BRAIN HEALTH AND DEMENTIA

                         BRAIN HEALTH AND DEMENTIA

  • “I am my ‘connectome’.” Joseph Maroon, MD {mindful.org “The magnificent, wonderful, wild connected brain.”}
  • “No man ever steps in the same river twice, for it is not the same river and he’s not the same man.” Heraclitus

          There are over 30 million symptomatic individuals with Alzheimer’s dementia worldwide and many more in the pre-symptomatic phase. {According to the 2009 World Alzheimer’s report.} In the US there are over 5 million individuals with Alzheimer’s dementia with an estimated annual cost of $200 billion. The number of individuals is projected to rise to 13 million by 2050.

“Almost 40 per cent of people over the age of 65 experience some form of memory loss. When there is no underlying medical condition causing this memory loss, it is known as “age-associated memory impairment,” which is considered a part of the “normal aging process”. Age-associated memory impairment and dementia can be told apart in a number of ways. Below are some examples.

Normal Aging  Dementia
Not being able to remember details of a conversation or event that took place a year ago Not being able to recall details of recent events or conversations
Not being able to remember the name of an acquaintance Not recognizing or knowing the names of family members
Forgetting things and events occasionally Forgetting things or events more frequently
Occasionally have difficulty finding words Frequent pauses and substitutions when finding words
You are worried about your memory but your relatives are not Your relatives are worried about your memory, but you are not aware of any problems

     Tips for coping with normal age-related memory difficulties

  • Keep a routine
  • Organize information (keep details in a calendar or day planner)
  • Put items in the same spot (always put your keys in the same place by the door)
  • Repeat information (repeat names when you meet people)
  • Run through the alphabet in your head to help you remember a word
  • Make associations (relate new information to things you already know)
  • Involve your senses (if you are a visual learner, visualize an item)
  • Teach others or tell them stories
  • Get a full night’s sleep {According to the Alzheimer’s Society of Canada.}”

About 60 to 70% of dementias are due to Alzheimer’s Disease. “The most common early symptom is difficulty in remembering recent events (short term memory loss). As the disease advances, symptoms can include problems with language,  disorientation (including easily getting lost), mood swings, loss of motivation, not managing self-care, and behavioral issues. As a person’s condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years.” {According to Wikipedia.} 2/3 of people with AD are women, and the risk of AD increases with menopause along with a decrease in brain activity.

There is a critical window of opportunity to detect cognitive impairment and to implement strategies for treatment: the earlier the better; preferably <5 years after menopause. A drop in estradiol levels causes a decrease in memory function, increased total body and neuro-inflammation, increased insulin resistance, with increased central adiposity and obesity. Cognitive impairment associated with type 2 diabetes is thought of as “Type 3 Diabetes”. Estradiol is neuroprotective and an antioxidant. The hormone symphony needs to be evaluated: start with evaluating insulin, then adrenal functions, then thyroid functions, then the sex hormones, then estrogen metabolism. Personalized Medicine is required to evaluate the whole picture. When evaluating studies, look at the data and not just the conclusions, because when pooling data in meta-analyses, BHRT results are diluted when included with horse urine estrogen and/or progestin studies.

 Appropriate memory management requires an accurate assessment and diagnosis. 1) Is the file clerk working? The frontal lobes accumulate information and put it into the memory file cabinet. As we get older: a) we don’t hear as well—information needs to be repeated to get it into the file cabinet; b) we don’t move as quickly—it takes longer to retrieve a memory; and, c) we don’t see as well—we need a hint or a cue to find the right memory, so it may take retrieval extra-time. 2) What is the diagnosis? The new memory file cabinet is the hippocampus and related structures. The old memory file cabinet is the cortex. The hippocampus attaches meaning and emotion to a memory. Alzheimer’s disease destroys the hippocampus. Information can’t be retrieved if no information is in the file cabinet. People with AD often get lost, lose things, and repeat stories and questions. Diagnosis occurs along a frequency and a spectrum of symptoms. Rapid forgetting is NEVER normal. 3) What is the cause for the memory loss? Is the dementia due to a vitamin deficiency? Depression? Vascular compromise? Frontal lobe trauma? etc. 50% of people with “mild cognitive impairment” develop AD: someone is concerned about memory, testing confirms impairment, but day-to-day functioning remains normal. With “subjective cognitive decline”: someone is concerned about memory, testing is normal, yet, over time impairment occurs, and by 7 years over 50% develop a diagnosable disorder. 4) Treat your memory loss. Due to an infection? Due to too much amyloid-beta? Tau proteins release sticky tangles which trigger inflammation which kills cells. Cells make acetylcholine. With decreased cells there is decreased acetylcholine available. Treatment with medications that stimulate acetylcholine helps delay symptoms for 6 to 12 months. Treatment is continued because stopping the medication will cause a rapid cognitive decline: losing 6 to 12 months in 2 weeks because the clock can’t be reversed. Mamentine is helpful for late-stage AD by keeping a person more alert and motivated. It is not a disease modifying medication. 5) Modify your lifestyle. Aerobic exercise increases the size of the hippocampus, especially at one year—improving the new memory file cabinet. {Cardiac fitness is best assessed by measuring VO2Max.} Exercise decreases depression and improves sleep. Sleep helps one to pay attention; helps transfer memories from the old storage cabinet to the new cabinet for “consolidation”; and, clears amyloid-beta during NREM sleep cycles. Sleep also triggers brain derived neurotropic factor which improves cell growth and memory. The Mediterranean Diet with extra-virgin olive oil is also supportive. 6) Strengthen Your Memory. Engage in novel, stimulating cognitive activities. Be involved in social activities. Keep a positive mental attitude. Pay attention to names: practice mindful attention; say the name out loud; make connections; create visual images; find something in their visual appearance to remind you of their name; then, repeat their name in minutes, hours, days. If you are trying to recall a name: relax and don’t block it. Think about things that you know about the person. Memory strategies take effort and work, but they are effective. Doing puzzles improves your ability to do puzzles, but does not improve overall brain health. However, they are much better than just watching TV.

                        OUR CONNECTOME

Our brains have over 100 billion neurons, with over 100 trillion synaptic connections. Our thoughts affect the architecture of our brain. Because, the brain is neuroplastic and keeps changing throughout life. “What fires together, wires together.” Certain mental health problems have ‘aberrant wiring diagrams’: such as, autism, early onset schizophrenia, and ADHD. There are functional and structural changes that correlate with the peculiar behavioral activities. There are neuroepigenetic factors responsible for neuroplasticity and modulation of the connectome. Our DNA is not our destiny: modifying epigenetic factors is the key to health. Epigenetic factors affect gene activation (transcription factors) that translate our DNA by RNA transcription for the manufacture of proteins. There are 4 key epigenetic factors: 1) Exercise; 2) Environment; 3) Nutritional factors; and, 4) Emotional Health. Intracellular oxidative stress creates inflammatory cytokines which amplify the oxidative stress and result in chronic inflammation, cardiovascular disease, and cancers.

For example, we can modify certain epigenetic factors involved in mood disorders, and move along the spectrum from vulnerability to resilience. Mental and physical exercises can help to heal traumas by re-wiring circuits with the strength of repetition. Repetition is critical. Neuroconnections are reinforced to enable us to improve and to strengthen our future capability. New learning stimulates neurogenesis. Literally, our thoughts can change the structure of our brains. Key supplements to support this enhancement include: Omega-3s, curcumin, resveratrol, NAD+, carnitine—molecules that support mitochondrial function.

 

CLUES TOWARDS AN UNDERSTANDING OF ALZHEIMER’S DEMENTIA    

 AD is multifactorial, although the causes are poorly understood. It is believed that about 70% of the risk for AD is genetic. Additional risk factors include: head injury, hypertension, obesity and depression.

Various inflammatory processes and cytokines may have a role in the pathology of Alzheimer’s disease. Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in AD or a marker of an immunological response. Brain inflammation can be demonstrated approximately 20 years before the onset of cognitive problems. {Brain. 2016 Jan 26.} Neuronal function, measured by glucose metabolism, began to decline approximately 7 years before disease symptoms.

There have been 2 consistent findings in patients diagnosed with Alzheimer’s disease: 1) Neurofibrillary tangles caused by “tauopathy”; and, 2) amyloid-beta plaques.

“The Tau Protein hypothesis proposes that tau protein abnormalities initiate the disease cascade. In this model, hyper-phosphoralated tau proteins dissociate from microtubules within neurons, then mis-fold and begin to pair with other threads of tau forming insoluble aggregates. Eventually, they form neurofibrillary tangles inside nerve cell bodies. When this occurs, the microtubules are destabilized and disintegrate, destroying the structure of the cell’s cytoskeleton which collapses the neuron’s transport and intracellular communication systems. This may result first in malfunctions in biochemical communications between neurons and later in the death of the cells.”  {According to Wikipedia.}

Examining the orthodox “Amyloid-beta Hypothesis”:  “In 1991, the “amyloid-beta  hypothesis” postulated that extracellular amyloid-beta deposits are the fundamental cause of the disease. Accumulation of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell’s calcium ion homeostasis, induces programmed cell death (apoptosis). It is also known that amyloid-beta selectively builds up in the mitochondria in the cells of Alzheimer’s-affected brains, and it also inhibits certain enzyme functions and the utilization of glucose by neurons. Support for this postulate comes from the location of the gene for the amyloid precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21(Down’s Syndrome) who have an extra gene copy almost universally exhibit at least the earliest symptoms of AD by 40 years of age. Also, a specific isoform of apolipoprotein, APOE4, is a major genetic risk factor for AD. While apolipoproteins enhance the breakdown of amyloid-beta, some isoforms are not very effective at this task (such as APOE4), leading to excess amyloid buildup in the brain. Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimer’s-like brain pathology with spatial learning deficits.

