If you ask people what illness they fear most in old age, a surprisingly large number will say just one word, Alzheimer’s. And yet, if you ask them what they are doing to avoid this dreaded illness a vast majority will give another one-word answer, nothing. I recently asked this question about the possibility of preventing and reversing Preventing Alzheimer’s Disease at a workshop and nearly everyone in the room indicated that they did not think that Alzheimer’s could be prevented or reversed. In fact, there was one person who was adamant about it as she insisted that her family had found the “best doctors” for one of her grandparents and they could do absolutely nothing to help. I felt sorry for her, and her family, but I had to inform her that she had not actually found the best doctors as she claimed. In fact, as you will see from this article there are many doctors and clinical studies showing that Alzheimer’s is both preventable and reversible in many cases. It really depends on how soon a person gets the right tests and how serious they are in applying the proven lifestyle changes that are at the heart of impressive science that has been found over the past several years.

1. Defining Alzheimer’s—All cases that are diagnosed as Alzheimer’s disease are not the same and are not necessarily Alzheimer’s. In fact, there are at least seven different forms of “dementia type” brain challenges and they each require a slightly different treatment protocol in order to optimize the potential benefits. The types and names identified by the Bredesen team are as follows.

• Dementia
• Vascular dementia
• Frontotemporal dementia
• Lewy body dementia
• Alzheimer’s disease
• Subjective cognitive impairment
• Mild cognitive impairment

2. The symptoms of Alzheimer’s or Alzheimer’s type illness—These symptoms may occur one at a time or in clusters and may not always occur in the same sequence or level of intensity.

• Facial blindness
• Decreased mental clarity
• Decreasing ability to recall
• Decreasing vocabulary
• Mixing up common words and phrases
• Trouble speaking foreign languages
• Decreasing mental processing speed
• Increased anxiety in finding your way
• Difficulty remembering your to do list
• Sleep disruption
• No usual boost from caffeine

3. The causes of Alzheimer’s—There are many causes of Alzheimer’s or related conditions, however most of them can be categorized in the following six ways.

• Those related to inflammation and responses to inflammation such as infections like Lyme Disease; Advanced Glycation End Products (AGES) when protein and sugar interact incorrectly; excessive exposure to trans fats; overexposure to pathogens such as bacteria, fungus or parasites; damage to the intestines such as leaky gut; bacteria from damaged gums; sugar toxicity with insulin resistance; and inflammation caused by consumption of dairy products.
• Those related to exposure to toxins, which can be found in the air, water, and the soil. These toxins produce free radicals, which are molecules without a paired electron. These missing electrons steal electrons from our healthy cells causing damage in our circulation system, which causes the release of cholesterol from the liver leading to the build-up of plaque. Free radicals can attack any organ in the body, including the brain, which then causes disruption to neurons and other parts of the brain.
• Those related to nutritional deficiencies, which lead to cells becoming stressed, then weakened, then dysfunctional, then mutated and then finally diseased. When cells begin this deterioration process they become less able to perform the jobs they are supposed to do, including all of the many functions of the brain. This is one of the main causes of many brain-related challenges, including those related to Alzheimer’s.
• Those related to genetic predispositions, which primarily involve the APO-4E gene. The presence of this gene can increase the risk of Alzheimer’s by anywhere from 30 to 50 percent. There is also a gene known as the APO-E3 gene, which can increase the risk of Alzheimer’s by nine percent. It all depends on how many parents have these genes, with both parents obviously being the worst-case scenario. This genetic influence is only found in 5 – 10 percent of the population, which means that most cases are caused by preventable factors.
• Excessive amyloid production can be a major factor. Amyloid plaque is actually one of the brains primary protection mechanisms. Just as cholesterol tries to repair damage to the heart and the circulatory system, amyloid plague tries to protect the brain from too much sugar or too much pathogen exposure. When there is too much of these two influencing factors the body produces insulin-degrading factor, which is supposed to neutralize both of these influences. However, if there is too much sugar (which must be accompanied by insulin) or too many pathogens, then the body cannot cope and allows for a build-up of one or both of these items. If too much insulin builds up then diabetes can occur, which is why Alzheimer’s is sometimes referred to as Type 3 diabetes. If too many pathogens are present then amyloid also can build up and lead to gradual brain dysfunction, and eventually Alzheimer’s.
• Volumetrics involves shrinking of the brain, with the hippocampus being the most significant area. There are many factors that can influence brain shrinkage including exercise, which stimulates the hippocampus to increase brain volume. Water is also an important factor since the brain is the first organ impacted by low consumption of water. Fat is crucial since 70 percent of the brain is comprised of fat. Long and medium chain fats are preferred and they include omega 3 fats, as well as coconut oil. Another key shrinkage factor is stress, which can shrink the brain by as much as 15 to 20 percent if it experiences continuous chronic stress for up to three months. An MRI is the best way to determine if the brain is shrinking, which can then be used to measure increased brain size as a result of increasing the protocol elements know to influence brain size.

