Are you over 40 and haven’t head a cognoscopy yet? That’s cognoscopy, not colonoscopy, an evaluation of all the potential contributors and risk factors for cognitive decline. It’s interesting that in our medical culture we’re more familiar with the latter, whilst ignoring the most important organ in the human body: the brain.
As mentioned in a previous article, neurodegenerative illness is asymptomatic until it’s very advanced. So how do you know if your brain is healthy or whether you’re heading at full speed towards cognitive decline?
Undergoing a cognoscopy will give you the answer. The cognoscopy assessment includes a combination of blood tests, genetic tests, a simple online cognitive assessment, and an MRI with a computer assessment of brain volumes. A complete brain evaluation should include:
- Genetics: What is your ApoE4 status? How about the other SNPs related to neurodegeneration: APP, PS1, PS2, CD33, TREM2, CR1, NLRP1?
- Homocysteine: This amino acid is causally associated with brain atrophy and Alzheimer’s and levels become high when its conversion back to methionine is impossible due to suboptimal nutritional status in vitamins B12, B6, folate and betaine. A healthy homocysteine level is less than 7 micromolar.
- Nutritional status: Having adequate levels of several key nutrients is essential for brain health: B12, B6, folate, B1, vitamin E, vitamin D3, the copper to zinc ratio, magnesium, selenium. For instance, for optimal brain function, vitamin B12 should be between 500-1500 pg/ml, B6 60-100mcg/L and folate 10-25ng/ml. If you need supplements to reach optimal levels, make sure to take the activated forms of B vitamins: methyl-B12 not cyanocobalamin, methyltetrafolate not folic acid, pyridoxal-5-phosphate not pyridoxine.
- Inflammatory markers: C-reactive protein (CRP) is produced by the liver in response to any type of inflammation. Your hs-CRP (high sensitivity CRP) status should be below 0.9mg/dL. If it is above this threshold, the source of inflammation could be anything from too much sugar, or trans fats, gluten sensitivity, gut permeability, poor oral hygiene, specific toxins, etc.; the omega 6 to omega 3 ratio in red blood cells is another marker of inflammation since the former are pro-inflammatory while the latter are anti-inflammatory (this should be less than 3 but not below 0.5); the cytokines interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα) should be less than 3pg/ml and 6.0pg/mL respectively; the ratio of albumin to globulin (A/G ratio) should be at least 1.8, with albumin above 4.5g/dL
- Infections: there is rapidly accumulating data implicating several infections in Alzheimer’s, e.g. Herpes simplex-1, Borrelia (the infectious agent in Lyme disease), P. gingivitis (an oral bacterium), various fungi
- Glucose and insulin status: High insulin and high glucose are two of the most important risk factors for Alzheimer’s. Insulin binds to the insulin receptor and triggers signalling that supports neuronal survival but this doesn’t happen with insulin insensitivity. At the same time, the enzyme that degrades insulin after it has done its job (IDE) is also the enzyme that degrades beta-amyloid and the medical thinking goes that if IDE is tied up degrading insulin, it doesn’t do a good job of degrading beta-amyloid which then keeps accumulating in the brain. Excessive glucose attaches to various proteins, interfering with their functioning, and leads to AGEs (advanced glycation end products) which cause inflammation and free radicals which damage DNA and cell membranes. An optimal fasting insulin should be less than 4.5 microIU/ml, fasting glucose 70-90 mg/dL and haemoglobin A1c (one of the many proteins that high glucose can alter) less than 5.6 per cent; if prediabetic, your risk factor increases exponentially
- Hormonal status: Many hormones (thyroid hormones, oestrogen, progesterone, testosterone, cortisol, DHEA, pregnenolone) are crucial to optimal cognitive function and when their levels are out of balance, either too high (e.g. cortisol) or too low (estrogen, testosterone, DHEA), cognition declines significantly. For instance, since thyroid function affects metabolic speed, it also affects your mental sharpness and suboptimal thyroid function is a common finding in people with dementia or mild cognitive impairment. Moreover, you can have suboptimal thyroid function even with a normal THS, which is usually the only marker doctors test for. It is however vital to check the status of free T3 (the active thyroid hormone) which should be between 3.2 to 4.2 pg/ml, free T4 (the storage form of thyroid hormone) which should be between 1.3 to 1.8 as well as reverse T3 which inhibits the conversion of T4 to T3, usually due to stress (this should be less than 20ng/dL)
- Toxic exposures: Mercury alone can induce the signature pathology of Alzheimer’s, amyloid-beta plaques and neurofibrillary tangles. Arsenic (from groundwater, conventionally raised chicken), lead (from old paint and dust in cities) and cadmium (from cigarette smoke and paints) and other well-known dementogens. Mycotoxins from mould exposure also contribute in a significant way to Alzheimer’s.
