Maintain Your Brain – Part 4: The Importance of Testing

Put it to the test . . .

You may just want to start by taking advantage of what be can learned from the ReCODE protocol – with or without having some lab work done – and include what works for you in your day-to-day routine.

But . . . you can’t fix a problem you’re unaware of.

So . . . whether you are interested in preventing cognitive decline or reversing it, you first need to determine in detail where you stand in terms of your vulnerability to the three insults of inflammation, suboptimal hormones and other brain nutrients, and toxic compounds. Only then can you identify what needs to be addressed in order to improve cognitive function.

The blood tests that will tell you this are increasingly available, often without a prescription from your physician. (For more about why testing is so important, go now to Appendix A).

Homocysteine level should test below 7 micromolar, which can be accomplished by adequate intake of the active forms of vitamins B6 (pyridoxal-5-phosphate – or P5P),   B9 (methyltetrahydrofolate or methyl-folate), and B12 (methylcobalamin). Lab test results should fall within these ranges: vitamin B12 = 500– 1500 pg/ ml; folate = 10– 25 ng/ ml; vitamin B6 = 60– 100 mcg/ L.22

Homocysteine >6, take daily:23

  • Vitamin B6 (P5P form) 20 – 50 mgs
  • Vitamin B12 (methylcobalamin) 1 mg (1,000 mcg)
  • Vitamin B9 (methyltetrahydrofolate or methyl-folate) 0.8 – 5 mgs

Insulin Resistance

High insulin, as well as high glucose are 2 of the most import risk factors for Alzheimer’s disease. The human body is not designed to process more than 15 grams of sugars per day, far less than a regular soft drink (40 to 100 grams). When you eat foods with a high glycemic index (sugars, but also starchy foods like white bread, white rice, white potatoes and baked goods), your body produces large amounts of insulin to keep glucose levels from becoming toxic.. Cells become insensitive to a constant flood of insulin. This is insulin resistance, which contributes to type 2 diabetes, fatty live, metabolic syndrome and Alzheimer’s disease. In addition, the excess insulin that glucose calls for must be degraded, after it deals with the glucose, by the same enzyme that degrades the amyloid-beta that contributes to Alzheimer’s disease. It can’t be as effective at degrading amyloid-beta if it is also busy degrading insulin.

GOAL: fasting insulin <4.5 microIU/ml, hemoglobin A1c <5.6%, fasting glucose = 70-90 mg/dL24

Inflammation testing measures

  • C-reactive protein: hs-CRP should be below 0.9 mg/ L.
  • Ratio of albumin to globulin in your blood (A/ G ratio): at least 1.8
  • Ratio of omega-6 to omega-3 in your red blood cells: should be in a range from 0.5 to 3
  • Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα): IL-6 < 3 pg/ ml; TNFα < 6.0 pg/24 ml.

Vitamin D3 (measured as 25-hydroxycholecalciferol) between 50 to 80 ng/ ml.25

  • Take 2,500 IU daily until you test within the 50 to 80 range. Or subtract your current level from your goal and multiple by 100. For example, if your goals is 70 and your current level is 20, multiple the difference by 100.  70-20 = 50 X 100 = 5,000 IU per day/

Hormone Status— Controversial but Critical

  • Thyroid status: Optimal thyroid function is crucial for optimal cognition, and suboptimal thyroid function is common in Alzheimer’s disease. To measure the speed of your metabolism, simply take a standard thermometer, shake it down, and place it next to your bed before you go to sleep. Before getting out of bed in the morning, place the thermometer in your armpit for 10 minutes. It should read between 97.8 degrees and 98.2 degrees Fahrenheit. If it is lower, you likely have low thyroid function.  It is essential to know your thyroid hormone status, which can be assessed by measuring levels of free T3 (this is the active T3), free T4, reverse T3, and TSH (thyroid-stimulating hormone). Why so many tests? Most physicians check only TSH, but using this test alone fails to identify many patients who have suboptimal thyroid function. OPTIMAL ranges: TSH < 2.0 microIU/ ml; free T3 = 3.2– 4.2 pg/ ml; reverse T3 < 20 ng/ dL; free T3 x 100: reverse T3 > 20; free T4 = 1.3– 1.8 ng/ dL.26
  • Estrogens and progesterone: GOAL: estradiol level = 50– 250 pg/ ml; progesterone = 1– 20 ng/ ml; estradiol:progesterone ratio = 10– 100 (and optimize to symptoms).
  • Testosterone: GOAL: total testosterone = 500– 1000 ng/ dL; free testosterone = 6.5– 15 ng/ dL.
  • Cortisol, pregnenolone, and dehydroepiandrosterone (DHEA): High levels of cortisol damage neurons, especially in the hippocampus, making chronic stress an important contributor to hippocampal damage and thereby cognitive— and especially memory— decline. Pregnenolone is the master steroid hormone from which all others are derived. Pregnenolone supports memory and is neuroprotective; thus an insufficient level of pregnenolone is a risk factor for cognitive decline. DHEA, like pregnenolone, is a “neurosteroid” that supports response to stress. GOAL: cortisol (morning) = 10– 18 mcg/ dL; pregnenolone = 50– 100 ng/ dL; DHEA sulfate = 350– 430 mcg/ dL in women, and 400– 500 mcg/ dL in men.27

