Many studies have proposed that inflammatory dysfunctions are associated with psychiatric disorders and neurodegeneration in both animal models and human patients.58,59
Self-Help: A strong alkaline, anti-inflammatory diet is critical as part of an overall treatment strategy.
Neurogenesis and Brain Plasticity. The human brain is capable of forming new connections between neurons. When we take in new information, an electro-chemical signal is sent across the space between neurons (called the synaptic space). This ability of the brain to form new connections or neural pathways to communicate with each other is often referred to as brain plasticity. Brain plasticity is now understood to be the very foundation of learning and memory.
Neurogenesis is the brain’s ability to product new brain cells. Researchers noted in the 90s that neurogenesis decreases with aging.60 But the number and type of stem cells in the neurogenic region of the hippocampus apparently does not decrease with aging, rather they become inactive or dormant.61 Neurogenesis occurs through stem cells that can differentiate into many other types of cells, including nerve cells.
Neurotrophic factors are molecules produced by the body (biomolecules), mostly peptides and proteins. The three known neurotrophins are brain-derived: neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF). Loss of neurotrophins cause impaired brain plasticity, which results in loss of cognitive capacity expressed in conditions like Alzheimer’s disease. These growth factors are responsible for the ability to utilize and put into action essential proteins in the brainand thepromotion of health and re-growth of neurons.
Neurotrophic factors keep the brain nourished. When they are working well, our ability to think and process information stays healthy. When their action is impaired, learning and remembering becomes more difficult, and the brain actually withers and shrinks over time. Neurotrophic factors are positively affected by having a healthy diet, being emotionally balanced, managing stress, and exercising regularly. Negative influences include an unhealthy diet, sedentary lifestyle, tobacco and alcohol use, mood disorders, oxidative stress, emotional imbalances such as excessive fear or anger, chronic pain, deficiencies in certain essential vitamins, and some medications.
Brain derived neurotropic factor (BDNF) regulates hippocampal neurogenesis.62,63 It is required for the development of the nervous system, proper cognitive function, and memory formation, and is known to be critical for the development of the brain, neuron survival, 64 neuronal regeneration, and synaptic plasticity.65-68 When BDNF levels are irregular or declining, neurological diseases such as Alzheimer’s, Parkinson’s, Huntington’s disease, and amyotrophic lateral sclerosis can develop.69
Nerve growth factors (NGF) have been shown to improve neural regeneration in neurodegenerative diseases, such as Alzheimer’s,70,71 and Huntington’s disease.72 Neurotrophins have also been found to be located in adult stem cells niches and therefore may promote tissue regeneration outside of the nervous system.
Microglia. Microglia are the resident macrophages (large cells) and primary immune cells of the brain, and they have a multitude of functions, including attacking and consuming bacteria (phagocytosis), removing waste, providing neuroprotection, and contributing to the growth of new neurons. They interact with a number of cell types, including astrocytes, neurons, and endothelial cells. In conditions such as AD, they fail to clear away waste, including beta-amyloid deposits.73
Glial Cells. Glial cells maintain homeostasis, form the myelin sheath that protects nerve cells, and provide support and protection for neurons. In addition, they support synaptic contacts and the signaling abilities of neurons. Glia are more numerous than nerve cells in the brain, outnumbering them by a ratio of perhaps 3 to 1.
Glial cells include astrocytes, which are essential in maintaining brain homeostasis and neuronal metabolism. They support brain plasticity and synaptogenesis, provide neurons with mechanical support, control neuronal cell development, release nutritional and energy substrates like glucose and lactate that regulate neurotransmission, vasomodulation, and repair, and protect neurons from oxidative damage, and control the blood brain barrier and blood flow.74,75 Oligodendroglia cells are found in the central nervous system. Their main function, along with Schwann cells (found in the peripheral nervous system), is the formation of myelin, the protective covering of nerve cells. Satellite cells are glial cells that cover the surface of nerve cell bodies in sensory, sympathetic, and parasympathetic ganglia, and help regulate the external chemical environment. Like astrocytes, they are interconnected by gap junctions and respond to ATP (as a neurotransmitter) by elevating intracellular concentration of calcium ions.