- Immune system function: The immune system plays a crucial role in Alzheimer’s, in particular the innate immune system, the evolutionarily older part of the immune system that is the first one to respond to infections. Mould exposure for instance can trigger a chronic inflammatory response syndrome (abbreviated CIRS), which is what happens in 25% of the population with a certain variant in the gene HLA-DR/DQ. You can also find out if your immune system is activated using blood tests for C4a, TGF-β1 and MSH.
- Microbiome: Apart from optimising the gut microbiome that everyone knows about, the nasal microbiome is extremely important in Alzheimer’s since the quickest way to the brain is through the nose. Chronic rhinosinusitis is a bad sign and is often due to mould species or bacteria such as MARCoNS (Multiple Antibiotic Resistant Coagulase Negative Staphylococci – staph bacteria that form protective coating called biofilms and are resistant to many antibiotics). There are now probiotics for the nose and sinuses as well as nasal sprays that can treat infections.
- The blood-brain barrier: There is evidence of abnormalities in the blood-brain barrier function very early in the disease, as a result of which many disease-causing bacteria, viruses, fungi and other microbes are detected in the brains of patients with Alzheimer’s. There are now tests that can assess the response to leaked blood-brain barrier proteins.
- The body-mass index: For optimal cognition, your BMI should be between 18 and 25, although a more accurate indicator is visceral fat status, especially in the liver, which can be determined with an ultrasound or MRI. Another good indicator is your waistline which should be less than 88cm in women and less than 100cm in men.
- Volumetrics: MRI with volumetrics is a critical test that measures the volume of various brain regions. Imaging the brain can show which, if any, regions have shrunk or which are using less energy than they should be.
The above recommendations about taking a cognoscopy were compiled from Dr Dale Bredesen book The End of Alzheimer’s. The First Programme to Prevent and Reverse the Cognitive Decline of Dementia.
Dale E. Bredesen, MD is internationally recognised as an expert in the mechanisms of neurodegenerative diseases such as Alzheimer’s disease. He earned his MD from Duke University Medical Center in Durham, North Carolina. He served as chief resident in neurology at the University of California, San Francisco (UCSF) before joining Nobel Laureate Stanley Prusiner’s laboratory at UCSF as a National Institutes of Health postdoctoral fellow. He has held faculty positions at UCSF; University of California, LA; University of California, San Diego. Dr Bredesen directed the Program on Aging at the Burnham Institute before coming to the Buck Institute in 1998 as its founding president and CEO.
In 2014, his personalised therapeutics for the reversal of cognitive decline – the ReCODE protocol, initially called MEND – led to the first-ever scientific publication of a study in which 9 of the 10 patients displayed subjective or objective improvement in cognition within 3-6 months, with the one failure being a patient with very late stage AD. Three subsequent papers, in 2015 and 2016, confirmed this first study. Since then, hundreds of patients have been successfully treated using his ReCODE protocol.
This article about using a cognoscopy to better prevent alzheimer’s is part 2 in a series about maintaining positive brain health. Read part one here.
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