Just say NO: What’s Good For the Gander Is Probably Good For the Goose Part II.

By George Gillson MD PhD CCFP

As threatened, this post will talk about Dr. Bredesen’s approach to dementia/declining cognitive function. Of course, I can only present an overview here; if you are truly concerned you will need to work with your Integrative Medicine practitioner. But basically, Bredesen’s hypothesis is that there is no single cause of Alzheimer’s Disease; instead, there are multiple metabolic derangements. He calls it “a metabolic problem that is destroying your brain.”

This metabolic problem creates, to paraphrase his words, an imbalance in the activity of the brain cells that remember/build connections between neurons (synaptoblasts) and cells that forget or “prune” connections between neurons (synaptoclasts). This concept mirrors what goes on with osteoporosis, where there is an imbalance in the activity of cells that remove bone (osteoclasts) and cells that rebuild bone (osteoblasts). Osteoporosis is driven by many of the same metabolic issues that cause trouble in the brain.

In Alzheimer’s, tangles of abnormal proteins accumulate both inside neurons (tau proteins) and in the spaces between neurons (amyloid proteins). Neurons die and aren’t replaced. The affected brain actually shrinks. Nerve connections are lost and not re-made. It’s as if the electrical wiring in your house was gradually removed until all the lights eventually go out.

Dr. Bredesen developed a long list of the metabolic issues that need to be addressed in Alzheimer’s Disease and says,  “Think about it like 36 holes in the roof. You can’t just plug one hole.” He does define various subtypes of Alzheimer’s Disease, though, differentiated by nature of deficits/clinical course, age of onset,  various and laboratory markers. Classification into subtypes aids in individualization of treatment and helps focus treatment strategies.

I’m not going to get into detail on the subtypes but they are useful in identifying the main drivers for any given patient, and those are:

-Inflammation (could be caused by infection, genetic defects in pathways regulating inflammatory response, food choices-leading to leaky gut, inappropriate antibodies, exposure to toxins)

-Insulin resistance/dysregulation of blood sugar

-Hormones that drive/inhibit tissue repair are out of range low or high (sex hormones, cortisol, progesterone, Vitamin D, thyroid hormones, insulin). Often, this is driven by too much stress.

-Toxins* (refined sugar, high fructose corn syrup, environmental pollutants, vaccines, prescription drugs, recreational drugs, excessive alcohol, EMF, but also inability to “houseclean” due to genetics or sleep deprivation/shiftwork/poor sleep hygiene). *Bredesen calls chemical toxins “dementogens.”

-Reduced oxygen to the brain (cerebrovascular disease, decreased cardiac output due to damaged heart muscle or valve problems, sleep apnea)

-Head trauma (acute, high severity or recurrent, low/moderate severity)

I could devote several pages to any one of the above issues. But I won’t. The take-home message is that just as your brain is at the apex of your body, if you happen to be a bipedal humanoid (!), treatment of dementia is the apex example of the application of Integrative/Functional Medicine. There are no effective mainstream pharmacologic treatments for dementia, yet the Integrative/Functional Medicine approach appears to get traction where nothing else can. We develop these debilitating, often fatal, devastating chronic diseases primarily because our modern lifestyle is colliding with our physiology.

These posts can start to sound like broken records (pardon the anachronism) because the same themes keep recurring no matter whether it’s cardiovascular disease, cancer, diabetes, osteoporosis, rheumatoid arthritis, asthma, erectile dysfunction and so on. We might need to do more of a full-court press to beat back Alzheimer’s Disease but the game is definitely on.

Stopping or reversing the manifestations of Alzheimer’s Disease through a lifestyle approach takes time, dedication and patience. It is not a sure thing but our understanding is growing almost weekly. An experienced Integrative Medicine practitioner is definitely your best partner/teammate to deal with declining cognitive function! Please don’t give up hope if you or someone you know is facing this challenge. Help is available!

P.S. As an appendix, I’m including a modified treatment list adapted from a post entitled “36 ‘Holes in the Roof’ The Dawn of the Era of Treatable and Preventable Alzheimer’s Disease”. The services highlighted below are offered at the EvolveWell clinic, which also has much expertise in the use of the supplements mentioned, as well as others not mentioned. It is by no means intended to be medical advice but it gives you a sense of the comprehensive approach needed to restore the function of our marvellous and mystifying brains.


Therapeutic System 1.0

1. Optimize diet: minimize simple carbohydrates (read white sugar and high-fructose corn syrup), minimize inflammation – there are various low glycemic, low inflammatory, low grain diets that are used depending on individual circumstance. The aim in each case is to maximize insulin sensitivity and minimize inflammation. IgG Food Antibody testing can be helpful to identify potentially inflammatory responses to foods.

2. Enhance autophagy (housecleaning of wastes/dead cells), trigger ketogenesis by fasting for 12 hours each night, including 3 hours prior to bedtime. This reduces insulin & beta-amyloid plaque buildup.

3. Reduce stress – with yoga, meditation, music, relaxation apps. This aims to reduce inappropriately high cortisol. Prolonged high cortisol shrinks your hippocampus, crucial for memory. Heart-rate Variability (HRV) testing can help assess how you are coping with stress.

