Why Alzheimer's Occurs
Dr Dale Bredesen in his new book The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline describes the cause of Alzheimer's disease as the brain trying to protect itself from three metabolic and toxic threats, these three threats are listed below.
- Inflammation (from infection, diet, or other causes), this occurs more often in people who have either 1 or 2 copies of the ApoE4 gene
- Decline and shortage of supportive nutrients, hormones, and other brain-supporting molecules, this is also more common in people who have either 1 or 2 copies of the ApoE4 gene
- Toxic substances such as heavy metals or biotoxins which includes mold toxicity, viral and bacterial infections. This is more common in people who have the ApoE3 gene rather than the ApoE4 gene.
For many years it has been thought that Alzheimer's disease is irreversible, once you have it there is a steady decline, this has been highlighted by the millions of dollars spent on research and the failure of every drug that has been trialled to treat Alzheimer's.
But for the last few years Dr Dale Bredesen and his team from MPI cognition have shown that it is possible to both prevent and reverse Alzheimer's disease, but rather than use one drug or treatment they have adopted a holistic approach to addressing the underlying cause of mental decline.
Dr Bredesen describes this approach as fixing a leaking roof with 36 holes, you will not get great results focusing on 1 or 2 of the holes but you have to address most of the 36 holes to prevent further damage. Likewise to reverse Alzheimer's you need to address the underlying cause before you can make progress. To find out the underlying cause Dr Bredesen recommends what he calls a Cognoscopy.
Alzheimer's and ApoE4 Gene
The risk of getting Alzheimer's disease is increasing, this is likely to do with people eating more processed foods, sleeping less, higher stress, more environmental toxins and other changes that have occurred in the last 100 years, BUT the biggest risk factor for developing Alzheimer's is the ApoE4 gene.
The risk for developing Alzheimer's is about 9%, but that risk increases to about 30% if you have a single copy of the ApoE4 gene, and the risk for developing Alzheimer's goes above 50% if you have two copies of the ApoE4 gene.
Some people may not want to know there genetic information so as not to create extra stress worrying about their risks for developing certain diseases, but with conditions like Alzheimer's disease developing over a 20 year period there is plenty that can be done to proactively prevent Alzheimer's.
With the latest research showing that Alzheimer's is preventable in most cases, and there is diet and lifestyle changes that you can do to minimize the risk of having the ApoE4 gene, I think getting your genes tested through companies like 23andme is important.
I have a single copy of the ApoE4 gene which put's me at a 30% risk of Alzheimer's, I also know that I have genes increasing my risk of diabetes, but knowing this information enables me to implement diet and lifestyle strategies to reduce my risk of developing these conditions to close to zero chance.
How to do a Cognoscopy
With cognitive decline and Alzheimer’s disease steadily increasing how do you know if you are at risk of developing at risk of Alzheimer’s? With what Dr Dale Bredesen from “Reversing Alzheimer’s” calls a cognoscopy, similar to getting a colonoscopy to test for colon cancer risk, a cognoscopy is a number of assessments that looks at the possible causes that can lead to mental decline.
Once you have the results of your cognoscopy this will help you to address the possible risk factors and potential causes that can lead to Alzheimer’s and dementia, also by optimizing these risk factors you are going to improve every aspect of your mental and overall health.
While most people are diagnosed with Alzheimer’s in their 60’s and 70’s the actual mental decline and damage to the brain has already been happening for the past 20 years, so if we can identify the risk factors early we can eliminate the risk of Alzheimer’s disease. This is why the earlier that you have a cognoscopy the earlier we can identify potential risk factors, anyone can do this from the age of 45, and if you are older the sooner that you do a cognoscopy the sooner you can prevent and even reverse mental decline.
You will not be aware of the changes to your brain in the early stages of Alzheimer’s as symptoms only start to appear after about 20 years of brain changes, you can’t fix a problem unless you know the specific cause of the problem. With Alzheimer’s there is many different causes which is going to vary from person to person, understanding your risk factors and taking the necessary steps to reverse them, has been shown to prevent and reverse mental decline.
The first step is to do a comprehensive pathology test, this will be a lot more detailed than the basic test done by your doctor, and we are not looking to see if you fall into the reference range but rather the optimal range.