In 2009, this theory was updated, suggesting that a close relative of the amyloid-beta protein, and not necessarily the amyloid-beta itself, may be a major culprit in the disease. The theory holds that an amyloid-related mechanism that prunes neuronal connections in the brain in the fast-growth phase of early life may be triggered by age-related processes in later life to cause the neuronal withering of Alzheimer’s disease. N-APP, a fragment of APP from the peptide’s N-terminus, is adjacent to amyloid-beta and is cleaved from APP by one of the same enzymes. N-APP triggers the self-destruct pathway by binding to a neuronal receptor called death receptor 6 (DR6). DR6 is highly expressed in the human brain regions most affected by Alzheimer’s, so it is possible that the N-APP/DR6 pathway might be hijacked in the aging brain to cause damage. In this model, amyloid-beta  plays a complementary role, by depressing synaptic function.” {According to Wikipedia.}

Robert Moir is an assistant professor of Neurology at Harvard Medical School, who works with Rudolph Tanzi.  On December 18, 2017, Amy Proal published an Interview with Dr. Moir:  In that interview he discussed key concepts:  The “Grandmother Hypothesis” acknowledges that birth is a dangerous and potentially deadly time for women (and for  infants). Especially as a woman gets older, there is an increasingly high risk of death from childbirth. Menopause allows aging mothers to stop reproduction, and to survive to help with raising the younger generations. Because human infants take such a long time to mature to the point of independence, having a grandmother to help successfully raise the grandchildren ensures that their genetic material is passed on to future generations.  Any gene that would negatively impact grandmother survival and their valuable store of accumulated knowledge and experience would be selected against, changed, or eliminated. This is important to understand when considering the impact of amyloid-beta and its association (not cause and effect) with Alzheimer’s dementia. The genes for the production of amyloid-beta have been 100% preserved for over 400 million years. It is one of the most conserved proteins across species in Biology. Thus, amyloid-beta must serve an important purpose.

 THE INFECTION HYPOTHESIS:  Amyloid-beta self-assembles to build multiple differently shaped molecules called “oligomers”. Each particular oligomer structure has a unique antimicrobial activity. Thus, amyloid-beta is a crucial part of the “innate immune system” because it spontaneously generates a population of diverse oligomers able to target a broad spectrum of pathogens, and toxins released during infection. Oligomers are simpler, metabolically cheaper, and a far more ancient immune strategy than antibodies (part of the “adaptive immune system”). Amyloid-beta is found in jelly fish and all vertebrates and contributes to survival fitness. Thus, the initial idea that amyloid-beta was accumulated “junk” that is toxic to brain neurons must be false. In fact, with increasing knowledge about the brain’s microbiome, it is now understood that amyloid-beta is a crucial antimicrobial peptide (that can work against viruses, bacteria and fungi) that is one hundred times stronger than penicillin, and which is needed to prevent brain dysbiosis and disease. Thus, a re-thinking about the etiology of Alzheimer’s disease is required.

 

***THE ANTIMICROBIAL RESPONSE (PROTECTION) HYPOTHESIS OF ALZHEIMER’S DISEASE***

 

The “antimicrobial response hypothesis” merges the infection hypothesis with the amyloid-beta hypothesis. Amyloid entrapment provides immediate, effective protection from infections. However, chronic infections or dysbiosis results in brain inflammation which triggers a cascade of pathologic responses resulting in Alzheimer’s disease.

 

          The BRAIN HAS A MICROBIOME!!  Not including viruses, there are over 200 organisms in a healthy brain. Perhaps Alzheimer’s disease occurs when there is a disruption of this microbial community {just like with Chron’s colitis}. Certain key pathogens may “push” the community out of balance. Amyloid-beta arises to do battle in cases of brain microbiome dysbiosis (imbalance). Part of this response is inflammation. However, prolonged activation of this innate immune inflammation may lead to tissue damage and neuro-degeneration.

Amyloid-beta was discovered in 1984. Initially it was thought to occur only under disease conditions found in Alzheimer’s dementia. However, for 20 years it has also been found to be manufactured in normal brains. In experiments, if amyloid-beta is added to a broth of microbes, it will inhibit and kill a range of microbes. Further experiments in living organisms demonstrate that amyloid-beta plaques trap and neutralize microbes. There is mounting evidence associating Alzheimer’s disease with infectious organisms. Multiple studies show a positive correlation between Herpes Simplex Virus- 1 (HSV-1) and the incidence of Alzheimer’s disease. Several autopsy studies have found HSV-1 DNA in the tangles and plaques in the brains of humans and animals with Alzheimer’s disease. HSV-1 is more prominently found in the frontal and temporal lobes of damaged brains. And, when the classic sticky amyloid-beta plaque (associated with the disease) was placed in a test tube with nerve cells, the production of the classic signs of Alzheimer’s disease in those tissues was slowed. In addition to an infectious process, the immune pathways in Alzheimer’s disease may become dysregulated and pathological. {Ref:  Neuron, June 21, 2018, “Pathogen Hypothesis of Alzheimer’s disease”.} Human Herpes Virus 6A (HHV-6A) and Human Herpes Virus-7 (HHV-7) are associated with the cause and the progression of amyloid plaques, brain tangles, and the severity of Alzheimer’s disease. A Canadian study in 1982 suggested this association. And, a Swedish study in October 2014 also linked “cold sores” to Alzheimer’s dementia.}  In addition to the Herpes simplex virus {which has been detected 60% of the time}, Chlamydia pneumonia is also a candidate for brain infections. And, the slow progression of AD fits with the chronic nature of some systemic fungal infections, which can be asymptomatic and thus, unnoticed and untreated. Thus, there is no single pathogen driving the disease.        

 

THE GUT-BRAIN CONNECTION

The “Enteric Nervous System (ENS)” is separate from the Central Nervous System (CNS). It is composed of 2 thin layers of over 100 million nerve cells—more than in the spinal cord. The ENS lines the GI tract and controls blood flow, secretions and contractions. It also helps us to unconsciously “feel” (like a second brain) what is occurring in the GI tract. It has glial cells to support the gut neurons. It uses over 40 different neurotransmitters. It produces 50% of the body’s dopamine and 95% of the body’s serotonin. L. brevis can produce GABA. It has a barrier, similar to the blood-brain barrier, for protection. It may have its own memory (although it is not capable of thought). The gut and the brain are connected by the vagus nerve with about 90% of the signals going from the gut to the brain. {The vagus nerve also connects cardiac functions.} The bi-directional communication occurs by various physiological channels including autonomic pathways, neuro-endocrine pathways and neuro-immune pathways. {People with Parkinson’s disease have the same protein clumps in the ENS as in the CNS. And, people with Alzheimer’s disease have the same neurofibrillary tangles and amyloid plaques in the ENS as in the CNS. Thus, a gut biopsy may make earlier diagnosis possible.}

Both external and internal STRESS can create a challenge or a threat that disrupts an organism’s homeostatic balance. It can alter the composition and the function of the gut microbiota. For example, maternal stress can affect the fetal gut microbiome directly and through epigenetic factors. This can affect systemic dysregulation in early life and persist into adulthood. Potentiation of heightened anxiety may be transmitted because of this complex mixture of both biological factors as well as psychological factors that act in feedback loops. Chronic stress is associated with dysregulation of the Hippocampal-Pituitary-Adrenal (HPA) axis. (Irritable bowel syndrome results from a heightened gut sensitivity and limited ability to modulate an acute stress response.)

Changes in the microbiota may help to ameliorate psychological disorders. For example, if the gut microbiome is disrupted, there is a link with depression. A probiotic cocktail has been associated with improving depression on the Beck Depression Inventory. Also, L. helveticus can improve sustained attention in older adults. And, polyunsaturated omega-3 fatty acids can modify the gut microbiome resulting in improved cognition, dampened HPA activity with less anxiety and depression, and improved psychological well-being. Products of fermentation, short-chain fatty acids (SCFAs) travel via the vagus nerve where immune cells in the brain need them to mature. Also, certain gut bacteria live off chemicals generated in the brain which are transported to the gut. Vagus nerve traffic includes bacterial signaling molecules called “quorum sensing” molecules. It’s a two-way axis. Gut microbes and brain microbes may be “talking” and deciding what to do next!  Additionally, efferent nerves from the nasal bulb trace straight back to brain areas where amyloid-beta formation starts, and may be another primary source of entry for microbes. An important question is: can we modulate disease progression by manipulating the microbiome, or the gut-brain axis?

 

Amyloid has a general role in immunity. For example, diabetes is an amyloid disease. “Amylin” is produced in both type 1 and type 2 diabetes. At high levels, amylin is toxic to pancreas islet cells and highly pro-inflammatory. Yet, it is also protective against microbes, including E. faecalis which is a common cause of pancreatitis. Additionally, an amyloid is generated in the heart and has been linked to heart disease. Yet, it has antimicrobial protection. So, is amyloid-beta really the problem? It may be that prolonged microbial exposure with resultant inflammation and dysregulation of the immune system is the primary problem. Amyloid plaques, which trap and destroy microbes, are, therefore, found and associated with the diseases, but are not the cause of the disease.

 

A drug has been produced by Merck which lowers amyloid-beta without slowing the disease. Although, to date, the “amyloid is bad” idea continues to dominate, and most academic efforts are still focused on this model, because of costly drug trial failures, “Big Pharma” is now open to exploring alternative models. Current anti-inflammatory agents target the adaptive immune system, but don’t impact the innate immune system, and also don’t seem to have much impact on Alzheimer’s disease: perhaps because anti-microbial peptides, such as amyloid-beta, are a part of the primitive, innate immune system. For example, one target that is being examined is the gene “CD33”, which is an on/off switch for immune cells in the brain. Research is now being directed to manipulating this gene’s activity. Another line of research is combining anti-herpes virus drugs along with anti-amyloid drugs to influence early Alzheimer’s disease, and then targeting inflammatory molecules to possibly benefit later disease.

 

[***BE AWARE:  There are many supplements to slow viruses down. Consider using the amino acid Lysine, 1,000 mg to 3,000 mg daily, plus Zinc 20 mg/d, and Vitamin C at least 6,000 mg/day to boost your immune system. Other supplements to consider include: garlic, grapefruit seed extract, oil of oregano, and olive leaf extract.]

 

                         ***THE BREDESEN PROTOCOL***   

 

Cognitive decline is associated with a well orchestrated strategic downsizing of synaptic density. When there is a mismatch between the requirements from the many different inputs and what is required to maintain those synapses, something has to change in the neuro-remodeling. Essentially, early on anyway, giving up the ability to learn new information is sacrificed in order to retain all the important things which have already been learned during the rest of one’s life. For example, in younger women, estrogen receptor binding alters the cleavage of APP towards the desirable anti-Alzheimer’s side. However, with menopause and the withdrawal of sufficient estrogen to bind to these receptors, the cleavage of APP pushes towards the pro-Alzheimer’s side. Thus, looking for a “silver bullet” has been expensively unsuccessful. Perhaps what is required is a “silver buck-shot” approach. Dr. Bredesen has identified 36 factors which push APP cleavage towards supporting brain growth and maintenance. In order to prevent synaptic downsizing, all 36 factors need to be supported. His program is “programatic”, personalized and complex, and represents the future for treating chronic ills. Patients on the program noted symptom improvement in 3 to 6 months.

