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                   RENEWING
                THE AGING BRAIN
                                                                                Presented by BRANDON                         BROCK,
                                                                                                       RN, BSN, MSN/FNP, DC, DACNB, FACFN,
                                                                                                           FABES, FABVR, FICC, RNCST, CNCT

                                                                                   Written by DATIS                   KHARRAZIAN,
                                                                                                                  DC, DHSc, MS, MNeuroSci,
                                                                                  Associate Professor of Clinical Neurology - Carrick Institute
                                                                                      Fellow of the American College of Functional Neurology
                                                                                    Fellow of the American Board of Vestibular Rehabilitation
                                                                                  Fellow of the American Academy of Chiropractic Physicians
                                                                                         Diplomate of the American Board of Clinical Nutrition
                                                                                                Diplomate of the Board of Nutrition Specialists
                                                                                  Diplomate of the International Board of Applied Kinesiology
                                                                                  Diplomate of the American Board of Chiropractic Neurology


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INTENDED USE STATEMENT

    The content of this course is intended for informational purposes only. The medical
    information in this course is intended as general information only and should not
    be used in any way to diagnose, treat, cure, or prevent any disease. The goal of
    this course is to present and highlight nutritionally significant information, and
    offer suggestions and protocols for nutritional support and health maintenance.
    Homeopathic protocols are intended for use in symptom relief and OTC indications
    only.

    It is the sole responsibility of the user of this information to comply with all local
    and federal laws regarding the use of such information, as it relates to the scope
    and type of user’s practice.

    The nutritional protocols and suggestions presented in this course are based on
    the presenter’s clinical experience and research and are not intended to represent
    any claims regarding product performance or benefits by the manufacturer, its
    distributors, or the sponsors of this seminar.

    Statements regarding nutritional products in this seminar have not been evaluated
    by the Food and Drug Administration. Nutritional products presented in this
    seminar are not intended to diagnose, treat, cure, or prevent any disease.



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DISCLAIMER AND NOTICES

   The information and recommendations outlined in this presentation are not intended as a
   substitute for personalized medical advice. The presentation proposes certain theoretical
   methods of nutrition, not necessarily mainstream. It is left to the discretion, and it is the
   sole responsibility of the user of the information indicated in the presentation, to determine
   if procedures and recommendations described are appropriate for a patient. Neither the
   authors nor the sponsors (such as Apex Energetics) of this information can be held
   responsible for the information or any inadvertent errors or omissions of the information.

   The information in this presentation should not be construed as a claim or representation
   that any procedure or product mentioned constitutes a specific cure, palliative
   or ameliorative. Procedures and products described should be considered as adjunctive
   to other accepted conventional procedures deemed necessary by the attending
   licensed doctor.

   It is the concern of the Department of Health and Human Services that no homeopathic
   and nutritional supplements be used to replace established, conventional medical
   approaches, especially in cases of emergencies, serious or life threatening diseases
   or conditions.

   We share in this concern, as replacing conventional treatment with such remedies,
   especially in serious cases, may deprive the patient of necessary treatment and
   thereby cause harm as well as potentially pose a major legal liability for the health
   professional involved. Apex formulas should not be used as replacements for
   conventional medical treatment.
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The Glia System




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Healthy and Unhealthy Neurons




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How Old is Your Brain?




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Atrophy of the Memory Centers




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The Aging Brain




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Questions to Ask
           • Is it too late?

           • Is it permanent?

           • What changes can be made?

           • Will it get worse?




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What are the
                                           Earliest Signs of
                                           an Aging Brain?


