It was long believed that neurons in the human brain were incapable of growth and repair after maturity. We now know this to be false and that the human brain retains the potential for self-renewal throughout our lives. Even more exciting is that self directed neuroplasticity is a real possibility.
Neuroplasticity: The ability of the brain to form and reorganize synaptic connections, especially in response to learning or experience or following injury. Even more exciting is that self directed neuroplasticity is a real possibility.
Neurogenesis: is the process by which neurons are generated from neural stem cells and progenitor cells.
Brain-derived neurotrophic factor (BDNF): A growth factor encoded by the BDNF gene that promotes both neuroplasticity and neurogenesis.
Much to the chagrin of the pharmaceutica industry, there is no “silver bullet” for preventing and reversing cognitive decline and diseases like Alzheimer’s and Parkinson’s. Instead, what we do have is “silver buckshot” in the form of numerous dietary and lifestyle interventions that can increase the body’s production of BDNF.
Things you can take to increase neuroplasticity, and neurogenesis and BDNF levels include:
- Exercise and movement (e.g. 10,000 steps per day)
- High Intensity Interval Training (HIIT)
- Ample high quality sleep
- Healthy diets mediterrainin diet, high fruits, veggies, antioxidants, EFA’s, prebiotics (fiber), and limited carbohydrates, fats and red meat.
- Social interaction and learning new things
- Relaxation and Reducing and manging emotional stress
- Probiotcs 50-Billion CFU 2x/day
- Reduce inflamaiton with Turmeric/Curcumin
- Herbs like Ashwaganda root and Cats Claw
- Nicotinamine Riboside, 125mg 2x/day
- DHA/EPA (from fish oil) 2000-3000 mg daily
- R-lipoic acid (RLA): a fat soluble antioxidant 100mg 2x/day
Let’s review some key brain anatomy related to memory, stress, emotional processing, anxiety and vigilance:
The Limbic System: A complex set of structures that lies on both sides of the thalamus, just under the cerebrum. It includes the hypothalamus, the hippocampus, the amygdala, and several other nearby areas. It appears to be primarily responsible for our emotional life and has a lot to do with the formation of memories. This system is reponsible for maintaining what is called the “Limbic System Trauma Loop.”
Hypothalamus: the Grand Central Station of the brain located just below the thalamus. It sits just inside the optic nerve tracts and just above the pituitary gland. The hypothalamus maintains homeostasis–returning various bodily functions to their set points like a thermostat. The hypothalamus is also responsible for regulating hunger. Leptin is a hormone released by fat cells when we overfeed. The hypothalamus senses the levels of leptin in the bloodstream and responds by decreasing appetite. It also governs thirst, pain response, pleasure, sexual satisfaction, anger and aggression. Even more basic to life, the hypothalamus governs the of autonomic nervous system manages pulse, blood pressure, breathing, and arousal in response to emotional circumstances.
Amygdala: These are two almond-shaped masses of neurons on either side of the thalamus at the lower end of the hippocampus. The amygdala processes survival-related info and encodes emotional memory. It categorizes incoming information into 2 distinct categories, safe or unsafe. The Amygdala responds immediately to both our internal and external environment. When stimulated electrically, animals respond with fear and aggression. If the amygdala is removed, animals get very tame and no longer respond to things that would have caused rage, fear, and sexual response. Prenatal and postnatal maternal depressive symptoms and cortisol (the primary stress hormone) are both associated with larger right amygdala volume (in girls, but not in boys). Cortisol secreted by the adrenal glands is secereed in response to real and perceived stress. This stress hormone readily crosses the blood brain barrier. Once there it affects the amygdala and effects our sense of the salience of events, thoughts and emotions. This is part of how stress makes us feel that even truly trivial events are of overwhelming importance; it creates a false sense of urgency.
Hippocampus: is a small organ located within the brain’s medial temporal lobe and forms an important part of the limbic system, the region that regulates emotions. This region is necessary for forming memories and associations. The hippocampus processes and stores information. The hippocampus is associated with processing sensory information and helps store process short and long-term memory. The organ also plays an important role in spatial navigation. The hippocampus is particularly sensitive to the effects of cortisol, and this is why chonic stress is detrimental to memory and emotional regulation.
Frontal lobes: Initiates thoughts and behavior, planning for the future, abstract conceptualization and helps to modulate emotional responses.