4. Alzheimer’s caused by cellular death—Research has identified 21 “dependence receptors” that can influence the health of brain cells and eventually lead to cell death if they are not protected in some way. Messages are sent to these brain receptors that reside on all neurons. Some of the influencing factors include:

• Thyroid hormones
• Dopamine
• Vitamin D (also a hormone)
• Insulin
• Estradiol
• Serotonin

These are called anti-trophic influences and another important one is amyloid-beta. This is a form of plaque that can build up in the brain and contribute to the development of Alzheimer’s. This amyloid-beta can form into small groups called oligomers, which can eventually create the “die signal” for brain cells. Amyloid precursor peptide (APP) is a molecule that sticks out of neurons and is one of the key molecules that determines if brain cells die or not. The process for protecting neurons involves cutting these peptides very precisely with the use of molecular scissors called protease (an enzyme). If the protease scissors make one cut of the peptide, then the neuron will remain healthy and continue to function properly. However, if the protease scissors make three cuts, producing four peptides, the neuron will be destroyed and the brain cell will die. This improper peptide cutting can occur when too many or not enough receptor influencing molecules are present. In other words, if key nutrients and hormones are not available in the necessary amounts this biochemical disruption can lead to brain cell death causing Alzheimer’s disease.

Synapses are the connecting spaces between neurons and neuron receptors. These synapses need to be maintained and even rebuilt occasionally. When new learning occurs these synapses must be remodeled or new synapses must be created. To accomplish this, synapses need raw materials and other process helpers (amino acids, vitamins, enzymes, energy, and brain activity). As we age these materials and process helpers begin to decline and the brain begins to downsize synapse remodeling as a protection mechanism. The brain will even begin to establish priorities for what will be retained by the brain. A sampling of these priorities follows, in priority sequence.

1. Breathing/other involuntary functions
2. Regulation of body temperature
3. Working skills
4. Favorite hobbies
5. Long-term memories
6. Grooming skills
7. Names and recent acquaintances
8. Short term memories

These “symptoms” are the well-established symptoms of dementia or early onset Alzheimer’s. However, these symptoms may be able to be avoided by optimizing brain protection factors. The following protective factors are known to discourage brain cell death by creating a healthy environment for brain receptors and synapses.

• Optimized vitamin D3 levels
• Balanced or high levels of resveratrol
• High levels of testosterone
• Balanced levels of estrogen
• Balanced thyroid hormones—T3 and T4
• Low inflammation makers—C-reactive protein and homocysteine
• Low levels of toxins-especially heavy metals
• Low levels of glucose
• Low levels of insulin
• High levels of neurotransmitters such as dopamine,serotonin, GABA, etc.
• High levels of energy optimizers such as CoQ10
• High levels of antioxidants such as vitamin C, vitamin E, NAC, etc.

5. The influence of genetic factors—APO E genetic influences began as a reaction to more inflammation in the body about seven million years ago. The risk of Alzheimer’s occurs in varying degrees as follows.

• Most people carry two copies of the APO-E3 gene, which results in a risk of 9 percent.
• About 25 percent of people carry one copy of the APO-E4 gene, which results in a risk of 30 percent.
• About three percent of people carry two copies of the APO-E4 gene, which results in a risk of 50 percent.