In a pilot study called “Reversal of cognitive decline: a novel therapeutic program” {Aging; 2014 Sept: 6(9):707-1 and, Integrative Medicine; 2015 Oct; 14(5):26-29}, Dr. Bredesen with the UCLA/Buck Institute offered personalized, multi-variate strategies for each patient and demonstrated REVERSAL OF MEMORY LOSS in 9/10 patients in their initial study!! {Now the study participants exceed 70 patients, and the findings remain consistently remarkable, and hopeful. However, when the program is not followed, cognitive decline is noted within 2 weeks!} For chronic diseases, a mono-therapeutic approach is simplistic, not optimal, and unsuccessful. [The paradigm shift began with the successful use of triple therapy for HIV.]  Although no patient followed all 36 recommendations, there seems to be a threshold number of modifications needed, which has yet to be determined, in order for symptom reversal to be noted {and seems to be >12 factors}. On follow-up evaluations, recommendations are “tweaked” to better fit with a person’s life-style, which simplifies yet optimizes its applications.

Dr. Bredesen addresses known associations with Alzheimer’s disease such as mitochondrial health, insulin resistance and the metabolic syndrome, metal homeostasis, chronic inflammation, hypertension, hypercortisolemia, hypothyroidism, high interleukin-6 levels, hypovitaminosis D; hyperhomocysteinemia, and hormonal deficiencies. Since there are at least 3 different categories of Alzheimer’s disease, with different responses to therapeutics, people need to be treated differently. A Functional Medicine approach is most appropriate: examining the cause(s) and treating the cause(s). Functional Medicine asks: Why did one develop this problem? How can it be reversed?

Metabolic profiling has distinguished at least three subtypes of Alzheimer’s disease. {Dale Bredesen, Aging, 2015 Aug; 7(8).} 1) Inflammatory: amnesic, occurring in the 70s with hippocampal atrophy, and increased inflammatory markers such as hs-CRP and globulin/albumin. It is associated with the APOE gene. 2) Non-Inflammatory: amnesic, occurring in the 80s, associated with metabolic abnormalities, but inflammatory markers are not increased. It is also associated with the APOE gene. {APOE4 exerts pro-inflammatory effects.} 3) Loss of long term memory maintenance: affecting relatively younger people in their 50s and 60s, with widespread cortical involvement, characterized by dyscalculia and aphasia, and a passive child-like demeanor, and often depression. Individuals are APOE gene negative. There is a striking association with zinc deficiency. Over 300 enzymes require zinc as a co-factor. Zinc deficiency causes increased inflammation, induces insulin resistance, decreases the immune responses, increases susceptibility to toxins and infections, increases harmful reactive oxygen species (ROS), decreases hormone functioning including decreased adrenal hormone support, increases gastrointestinal permeability, and increases susceptibility to copper toxicity. Thus, treatment with zinc can mitigate cognitive decline.

Zinc deficiency is common. Decreased gastric acidity (because of age and the common use of PPIs and antacids for reflux and gastritis) causes decreased zinc absorption. Alcohol use and a diet deficient in zinc, adrenal fatigue due to poor coping with stress, diabetes, toxin exposure, intestinal parasites, and aging all may result in a zinc deficiency. Measuring serum zinc is an insensitive test. If it is low, then zinc deficiency is severe. However, a normal serum zinc level may still indicate a significant zinc deficiency. A more accurate measurement would be evaluating the red blood cell zinc level.

  ***STRATEGIES used in the Bredesen therapeutic program included: a) eliminating all simple carbohydrates, gluten, and processed foods from the diet, and eating more vegetables, fruits and non-farmed fish. b) Meditating twice a day and beginning yoga to reduce stress. c) Sleeping 7 to 8 hours per night, up typically from 4 to 5 hours per night. d) Taking melatonin, methylcobalamin (vitamin B12), vitamin D3, fish oil, folate and CoQ10 daily. e) Optimizing oral hygiene by using an electric tooth flosser and an  electric toothbrush. f) Reinstating bio-identical hormone replacement therapy (if previously discontinued.) g) Fasting a minimum of 12 hours between dinner and breakfast. And, h) Exercising a minimum of 30 minutes, four to 6 days per week.

{Reference: Discover Magazine, December 2018, “Alzheimer’s Under Attack” by Linda Marsa, pp. 32-41.}

                   ARE LEAKY CAPILLARIES A CAUSE OF AD?

According to Nature Medicine {online, 2019 Jan 14 “Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction:” as reported in The People’s Pharmacy blog}  “Drug companies have invested heavily in medications that could lower levels of amyloid in the brain. To date the results have not been promising. The authors of the new research in Nature Medicine report that leaky blood vessels may play an independent and crucial role in cognitive decline and Alzheimer’s disease. ‘Our data show that individuals with early cognitive dysfunction develop brain capillary damage and BBB breakdown in the hippocampus irrespective of Alzheimer’s Aβ [amyloid beta] and/or tau biomarker changes, suggesting that BBB {blood-brain barrier} breakdown is an early biomarker of human cognitive dysfunction independent of Aβ and tau.’  The authors of the new research in Nature Medicine report that leaky capillaries can be detected long before Aβ and tau show up. ‘Our present findings support that neurovascular dysfunction may represent a previously under appreciated factor contributing to cognitive and functional decline, independent of the classic pathophysiological hallmarks of AD [Alzheimer’s disease].’

What causes leaky brain blood vessels or neurovascular permeability? The answer is complicated. Brain inflammation can do it. So can the resulting tissue trauma after head injury. Toxins and brain infections may also disrupt the blood brain barrier and lead to leaky blood vessels. Whether it is possible to reverse capillary permeability and delay or prevent the onset of dementia remains to be seen.”

IS THE CYANOBACTERIA TOXIN—BETA-METHYLAMINO-L-ALANINE (BMAA)– RESPONSIBLE FOR THE NEURODEGENERATION OF AD AND ALS?

          The ethnobotonist Paul cox has proposed that chronic exposure to the cyanobacteria (blue-green algae) toxin BMAA is linked to the neurodegeneration of AD and ALS. BMAA insinuates itself into protein chains in place of one of the 20 standard amino acids causing a protein mis-folding which triggers neuron death. Cyanobacteria are loaded with BMAA. The toxin gets into the food-chain via crabs, shrimp and other marine life that can be found in algae blooms. Preclinical studies suggest L-serine may benefit those exposed to the neurotoxin beta-methylamino-L-alanine (BMAA). Our cells can mistake BMAA for L-serine and misincorporate it into proteins, which can lead to cell death and may increase biological markers of Alzheimer’s. Laboratory studies indicate that L-serine may prevent misincorporation of BMAA and cell death. However, it is unclear whether L-serine affects biological markers of Alzheimer’s in the absence of such neurotoxins.

The amino acid L-Serine at a dose of 30 gm/day may slow the progression of AD by 85% (which is greater than with existing drugs). L-serine is essential for the synthesis of phosphatidylserine which is an essential component of all neuron cell membranes. It is also needed for the growth of neuronal processes.  Supplementation may inhibit brain inflammation. L-serine is safe for humans and relatively inexpensive. [NOTE: This is counter to the prevailing Amyloid-beta Hypothesis.]  L-serine is a naturally occurring dietary amino acid. It is abundant in soy products, sweet potatoes, eggs, meat, and some edible seaweed. (Also Note: there is a lot of L-serine in bacon.)  L-serine is also sold as a dietary supplement in capsule and powder forms. The dose used in an ongoing Alzheimer’s trial is 15 grams, twice daily, in the form of gummies. Most supplements come in the form of 500 mg capsules.   {Reported in Fortune, 1/18/2019 in an article by Rich Tetzeli}

                              SLEEP AND THE GLYMPHATIC SYSTEM

          SLEEP IS CRUCIAL:  The more waste products lying around the brain, the greater the chance for Alzheimer’s disease to take root. Since 25% of the body’s overall energy is regularly consumed by the brain, there are a lot of waste products to be cleaned up. The “glymphatic system” is the brain’s clean-up system. Specialized brain cells scavenge diseased and damaged bits of protein and metabolic waste. With age, these cells become impaired. Also, the neuron surrounding supportive glial cells shrink in size when sleeping, opening spaces between cells by as much as 60% which allows cerebral spinal fluid to be pumped through and clear out waste. Lymphatic vessels surrounding the brain then deliver the waste to the lymphatic system of the body which gets rid of the toxins. With aging, adults often struggle to get enough sleep, which impairs the clean up system. THUS, especially since NREM deep-wave sleeping is crucial for removing toxins, keeping a regular sleep schedule becomes increasingly important with aging. Irregular sleep hours and long day time naps can disturb an effective sleep cycle clean-up process. Also, sleeping on your side, in a fetal position, rather than on your back or stomach, does a better job of cleaning house. And, sleeping on your left side maximizes your body’s circulation, because most venous return travels up your right side and these veins can be compressed when you lie on them. However, getting good sleep is much more important than worrying about whether or not you sleep on your side, and what side you sleep on.

                       DEVELOP STRICT SLEEP HYGIENE HABITS

 

Here are some suggestions to try before considering a prescription medication. AVOID CAFFEINE (coffee, tea, caffeinated sodas), NICOTINE, and other  Stimulants such as chocolate, Sudafed or Afrin nasal spray, or, if that is too much of a challenge, then don’t use any for at least 6 hours before bedtime. AVOID HEAVY MEALS and  ALCOHOL before sleep. AVOID SUGARY OR SPICY FOODS 4 to 6 hours before bedtime. However, if awakening during the night is a problem, then try eating a light snack  of good fats (not carbs) before bedtime. A couple almonds, a few spoons of yogurt, a couple teaspoons of almond butter or peanut butter on a cracker can frequently do the trick. Drinking warm milk and/or eating a banana may help you get ready for bed. The amino acid tryptophan in these foods can help you to sleep.