Metal Detection— Not Just for Airports: Too much copper and too little zinc are associated with dementia. Your blood levels of both copper and zinc should be approximately 100 mcg/ dL (micrograms per deciliter), and thus the ratio 1: 1. Ratios of 1.4 or higher have been associated with dementia. GOAL: copper:zinc ratio = 0.8– 1.2. Zinc = 90– 110 mcg/ dL (or red blood cell zinc = 12– 14 mg/ L). ADDITIONAL, OPTIONAL TARGET: copper minus 3x ceruloplasmin ≤ 30.28

Red blood cell magnesium: Magnesium is critical for brain function. GOAL: RBC (red blood cell) magnesium should be between 5.2 and 6.5 mg/ dL.

Selenium and glutathione: Selenium works with the peptide glutathione to mop up free radicals, the molecules with unpaired electrons that damage cell membranes, DNA, proteins, and overall cell structure and function. Low levels of glutathione can contribute to inflammation, toxicity, and loss of support for synapses— and, therefore to all three subtypes of Alzheimer’s disease. GOAL: serum selenium = 110– 150 ng/ ml; glutathione (GSH) = 800– 1230 micromolar.29

Heavy metals: When we eat ocean fish, we run the risk of high levels of mercury, which can induce the signature pathology of Alzheimer’s disease— amyloid-beta plaques and neurofibrillary (tau) tangles. “SMASH fish”— salmon, mackerel, anchovies, sardines, and herring— are safer. Arsenic, lead, and cadmium can also affect brain function. Arsenic is found in groundwater in some parts of the western U.S. and is also present in chicken, but is much lower in organic chicken. Arsenic has been associated with impaired executive function (including problem solving, planning, organizational ability, and other forms of higher-order thinking), reduced mental acuity, and deterioration of verbal skills, as well as depression— exactly the sort of deficits that occur with type 3 (toxic) Alzheimer’s disease. A very sensitive test called the Mercury Tri-Test, developed by Quicksilver Scientific, measures mercury from hair, urine, and blood without the need for chelation.Quicksilver also offers a very sensitive blood test for other metals, including calcium, chromium, copper, lithium, magnesium, molybdenum, selenium, zinc, aluminum, antimony, arsenic, barium, cadmium, cobalt, lead, mercury, silver, strontium, and titanium. GOAL: mercury, lead, arsenic, and cadmium all < 50th percentile (by Quicksilver); or, if blood levels are evaluated by a standard laboratory: mercury < 5 mcg/ L; lead < 2 mcg/ dL; arsenic < 7 mcg/ L; cadmium < 2.5 mcg/ L.30

Sleep and Sleep Apnea: Sleep is one of the most powerful weapons in the large anti-Alzheimer’s arsenal. Sleep benefits cognition in several ways:

  1. Sleep alters the cellular anatomy of your brain, allowing the space in between brain cells, to expand and more calcium and magnesium ions to flow through. This is thought to flush out cellular debris, including amyloid.
  2. Sleep is also associated with a reduced formation of the amyloid.
  3. We don’t eat when we’re asleep. Fasting improves our insulin sensitivity.
  4. During sleep, our brain cells activate autophagy, a process of recycling and refreshing our cells comparable to getting fresh batteries and shiny new parts.
  5. Growth hormone increases during sleep, repairing cells, and new supportive brain cells are produced. during sleep, among the many reparative processes that occur during sleep.

Sleep apnea, which jolts you awake repeatedly, contributes to cognitive decline and can be tested for inexpensively at home. GOAL: AHI (apnea-hypopnea index) of fewer than 5 events per hour (preferably 0).31

Cholesterol and Other Lipids: Low rather than high cholesterol is associated with cognitive decline. When total cholesterol falls below 150, you are more likely to suffer brain atrophy— shrinking. To identify and target bad cholesterol: measure the oxidized LDL, small dense LDL, or LDL particle number, along with the degree of inflammation (oxidized LDL and hs-CRP that was described earlier). GOAL: LDL-p (LDL particle number) = 700– 1000; OR sdLDL (small dense LDL) < 20 mg/ dL or < 20% of LDL; OR oxidized LDL < 60 U/ l; total cholesterol > 150 (yes, more than 150, not less than).