• The nine percent group will usually begin to show symptoms in their 60’s and 70’s.
• The 30 percent group will usually begin to show symptoms in their 50’s and 60’s.
• The 50 percent group will often begin to show symptoms in their 40’s and 50’s.

There were seven sub-types identified earlier for the development of Alzheimer’s and dementia, and each one has variations in terms of the factors that influence the development of symptoms. Genetic influences are just one factor and must be combined with other factors, such as those just mentioned in relation to nutrients, hormones, energy production, toxins etc. If someone is able to optimize these factors then the genetic risk factor will be altered to allow for a delay in the usual symptoms, and in some cases, may prevent them completely. However, if these biochemical factors are not optimized then the genetic factors will very likely manifest sooner and more aggressively than when they are not present. That is precisely why Dr. Dale Bredesen has decided to address all of the influencing factors that he could find in order to optimize the chances of both preventing Alzheimer’s before it can occur, as well as reversing as many symptoms as possible once they have begun.

6. Tests not usually considered—In order to determine the existing levels of the biochemical and other factors that can influence brain health a number of tests and assessments should be used. These are not the typical tests and assessments used by doctors who are trying to assess a person for their risk of Alzheimer’s, however they are all used by many doctors for the presence of illnesses related to other chronic illnesses. Dr. Bredesen has identified 36 factors that can influence brain health and each one of these factors can be tested using the following tests and assessments. If these factors can be identified early there is a much better chance to avoid or prevent dementia and Alzheimer’s.

• Genetics
• Inflammation
• Infections
• Homocysteine
• Fasting insulin
• Hormone status
• Toxin exposure
• Immune function
• Microbiome
• Blood brain barrier
• BMI
• Pre-diabetes
• Brain shrinkage
• Prescription meds
• Nutritional status
• Stress assessment
• Sleep assessment
• Vitamin D levels
• Leaky gut
• Mitochondria function

There are also some guidelines for how best to address any imbalance that might exist.

a) Strive for optimal levels, not standard or “normal” levels
b) Address as many deficiencies as possible
c) Address the root cause of any problem if possible
d) Make protocols sensitive to personalized situations and assessments
e) Achieve threshold levels in order to reverse pathogenic synapse improvement
f) Watch and monitor gradual improvements
g) Use drugs as an adjunct to natural treatments
h) Begin the assessment ASAP; at the first sign of symptoms or even before, for prevention
i) Remember that most strategies have a “work around” if initial efforts don’t succeed

7. Nutritional guidelines—Research by Dr. Bredesen and his team has confirmed that several key nutrients are able to optimize cellular resistance to dementia and Alzheimer’s. These nutrients allow the body to continue to resist the negative influence of pathogens as well as encourage the neuron related remodeling; the rebuilding that is necessary to maintain a high level of brain function.

1. Flexitarian diet (small protein)
2. Consumption of coconut oil or MCT
3. Low glycemic food intake
4. Avoid fruit juices
5. Consume high fiber diet
6. Avoid gluten consumption
7. Avoid dairy consumption
8. Eat detoxifying plant foods
9. Avoid processed foods
10. Avoid sugar and simple carbs
11. Avoid alcohol
12. Consume probiotics daily
13. Consume digestive enzymes daily
14. Fast 12–16 hours from dinner to breakfast
15. Follow the SMASH program, which involves eating fish such as salmon, mackerel, anchovies, sardines and herring.

The evidence clearly shows that the best results are realized when patients are able to follow these nutritional guidelines as closely as possible.