Allow enough time for sleep. Most people need 7 to 9 hours of sleep each night. Fix a bedtime and an awakening time. Avoid napping during the day. And especially in the evening.  Arrange a sleep environment that is very dark, comfortable, quiet and cool {set the thermostat for 65 degrees in the bedroom} to facilitate falling asleep quickly and staying asleep. Use comfortable bedding and keep the room well ventilated. Block out all distracting noise. Consider a white noise generator. Reserve the bed for sleep and sex. Don’t use the bed as an office, work or recreation space. Let your body learn to associate the bed with sleeping. AVOID TV in the bedroom. Don’t take your worries to bed. Worrying is a prayer for that which you don’t wish to happen. Instead, practice relaxation techniques before going to bed. Yoga, deep breathing, visualizations, progressive muscle relaxation can all help relieve anxiety and muscle tension. Establish a pre-sleep ritual such as a warm bath (especially using Epsom salts—5 cups: the magnesium will relax your muscles), or a few minutes of reading or praying. Get into your favorite sleeping position. If you don’t fall asleep within 15-30 minutes, get up and go into another room and read until you get sleepy. Consider elevating the foot of your bed a few inches to increase circulation to your brain.  Regular AEROBIC EXERCISE is the best way to improve your sleep and modify pain. However, don’t do heavy exercise within 3 hours before bedtime because it raises your core body temperature and it takes several hours to return your core body temperature to normal. The best time for aerobic exercising is in the morning.

 

          COGNITIVE-BEHAVORAL THERAPY (CBT):  is the most effective psychological intervention to help with insomnia. It consists of a comprehensive program for educating and modifying behaviors.  The most effective use of CBT combines several of these methods. Rather than just relieving symptoms, it addresses the underlying cause(s) of insomnia. 1) Sleep Education: understanding the sleep cycles and learning how beliefs, behaviors and outside factors affect sleep. 2) Cognitive Control and Psychotherapy: helps control or eliminate negative thoughts and worries that keep one awake. It may help to eliminate worrisome beliefs about sleep such as a single restless night will make one sick. 3) Sleep Restriction: limiting the amount of time spent in bed rather than lying in bed awake which can become a habit leading to poor sleep. 4) Remaining Passively Awake: avoiding any effort to fall asleep. Worrying that one can’t sleep can keep one awake. 5) Stimulus Control Therapy: helps remove factors that condition the mind to resist sleep. Eg. One is coached to use the bed only for sleep and sex; and, to leave the bedroom if unable to sleep within 15 minutes. 6) Sleep Hygiene: changing basic lifestyle habits that can influence sleep: eg. Smoking or drinking caffeine late in the day; drinking a “nightcap” of alcohol; not regularly exercising; avoid napping; winding-down 2 hours before sleep time. 7) Relaxation Training: learning to calm the mind and body: eg. meditation, progressive muscle relaxation and hypnosis. 8) Biofeedback Training: learning to influence heart rate, skin temperature, muscle tension and skin electrical conduction. 9) Sleep Diary: keeping a detailed record of sleep patterns and influences for 2 weeks.

 

      ADDITIONAL KEYS TO MAINTAINING YOUR MEMORY:

  • Physical Activity and Exercise: Regular exercise is a key to health, wellness and longevity. Regular exercise will help you to sleep better. Exercising increases blood flow to the brain helping to create new brain cells and blood vessels because of the increased Brain-Derived Neurotropic Factor (BDNF). This repairs and protects the brain cells from degeneration, both by repairing and restoring cellular mechanisms. Exercising releases endorphins and other chemicals that dull pain and improve your mood, especially decreasing your anxiety and lightening your depression. This helps with building and maintaining your resiliency.   Regular exercise enhances memory and quicker learning. Your work will be more productive. Also, you’re medical costs will be less. You’ll have decreased risks for developing chronic diseases: for example, you can help to prevent and treat dementias. The increased blood flow reduces toxins that cause aging and cell death, and reduces inflammation.

Some exercise is better than none, and even a little exercise can do you a lot of good. The goal is 150 min/week of aerobic activity. For time-conscious people: High Intensity Interval Training can produce the same results in half the time.  In addition to regular aerobic exercising, Total Fitness is achieved by enhancing your muscle strength, doing regular stretching, and, improving your balance and coordination. Your physical fitness is perhaps the best tool for minimizing cognitive impairment.

          RESISTANCE TRAINING increases your muscle mass, thus, generating more strength, and faster muscle force (power). Unless you over do it, you won’t become muscle bound. Resistance training also helps to make your bones more dense. Ten million Americans (80% are women) have osteoporosis (thin and breakable bones). {A decrease in sex hormones with aging helps to create this common problem.}  Resistance training also helps to improve your metabolism, increase your glucose tolerance (or, said another way, decrease your insulin resistance) and decrease your risks from type 2 diabetes. It also helps to decrease both coronary artery disease and cerebrovascular disease risks. Other than doing free weight lifting or using a dynamic weight resistance machine, such as a Nautilus device, there are various simple ways to do resistance training such as: Yoga, Tai Chi, Pilates, using flexible bands, sitting up and down using a chair and your own body weight, swimming, doing Zumba dancing, doing heavy gardening such as raking and digging, doing vigorous house cleaning, taking the stairs rather than using an elevator, jumping rope, etc. The stronger you are,  the more self-esteem, confidence, and positive thinking you will usually have.  However, because resistance training requires work and effort, only about 20% of people actually follow strength training recommendations. PLEASE DON’T BE LAZY.  Resistance exercises have an even greater impact on cognitive function than aerobic exercises. It increases blood flow to the brain, thus, increasing oxygenation and the provision of nutrients. It helps to promote angiogenesis from existing blood vessels and neurogenesis from stem cells in the hippocampus {an area responsible for organizing memories}. It increases the production of neurotransmitters: serotonin {which helps to regulate mood and sleep}, acetylcholine {which helps with cognition, learning and memory}, and GABA {the main inhibitory modulator}. It also increases neurotropins {proteins that regulate neuron survival}.  [Mavros, et. al. “Mediation of cognitive function improvements by strength gains after resistance training in older adults with mild cognitive impairment: outcomes of the study of mental and resistance training,” J. of the American Geriatric Society, October 2016.]

  • The MEDITERRANEAN DIET: A diet high in fresh fruits and vegetables, whole grains, nuts and olive oil is optimal, along with eating fish and poultry in moderation, and red meat as a condiment. A 2017 study of 6,000 people eating a Mediterranean diet had a 35% decreased risk of cognitive impairment compared with people who didn’t. Remember: what’s good for the heart is good for the brain AND what’s good for the brain is good for the heart. Additionally, the “MIND” Diet optimizes neurological function: A) Focusing on increasing the ten brain healthy food groups: 1) Green leafy vegetables; 2) Other vegetables; 3) Nuts; 4) Berries; 5) Beans; 6) Whole grains; 7) Fish; 8) Poultry; 9) Olive Oil; and, 10) moderately drinking wine. And, B) Reducing or Avoiding brain damaging foods: 1) limiting pastries and sweets to under 5 servings per week; 2) limiting red meats to under four servings per week; 3) limiting cheese to one serving per week or less; 4) limiting butter or margarine to under 1 tablespoon per day; 5) limiting fried/fast foods to under one serving per week.
  • Friends and Family: The social aspect of activities helps with persistence of activities as well as with providing encouraging feedback, which enhances learning new things. {According to Jo Ann Jenkins: AARP Bulletin, June 2018:}  Cognitive health is maintained with building strong social connections, reducing loneliness and social isolation, realizing a sense of purpose, and developing a more positive and optimistic outlook on aging. Social connections are important for health. People with close friends are more likely to get plenty of sleep, eat healthy foods, maintain peace of mind and have less stress, engage in brain healthy activities, and take on new challenges and hobbies. Loneliness is as bad as inhaling 15 cigarettes daily. It can decrease 8 years of life expectancy; decrease one’s quality of life; increase health care consequences and medical bills; and, mortality risk associated with loneliness is greater than for obesity. For many, having a sense of purpose is more important than making money. Having a meaningful life is associated with better health outcomes. And, optimism adds 7 1/2 years to life: people recover from disabilities better; there is a larger hippocampus (associated with organizing memory); there is less anatomic evidence of Alzheimer’s disease on brain MRI scans; and, there is an 80% decreased risk of CVD. The key is to approach each day with a smile of appreciation, and, then, having someone to share one’s purposeful life with.
  • Managing Blood Pressure: High blood pressure damages small blood vessels in the brain, particularly in women, which is associated with dementia. Normalizing BP is very important.
  • Managing Glucose Intolerance and Diabetes: Glycation is the process where sugar molecules react chemically with proteins in the body causing the proteins to cross-link and lose their functionality. Not only does this cross-linking prevent proteins from doing their intended jobs, it creates harmful molecules called Advanced Glycation End products (AGEs). Glycation causes inflammation that damages mitochondria, and mitochondrial dysfunction exacerbates glycation. This results in an age-accelerating cycle as glycated proteins accumulate in tissues throughout the body. Excess blood sugar causes “glycation” which damages enzymes and also damages small blood vessels in the brain. Insulin resistance sets the stage for neurofibrillary tangles and amyloid plaque accumulation. Thus, controlling glycation is very important.
  • Smoking Cessation: Smokers have about a 60% increased risk of Alzheimer’s disease compared with non-smokers. Tobacco increases oxidative stress and produces cell-damaging free-radicals. Quitting smoking helps arteries become healthier within 6-months and helps to reduce strokes, which accelerate dementia.
  • Avoiding Falls: Loss of consciousness for at least 30-minutes and repeated concussions can increase the risk of dementia by 4.5 times. Preventing falls can help the brain as well as help to avoid hip fractures and spinal compression fractures (associated with osteoporosis) which can seriously impair the quality of life and longevity.
  • A Healthy Microbiome: Dysbiosis in the gut is associated with dementia. Healing the gut lining by eating bone broth, fresh fruits and vegetables, fermented foods, and supplementing with a mixture of soil-based spore-forming probiotics and a variety of lactobaccilli and bifidobacteria can keep the gut-microbiome healthy and balanced. I suggest reading the book “Eat Dirt” by Dr. Josh Axe.  
  • Bioidential Hormone Replacement Therapy (BHRT): When BHRT is started with the sex hormones: estrogen, progesterone, and testosterone with menopause (and andropause), cognitive decline can be significantly delayed. Hormones are the strongest tools that we have to promote cognitive vitality: especially, melatonin, oxytocin, and thyroid hormone.