Vitamin E is an important protector of your cell membranes, an antioxidant with an anti-Alzheimer’s effect. GOAL: vitamin E (measured as alpha-tocopherol) = 12– 20 mcg/ ml.

Vitamin B1 (Thiamine) is critical for memory formation. It is important to know if your levels of thiamine are sufficient to support healthy cognition. This is best done by measuring thiamine pyrophosphate (TPP) in your red blood cells. GOAL: serum thiamine = 20– 30 nmol/ l OR red blood cell thiamine pyrophosphate (TPP) = 100– 150 ng/ ml of packed cells.32

  •   Unless level is optimum, take 50 mg daily

Gastrointestinal Permeability (“ Leaky Gut”) can occur due to gluten sensitivity, damaging chemicals like those in pesticides, soft drinks or alcohol, sugar, processed foods, and preservatives; inflammation, chronic stress, yeast, and medications such as aspirin or acetaminophen. Now it is not just amino acids, the simplest sugar molecules, like glucose or fructose, and vitamins that reach the bloodstream. So do larger fragments. These fragments are recognized by the immune system as foreign, triggering inflammation. Since inflammation is a key cause of Alzheimer’s— especially type 1— it is crucial to keep these large protein fragments from leaking out of the gut and into the bloodstream. GOAL: Cyrex Array 2 (or other measure of gut permeability) negative.33

Blood-Brain Barrier Permeability: The Alzheimer’s brain is a veritable zoo of potentially harmful organisms. How do these organisms get into the brain? Normally the brain is protected by the blood-brain barrier, but this barrier can break down. The Cyrex Array 20, which evaluates the response to leaked blood-brain barrier proteins, can assess the status of your blood-brain barrier. GOAL: Cyrex Array 20 negative.34

Gluten Sensitivity and Related Sensitivities: The gut-brain connection is critical for cognition. Many of us may suffer damage to our gastrointestinal tracts— and especially the tight junctions between the cells— from gluten. Since gluten sensitivity can cause leaky gut, which (as described above) can trigger the kind of chronic inflammation that leads to Alzheimer’s, it is important to evaluate gluten sensitivity. One way is to assess tissue transglutaminase antibodies in serum, which is a standard blood test. Another is to undergo Cyrex Array 3 and Array 4 testing. GOAL: tissue transglutaminase antibodies negative OR Cyrex Array 3 negative and Cyrex Array 4 negative.35

Autoantibodies attack brain proteins and are an important contributor to cognitive decline. GOAL: Cyrex Array 5 negative.36

Toxins, Type 3 Alzheimer’s Disease, and CIRS: Surprisingly, toxins are turning out to be an important cause of Alzheimer’s disease. Recommended are: a genetic blood test for HLA-DR/ DQ; simple blood tests for C4a, TGF-β1,and MSH; urine tests for the most dangerous mycotoxins: trichothecenes, ochratoxin A, aflatoxin, and gliotoxin. GOAL: C4a < 2830 ng/ ml; TGF-β1 < 2380 pg/ ml; MSH = 35– 81 pg/ ml; HLA-DR/ DQ with no CIRS propensity; urinary mycotoxin test negative for trichothecenes, ochratoxin A, aflatoxin, and gliotoxin derivative.36

Mitochondrial Function: Like tiny batteries, mitochondria supply the energy that allows our cells to function. They convert every from the food we eat and the oxygen we breathe into the molecule ATP, which powers our cells. Many chemicals damage mitochondria, including antibiotics, statins, alcohol, L-DOPA, griseofulvin, acetaminophen, NSAIDs (such as aspirin and ibuprofen), cocaine, methamphetamine and AZT. Because there are no simple blood tests that assess mitochondrial function, all we can do is beware aware of, and limit exposure to, the mitochondrial-damaging agents listed above.37

BMI (Body Mass Index): An unhealthy BMI increases the risk for cognitive decline. Ideally, it should be between 18 and 25. Here is a link for a quick and easy online calculator provided by the National Heart, Lung and Blood Institute of the U.S. Department of Health and Human Services that you can use to calculate BMI:

https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm

Visceral fat status, determinable by an ultrasound or MRI  is a more accurate indicator, according to Dr. Bredesen. Other good indicator is waistline: no more than 35 inches for women and 40 inches for men.38

Genetics affect your risk for Alzheimer’s disease, but your Alzheimer’s fate is by no means written in your DNA. Instead, much more than you might expect, you are in control of your own fate. In order to optimize your control, you want to know your genetic status: for one thing, your optimal diet will be different if you are ApoE4 positive than if you are ApoE4 negative. In April 2017, the FDA approved ten DNA tests from 23andMe, including one for late-onset Alzheimer’s disease risk, which evaluates ApoE status. GOAL: Knowing your ApoE status. OPTIONAL TARGET: Knowing your status on all SNPs related to neurodegeneration, such as APP, PS1, PS2, CD33, TREM2, CR1, and NLRP1.39