8. Nutritional supplements for the prevention of Alzheimer’s:

a. Green leafy vegetables—Eating an average of 1.3 servings of green leafy vegetables daily (kale, spinach, etc.) kept participant’s brains ten years younger than people who ate an average of .5 servings or less daily. Rush University Medical Center published in the Journal of Neurology, December 2017.

b. Lithium Orotate—Participants who consumed water with at least 40 mcg/liter lithium experienced a significant reduction in the risk of Alzheimer’s. In a similar study of over 73,000 people aged 50–90, 15 mcg of lithium was able to reduce the risk of dementia by 17 percent. Both studies were reported in the Journal of Alzheimer’s Disease in January 2018.

c. Vitamin C—A study from the Lund University Molecular Medicine Department in Sweden found that vitamin C was able to dissolve the toxic brain plaque associated with Alzheimer’s disease. These amyloid plaques eventually kill brain cells. Published in the Journal of Biological Chemistry.

d. Vitamins B6, B9 (folate) and B12—Taking these three methylators for two years allowed study participants to experience 30 percent less brain shrinkage in the hippocampus, which is one of the main factors in the development of dementia and Alzheimer’s. Those participants with the highest levels of shrinkage experienced much higher reductions of shrinkage from 50 to 500 percent. Oxford University, London.

e. Folate (vitamin B9)—Participants in this study took 800 mcg of folate for three years and experienced memory improvement of 4.7 years, information processing improvement of 2.1 years, improvement in motor-sensory speed of 1.7 years and improvement in global cognitive function of 1.5 years. Folate concentrations increased by 576 percent. Published in Lancet.

f. Folate(vitamin B9)—This study on folate began with 1400 people in 1958. Over that time period, the participants took 400 mcg per day and experienced a 55 percent reduction in the risk of Alzheimer’s. Very few participants were able to get this level of folate from food alone. University of California.

g. Vitamin B1(thiamine)— Various studies have established that thiamine increases the synthesis of acetylcholine, a neurotransmitter associated with the protection of memory in the brain. The effective dose has been set at 50–75 mg/day for most people. “Awakening from Alzheimer’s” by Peggy Sarlin, 2016.

h.Vitamin B6—This vitamin is one of the key nutrients needed for the body to manufacture neurotransmitters such as serotonin, dopamine, Nora dopamine, and adrenaline. These biochemicals are vital to the brain’s messenger service allowing thoughts and information to jump from one neuron to another. The usual recommended dosage is 50–85 mg/day. “Awakening from Alzheimer’s” by Peggy Sarlin, 2016.

i. Vitamin B3 (niacin)—Mice were genetically manipulated to develop Alzheimer’s and then given niacin at the human equivalent of 1500 mg twice daily. These were the results of this study.

All of the initial cognitive decline was completely reversed.
All tau protein plaque was totally removed.
All memory tests were normal as if the mice had never had Alzheimer’s.

Published in The Journal of Neurosciencein 2008.

j. Vitamin E—In this study of people over the age of 65, those with the highest levels of vitamin E were 67 percent less likely to develop Alzheimer’s. The biggest consumers of vitamin E were 8–10 years younger mentally than those participants who consumed the lowest level of this vitamin. Chicago Health and Aging Project. Similar results were realized in studies the Massachusetts’s General Hospital, the VA Bedford Center, Harvard Medical School and Oregon State University.

k. Vitamins C and E together—In this study, 4,740 residents in Utah took a combination of vitamin C and vitamin E and experienced reduced their risk of Alzheimer’s by 78 percent. John Hopkins University Bloomberg School of Public Health.

l. Vitamin D—In this study in Japan vitamin D helped to remove amyloid beta protein plaque in the brain. Vitamin D appears to help transport this plaque out of the brain using vitamin D receptor cells. Tohuko University 2011.

m. Sage—Experts now recognize the memory-enhancing capacity of sage in individuals with and without Alzheimer’s disease. In the Journal Pharmacological Biochemical Behavior, the study authors wrote, “These results represent the first systematic evidence that Salvia (sage) is capable of acute modulation of cognition in healthy young adults. A double-blind, randomized, and placebo-controlled trial reported in the Journal of Clinical Pharmacy and Therapeutics found that Salvia officinalis boosted cognitive function and demonstrated effectiveness in the management of mild to moderate Alzheimer’s. Additionally, a study reported in the Journal of Pharmacology and Experimental Therapeutics demonstrated the nerve cell-protective effect of sage against damage linked to the abnormal amyloid proteins found in those with Alzheimer’s. Researchers believe that the compound rosmarinic acid may contribute to the beneficial effects of sage.