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Earliest Signs of an Aging Brain
           • Fatigue promoted by brain activity – driving,
             reading, brain tasks

           • Depression – lack of healthy brain firing leads
             to depression

           • Poor Digestive Function – 90% of the brain’s
             output goes to the pontomedullary system


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Autonomic Nervous System




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Moderate Signs of Aging Brain
           • Inability to focus or concentrate
           • Difficulty learning new tasks
           • Chronic constipation, opportunistic intestinal
             overgrowth, digestive enzyme insufficiency
           • Increased sympathetic tone leading to:
              – Increased blood pressure
              – Increased resting heart rate
              – Stress susceptibility
              – Poor blood flow
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Significant Brain Aging
            • Inability to work professionally
            • Inability to appreciate life
            • Inability to perceive neurological loss
            • Early signs of neurological disease
               – tremors
               – inability to find directions
               – etc.
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Severe Brain Aging
            • Neurodegenerative disease
            • Uncontrolled bladder tone
            • Bowel obstruction and inability to digest food
            • Inability to taste, smell, or develop social
              relationships
            • Dependency on family and medical staff for
              daily functions

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Where are you?



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What are the Mechanisms
        for Poor Brain Aging?


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Brain Aging of the
                                    Memory System
                           Dementia and Alzheimer’s Disease



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The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD.
                                                          Memory and the aging brain.




           • Studies that look at only the healthiest
             elderly tend to find minimal cognitive decline
             even into the ninth decade.




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The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD.
                                                          Memory and the aging brain.




           • It is clear that significant cognitive decline is
             not an inevitable consequence of advanced
             age.




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The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD.
                                                          Memory and the aging brain.




           • More than 4 million Americans have
             dementia, and the number is projected to
             grow to 14 million in the next 50 years.




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The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD.
                                                          Memory and the aging brain.




           • Currently there is no cure for dementia.

           • All people are at risk for dementia, with the
             greatest risk factor being increased age.




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• Are you getting older?
                  • Do you have the earliest
                    signs of dementia?
                  • Are you taking this seriously?



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Earliest Signs of Dementia
           • Poor short-term memory
           • Difficulty learning
           • Difficulty with directions
           • Decreased brain endurance

           If you have the symptoms, when did they
           start and how fast are they going?

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Papez Circuit




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Acetylcholine Pathways




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Early Alzheimer’s Disease




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Progressed Alzheimer’s Disease




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Healthy Neuron




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Beta-Amyloid Being Cleaved




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Beta-Amyloid Plaque Formation




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Tau Proteins




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Neurofibrillary Tangles




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Clock Drawing Test




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Acetylcholine Pathways




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Brain Affected Areas
                                      in Alzheimer’s Disease




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Symptoms of Cholinergic
                                Pathways Degeneration
           • Loss of photographic memory
           • Difficulty with sense of directions
           • Poor memory
           • Memory lapses
           • Poor verbal memory
           • Slow mental speed
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Signs of Cholinergic
                                  Pathways Degeneration
           • Constantly losing keys, phone, etc.
           • Constantly forget where car is parked
           • Dependency on navigations system for
             directions
           • Must write everything down
           • Constantly forgetting appointments,
             tasks, etc.
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ACETYL-CH® ACTIVE (K40)
               • Huperzine A
               • Alpha-GPC
               • N-Acetyl L-Carnitine
               • Pantothenic Acid




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Brain Aging of the
                                  GABAergic System
                          Anxiety, Restlessness, Panic Attacks




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GABAergic Pathways




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Symptoms of GABAergic
                                  Pathway Degeneration
         • Feelings of anxiety or panic for reasons
         • Difficulty shutting mind off
         • Feelings of being overwhelmed for no reason
         • Disorganized attention
         • Feelings of restlessness

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Signs of GABAergic
                                     Pathway Degeneration
           • Anxiety episodes
           • Cannot initiate projects due to constant
             distractions
           • Startled easily and difficulty calming down
             afterwards
           • Severely sensitive to light and sound
           • Increased resting heart rate

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GABATONE® ACTIVE (K39)
        •       Valerian Root extract
        •       Lithium Orotate
        •       Passion Flower extract
        •       L-Theanine
        •       L-Taurine
        •       Pyridoxal-5-Phosphate
        •       Manganese Succinate
        •       Zinc Glycinate
        •       Magnesium Succinate

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Brain Aging of the
                           Serotonergic System
                         Depression, Loss of Joy, Poor Focus,
                             Sense of Self and Purpose


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Serotonergic Pathways




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Symptoms of Serotonergic
                             Pathway Degeneration
           • Guilty depression
           • Inability to feel joy from hobbies, friends,
             music, food, etc.
           • Depressed with overcast weather or chronic
             lack of sunlight
           • Loss of interest in life