High levels of homocysteine are important contributors to Alzheimer’s disease. Three of the causes of synapse loss are inflammation, nutrient deficiencies and toxin exposure, and homocysteine is a marker of these. It is a marker of inflammation, but it is also increased when nutritional support is suboptimal.
Homocysteine recycling requires vitamin B12, vitamin B6, folate, and the amino acid betaine. If you have healthy levels of these molecules you will have no trouble recycling your homocysteine, and its levels will remain healthily low. But if, like many people, you have genetic polymorphism’s like MTHFR or nutrient deficiencies in these B vitamins, your homocysteine will build up, damaging your blood vessels and brain.
Keeping your homocysteine in the optimal range between 5 - 7 requires sufficient levels of vitamins B6, B9 (folate), and B12, all in their active forms. Pyridoxal-5-phosphate (P5P) is the active form of vitamin B6, methylcobalamin is an active form of vitamin B12, and methylfolate is an active form of vitamin B9.
Test homocysteine and these B vitamins to make sure that you are in the optimal range, I don't recommend taking B vitamins, especially in a high dose if you don't need them which is why testing is so important as it guides you on how much you need to take.
GOAL: vitamin B12 = 500–1500 pg/ml; folate = 10–25 ng/ml; vitamin B6 = 60–100 mcg/L.
High insulin and high glucose are two of the most important risk factors for Alzheimer’s disease, as well as many other chronic illnesses. Many people associate high glucose with diabetes but it can also affect many aspects of your health including Alzheimer’s, in fact some researchers say that Alzheimer’s is a form of diabetes of the brain.
Insulin signaling is one of the most important signals for the support of your brain’s neuron’s, if you have insulin resistance and high circulating insulin levels your brain won’t be able to effectively utilize glucose. Insulin resistance also cause Amyloid-beta levels to increase, contributing to Alzheimer’s disease.
Hemoglobin A1c is a simple measure of elevated glucose, and it gives you an indication of your average glucose levels from the past 3 months. Elevated glucose cause biochemical reactions to produce advanced glycation end products, or AGE. These AGE molecules affect your brain by several different mechanisms, this includes inflammation, DNA damage, reducing nutrient availability to the brain and causing “leakiness” of the blood-brain barrier.
Your fasting insulin level should be 4.5 or below. Your fasting glucose should be 90 or lower, and your hemoglobin A1c should be less than 5.5 percent. More advanced testing includes Glycomark and Fructosamine if the initial results are not optimal.
The evidence that inflammation contributes to chronic diseases like diabetes, cardiovascular disease and Alzheimer’s disease is overwhelming. Inflammation causes a chronically activated immune system which can lead to attacks on the body’s own tissues. Inflammation causes both damage to healthy brain cells and a buildup of Amyloid-beta as the brain tries to protect itself, but constant inflammation over many years can lead to Alzheimers.
There are several key measures of inflammation:
CRP is produced by the liver in response to any type of inflammation. Specifically, you want to know your hs-CRP (high-sensitivity CRP), as the standard CRP test that doctors use only measures if your levels are above 5, but the optimal range is below 1. If your HsCRP levels are above 2 you need to determine the source of the inflammation.
Albumin/ Globulin ratio
The ratio of albumin to globulin in your blood (A/G ratio) is also a measure of inflammation, and is best when it is at least 1.8.
Omega 6/ Omega 3 ratio
The ratio of omega-6 to omega-3 in your red blood cells: While both of these fatty acids are important for health, omega-6s are pro-inflammatory while omega-3s are anti-inflammatory. The ratio of omega-6 to omega-3 should be less than 3 but many people have a ratio of 1 to 20 due to the high amounts of omega-6 in processed foods.
Interleukin-6 (IL-6)/ tumor necrosis factor alpha (TNFα)
Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) are two of the many cytokines that may be increased in inflammatory Alzheimer’s disease and other inflammatory conditions, these are done as part of a specialized blood testing panel.
Reduced vitamin D activity is associated with cognitive decline. Vitamin D travels through your blood and tissues and operates more like a hormone which can easily cross the blood brain barrier, entering your cells. Once inside, it binds to a receptor molecule called, appropriately enough, the vitamin D receptor (VDR), allowing the vitamin D to enter the nucleus (which houses your DNA) and turn on over 900 genes. Some affect bone metabolism, others suppress tumor formation, others reduce inflammation, and importantly for Alzheimers others are essential for creating and maintaining brain synapses.