Melatonin helps promote restful and restorative sleep. It helps to decrease aluminum toxicity in the brain, calms nervous agitation associated with “sundowning”, and improves memory and cognitive function. Treatment involves at least 1 mg at bedtime. Sublingual dosing seems to work better than oral dosing. The higher the serum level of melatonin, the better the effects. It often takes 2-3 months for full improvement.

Oxytocin helps one to feel better and to feel cooperative, with decreased aggression, improved eye-contact, and increased facial smiling and flushing. It is the hormone of trust, affection and sociability. {Treatment: The dose is compounded—a  sublingual or nasal spray: 5- 10 IU 1-2x/day can reduce paranoid behaviors, meanness and aggression often accompanying dementias.}

Thyroid hormone helps one to be alert, motivated, and energized. Subclinical hypothyroidism is very common. Symptoms indicative of a low T3: memory is worse early in the morning, and, one is slow to find words (nouns). Treatment with Armour Thyroid to increase the free T3 level will improve blood flow in the brain, increase arousal and alertness, attention and wakefulness, increase brain excitability, increase glucose consumption and brain energy, and decrease brain inflammation. It takes 2 months to note some improvement and 10-12 months for a full improvement.

IGF-1 (associated with human growth hormone), estrogen and testosterone all help with long term memory. If there is a deficiency of IGF-1, there is severe and profound permanent memory loss. There is also a decrease in brain mass. Treatment helps to reverse atrophy, decrease anxiety, and improve both short-term and long-term memory. IGF-1 is inversely correlated with cognitive impairment. A high IGF-1 is linked to increased longevity, decreased cancers, and improved memory and cognition. High IGF-1 levels are linked with increased brain processing speed and increased perceptions. It crosses the blood-brain barrier and is neuroprotective. {Treatment is subcutaneous injections of 0.3-1 mg hs to decrease AD. It takes 2-4 months for initial improvement, then 24-36 months for full improvement. It is recommended that the SQ injections occur around the eyes to be located with vessels near the brain. Intranasal IGF-1 is another effective route through the olfactory bulb to the CNS. It can be used to help decrease infarct size, and repair functions after a stroke.

Vasopressin, pregnenolone, and triiodothyronine (unbound or Free T3) help with short-term memory.  Estrogen therapy decreases the risk of AD by 3 to 7 fold. It improves mood, releases depression, and protects the brain against ischemia. Testosterone helps to decrease hesitations and improve memory loss. Pregnenolone levels are higher in the brain than in the blood. It is a neurotransmitter that improves memory. The dose is 50 mg in the morning. Desmopression nasal spray can be used instead of vasopressin at a dose of 0.1 mg twice per day to help improve short-term memory.

  • BE AWARE:  Microglia are immune cells which shoulder the responsibility for “brain cleanup”. They are rich in lysosomes which breakdown “junk proteins” with bursts of acid. Proton Pump Inhibitors (PPIs) commonly used to manage reflux esophagitis and gastritis pass through the blood-brain barrier and reduce the amount of acid contained in the lysosomes, which means they are less able to clear dangerous proteins which consequently results in cell death, inflammation, and neuronal dysfunction, typical of Alzheimer’s disease. (Eur J Neurosci. 2013;37(12):1949-61.) Even short term use of PPIs impairs cognitive function. In otherwise young, healthy adults, after just 7 days of exposure to a PPI, all had statistically and clinically significant impairment in cognitive functions. Omeprazole (Prilosec) was the worst offender. (Alzheimers Res Ther. 2015;7:79.)  

                           SUPPLEMENTS TO CONSIDER

I follow the principle: “First do no harm.” Alzheimer’s disease is a progressive and devastating problem for patients and their families. While there are no definitive studies for the following suggestions, these suggestions will not cause harm by following them.

A)  Supplements to slow viruses down (Anti-Viral)

  1.  The amino acid Lysine, 1,000 mg to 3,000 mg daily
  2.   Zinc 20 mg/d
  3.   Vitamin C at least 6,000 mg/day to boost your immune system
  4.   Garlic, Grapefruit Seed Extract, Oil of Oregano, and Olive Leaf Extract.

B)  Mitochondrial Support: nutrients to refuel the mitochondrion1. 

  1.  D-Ribose 5 gm/tsp: 1-2 tsp up to 3 times/day
  2.   ALA: 300-400 mg/day;
  3.   CoQ10 200+ mg/day;
  4.   NAD+: 100 mg/day; and,
  5.   L-Carnitine: 2,000-3,000 mg/day. Also,
  6.   Membrane phospholipids (NT factor)
  7.   Glycation can also damage mitochondrial function. Pyrroloquinoline quinone (PQQ) and Taurine can also help to limit glycation and, thus, restore cellular energy. PQQ is a vitamin-like molecule that promotes the production of new mitochondria in cells. Taurine is an amino acid found in high concentrations inside mitochondria where it regulates the enzymes responsible for harvesting energy from food molecules.