• Increased gut permeability causes more inflammation and the gut is one of main places where inflammation is mediated or controlled.
• Good fats can help the gut to function better, however fats like LPS (Lipo polisacaride) can cover the bacteria in the gut, causing them to be less effective in doing their jobs.
• LPS can leak into a healthy gut and get into the bloodstream where they can have an unhealthy influence on the fat in the brain. The brain is 70 percent fat.
• This LPS influence has also been identified as an influencing factor in other brain-related illnesses such as Lou Gehrig’s disease and Autism.
• Over 90 percent of serotonin is produced in the gut, not in the brain.
• Supplements that help the gut include pro-biotics, Omega 3 DHA, Alpha lipoic acid, CoQ10, Vitamin E, L-glutamine and Vitamin D3.
• Pre-biotic foods such as kombucha, artichoke, and sauerkraut also help.

Contributing Author Eric Dohner, MD

THE DOMINANT RISK FACTOR FOR DEMENTIA IS ADVANCING AGE, UNFORTUNATELY, NO ONE KNOWS HOW TO REVERSE AGING. HOWEVER, THE SECOND MOST IMPORTANT RISK FACTOR IS POOR CIRCULATION, AND THIS IS SOMETHING YOU CAN EASILY CORRECT.

Advancing age is the dominant risk factor for dementia. Individuals under age 65 rarely develop dementia, but then risk doubles every five years after age 65. In individuals over age 85, up to one-half exhibit signs of the onset of dementia.

There is little we can do about aging, but we can address other dementia risk factors which arise with aging. In particular, low blood flow to the brain has repeatedly been shown to be one of the most important risk factors for dementia, and it is an easily correctable factor.

Brain Blood Flow and Blood Pressure

Though the brain makes up only about two percent of the body, 15 to 20 percent of the blood circulation in young adults goes to the brain to provide the necessary oxygen to support the energy demands of the brain. However, as we age, blood flow to the brain steadily declines. In men, brain blood flow falls about 15 percent over 50 years. In women, the decrease in brain blood flow is far greater, up to 30 percent by age 75.

Blood flow to the brain declines with age because blood pressure typically declines with age. Lower blood pressures correspond to lower brain blood flow, particularly when sitting or standing as the brain is at the top of the body, and blood pressure must overcome the force of gravity. While in middle-aged people a major health concern is high blood pressure (hypertension), in older individuals, low blood pressure (hypotension) is common and can become a serious health issue, particularly with respect to brain health.

Blood pressure begins to decline around age 60, and by age 75, half of Americans have a resting diastolic blood pressure (the lower number in a blood pressure recording) below 70 mmHg. 70 mmHg is considered a critical threshold for dementia risk, as the risk of dementia more than doubles for an older individual with a resting diastolic pressure below 70 mmHg for several years or more. By age 85, two-thirds of people have a resting diastolic pressure below this level.

Blood Pressure and Dementia—The Evidence

The influence of low blood pressure on the development of Alzheimer's was first reported more than 20 years ago in a Swedish study of 1800 people which showed that below normal (less than 120/80 mmHg) blood pressures were associated with a 2-fold to 10-fold increased risk.¹

The Bronx aging study subsequently confirmed that below normal blood pressures were associated with an increased risk of Alzheimer's, and also indicated that for individuals with resting diastolic pressures below 70 mmHg, the risk increased by a factor of two or more.² Additional confirmation has recently been provided in a very large study completed in Norway and involving almost 25,000 patients who were followed for up to 27 years.³

Additional research also confirms that reduced brain blood flow arising from chronic low blood pressures is likely the primary underlying cause of dementia. Direct measurements of brain blood flow have shown that increased blood flow is associated with reduced risk of dementia.⁴ Also, a very recent mouse study completed in Israel demonstrated that one hour daily exposures in a hyperbaric chamber, which increased oxygen levels in the blood, significantly reduced the physiologic nd behavioral effects of Alzheimer's within a two week period of time.⁵

Blood Pressure and Aging

So why does resting blood pressure fall as we age? Whenever we are sitting or standing, gravity is pulling the blood in our veins, and other fluids in our body, down towards our legs. Because people have relatively soft skin (women more so than men), our skin expands allowing blood and fluid to pool into our legs and lower body.

