucose sensitivity causes leaky gut. Test with tissue transglutaminase antibodies negative or Cyrex Array 3 and Cyrex Array 4 negative

Page 150-1 Auto antibodies if immune system attacking your brain you should know! Cyrex Array 5 negative

{11/22/18: 1.5 hours to page 151.  11/26/18:  5 hours to page 149.  11/27/18: to end of book}

Page 151 toxins are an important cause of Alzheimer’s

Page 151 they set up a way to rest chemical / toxin effects on synapse re-organization vs maintenance.  Then they tested every FDA approved drug and many others

Page 152 several statins tip balance against neuron survival; Baycol worst (cerivastatin).

Page 152 mycotoxins also very bad. See Dr. Shoemakers 2010 book Surviving Mold

Page 152 CIRS = chronic inflammatory response syndrome results from prolonged mold exposure

Page 153 genetics test for mycotoxin adaptive immunity. (25% of people do not have!) And an activated innate immunity

Page 153 Goals for mycotoxins

Page 154 long list of mitochondria damaging agents, etc. AZT, antibiotics, aspirin, ibuprofen, etc.

Page 155 optimum BMI for cognition is 18-25. Or a waist line of <40 inches for men or a Tanita score of 1-12

Page 156 optimum diet is different if you are ApoE4+

Page 156 Know your genetics.  You want to know your genes for APP, PS1, PS2, CD33, TREM2, CRI, NLRP1

Page 157 link to Montreal Cognitive Assessment test A normal score is 26-30, other links: MMSE, SAGE etc.

Page 158-9 brain imaging

Page 159 in AD the CSF has decreased amyloid-beta 42 and & increased tau and phospho-tau

Page 159 ECG useful to look for seizure activity.

Page 161 neural exosomes (trash from the brain): billions/oz of blood! Can detect AD with.

Goal: normal neural exosome levels of amyloid beta 42, phosphor-tau, casthepsin D,  REST and phosphorylation ratio of IRS-1

Page 162 back of eye gets plaque and best way to see if it is decreasing

Page 163 loss of novel object recognition occurs early in AD, test it.

Page 163-5 list of questions about lifestyle that affects AD

Page 167-9 Table 2: summary of Key tests and optimum tests

Page 172 people with cognitive decline have 10-25 sub-optimal blood chemistry values; healthy people 3-5.

Page 174 each of these values can be returned to optimal

Page 174-6 Key points for the ReCODE protocol :

Page 174 Key conceptual concepts for treating dementia (each is discussed at length):

1. Go beyond normal to optimal

2. Address as many abnormalities as possible

3. Goal is to treat roof cause of problem

4. ReCODE personalized, based on lab values

5. Threshold effect : once enough of the network components optimized, disease can be halted/reversed

6. Iterative program

7. Drugs are not the first line of treatment

8. Earlier you start, greater chance for reversal

9. For almost every element, there is work around

Page 176 helpful to have a health coach

Page 176 Homocysteine: if over 6, lower it by taking B6, B12, folate. Take activated. (More)

Page 177-8 Insulin resistance: diet, exercise, sleep, decrease stress

Page 179 Ketoflex 12/3 diet. Mild Ketosis is optimal

Page 180 should buy a ketone meter, if you are going to do any kind of ketone targeted diet.

Page 181 benefit of fasting: promotes autophagy

Page 181 break the fast with water with lemon to detoxify

Page 182-9 specifics of Ketoflex 12/3 diet

Page 182 websites: glycemic indices; “Dirty dozen clean 15”

Page 182 want food with glycemic indices <35

Page 184 list of detoxifying plants.  See also ApoE4.info

Page 185 need 0.8-1.0 g protein per day per Kg body

Page 187 The ketoflex diet is a fat-rich diet

Page 187 vitamins to take to optimize nutrition

Page 189-90  things to try if hemoglobin A1c >5.5 or if fasting glucose >90 (only try 1 at a time until get results). Eg zinc, Mg, cinnamon, Alpha-lipoic acid, chromium