C) Memory Support

  1. ***The Ayurvedic herb known as “Brahmi” or “BACOPA” (bacopa monniera) can prevent and treat dementia without side-effects! It is a cognitive enhancer and neuroprotective agent. Studies demonstrate the improvement of new memory acquisition and information retention. Additionally, studies demonstrate improved accuracy for spatial working memory (which is critical for being able to find things and remember where they are). Bacopa also brings a calmness and clarity of mind. The typical dose is 500 mg/day. Studies demonstrate improvement of anxiety. (Also, in patients with schizophrenia, bacopa helps control symptoms.) Like the patent acetylcholinesterase inhibitor medications (such as Aricept and Exelon), bacopa suppresses acetylcholinesterase. It also increases the enzyme activity of the sodium-potassium pump which helps to repair oxidative damage. It has been found to improve memory, concentration, learning ability, reduce irritability, and improve energy and lessen fatigue. Triterpenide saponins and bacosides in the herb improve brain cell communication. Here’s a source for this: himalayausa.com. Another product combining bacopa plus additional complementary Ayurvedic herbs (from the same source) is called “MindCare”. In addition to improving cognitive function, it helps to ease stress and anxiety, combat mental fatigue, smooth digestive symptoms and bring calmness and clarity. The recommended dose is 2 caps twice daily with meals for about $34 per month.
  2. *** I like a proprietary product from LifeExtension.com called “Cognitex” which combines 11 ingredients for brain protection and optimal function. 3 capsules daily contains: a) 600 mg of Alpha-Glyceryl Phosphoryl Choline which boosts levels of acetylcholine, which enables brain cells to communicate. b) 50 mg of Gastrodin which supports healthy levels of blood flow. c) 150 mg of Grape seed extract which boosts brain oxygen flow. d) 20 mg of Vinpocetine which increases circulation and brain cell conductivity. e) 100 mg of Phosphatidylserine which encourages improved concentration. f) 50 mg of Pregnenolone which promotes mental energy. g) Additionally, it includes 150 mg of wild blueberry extract, 125 mg of Ashwagandha extract, 50 mg of Uridine-5-monophosphate, and a blend of Perluxan hops extract and Rosemary extract which helps to facilitate neuron function and communications. Another proprietary product from the same company is called “Dopa-Mind” which is an extract from wild green oats that improves cognitive health and mental performance by inhibiting the MAO-B enzyme which then promotes healthy dopamine levels. Another proprietary product called “Dr. Cass’ Brain Cell Support Plus” from www.puretango.com contains similar compounds that can be helpful: Acetyl-L-carnitine, Cognizin citicoline, Dimethylaminoethanol, Phosphatidylserine, Ginko biloba, Gotu Kola, Huperzine A and Vinpocetine.
  3. ***GINKGO BILOBA extract EGb 761, a dry extract of the leaves standardized to 22% to 27% ginkgo flavonoids has been extensively studied and a dose of 240 mg per day has similar efficacy to anticholinesterase medications currently approved for treatment of Alzheimer’s dementia (eg. Aricept, Razadyne, Exelon, and Namenda). Adverse effects were infrequent and included headache and dizziness. There were no increased bleeding events nor changes in coagulation parameters. Thus, it is an alternative first-line treatment for dementia. Find a supplement such as “Nature’s Way Ginkgold” that matches EGb 761.
  4. ***MELATONIN: Melatonin is a hormone secreted by the Pineal gland in the brain. It influences stage IV sleep and REM dreaming sleep and improves the sleep pattern as well as the depth and quality of sleep. It is a body energizer and a mood enhancer. It affects the body’s circadian rhythms and modulates our immune function. It increases natural killer cells which helps against infections  and helps protect against cancer. Melatonin scavenges and neutralizes free radicals and it possesses potent anti-oxidative effects. After middle age, melatonin levels drop precipitously leaving our brains increasingly susceptible to the growing impact of oxidative damage. Such damage leads to the increased risk of neurodegenerative diseases and stroke and increased vulnerability to the effects of head trauma. A deficiency of melatonin causes poor sleep, irritability, hypersensitivity and anxiety and depression. Profound reductions in melatonin levels have been found in Alzheimer’s disease patients. “Sundowning” and sleep disorders such as insomnia, restlessness, and poor sleep quality occur in about 45% of Alzheimer’s dementia patients. Melatonin crosses the blood brain barrier and reduces inflammation.  When melatonin is supplemented early in the course of the disease, these changes can be ameliorated. Melatonin is an antioxidant and neuroprotective. It can reduce the damage caused by inflammatory amyloid beta proteins and tau proteins. It helps to reduce learning and memory deficits and slow the progression of cognitive impairment. It also prevents the production of alpha-synuclein, an oxidizing and inflammatory protein that accumulates in brain regions that control movement and balance with patients who have Parkinson’s disease. Additionally, it helps to neutralize existing adverse protein molecules for cellular cleanup, and, it helps to restore the normal activity of enzymes involved in dopamine production. It can be purchased over the counter. The “micronized” form is best. Some people find that an under the tongue product works better for them than an oral product. The dose range is 1 to 30 mg. The starting dose is usually 3 mg and the average dose for women is 3 to 10 mg and for men 5 to 15 mg. Vivid dreaming may be a side effect. If melatonin isn’t tolerated, you can support the production with methionine 500-1000 mg in the morning, 5-HTP 50-100 mg twice daily and a vitamin B complex with tryptophan 100-200 mg at bedtime. Improving sleep improves the immune system and improves the overall quality of life.
  5. ***VIRGIN COCONUT OIL: While there are no scientific studies supporting the use of virgin coconut oil, it is a safe and tasty dietary supplement with no side effects. The proposed dose is 2 tablespoons (solid at room temperature) three times per day with meals. This provides an alternative (to glucose) energy source for the brain. This may also benefit other debilitating neurological diseases such as Parkinson’s disease and multiple sclerosis. Reportedly, it bypasses the need for insulin to be able to transport glucose molecules for nutritional energy into brain cells.
  6. ***Magnesium-L-Threonate is a chelated form of magnesium that easily crosses the blood-brain barrier and assists in maintaining neurosynaptic connections, and inhibiting dysregulation of signaling pathways. There are proprietary products from LifeExtension.com called “Neuro-Mag Magnesium-L-Threonate capsules” and another product from www.reddremedies.com called “Brain Awakening” containing “Magtein” (magnesium threonate), Lion’s Mane (a mushroom used in Traditional Chinese Medicine), and “amla”—Indian gooseberry (used in Ayurvedic medicine) which purport stabilizing and improving cognitive function.  Magnesium is the “Great Relaxer”. Over 50% of the population is magnesium deficient due to soil depletion, food processing, and inadequate intake, coffee, tea and alcohol depletion, GI conditions that impair absorption, and medications that cause depletion: such as birth control pills, thiazide diuretics, PPIs, and asthma medications. Magnesium is a co-factor in over 300 enzymes, maintains normal muscle and nerve functions, and is crucial for bone, brain, and heart health. Treatment with magnesium can help relieve headaches, brain fog, muscle twitches and cramps, improve glucose management, alter/improve moods, improve fatigue and muscle weakness, and helps with anxiety and depression. Magnesium stabilizes ATP, signals methylation, and is important for de-toxification supporting glutathione production.
  7. ***Supplementation with Omega-3 fatty acids (7 to 8 gms/day) plus alpha lipoic acid (600 mg/day) slows functional and cognitive decline in Alzheimer’s disease patients. Also, a study in the Journal of Alz. Disease by Nolan, et. al. In June 2018 demonstrated that supplementing with carotenoids plus fish oil improved memory, vision and mood.
  8. ***Hericium erinaceus, commonly called “Lion’s Mane” mushrooms should be a staple in the prevention and treatment of neurological illnesses such as Alzheimer’s dementia and Parkinson’s disease. “Hericenones” are isolated compounds found to be able to cross the blood-brain barrier and stimulate the production of Nerve Growth Factor (NGF). NGF is necessary for brain cells to function and to heal. They also lower cell damage caused by beta amyloid peptide and lessen the apoptosis of neurons and other brain cells. “Dilinoleoyl-phosphatidylethanolamine” (DLPE) is another isolated compound that protects brain cells from oxidative damage in a variety of neurodegenerative diseases. A combined product of hericenones plus DLPE called “amyloban” proved superior to the prescription drug “Donepezil” in memory test of Alzheimer’s disease patients. Additionally, a study of women with mood disorders demonstrated improved standardized tests for depression and anxiety after 4 weeks of using Lion’s mane mushrooms. In a small study, patients with schizophrenia also showed improvement on standardized tests. Healthy subjects reported an improved sense of well-being, energy and mood after using Lion’s mane extract for 2 months. You can find safe, natural and effective Lion’s mane supplements in the form of a pill, liquid extract or powder to add to smoothies or cook with. One source to consider is mushroommatrix.com. Also, check-out writings and YouTube presentations by Paul Stammets.
  9. ***Culinary doses of Sage, Rosemary and Curcumin may preserve memories and alleviate symptoms of dementia. A) SAGE: Salvia officinalis extract: 60 drops/day improved cognitive function and decreased agitation in one small study. In another study, 333 mg/day of sage extract improved thinking, recall and attention. B) ROSEMARY: 750 mg of dried rosemary leaf powder daily improved cognitive function in a small study. The aroma of rosemary’s essential oil improved concentration and cognitive testing performance. C) CURCUMIN prepared from the root of the turmeric plant: 2-8 GMS/day helps to reduce beta-amyloid plaques by pulling apart fibrils and stimulating macrophages to eat toxic accumulations. It is also a potent anti-inflammatory and anti-oxidative agent. There is a combination product called “Sage Memories” that includes 25 mg of lithium, 500 mg of niacinamide and 650 mg of extracts of sage, rosemary and curcumin in 4 capsules/day. This can be obtained on the internet at biotechpharmacal.com or www.tahomadispensary.com. This can be safely used for prevention and for treatment of early Alzheimer’s dementia.
  10. Many people are functionally vitamin B12 deficient. Vitamin B12 is critical for hormone functioning, brain metabolism and in the energy cycle for every cell. With aging, vitamin B12 is poorly absorbed due to a lack of both hydrochloric acid and intrinsic factor in the stomach. Hydrochloric acid in the stomach is needed to release vitamin B12 from foods such as red meat, fish and dairy products, and “intrinsic factor” from the stomach is needed to absorb it. Acid suppressing medications and age impair the release and absorption of vitamin B12, which must be consumed on a daily basis, because it is water soluble, and eliminated if not utilized. Most people over age 40 are vitamin B12 deficient. {Use of Proton Pump Inhibitors and Histamine type 2 Blockers for acid reflux and for gastritis can also create a vitamin B12 deficiency.} An imbalance in the gut flora can also inhibit absorption. The medication Metformin, which is commonly used to manage type 2 diabetes, interferes with the absorption of vitamin B12. {A combination of these medications can make the situation even more likely and worse.} On a complete blood count (CBC) a mean corpuscular volume  (MCV)  >90 suggests a functional vitamin B12 and/or folate deficiency. NOTE: A serum vitamin B12 level can be in the normal range or high even while intracellular levels and especially central nervous system levels are low!!  Methylcobalamin is the most biologically active form of vitamin B12 that can cross the blood brain barrier without biotransformation to nourish the brain. Additionally, its methy group stimulates the neurotransmitter serotonin’s creation to enhance moods and it also protect against toxins damaging the brain. Methylcobalamin protects against glutamate-induced “excitotoxic” neurologic damage. Acute low vitamin B12 levels can manifest as mood changes: lack of motivation and feelings of apathy; mental fogginess, memory impairment, muscle weakness, and fatigue. Chronic low vitamin B12 levels can cause nerve damage, dementia and psychiatric problems that can mimic mental illness such as bipolar disorder, severe depression, paranoia or schizophrenia. Only about 12% of a dose of the cheaper, manufactured form of vitamin B12 called cyanocobalamin  is converted to the active form, and, the liver must detoxify the cyanide molecule binding it.  I restrict using cyanocobalamin to monthly injections to avoid accumulation of the cyanide moiety.  A case can be made for monthly up to weekly injections of Methylcobalamin. for anyone over 70 years old, and certainly sublingual vitamin B12 lozanges should be taken daily.  Additionally, you would need to take oral Folate 1 mg daily (NOT the oxidized synthetic form of folate known as “folic acid”). or the methylcobalamin injections can be compounded with 400 mcg Folate. The Folate may be part of a multivitamin/mineral complex.  Note: sunlight will destroy the natural forms of Folate: methylfolate, and folinic acid. Good food sources of Folate include: spinach and other deep green leafy vegetables, brewer’s yeast, beans (especially lima beans), cantaloupe, watermelon, wheat germ, and liver (from organically raised animals). Folate insufficiency and deficiency is a risk factor for skin cancer, colon, breast and other cancers.