The prefrontal cortex (PFC): is closely linked to the limbic system and lies in front of the motor area of the frontal lobe. It is involved in thinking about the future, making plans, and taking action, it also plays a part in both pleasure and addiction. The Ventral Medial Prefrontal Cortex (vmPFC): processes risk and fear and plays a role in the inhibition of emotional responses, and in the process of decision making. People who have a lot of anxiety or other overwhelming emotions would do well to strengthen the PFC. The human brain has a “negativity bias” meaning we remember and focus on the negative more than the positive. This is from millenia of evolutionary success through avoiding life’s proverbial “sticks” more than celebrating the times when we find the proverbial “carrots”. This is one more reason that it is very helpful to consciously engage the PFC to calm down the brain’s anxiety center, the anygdala.
Cingulate Gyrus: The pathway from the thalamus to the hippocampus, responsible for focusing attention on emotionally significant events, and for associating memories to smells and to pain. It acts as the gaurd at the gate feeding information to the amygdala.
Anterior Cingulate: The anatomical brain pathway connects the limbic system to the frontal lobe and allows the frontal lobe to modulate emotions like anxiety, anger. This a pathway worth strenthening if persistant worry and anxiety is overwhelming.
The Locus Ceruleus (LC): is a nucleus located in the brain stem. It is primarily responsible for the body’s responses to panic and stress. The LC is a major wakefulness-promoting nucleus, resulting from dense excitatory projections to the majority of the cerebral cortex that relate to cholinergic, serotonergic and GABAergic centers of the brain. Activation of the LC thus results in the enhancement of alertness through the innervation of these varied nuclei.
Why are some people more sensive to trauma and more likely to develop PTSD than others?
A lot of people experience trauma, but we now know that only a small subset of those people are likely to develop clinical PTSD. What this means is that individual susceptibility to developing PTSD is more important than the experience of trauma itself. Exposure to high levels of maternal cortisol en utero tends to increase the size and function of the amygdala (increasing tendencies for anxiety and hypervigilence), and decreasing the size of the hippocampus (decreasing emotional regulation) and the anterior cingulate (decreasing the ability of the prefrontal cortex to modulate emotions).
What causes Alzheimer’s disease (AD) and can we slow and possibly reverse it?
A frightening public health fact is that About 15% of people alive today will develop Alzheimer’s disease (AD) in thier lifetimes. It is now considered the 3rd leading cause of death in the US, and is of greater concern than cancer in the elderly population. That concern is based in reality. Woman in America today have a greater risk of developing AD than breast cancer. AD is caused by the the accumulation of beta-amyloid protiens tangles around the neurons in the brain. What’s suprising is that the beta amyloid protien is actually a protective response of our innate immune response to 3 different common brain insults: inflammation, trophic withdrawal, and toxic exposures. It is easy to point the finger at Amyloid beta as the problem. However, like most natural processes in the body, it has, or at least had a purpose in the evolutionary environment. Amyloid beta is produced as an endogenous antimicrobial that protects the brain from infection–that was a lot more common in our evolutionary environement.
We are learnign more about which patients are at greater risk of developing AD. Patients with the APOE-4/x (heterozygotes) gene and 4/4 (homozygotes) genetics are of much greater risk od developing AD. APOE-4 is the oldest version of the gene and dates back to hominids 7 million years ago. By comparison, APOE-3 is only 220,000 years old, adn APOE-2 is just 80,000 years old. The APOE-4 genetics were actually a big advantage to our primitive forebears. They were exposed to significantly more injury and infection (and exercise and clean food, air, and water). There are 75 million US residents with 4/x genes (~25% of the gene pool) and 7 million have the more serious 4/4 genetics (~2.25%). We used to think that APOE-4 was simply a “fat bucket” that carried cholesterol around the body and cells. This is true and we also now know that ApoE-4 crosses into cell nuclei and binds to the promoter region of 1,700 genes, including genes that have profound effects on inflamation, glucose regulation, nerve growth factors, aging, and cell death.
Here are some more facts about ApoE-4:
- 0 copies (e.g., ApoE3/3 or 2/3) = 9% lifetime risk of AD.
- 1 copy ApoE4 (heterozygous) = 30% lifetime risk (75 million Americans).