Vitamin D is another example of the reference range being inadequate, don’t accept your doctor’s opinion that “everything is fine” you need to aim for 50 to 80 if you are in the U.S and between 100 and 150 if you are in the rest of the world.
I recommend Vitamin D and K2 to be taken together, and a liquid supplement like this one from Thorne Research can quickly get your Vitamin D into the optimal range.
Optimal thyroid function is crucial for optimal cognition, and suboptimal thyroid function is common in Alzheimer’s disease.
It is essential to know your thyroid hormone status, and I don’t mean just checking your TSH levels which is what doctors normally do, TSH is a poor measurement of thyroid function plus the reference ranges are quite broad and many people with suboptimal thyroid function can be missed. The best way to assess thyroid is to measure TSH, Free T4, Free T3, revere T3 and the thyroid antibodies
Free T3: Optimal levels are 3.2 to 4.2, measured in picograms per milliliter (pg/ml) in the U.S or between 4.0 and 5.5 pmol/l in the rest of the world
Free T4: Optimal levels are 1.3 to 1.8 in the U.S or 14 to 18 pmol/l in the rest of the world
Reverse T3: The free T3:reverse T3 ratio should be at least 20 in the U.S and less than 300 pmol/l in the rest of the world
TSH: between .5 and 2.0 microIU/ml (not the reference range is often .5 to 5.0 which is too broad)
The sex hormones are a crucial player in the prevention of dementia. Studies from the Mayo Clinic have shown that women who have their ovaries removed by age 40 without hormone replacement therapy have double the risk of Alzheimer’s disease. It is not just the level of estrogen and progesterone that is important, too much estrogen compared to progesterone can cause other unwanted symptoms like weight gain, food cravings “brain fog” and poor memory.
The sex hormone testosterone, which is present in both females and males but at higher concentrations in males, supports the survival of neurons. Men in particular with the lowest levels of testosterone concentrations are at increased risk for Alzheimer’s disease.
I recommend the DUTCH hormone test to measure both the sex hormones and adrenal hormones in comprehensive detail. It is important to only take hormone replacement therapy if needed, and often diet, lifestyle, nutritional and herbal options can help to optimize your hormone levels.
The adrenal hormones include Cortisol, Cortisone, and dehydroepiandrosterone (DHEA), and for optimal health they need to be in the right balance, which is not too high and not too low.
Chronic stress can lead to dysfunction of the hypothalamus - pituitary - adrenal axis, commonly known as the HPA axis (some people also call this adrenal fatigue). When this happens, the adrenal glands either produce too much of the stress hormone cortisol, or in chronic cases not enough cortisol to deal with stresses such as infections, toxins, or lack of sleep.
An imbalance in cortisol and the HPA axis can lead to a loss of neurons in the brain, and can exacerbate cognitive decline.
DHEA is a “neurosteroid” that supports response to stress, and it is usually measured as DHEA sulfate.
The DUTCH hormone test is the best option for measuring the stress hormones and the sex hormones
Copper / Zinc Ratio
Too much copper and too little zinc is associated with inflammation which is one of the driving forces behind Alzheimers, especially type 1 Alzheimers.
Many people are deficient in zinc but have excess copper. This is can not only lead to cognitive decline but also be a cause of anxiety and depression, especially if it is associated with pyroluria.
Zinc is important for immune function, sex hormones, cardiovascular health insulin synthesis, and much more, while it is an important mineral the body is very good at coping with a deficiency in the short term, but it can lead to many long term health consequences.
Measuring zinc in red blood cells produces a more accurate reading than measuring it in serum.
copper:zinc ratio = 0.8–1.2. Zinc = 90–110 mcg/dL
Zinc 80 - 120 pg/dl and Copper 80 - 120 pg/dl
Magnesium regulates over 300 different enzyme reactions in the body, once again your body is fantastic at regulating what are the essential functions for survival right now, but that can have a role in conditions like Alzheimer’s and dementia later.