4. Optimize sleep – 8 hours a night, with 1-3 mg of melatonin at night, tryptophan 500 mg 3X per week, rule out/treat sleep apnea, attend to sleep hygiene (avoid light exposure in the evening, keep a regular sleep schedule).

5. Exercise – 30-60 minutes per day, 4-6 days/wk. Weight training is critically important.

6. Scientifically-validated brain training e.g BrainHQ & other brain stimulation (reading, playing a musical instrument, word puzzles)

7. Drop Homocysteine below 7, with Methylcobalamin, MTHF (methylenetetrahydrofolate), P5P (pyridoxal-5-phosphate), TMG (trimethylglycine) if necessary. Know your methylation genetics

8. Maintain serum B12 > 500, with Methylcobalamin.

9. Keep hs-CRP < 1, Albumin/Globulin > 1.5 with an anti-inflammatory diet and supplement: curcumin, DHA/EPA, measure your fatty acid profile e.g. OmegaQuant dried blood spot profile

10. Optimize fasting insulin < 7 and HbA1C < 5.5 via diet guided by consultation with Lifestyle Coach

11. Optimize hormone balance via serum and urine testing and bioidentical hormone replacement as needed: Free T3, Free T4, TSH, Pregnenolone, Progesterone, Estradiol, Testosterone, Cortisol & DHEA

12. Maintain GI health, address leaky gut/leaky brain – with probiotics and prebiotics if necessary, specialized testing of GI function and IgG Food Antibody testing

13. Reduce beta-amyloid levels: supplementation with Curcumin, Ashwaganda

14. Supplement to promote cognitive enhancement: Bacopa monniera, magnesium threonate

15. Supplement Vitamin D3 and Vitamin K2: with Vitamin D3 dosing guided by serum testing

16. Increase Nerve Growth Factor (NGF): Lion’s Mane (H. erinaceus ), acetyl-l-carnitine, low-dose Lithium orotate

17. Provide building blocks to rebuild synapses: DHA, citicoline

18. Optimize antioxidants: supplement mixed tocopherols & tocotrienols, Selenium, blueberries, n-acetylcysteine, ascorbate, alpha-lipoic acid.

19. Optimize Zn: free Cu ratio guided by serum testing and judicious supplementation with zinc and copper

20. Measure fatty acids guided by testing: OmegaQuant dried bloodspot test supplement DHA for structure, EPA for function

21. Optimize mitochondrial function: CoQ10 or ubiquinol, alpha-lipoic acid, polyquinoline quinine (PQQ), n-acetylcysteine , ALCAR (acetyl-L-carnitine), Se, Zn, resveratrol, ascorbate, thiamine

22. Increase focus/increase acetylcholine synthesis: pantothenic acid

23. Increase Sirtuin enzyme function: resveratrol

24. Identify toxicity: evaluate toxic element burden (lead. Mercury, cadmium, aluminum)typically done by urine testing and detoxify/remove as necessary. Some people are very sensitive to EMF (wifi, cell towers, etc), screen for mold toxins and other environmental toxins. Detoxify as needed

25. Medium chain triglycerides: coconut oil as an alternate brain fuel

26. Assess genetic factors such as ApoE3/E4 status that can contribute to Alzheimer’s Disease via DNA testing

27. Supplement to reduce cortisol: phosphatidyl serine, phellodendron

George Gillson MD PhD

Author: George Gillson, MD, PHD, CCFP
EvolveWell Medical Director





Bredesen DE. Reversal of cognitive decline: a novel therapeutic program. Aging (Albany NY). 2014 Sep;6(9):707-17. doi: 10.18632/aging.100690. PMID: 25324467; PMCID: PMC4221920.

Bredesen DE, Amos EC, Canick J et al. Reversal of cognitive decline in Alzheimer’s disease. Aging (Albany NY). 2016 Jun;8(6):1250-8. doi: 10.18632/aging.100981. PMID: 27294343; PMCID: PMC4931830.

Gualtieri CT, Johnson LG. Reliability and validity of a computerized neurocognitive test battery, CNS Vital Signs. Arch Clin Neuropsychol. 2006 Oct;21(7):623-43. doi: 10.1016/j.acn.2006.05.007. Epub 2006 Oct 2. PMID: 17014981.

Rao RV, Kumar S, Gregory J, Coward C, Okada S, Lipa W, Kelly L, Bredesen DE. ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline. Biomedicines. 2021 Sep 29;9(10):1348. doi: 10.3390/biomedicines9101348. PMID: 34680464; PMCID: PMC8533598.

Saleh RNM, Hornberger M, Ritchie CW et al. Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort. Alzheimers Res Ther. 2023 Jan 9;15(1):10. doi: 10.1186/s13195-022-01121-5. PMID: 36624497; PMCID: PMC9830747.

Toups K, Hathaway A, Gordon D, Chung H, Raji C, Boyd A, Hill BD, Hausman-Cohen S, Attarha M, Chwa WJ, Jarrett M, Bredesen DE. Precision Medicine Approach to Alzheimer’s Disease: Successful Pilot Project. J Alzheimers Dis. 2022;88(4):1411-1421. doi: 10.3233/JAD-215707. PMID: 35811518; PMCID: PMC9484109.