- 2 copies (homozygous) = 50-90% lifetime risk (7 million Americans).
- ApoE4 increases inflammation, thus increases risk for AD but reduces risk for parasite-associated dementia, and also may reduce risk for type 3 AD.
- ApoE4 Affects Rx regarding diet, fasting time, fat absorption, lipid profile effects, treatment of inflammation, etc.
- This means that it is critical to identify early and prevent or reverse cognitive decline of AD in ApoE4 patients.
Five major risks and subtypes of AD include:
- Type 1 AD: Inflammation be it infectious (e.g., from bacteria, biofilms, parasites, viruses) or sterile (e.g., Omega 6 fats, oxidative stress, AGE-modified proteins).
- Tyupe 2 AD: The withdrawal of “trophic support” (e.g., nerve growth factors like BDNF & NGF, age related estradiol & testosterone declines, vitamin D, etc.).
- Type 1.5 AD: glycotoxic (type 1.5), in which the advanced glycation endproducts (AGEs) cause inflammation and the insulin resistance leads to trophic withdrawal signaling.
- Type 3 AD: Exposure to toxins, such as divalent metals (e.g., mercury, cadmium).
- Type 4 AD: sleep apnea (75% of which is undiagnosed), and vascular insufficiency
- Type 5 AD: Trauma which can lead to inflammation, trophic withdrawal, and toxic exposures.
Amyloid Precursor Protien (APP) is a mediator molecule in the brain that can go either being trophic & synanptoblastic (i.e. helpful to brain function) or anti-trophic & synaptoblastic (promoting the development or AD).
- Synaptoblastic APP products: sAPPa, aCTF.
- Synaptoclastic APP products: sAPPb, Ab, Jcasp, C31.
The probability of probabilty of developing AD is the sum of an individuals (synaptoclastic signals) devided by their (synaptoblastic signals). Therefore the goal in AD prevenmtion and reversal is to reduce all synaptoclastic signals, and increase all synaptoblastic signals.
Major synaptoclastic (i.e. bad) signals include: NFkB and other inflammatory mediators, homocysteine, PAMPs/DAMPs, trophic withdrawal, toxin exposure.
Major synaptoblastic (i.e. good) signals include: resolvins, anti-inflammatories (e.g., omega-3), neurotrophins (BDNF, NGF, NT-3, GDNF, etc.), hormones, vitamin D, toxin reduction, nutrients.
APP is a molecular switch, with prionic loop amplification. The beta amyloid actually begets more of itself, through interaction with APP—thus it is prionic (makes more of itself by inhibiting the production of the good synaptoblastic APP products. The positive news is that The same goes for the good (synaptoblastic) side. So the problems or benefits snowball in either the good or the bad directions in terms of developing AD.
Here are some clinical pearls from Dr Dale Bredeson an expert researcher and clinician in AD from the Buck Institute who recently spoke at the 2017 IFM Annual International Conference in LA:
- Identify and treat individual abnormalities until symptomatic improvement begins.
- It took decades to develop AD, and it takes time to slow and reverse it. Generally, do not expect improvement for 3-6 months. The first positive sign is that progression slows or stops.
- Modest improvement is an excellent sign of the possibility for continued improvement to come.
- Continued progression means that something has been missed—cognitive decline does not occur without reason.
- The most common reasons for failure are lack of compliance and ignoring or failing to identify key contributors.
Because AD is caused by myriad factors and processes, we can not now, and probably never will be able to rely on drug therapies to prevent or treat AD. There’s good news though: diet, stress, sleep, exercise all affect the APP signaling balance. Dr. Bredeson has reported (for the first time) the actual clinical and antoimical reversal of AD (e.g. increased hippocampal volume).
Amyloid beta protein accumulation is not a AD death sentence. Some people have amyloid accumulaiton without symptoms and others have symptoms without amyloid. Clinical Alzheimer’s is often accompanied by other pathologies. Pathogens are associated with AD risk due to chronic inflamation. Infectious sources include oral bacteria (e.g., P. gingivalis), fungi, spirochetes, viruses (e.g., HSV-1). Some may have a-synuclein (typical of Parkinson’s and Lewy body disease), vascular pathology.