Many people are deficient in magnesium, possible due to the increased stress of modern lifestyles combined with a nutrient deficient diet, this is why magnesium is one of the few supplements that I recommend most people take. For brain health Magnesium threonate is the the best option
The optimal range for RBC (red blood cell) magnesium is between 5.2 and 6.5 mg/dL or 1.8 and 2.2 mmol/l
Selenium works with glutathione to mop up free radicals, which can damage cell membranes, DNA, proteins, and overall cell structure and function. In protecting and restoring cellular health this way, glutathione is itself being used up and so must be constantly regenerated, this is why nutrients like selenium, n-acetyl-cysteine, zinc, B vitamins are essential to make more. Low levels of glutathione can contribute to inflammation, toxicity, and loss of support for synapses, and affect all three subtypes of Alzheimer’s disease. Selenium plays a key role in regenerating glutathione when it is used up scavenging free radicals, so it is not surprising that reductions in selenium have been shown to be associated with cognitive decline.6
The best food source of selenium is Brazil nuts.
Selenium = 110–150 ng/ml; glutathione (GSH) = 5.0–5.5 micromolar.
Heavy metals like mercury are neurotoxic, and most of us do not know we have been exposed to them. We are exposed to mercury when we eat fish which are larger and long lived, fish that contain high levels include tuna, swordfish, orange roughy, and shark. Fish like salmon, mackerel, anchovies, sardines, and herring are safer, plus they are rich in the omega 3 fatty acids.
The type of mercury found in fish is organic mercury, typically methylmercury and this is different to the mercury found in dental fillings, though still toxic.
The other major source of mercury is dental amalgams, this is inorganic mercury. Methylmercury and inorganic mercury can be distinguished in blood and urine tests, the best way to test mercury is with the Quicksilver Tri-Mercury test.
Arsenic, lead, cadmium and other heavy metals, as well as environmental toxins can also affect brain function. These can also be tested in blood, hair and urine tests but doing a questionnaire to assess your toxicity is a cheaper option, as well as the fact that it is hard to accurately assess for heavy metals in the body as they can be stored in fat cells.
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.
Sleep apnea is extremely common, often goes undiagnosed for a very long time unless it is more severe, but even mild sleep apnea contributes to cognitive decline.
Sleep affects cognition through multiple fundamental mechanisms:
- Sleep is also associated with a reduced formation of the amyloid.
- Sleep improves our insulin sensitivity.
- During sleep, our brain cells activate autophagy, the process of “self-eating” that recycles cellular components like damaged mitochondria, improving cellular health.
- Sleep is also a time of repair
- Growth hormone increases during sleep, repairing cells, and helping to promote new brain cells
- No wonder sleep deprivation impairs cognition. Moreover, it increases the risk of obesity, diabetes, and cardiovascular disease, all risk factors for Alzheimer’s.
Even if you are getting seven or eight hours of sleep each night, if you have sleep apnea, in which your breathing periodically stops, you will not be getting the benefits of sleep.
It can be an expensive process going to a sleep clinic but there are many apps and devices now that can track your sleep well enough to diagnose if you have a problem with sleep apnea, this includes iphone and android apps, as well as the Fitbit
Cholesterol is essential for survival, but has become demonised over the past 30 years and in the process has made drug companies billions of dollars selling statin medications, but cholesterol itself does not cause heart disease and is essential for cognitive health.
While you don’t want to have oxidised LDL, a high particle number or small dense LDL subfractions, you do want to have healthy levels of cholesterol as low levels are associated with cognitive decline. Many people taking statin medications are increasing their risk of Alzheimer’s.
So measuring total cholesterol to assess cardiovascular health is misleading, you need to do more advanced cardiovascular testing.
Other Nutrients to measure
In the January 2014 issue of the Journal of the American Medical Association (JAMA) a study was published showing that healthy levels of Vitamin E reduced the risk of Alzheimer’s disease
GOAL: vitamin E (measured as alpha-tocopherol) = 12–20 mcg/ml.
Vitamin B1 Thiamine is critical for memory formation. Many changes that occur in the brains of patients that have Alzheimer’s disease, including synaptic loss, changes in glucose metabolism, oxidative stress are thiamine-dependent processes.
GOAL: serum thiamine = 20–30 nmol/l
Gut Function / Leaky Gut
Testing gut function is important for preventing and reversing Alzheimer’s disease. This can be done with a stool test like the G.I Map or a CDSA test.