  11. The development of cognitive decline may be linked to oxidative damage. The antioxidant properties of mixed tocopherols and tocotrienols might be helpful in reducing oxidative damage in the brain. Foods that contain forms of vitamin E include: wheat bran, oat oil, coconut oil, grapeseed oil, meats, eggs, avocados, carrots, cauliflower, blueberries, almonds, and grapes. The best known source is palm oil, rice bran and oats. 100 to 200 mg daily as a supplement up to 1000 mg daily is safe. It is best absorbed when taken with food and separated in time by several hours from taking mixed tocopherol vitamin E.
  12. Consider using Niacinamide (vitamin B3) 1 gm three times per day. Anticipate symptom improvement within 3 to 4 weeks. This treatment is very safe and only occasionally a person may experience nausea. The nausea usually resolves by reducing the dose to 500 mg three times per day. (Incidentally, niacinamide has been used along with vitamin C to help treat schizophrenia.)
  13. Consider using lithium orotate or lithium aspartate 10 mg to 20 mg daily. Low dose lithium can remove aluminum from tissues for excretion from the body. It is speculated that aluminum toxicity is a factor in the development of Alzheimer’s dementia. Also, it can stimulate the growth of brain grey matter. (In an observational study, people with bi-polar disorder using lithium had half the risk of developing dementia as the group not using lithium.)  When using lithium, take flaxseed oil 1 tbs 1-3x/day plus mixed tocopherol Vitamin E 400 to 800 IU per day in order to avoid any possible toxicity. Naturally occurring mineral water containing lithium salts (lithium carbonate and lithium chloride) known as “Lithia water” has many testimonials to its health benefits. Some research demonstrates neuro-protective benefits of lithia water {Stroke 2003;34:1287-92.} Drinking lithia water improves mood and cognition {Biological Trace Element Research 1994;40:89-101.} Communities with naturally occurring lithia waters have lower suicide rates, mental hospital admissions, incidence of crime, and arrests related to drug addiction {British J of Psychiatry 2009;194:464-5.} Long term lithia water consumption is associated with increased life expectancy {Eur J Nutrition 2011 Feb;50(5):387-9.}
  14. Berberine reduces the damage caused by beta-amyloid and reduces cognitive impairment. It also inhibits cholinesterase (similar to Aricept). Consider using 500 mg three times per day. (A high quality product can be obtained from tahomadispensary.com). Some people experience GI discomfort for the first 4 weeks of treatment including diarrhea, flatulence, constipation and crampy pains. Reducing the dose to 300 mg three times per day and then gradually increasing it back to 500 mg three times per day can help resolve these side effects. Also, because berberine isn’t well absorbed from the GI tract, because it isn’t very soluble in water due to P-glycoprotein, taking it along with milk thistle, which is a natural inhibitor of P-glycoprotein, approx. 100 mg (S. marianum containing 60% flavolignans) improves absorption. (Incidentally, milk thistle is good for protecting the liver. Milk thistle extract 600-800 mg/day can benefit any associated liver disease. A product called “European Milk Thistle” from www.LifeExtension.com combines milk thistle extract with phosphatidylcholine to improve absorption of the important component “silybin” which doesn’t dissolve well in water.)
  15. SAFFRON (the spice):  a minimum of 15 mg twice per day: after a 16 week trial it proved to be safe and effective for mild to moderate dementia and was equally effective as Aricept for improving cognitive function scores.
  16. A molecule found in Green Tea, epigallocatechin-3-gallate (EGCG), prevents the mis-folding of specific brain proteins:  the metal-associated-amyloid-aggregates associated with Alzheimer’s disease. It also broke down existing aggregate structures in the proteins that contained the metals: copper, iron and zinc.
  17. Compounds in Cinnamon (cinnamaldehyde and epicatechin) reduce the aggregation of tau protein and beta-amyloid.  A derivative of cinnamon called MHCP (methylhydroxychalcone polymer) can also help prevent Type 2 diabetes as well as treat Type 1 and Type 2 diabetes. Any whole cinnamon product can be used if you are prepared to extract the desired water soluble fraction from the fat soluble fraction (which may be carcinogenic and genotoxic in large concentrations.) Anyone planning to use a 1 teaspoon of whole cinnamon daily should first boil it in water and then pour off the watery solution through a cheese cloth for use, discarding the solid remainder which contains the fat soluble fraction. OR, purchase MHCP from a health food store. A brand name product to consider is “Insulife” which contains the equivalent of 1 tsp of whole cinnamon along with chromium and other nutrients to be taken once per day in order to decrease insulin resistance. Choosing the right type of whole cinnamon IS important. Studies show that using Cinnamomum cassia or C. aromaticum  (Chinese cinnamon) is much preferred to the more common Cinnamomum zeylanicum (Ceylon or sweet cinnamon). The effective dose is 120 mg/d of the cassia extract.
  18. Carnosine can help to reduce oxidative stress and prevent oxidative damage that can cause cellular dysfunction resulting in memory loss. Carnosine lowers blood sugar and insulin levels, blocks oxidative and glycation-induced tissue damage, enhances cardiac muscle function and the quality of life in patients with CHF, and improves cognitive function.   The dose is 500 mg twice daily.
  19. ***Resveratrol can counteract the acetylation of tau proteins. Acetylation causes the tau proteins to collect and stick together leading to the development of neurofibrillary tangles commonly found in the brains of Alzheimer’s disease patients. Resveratrol can also activate the SIRT1 proteins and reduce inflammation and the activity of cell-damaging reactive oxygen species. Resveratrol can buffer damage by accumulated glutamate and quiet glial cell activation. It can benefit Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). Resveratrol has no specific dose guidelines—10 mg is effective and high doses are safe. Although a high content is found in red grapes, the best source for Resveratrol is eating boiled peanuts.
  20. ***Pyrroloquinoline quinone (PQQ) can help to protect memory and cognition, promotes brain cell survival, and stimulates the formation of new mitochondria and improves the function of existing mitochondria. It also improves gait disturbance seen with Parkinson’s disease. It decreases brain inflammation and lowers the inflammatory markers C-reactive protein and interleukin-6. It stimulates the production of nerve growth factor that supports neurons by maintaining their plasticity and leads to formation of new nerve cells. It also protects nerve stem and progenitor cells from oxidative damage. Using PQQ reduced the size of brain damage associated with an ischemic stroke, even when administered after the stroke, and improved neurobehavioral scores. It reduces excessive glutamate stimulation of brain cells, excitotoxicity, which triggers apoptosis and is a factor in the development of neurodegenerative disorders, stroke and schizophrenia. People with diabetes are 60% more likely to develop dementia. PQQ helps protect the brain against damage caused by high blood sugar. PQQ also reversed the toxicity of beta amyloid proteins and alpha-synuclein, reducing oxidative damage caused by these malformed proteins. Recommended supplementation is 20 mg daily. It is best when combined with CoQ10 100 mg daily. Products are available from LifeExtension.com.
  21. Vinpocetine (a periwinkle extract): It is beneficial for alertness, concentration, memory support and cognitive function. It improves circulation, increases levels of ATP/cellular energy in neurons, improves the brain’s utilization of glucose and oxygen, (in animal studies) accelerates the rate of learning by 40%, improves short-term memory, and increases the length of time that short term memory is retained. Additionally, it improves the circulation to the eyes, improving visual acuity; improves impaired hearing, vertigo and tinnitus; and, improves red blood cell flexibility that may help to prevent strokes. It activates the noradrenaline nerve cluster, the locus coeruleus, in the reticular activating system to improve alertness. It has a very low side-effect profile. The usual dose is 10 mg to 30 mg daily—typically 10 mg three times per day has been found to be most beneficial. While benefits can be noted  after only a few days of therapy, maximum benefit is seen when used for 3 months. High quality, pharmaceutical grade vinpocetine from Europe (rather than from China) can be obtained from TargetedNutrients.com.
  22. Another proprietary product from TargetedNutrients.com is called “AMG” which combines the brain nutrients adenosine triphosphate, methylcobalamin and glucoronolactone.  Adenosine Triphosphate (ATP) is the primary source of cellular energy which the brain requires in prodigious amounts daily, more than any other organ. Additionally, ATP is required to accompany neurotransmitters for them to be functional. The glial cells (neuron regulators) use ATP to communicate. With inadequate ATP you will feel irritable, tired and depressed, have poor mental functioning, and it will seem like the burdens of stress are causing significant wear and tear. Methylcobalamin is the most biologically active form of vitamin B12 that can cross the blood brain barrier without biotransformation to nourish the brain. Additionally, its methy group stimulates the neurotransmitter serotonin’s creation to enhance moods and it also protect against toxins damaging the brain. Acute low vitamin B12 levels can manifest as mood changes: lack of motivation and feelings of apathy; mental fogginess, memory impairment, muscle weakness, and fatigue. Chronic low vitamin B12 levels can cause nerve damage, dementia and psychiatric problems that can mimic mental illness such as bipolar disorder, severe depression, paranoia or schizophrenia. Hydrochloric acid in the stomach is needed to release vitamin B12 from foods such as red meat, fish and dairy products, and “intrinsic factor” from the stomach is needed to absorb it. Acid suppressing medications and age impair the release and absorption of vitamin B12, which must be consumed on a daily basis, because it is water soluble, and eliminated if not utilized. Most people over age 40 are vitamin B12 deficient. Only about 12% of a dose of the cheaper, manufactured form of vitamin B12 called cyanocobalamin  is converted to the active form, and, the liver must detoxify the cyanide molecule binding it. Glucoronolactone promotes brain energy, enhances mental clarity and induces a mild euphoria. It reduces sleepiness, increases focus, lightens the mood, quickens reaction time, enhances stamina, and produces a sense of well-being. It is produced in the liver from glucose, and can be found in a variety of plant gums and other natural sources, including wine.
  23. The amino acid Taurine  protects the brain from toxic chemicals, stimulates new brain cell formation, prevents brain cell death following a stroke helping to preserve neurological function, decreases the effects of toxic beta amyloid proteins, and improves blood sugar control. Additionally, studies suggest that Taurine can defend liver cells against free radicals and toxins, helping to reduce oxidative stress-induced liver injury that helps both alcohol induced liver disease and NAFLD.  Patients with chronic hepatitis taking 2 gm taurine three times daily for 3 months decreased serum markers of liver damage, markers of oxidative stress, and hyperlipidemia. A typical dose is 3 to 6 gm daily.
  24. Quercetin is a plant flavonoid that can help protect the body and mind against pathological effects of pesticide exposure. Quercetin protects brain cells from excitotoxicity and reduces toxicity of beta amyloid proteins that accumulate. Glutathione is activated which protects against free-radicals. Quercetin increases brain expression of protective paraoxonase 2 which scavenges free radicals that damage mitochondrial membranes and cause them to lose their electrical potential. Quercetin limits brain cell death that produces neurodegenerative diseases. The typical dose is 150 mg to 400 mg/d. A combination of quercetin with resveratrol provides complimentary health benefits. Quercetin inhibits pesticide damage by preserving energy, fatty acid, and sex hormone metabolism, inhibiting oxidative stress, protecting against DNA damage, and preserving kidney and liver function.  NOTE: Pesticides are found in our food, air and water. Systemic pesticides mixed in with fertilizer and absorbed by plants through their vascular systems are impossible for consumers to wash off. Pesticides can result in conditions ranging from learning disabilities to Parkinson’s disease to cancers. Organophosphate pesticides lead to microtubule derangements and tau hyperphosphorylation—a hallmark of Alzheimer’s disease. Serum levels of DDE (a metabolite of DDT) were 3.8 fold higher in patients with Alzheimer’s disease. Similarly, 76% of patients with Parkinson’s disease (compared to 40% without disease) had detectable levels of the pesticide beta-hexachlorocyclohexane (beta-HCH).
  25. CAT’S CLAW (Uncaria tomentosa): is from the Amazon rain forest with antioxidant and anti-inflammatory oxidole alkaloids in the bark which stimulate the immune system and polyphenols that impact neuroinflammation: Plaque-Tangles-Inflammation (PTI) for memory improvement {which seems to support the amyloid-beta hypothesis of AD: where plaques come first, then tangles, then inflammation, then microglia release cytokines which cause neuronal impairment and death.) Cat’s Claw is a natural inhibitor for the degeneration process. It decreases neuro-inflammation, decreases astrocytes and microglia, and improves memory. Focus and concentration are improved. {Alan Snow, PhD, “Memory Improvement with Cat’s Claw”, at the A4M conference 12/13/2018.}