In young individuals, the soleus muscles in the calf of the legs prevent this pooling from becoming excessive. These specialized muscles serve as pumps which collect the fluid pooling into the legs and pumps it back to the heart. The soleus muscles play such an important role in ensuring blood return to the heart that they are often called our "secondary hearts."

As we age, however, it is common for our soleus muscles to become unable to perform the task of continually pumping blood and lymphatic fluid back up to our heart. The soleus muscles are maintained through squatting activity, and while our ancestors squatted to rest, adults in the western world rarely squat. To rest, we sit in chairs, and sitting does not exercise the soleus muscles.

Weak soleus muscles allow fluid to continually build up in the legs during the day. This pooling is often first recognized by the presence of swollen feet or ankles, or by the appearance of varicose veins. But, if the fluids in your body are not being returned back to the heart, the output from your heart falls. This drop in cardiac output leads to a drop in blood pressure, and as a result, a decrease in blood flow to the brain.

Maintaining a Healthy Blood Pressure

The good news is that low blood pressure can be easily corrected. While low blood pressure can be due to medication interactions, or other condition, if you have swollen feet and ankles, varicose veins, unexplained fatigue, or cold hands and feet, it is most likely that the cause of your low blood pressure is weak soleus muscles.

Like any muscle, your soleus muscles can be retrained. The best way to do this, of course, is to replace your sitting time with squatting time or to take up Tai Chi or Yoga. But if active exercise does not fit your lifestyle, you have the option of utilizing a "passive exercise" approach to building up your soleus muscles.

The soleus muscles can be activated through a reflex initiated with an appropriate mechanical stimulation to the bottom of the feet. To take advantage of this reflex response, "passive exercise" devices have recently been introduced onto the market which allows you to exercise your soleus muscles while you sit. Retraining your soleus muscles generally requires a couple of hours a day of "exercise", but over the period of several months, your soleus muscles will regain their pumping ability, your symptoms of fluid pooling will disappear, and your resting blood pressure will return to normal.

Preventing Dementia

Recent research has provided encouraging evidence that correcting low blood pressure in older individuals is capable of reversing the earliest stages of dementia in a relatively short period of time.⁶ In a study on 70– 90-year-old participants living in an assisted living center, those with chronically low resting blood pressure were found to require twice as much time to complete a cognitive test than their fellow residents who had normal blood pressures. Undertaking soleus exercise for just one hour per day, over a four-month period of time, served to correct the low blood pressures, and cognitive test times fell by half.

While dementia is often considered an irreversible effect of aging, research has clearly shown that dementia arises, in large part, as a result of the reduced brain blood flow which occurs as we age. By maintaining normal blood pressure as we age, we should be able to slow, or even reverse, the development of dementia and perhaps even prevent future cases of Alzheimer's and other debilitating forms of dementia.

References

1. Guo Z, et al. (1996) Low blood pressure and dementia in elderly people: The Kungsholmen project. BMJ 312:805–8.
2. Verghese J, et al (2003) Low blood pressure and the risk of dementia in very old individuals. Neurology 611:1667–72.
3. Gabin, JM, et al (2017) Association between blood pressure and Alzheimer disease measured up to 27 years prior to diagnosis. Zlaheimer's Research and Therapy. DOI10.1186/s13195-017-0262
4. Ruitenberg A, et al (2005) Cerebral hypoperfusion and clinical onset of dementia. Annals Neurology 57:789–94.
5. Shapira R, et al (2018) Hyperbaric oxygen therapy ameliorates pathophysiology of 3xTg-AD mouse model by attenuating neuroinflammation. Neurobiology of Aging 62:105.
6. McLeod K, et al (2017) Reversal of cognitive impairment in a hypotensive elderly population using a passive exercise intervention. Clinical Interventions in Aging 12:1859–66.