There are a number of reasons why assessing and treating gut function is so important for health in general, and Alzheimer’s in particular.
Inflammation is one one of the driving forces behind chronic illnesses, and an imbalance in your gut microflora is one of the main causes of inflammation in the gut. Assessing your gut health with a stool test that measures your beneficial bacteria, commensal bacteria, pathogenic bacteria, parasites and yeast infections will help you to understand what needs to be done to improve your gut health.
This will not only help to reduce cognitive decline but also improve energy, help with weight loss, improve mood and reduce many other health symptoms that can be associated with an imbalance in your gut health.
The G.I Map test also measures zonulin which is the best marker of leaky gut, as well as beta-glucuronidase which is a marker for liver detoxification and transglutaminase which measures gluten sensitivity.
A 2016 study linked Small Intestinal Bacterial Overgrowth (SIBO) with cognitive decline, testing for SIBO is done with a simple breath test. You should have trillions of bacteria in your large intestine but very little in your small intestine, if bacteria are allowed to overgrow in the small intestine they can cause a lot of I.B.S symptoms as well as nutrient malabsorption and leaky gut.
Mold and Biotoxins
Mold and biotoxins are the cause of type 3 Alzheimer’s, these types of toxins can cause many different symptoms and are not picked up in the standard blood tests that your doctor does.
I recommend all of the other assessments be done before you test for mold and biotoxins, the symptoms of toxicity include chronic fatigue, headaches, muscle aches and pains, memory problems, brain fog. As you can see these symptoms are very general in nature and could relate to many other health conditions.
Not everyone reacts to mold and biotoxins the same way with the same exposure, 25 percent of people have a gene called HLA-DR/DQ which increases their sensitivity to mold, this can be assessed in a 23andme genetic test.
What to assess
Blood tests for C4a, C3a, MMP-9, VEGF, TGF-B1, and MSH can give us a good indication if our immune system is being affected by mold and other toxins.
You can also do urine testing for the presence of the most dangerous mycotoxins which includes Ochratoxin A, Aflatoxin group, Trichothecene group & Gliotoxins
Healthy mitochondria are important for all aspects of health, from energy production to cardiovascular disease, and of course cognitive health. There is not one perfect test for measuring mitochondrial function, the best way to assess mitochondrial function as well as many other health markers is with an Organic Acids Test, commonly known as OAT.
The OAT test is one of my favourite tests because it measures so many different markers of health, click on the link below to find out more.
The Montreal Cognitive Assessment is a 30 question assessment that takes about 10 minutes to do, this is not diagnostic of Alzheimer’s but is a good indicator of cognitive impairment. Doing this assessment can help to pick up early cognitive decline in an objective way to enable you to take preventative measures to reverse any further cognitive decline.
If you get a low score on the Montreal Cognitive Assessment it would be a good idea to get an M.R.I to further assess brain function.
There are many medications from the commonly prescribed statin drugs for cholesterol to proton pump inhibitors for reflux, as well as many others that can contribute to cognitive decline. Don’t suddenly stop your medications, but by working with an experienced functional medicine practitioner you maybe able to address the underlying cause of these conditions so that you no longer have the need for these medications.
Many medications are over prescribed and do not address the underlying cause so people are often stuck on them “forever” but all medications have side effects, and by doing the detailed tests described here and making the necessary diet and lifestyle changes you can often eliminate the need for many medications.
The Next Step For Preventing Alzheimer's
You don’t have to rush out and get every single one of these tests done, a good place to start would be with the advanced pathology testing to make sure your nutrient status, inflammatory markers and other biomarkers are all in the optimal range. Don’t accept your doctor's advice that your results are all “good”, get a copy for yourself and make sure they are in the reference range, or schedule a consultation with Planet Naturopath and we can walk you through your results, explain what they mean and let you know what needs to be improved.
If your doctor won’t do these tests for you then we can help you organize the right testing to be able to give you a full assessment.
If you have any digestive issues I would also include some of the advanced stool testing to identify the cause, this will not only help to guide us on the best treatment plan for you, but by improving your digestion you will improve every aspect of your health.
Still not sure where to start, you can schedule a consultation here and we will help to guide you through the process.