Quantitative Neuropsychological Testing: It is critical to know where you stand with your memory and other aspects of cognition, such as organizing, calculating, and speaking. There are many ways to do this. The simplest is to take the MoCA (Montreal Cognitive Assessment) test, which is freely available online and takes only about ten minutes (http:// dementia.ie/ images/ uploads/ site-images/ MoCA-Test-English_7_1. pdf). There are three versions, so you can repeat it without concern that any improvement comes from having seen the same test before. A normal MoCA score is 26 to 30; 19 to 25 is associated with MCI; 19– 22, if accompanied by difficulties with activities of daily living, usually means that MCI has converted to dementia, whether from Alzheimer’s disease or another cause; and scores lower than 19 indicate dementia.

Imaging, Cerebrospinal Fluid and Electrophysiology: Imaging can detect which, if any, of the regions of the brain have shrunk. Neuroreader, for example, calculates volume for 39 brain regions. GOAL: brain MRI with volumetrics normal, showing no atrophy. OPTIONAL TARGETS: negative FDG-PET scan, negative amyloid PET scan, negative tay Pet scan, and/or normal EEG, without seizure activity or slowing.40

On the Horizon – New Tests for Assessing Cognitive Decline:41

  • Neural exosomes are tiny fragments of cells and materials expelled from cells. Analyzing them helps identify increases in amyloid-beta and phosphorylated tau and has the potential to assess many more  biochemical signatures in the brain. GOAL: normal neural exosome levels of amyloid-beta 42, phosphorus-tau, cathespin D, REST, and phosphorylation ratio of IRS-1.
  • Retinal imaging is another exciting new approach to early evaluation and assessment of risk for cognitive decline. The back of the eye, or retina, is an extension of the brain and therefore reflects what is ongoing in there. That makes evaluating the retina for amyloid plaques a highly promising approach. It is possible to identify many, often hundreds, of very small plaques, map the location of each, and then follow up after treatment to see whether the number of plaques has declined. At several hundred dollars instead of a few thousand, retinal imaging is much less expensive than amyloid PET scans of the brain. It also identifies much smaller plaques, which may be more accurate sentinels of treatment effects, and also has the potential to reveal whether the amyloid affects the retina’s blood vessels (and by extension, likely the brain’s as well) in addition to the neurons and synapses themselves. This is important because amyloid in blood vessels can, in rare cases, lead to hemorrhage (bleeding), and thus in such cases blood-thinning agents such as fish oil and aspirin must be assiduously avoided.
  • Neurotrack and the mesial temporal lobe (novel object recognition): In 2016, Neurotrack released the Imprint Cognitive Assessment Test, a five-minute web-based visual cognitive assessment that, by tracking eye movements, detects which objects and other stimuli people recognize as novel. It thus detects impairment of the hippocampus and nearby structures, identifying people who have dysfunction of this region and may be manifesting the pathophysiology of Alzheimer’s disease. GOAL: normal preference for novel objects.

Historical/ lifestyle features

Critical as laboratory tests are for identifying genetic and biochemical factors that may be contributing to cognitive decline, life history can also provide crucial clues to what is causing it. It is therefore important to know if you currently or have ever had or done any of the conditions or things listed here in Appendix B.

Financing the Tests42

Testing can be costly or not so much, depending on your insurance. The trend in health care has been to to focus more on reaction than prevention, but that is beginning to change. The few hundred dollars to perhaps $1,000 can be seen as an excellent investment to avoid the negative personal and family effects of cognitive decline and the prospect of nursing home care for full-blown Alzheimer’s. A table listing the various recommended tests appears here in Appendix C. 

The last article in this series, the summary and recommendations, may be the most useful. You can go directly to it by clicking here: Maintain Your Brain – Conclusion: The Key Concepts and Recommendations.

Notes:

Bredesen, Dale. The End of Alzheimer’s, Penguin Publishing Group. Kindle Edition, pp.  119-120

ibid, p. 176

ibid. pp. 121-122

ibid. pp. 125-126

5 ibid. pp. 127

6 ibid. pp. 128-129

7 ibid. pp. 130-132

8 ibid. pp. 132-133

9 ibid. pp. 135-136

10 ibid. pp. 138-139

11 ibid. p. 140

12 ibid. p. 142-143

13 ibid. p. 146

14 ibid. p. 148

15 ibid. pp. 149-150

16 ibid. p. 151

17 ibid. p. 153-154

18 ibid. p. 154

19 ibid. p. 156

20 ibid. p. 157-159

21 ibid. p. 159-163

22 ibid. pp. 165-166

 

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