Parkinson’s Disease develops from the negative effects of neuronal death in the substania nigra. One of the primary contributing causes in PD is the specific uptake and accumulation of pesticides into the substantia nigra cells that in turn blocks mitochondrial electron transport chain (at complex 1). Mitochondrial health and function and ATP production is critical to cell health–especially in neurons. When mitochondria die, cells die, and this kind of neuronal death underlies most if not all neurodegenerative diseases.
The microbiome and Brain health
Another critical factor in brain and nuronal health is decreasing inflamation and oxidative stress, two other significant factors that dammage mitochondria. One of the ways to decrease systemic inflamtion is to have a healthy microbiome.
A simple way to address many cases of GI distress is to take a strong probiotic. I like the Jarrow brand 50B CFU. IF you buy three bottles, they are shipped in a well insulated cold pack.
Something that is suprising, is that we may actually be too clean and hygenic for our own good. Incidence of allergy and autoimmune disease have been going up significantly, and the absence of regular exposures to a broad array of bacteria, parasites, worms, and viruses. Studies show that paracite exposure is highly corelated with gut microbial diversity and
The gut brain connection is real. Obesity is associated with gut microbiome dysbiosis, and decreased hippocampal volume and this contributes to memory loss.
Other recent studies have shown that early life trauma is associated with gut dysbiosis, leaky gut, irritable bowel syndrome, systemic inflamation, mitochondrial dysfunction, neuronal death and loss of brain matter and function.
Cardiorespiratory fitness (peak V-O2) has a linear corelation with a diverse microbiome and by association lower levels of inflamation, healthier mitochondria, and better brain function. We’re not yet sure if interventional trials will show that increasing cr-fitness alone will increase your microbiome diversity, but it is interesting already that those who have achieved and maintained a higher level of fitness.
The connection between dysbiosis and systemic inflamation is a phenominon called intestinal permeability or “leaky gut”. This occurs when food, bacteria and their byproducts inside the gut are able to “leak” through dammaged or weakened zonulin boundaries between intestinal epithelia cells. The consequence of leaky gut is that immune system responds with all kinds of activity that ammounts to local and then systemic inflamation, mitochondrial dammage, cell death, and loss of tissue and organ function–especially in the brain. Outside of dysbiosis, other things that increase leaky gut include stress, antibiotics and other drugs, infections, gluten, and advanced glycated endproducts (AGEs) from elevated blood sugar are others.
There is a feed-forward cycle between dysbiosis, leaky gut, and inflamation. To be fully effective, alternative medical pratitioners must address this viscious cycle at every level.
One particular kind of dysbiosis related Altzheimers Disease (AD) is gram-negative (E coli) bacterial products leaking through a permeable gut barrier. Studies that looked at the levels of E coli proteins in the brains of AD patients, they found a massive increase.
Scientists looked at the brains of AD patients and chemically tagged amyloid protiens and bacterial toxin lipopolysacharide (LPS). The study showed that the amyloid protien tangles were closely associated withe LPS. This suggests that not only do leaky guts contribure to the development of AD, but also “leaky brains” in the form of hyperpermeable blood brain barrier that was letting the LPS through in the first place. ALS, Parkinsons, Autism are all the same and appear to all be related to dysbiosis and leaky gut and leaky brain.
What causes leaky brain? Inflamation, to which leaky gut and dysbiosis are key contributors. So hopefully it’s becoming clear now that if you want to protect your brain, protect your gut and promote a diverse microbiome through eating a diverse, vegetable and fiber rich diet, reducing stress, exercising, avoiding antibiotics, gluten and acid blockers.
On that last point, JAMA published a study in 2016 showed that elederly patients regularly taking a proton pump inhibitor had a staggaring 44% increased risk of developing dementia.
Stool analysis can determine if you have a diverse microbiome, paracitic infections, and especially problematic gut bacteria. Probiotics and prebiotics (indigestable fiber) can promote healthy flora. Zinc, glutamine, MSM, demulcent herbs like licorice, chamomile, aloe,
Reducing your blood sugar, HgbA1c, fasting insulin levels, waist circumfrance, are all other ways to reduce the dammage from sugars binding to and dammaging your proteins.
Glyphosate, (Roundup) is a direct antibiotic and also a direct mitochondrial toxin. Many genetically modified foods are modified to survive increased application of glyphosate and other herbicides and pesticides. This is why it is important to avoid GMO foods. They act like antibiotcs in your gut and directly harm your mitochondria