Epigenetics. The study of epigenetics has shown that gene expression could change throughout one’s lifetime, determined by many environmental factors, including diet, emotional nurturing, social interactions, exercise, smoking, alcohol consumption, air pollution and other exposure to toxins, working habits (particularly those who have shift work), chronic stress, and even how one sleeps. In diseases such as cancer, congenital diseases, neurodegenerative diseases, and neuropsychiatric disorders,76-79 various genes are switched into an opposite state, away from the normal/healthy state. Numerous historical studies show that patterns of famine, smoking, or breast feeding, affect future generations related to potential impact on development and health,80 especially during critical developmental periods.81
Vascular Risk. Chronic high blood pressure in which blood vessels lose their elasticity cause the muscular layer of the vessels to enlarge, making it more difficult for the body to get the blood effectively to the brain. Hypertension may contribute to cognitive decline by causing cerebral small vessel pathology and increasing neurofibrillary tangles and amyloid plaques.82 Elevated plasma homocysteine is an independent risk factor for cardiovascular disease, stroke, and dementia, including AD.83
Environmental Toxins. Children and young adults who live in areas with significant air pollution are much more likely to have the hallmarks of Alzheimer’s. These include twisted protein fibers, deteriorating neurons, and amyloid beta plaque deposits.84-86
Exposure to toxins in the environment can have a substantial effect on brain functioning. For example, high levels of blood lead (Pb) are associated with reduced ability to recall and define words, identify line-drawn objects, and difficulty in a perceptual comparison test,87 as well as fatigue, decreased processing speed, fine and gross motor deficits, and generally decreased cognitive functioning.88 These declines are greater than changes observed with normal aging alone.89
Cumulative lead exposure is associated with an increased risk of amyotrophic lateral sclerosis90,91 and Parkinson’s disease.92 In regions with high levels of air pollution even children exhibit the hallmarks of Alzheimer’s: twisted protein fibers, deteriorating neurons, and amyloid plaque deposits.93-95 The same is true of industrial-, combustion- and friction-derived nanoparticles.96
Cholinergic Circuit Dysfunction. Problems of the cholinergic circuit, such as with the neurotransmitter acetylcholine, are important factors. Cholinergic circuit dysfunction has been associated with neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s as well as psychiatric disorders such as schizophrenia.97
Blood Sugar Imbalances. A strong school of thought is that insulin resistance98 with chronic blood sugar elevations are involved in depression and neurodegenerative disorders such as Alzheimer’s disease.99-101 Insulin regulates glucose (sugar) and directs the body to store energy. In the brain, insulin not only breaks down glucose but also regulates the clearance of b-amyloid protein and tau phosphorylation (essential for avoiding AD). Insulin supports healthy blood flow and the removal of fats from the brain, inhibits apoptosis (cell death), manages the response to inflammation, supports the ability for the formation of new synapsis, and supports new memory formation. It can also facilitate neurotransmitter receptor trafficking.102 Therefore, any change in insulin balance can have serious consequences. There is a great similarity between AD and type 2 diabetes as both ultimately result in one’s body becoming resistant to insulin, thereby reducing its effectiveness. In both conditions, inflammation with increased levels of oxidative stress occurs. The b-amyloid levels increase in both the brain and pancreas along with hyperphosphorylated tau protein and cognitive decline. Fifty percent of Americans between the ages of forty-five to sixty-four and seventy-six percent of those over sixty-five have an insulin imbalance, which becomes a critical health issue for Americans.
High Cholesterol and Homocysteine Levels. One study concluded that high total cholesterol levels at midlife have been associated with a nearly threefold increase in the likelihood of developing AD, even after controlling for ApoE genotype.103
High homocysteine levels double the risk of Alzheimer’s.104 Elevated plasma homocysteine is an independent risk factor for cardiovascular disease, stroke, and dementia, including AD.105,106
Mitochondria. Mitochondria are the energy batteries of our cells, producing ATP, which powers metabolic processes. Mitochondrial dysfunction appears to be a critical factor in the pathogenesis of AD.107,108 This results in reduced membrane potential, increases permeability, and produces excess free radicals, which damage proteins, lipids, and nucleic acids.
Nutrients that support mitochondrial function (and against mitochondrial dysfunction) include vitamins B1, B2, B6, C, D, and E, l-carnosine, l-taurine, CoQ10, benfotiamine, alpha-R-lipoic acid, PQQ (pyrroloquinoline quinone), luteolin [from orange extract fruit), l-carnitine, trans-resveratrol, curcumin, magnesium, and schisandra.
Blood Brain Barrier Compromise (BBB). The BBB is critical for preventing particles and pathogens for reaching the brain, allowing only essential nutrients to pass through. Astrocyte destruction is associated with BBB (blood-brain-barrier) disruption.109 Astrocytes induce and maintain the BBB, and in particular form the glia limitans.110,111
Immune reactions to gluten (see Celiac Disease below) can break down the blood-brain barrier, increasing autoimmune reaction risk in the brain and nervous system.112
Nutrients that support the BBB include resveratrol and baicalein.
Glymphatic System. The glymphatic system is a waste clearance pathway for the central nervous system and may play a significant role in clearing waste build-up in the brain. It is most active during sleep and may have implications in headache and in neurodegenerative diseases associated with pathologic protein aggregation, including Parkinson’s disease and Alzheimer’s. disease. The glymphatic system functions much like the lymphatic system but is managed by the glial cells within the brain. Glial cells are non-neuronal brain cells with several regulatory and protective roles, including destruction of pathogens and removal of dead nerve cells.
The Gut-Brain Axis. Through two-way communication with the brain via the nervous system, endocrine system, and immune system, the gut and central nervous system form a gut-brain axis. They communicate with each other constantly, in both sickness and health.113 Researchers have concluded mechanisms that degenerate the neurons in the brain also degenerate neurons in the enteric nervous system.114 The enteric nervous system (ENS) is a large division of the peripheral nervous system (PNS) that can control gastrointestinal behavior independently of central nervous system (CNS) input.
Changes in gut microbiota affect the nervous system, and dysfunction of the delicate interconnections between the two are closely associated with neurodegenerative conditions such as Parkinson’s and Alzheimer’s diseases.115 In this way intestinal microbiota are directly linked to various forms of dementia because of the action of metabolic disease and chronic low-grade inflammation.116
Candidiasis and leaky gut syndrome are two common forms of flora imbalances in the gut. Brain infection was found in half of patients with systemic candidiasis.117 Leaky gut is often associated with fungal infections. Fungal proteins and diffuse mycoses in the blood of AD patients suggest that chronic fungal infection associates with high risk of AD.118
Celiac Disease (CD). CD is an immune-mediated affected by the intake of gluten (a protein present in wheat, rye, or barley) that occurs in about one percent of the population.119,120 Non-celiac gluten sensitivity (NCGS) also remains undertreated and under-recognized as a contributing factor to psychiatric and neurologic manifestations. NCGS is estimated to occur six times greater in the general population than CD.121