Page 190-1 sitting is detrimental to cognitive and physical

Page 191 exercise increases survival of newborn neurons

Page 192 getting good sleep is critical

Page 193 0.3-20 mg melatonin/day if needed, but 1 day/week off to help assure your body continues to make melatonin

Page 194 Tryptophan at bed time slows/stops middle of the night ruminating

Page 194 loss of progesterone as age gives anxiety brain fog and decreased sleep

Page 195 if awakening due to stress consider meditation or a recording like Neural Agility which drives brain frequencies

Page 195-6 list of good sleep hygiene activities

Page 196-8 reduce stress. Few deep breaths, massage, music, laughter

Page 198-9 Brain training. Mike Merzenich leading expert; suggestions on how to use his BrainHQ programs

Page 199 inhibit inflammation: omega 3 and curcumin with fats

Page 199 resolve inflammation: SPM Active 2-6 capsules/day for 30 days

Page 200 remove all inflammation sources

Page 200 healing the leaky gut (cyrex array 2)

Page 201 bone broth good for healing leaky gut.

Page 202 SCD diet to heal gut: draxe.com/scd.diet

Page 203 Table 3 : 5 core bacteria for probiotics

Page 204-5 website survingmold.com. 3 points on removing pathogens/mold

Page 205 mold: mycometrics.com ERMI , quantifies mold; > 2 is bad

Page 205-211 hormones.

Page 207 Thyroid: check iodine. If low, take pills or eat kelp

Page 209 especially important for women with type 3 SCI, MCI or AD to optimize hormone levels. For men if testosterone < 308 should use gel or cream to optimize levels. Monitor

Page 210 Adrenal function: pregnenolone = 50-100 mg/dL. If low take 10 mg daily pills

Page 210-11 if morning cortisol low evaluate if high maybe infection

Page 212 clear evidence APP responds to metals (APP is an amyloid precursor protein)

Page 212 some people have low mercury excretion

Page 213 method developed by Quicksilver to remove mercury via Nrf2 gene (also see pg 216: Detox Qube)

Page 213 zinc : cu ratio. Zinc picolinate 25-50 mg to increase zinc. Take V. C 1-3 g/day to chelate and remove Cu

Page 216-7 ways to excrete biotoxins: IV glutathione, intranasal vasoactive intestinal peptide, foods, chlorella, shower/sauna.

Page 221 Ayurvedic practice of oil pulling with coconut oil on teeth

Page 221 skin deep website: ewg.org/skindeep

Page 222 take vitamins D3 and K2 with vitamin A+fat to increase bioavailability

Page 222 timing of taking resveratrol and NAD supplements

Page 223 blue blocker glasses several hours before bed time also programs for computer & phone, etc to block blue light.

Page 226 social networking site: ApoE4.info

Page 228 personalize programmatic approach & large data sets yields cures for apoE4 patients.

Page 234-5 ReCODE : The basic plan (table)

Page 236 need to use protocol for 6 mo + before you see effects

Page 237 health coaches very helpful in assuring meet protocol

Page 237-8 keep optimizing! Tweak protocol based on lab tests

Page 238 list of companies that do neuropsychological testing like BrainHQ

Page 239 addressing the most important things may be good enough to slow/reverse Alzheimer’s

Page 241 document your cognitive states regularly

Page 241 structural brain status (atrophy) using Neuroreades or Neuro Quant

Page 242 if go off protocol, do it slowly. But most people start to decline again within 2 weeks of going off the protocol.

Page 243 can start program slowly (in phases)

Page 244 MoCA scores>24 have better chance for improvement

Page 245 Type 3 sub type is difficult to treat successfully

Page 245 people over 75 have a poorer response to protocol

Page 278-9 useful websites

Page 277 Appendix A: foods to eat and to avoid

Page 281 Appendix B: Ketone meter

Page 285 Appendix D: basis for approach to ReCODE and the evidence behind each point

Great Book!!!