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!!!
Defeating Aging 