                          ADDITIONAL CONSIDERATIONS

Studies in China have demonstrated efficacy for using intranasal near infrared red (NIR) LED light (810 nm pulsed at 10 Hz). The LED is inserted into the nostril and clipped to the nasal ala and used for 25 to 30 minutes per day, up to twice daily in patients with severe symptoms. There are no adverse side-effects. The Vielight 810 infrared LED (cost about $500) has deeper brain penetration than the 633 red (Qi-light—cost about $300). Both light systems have demonstrated improved cognitive function in patients with Alzheimer’s dementia, Parkinson’s disease, and after cerebral infarctions (strokes) and traumatic brain injury. Reportedly NIR can also help with insomnia, migraine headaches, mild cognitive decline, nasal allergies and acne. Depending on the severity of symptoms, results can be noticed from 10 days to several months. The light can destroy beta-amyloid plaques in Alzheimer’s disease and  lower serum 3-cholecystokinin-octapeptide levels in Parkinson’s disease.

          Near infra-red light acts like the red light spectrum for optimizing health. For Example:  MACULAR DEGENERATION:  Exposure to ultraviolet solar rays accelerates age-related visual loss. Wearing UV protective sunglasses outdoors can minimize this damage. Our round-the-clock use of smartphones and computers exposes our eyes to unnaturally high amounts of blue light which can damage the retina and other parts of the eye. Chronic exposure to blue light is associated with increased risk of developing age-related macular degeneration. Retinal damage is irreversible, so early and powerful protection is our only hope. Supplementing with multivitamins and xanthophyll carotenoids that include lutein, zeaxanthin, and meso-zeaxanthin can help to mitigate this loss. {Lancet. 2012;379(9827):1728-38.} They shield light sensing cells from photochemical damage and slow inflammatory reactions that aggravate light-induced damage, and can prevent development of blood vessel overgrowth that produces “wet” macular degeneration, (the leading cause of age-related blindness.) “MacuGuard” is available from www.LifeExtension.com.

Telomerase maintains telomere length; promotes lifespan; protects mitochondria from oxidative stress, and increases the survival of highly active cells, like neurons. The loss of telomerase can be slowed by using Omega-3 fatty acids, resveratrol, Vitamin D3, and curcumin, and by decreasing homocysteine levels.

According to literature and studies sponsored by the manufacturer, so please consider that there may be an economic influence, the only supplement found (so far) that increases telomerase is a proprietary product called “TA-65” from www.tasciences.com. It is derived from Astragalus membranaceus or “Huang Qi”. Astragalus is a nutritional supplement that has been shown to support immune health, and to help reverse some of the signs of cellular aging. It is a foundational herb in Traditional Chinese Medicine traditionally used to support energy levels and immune function. It contains Astragalosides (antioxidants), which support the integrity of the respiratory tract. The extract is predominantly the molecule cycloastragenol. In addition, the polysaccharides found in Astragalus are known for their immune supporting properties. Astragalus herb also supports deep immune functions by promoting normal levels of specific immune cells, and aids in their function. Astragalus appears especially effective when immune function is stressed by environmental or endogenous challenges.

Increasing telomerase prevents the constant erosion of our telomeres, and our lives, increasing our life span and our health span. Reportedly, TA-65 helps to protect the brain and the memory associated with short telomeres; protects the cardiovascular system by improving plaque stability; and, it is antiviral. It helps to improve glucose tolerance and decrease insulin, increases bone mineral density, reduces inflammation, decreases cytotoxic killer cells, improves BP, and reduces homocysteine levels. It reportedly improves the Metabolic Syndrome in 12 weeks. It also increases the function of the retinal pigment epithelium, thus, helping with macular degeneration. It decreases the number of senescent T-cells, and increases the number of naïve T-cells.

Additional things that can help to stabilize and/or increase telomere length include: the Mediterranean Diet, meditation and yoga, aerobic exercise, improved air pollution, decreasing ionizing radiation exposures, and, decreasing oxidative stress. (Older people are more vulnerable to radiation exposure because of telomere loss.)

Increasing telomerase will reportedly NOT increase cancers. (However, please note that cancers have an elevated amount of telomerase activity which helps to explain their immortality.) Short telomeres will increase the risk of cancers. Anecdotal reports say TA-65 has high bioavailability; improves presbyopic (age related decline in) near-vision, increases energy, increases attention and memory, improves peripheral neuropathy, increases aerobic capacity, decreases viral infections, decreases basal cell skin cancers, improves skin elasticity and coloration. Telomere length can be checked at UCLA Immunology Testing for about $350 with results in 10-14 days. There is no difference in the bioavailability of capsules vs. tablets. A standard dose is a 250 mg cap 1-2x/day. It should be taken on an empty stomach.

A 12 month study of 97 people showed the placebo group lost telomere length while the group taking 250 units of TA-65MD daily significantly increased the length of their telomeres. {Rejuvenation Research; 2016;19(6):478-484, and, Pinglira, et. al., Aging and Disease; 2017 Dec;8(6):868-886.} It helped prevent cognitive decline, decrease oxidative stress, stabilize and/or activate telomerase, improve macular degeneration, and, elongate telomeres which results in an increased lifespan. In a study with people infected with cytomegalo-inclusion virus (CMV) they had 2 times the increased degeneration of their telomeres vs. CMV negative people. Treatment with TA-65 increased their telomere length.

          BLUE (LED) LIGHT PROTECTION:  {According to a presentation by Dave Asprey called: “A Systems Approach to Metabolic Aging Through the Eyes,” at the A4M  International Congress in Las Vegas, 15 Dec 2018:}  Like food, light can be both a both a nutrient and a drug. Light exposure changes our biology and affects our cognitive function. The blue spectrum of light is like the high-fructose corn syrup of vision. Exposure to blue light increases insulin resistance, increases body fat weight, increase the incidence of CVD and strokes, and disturbs sleep. The dominant light spectrum in LED lights is blue. LEDs have economically replaced most incandescent light bulbs, and they dominate TV and computer screens and cell phone screens. Blue light hurts the eyes, slows mitochondrial function and decreases sleep quality. Blue light adversely affects the circadian rhythms, reduces melatonin release, decreases mitochondrial growth, increases depression and seasonal affective disorder (SAD), increases cancer risks, and increases anxiety.The red spectrum of light upgrade brain functions, energizes cells, and slows aging. Mr. Asprey advise everyone to wear orange colored glasses indoors to block out excessive blue light exposure. It will decrease eye stress, increase energy, improve blood sugar regulation, and improve sleep. The main effect of blue light is upon the mitochondria. It produces aging: increasing free radicals, damaging mitochondrial DNA, causes retinal ganglion cells melanopsin receptors to self-destruct—resulting in an increase in macular degeneration. Use red light bulbs after sunset, especially if you need to be up and functioning late at night, in order to protect your eyes, and help you to eventually sleep. Red lights also help to quickly resolve jet lag. Additionally, supplementing with bilberry extract, lutein, and astaxanthin in Krill Oil can also help to protect your eyes. Also, use red light strips or a red light bulb in your office to improve the ratio of blue to red light wavelengths. You will notice a decrease in your pain and inflammation, improved collagen density in your skin with decreased skin roughness, a reversal of photo-aging of your skin, increased nitric oxide production, and a rescue of neurons from apoptosis.

METFORMIN is a prescription medication with neuro-protectant properties. It activates AMPK: a cellular energy regulator. It reduces levels of an enzyme that generates beta-amyloid proteins; decreases the harmful effect of beta-amyloid on brain cell function; reduces levels of alpha-synuclein that causes damage in Parkinson’s disease; prevents the loss of dopamine-producing brain cells and improves motor coordination. In a 2016 study {J. Alzheimers Dis. 51(2):501-14}, older adults with mild cognitive impairment using Metformin 1,000 mg twice daily for 12 months had improved memory recall.

15 mg Nicotine patches, used with patients for 6 months who had early stages of Alzheimer’s disease, had neuroprotective effects with improvements in attention, memory and psychomotor speed, with excellent safety and tolerability, compared with using a placebo. While the many chemicals in tobacco (including anabasine, nornicotine, anatabine, cotinine, myosmine, and acetaldehyde) are highly addictive, pure nicotine is generally not addictive.

THIS IS VERY CONTROVERSIAL:  Based upon an hypothesis that autism, Alzheimer’s disease, Parkinson’s disease and other degenerative diseases of the brain are aggravated by mercury toxicity (found in thimerosol, formerly used in vaccinations as a preservative, and  older dental amalgams), a protocol has been developed by Dietrich Klinghardt, MD. He first recommends avoiding allergens and toxic foods in the diet such as gluten, dairy, and processed foods. Then, he adds sublingual vitamin B12 and folate to restore methylation which protects cells from toxins, including mercury. Most people’s immune systems can detoxify some mercury. However, 20% of the population has a genetic methylation defect which compromises their ability to detoxify mercury. He also recommends supplements to restore cellular metabolism {discussed in the book “The Puzzle of Autism” by Dr. Amy Yasko}. Finally, he adds transdermal-2,3-dimercapto-1-propanesulfonic acid (TD-DMPS) to chelate and eliminate mercury (and lead) from the central nervous system. {NOTE: if using TD-DMPS, take a balanced mineral supplement to replenish nutritional metals like zinc, copper, and molybdenum. It can be obtained from College Pharmacy at 866-828-8203.}

[Also, see my handout on “Toxin Management”]

A Potential New Test For AD:  The researchers analyzed the participants’ blood for a protein called neurofilament light chain that is released when brain cells disintegrate. The people with a gene for early Alzheimer disease had higher protein levels when first tested. Moreover, their levels of neurofilament rose steadily over time. The other participants had steady low levels of the protein.

Differences in the protein were detectable sixteen years before the expected onset of symptoms. Rapid increases in neurofilament light chain levels were also linked to brain shrinkage visible on scans. This preliminary test is not yet ready for clinical use, but the authors hope that it will someday allow doctor to diagnose Alzheimer disease when intervention might still make a difference.  {Preische et al, Nature Medicine, Jan. 21, 2019;  reported in The People’s Pharmacy, 1/25/2019.}

Optical Coherence Tomography Angiography (OCTA)– a tool for the early detection of AD:  {Reported by Yoon, et. al. Opthalmology Retina, on line March 11, 2019} Researchers at Duke Eye Center reported that by using OCTA imaging people with AD had fewer fine blood vessels and one layer of the retina thinner than people with mild cognitive impairment and with healthy cognitive functioning. This replicates a study done at the Goldschleger Eye Institute at Sheba Medical center in Israel. It is an early way to detect AD.

 

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