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Signs of Serotonergic
                                     Pathway Degeneration
           • Social isolation with unwillingness to go out
           • Depression
           • Cravings and overeating of carbohydrates
             and sugars
           • Slowed reflexes and coordination


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SEROTONE® ACTIVE (K38)
            •         5-Hydroxytryptophan
            •         St. John’s Wort
            •         SAMe
            •         Pyridoxal 5 Phosphate
            •         Niacinamide
            •         Magnesium Citrate
            •         Methylcobalamin
            •         Calcium Folinate

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Brain Aging of the
                      Dopaminergic System
                                 Depression, Loss of Motivation,
                                     Inability to Finish Tasks,
                                  Slow Movements, Slow Mind


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Dopaminergic Pathways




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Dopamine Receptors in the Brain




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Areas of the Brain in Depression




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Symptoms of Dopaminergic
                          Pathway Degeneration
           • Feelings of hopelessness and worthlessness
           • Inability to handle stress
           • Unable to self-motivate to start or finish
             tasks
           • Need to consume caffeine to stay focused
           • Depression
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Signs of Dopaminergic
                                     Pathway Degeneration
      •      Depression
      •      Isolation
      •      Quick to snap at every little thing
      •      Poor compliance with healthcare, exercise, etc.
      •      Anger episodes
      •      Hypokinesia (slow and diminished movements)
      •      Constipation with diminished smell or taste
             perception
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DOPATONE® ACTIVE (K41)
       •         Mucuna Pruriens
       •         Beta-Phenylethylamine
       •         Blueberry extract
       •         D,L – Phenylalanine
       •         N-Acetyl L-Tyrosine
       •         Pyridoxal 5 Phosphate
       •         Alpha Lipoic Acid
       •         Selenium
       •         N-Acetyl L-Cysteine

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Phosopholipid Integrity
                                        60% of the Brain is Made Up
                                            of Phosopholipids




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Phosopholipids and Neuron
                               Structure




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Neuroscience. 1999;94(1):305-14.
                                  Age-related changes in synaptic function:
                               analysis of the role of dietary supplementation.




           • DHA is used to enhance cell fluidity, neuronal
             signaling, neuronal dendrite growth, and
             brain function, as well as reduce
             inflammation, and decrease the incidence of
             neurodegenerative conditions.



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Int. J Neurosci. 1996 Nove;87(3-4):141-9.
                              Essential fatty acids preparation (SR-3) improves
                                    Alzheimer’s patient’s quality of life.




          • DHA intake has demonstrated the ability to
            boost brain function, improve quality of life,
            and reduce the incidence of
            neurodegenerative conditions.




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Current Enzyme Inhibition. 2005;1:11-20.
                        Sesamin and sesamolin: nature’s therapeutic lignans.




           • Sesamin and Sesamolin found in sesame seed
             oil and have exhibited properties to protect
             neurons and modulate microglia
             neuroinflammatory properties.




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Int J of Biomed Sci. 2006:2:284-288.
                            Neuroprotective effects of sesamin and sesamolin
                                  on gerbil brain in cerebral ischemia.



           • Sesamin and sesamolin have the ability to
             attenuate excess generation of oxidative
             stress stimulated by microglia and to
             reduce infarct size by approximately 50%
             when compared with the control group in
             a cerebral artery occlusion study.


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Biochem J. 1982;208(3):631-40.
                            Influence of dietary fat on lipid composition
                     of rat brain synaptosomal and microsomal membranes.


         • Phosphatidylcholine (PC) plays a crucial role
           in the formation and structural integrity of
           neurons and brain architecture.

         • PC supports cell-membrane integrity,
           fluidizing the membranes, and it supports
           intracellular communication.


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Artif Cells Blood Substit Immobil Biotechnol. 1994;22(1):83-9.
                                 Effects of lecithin-emulsified perflurochemical
                                      compounds in ischemic brain injury.




           • Dietary supplementation with
             Phosphatidylcholine has exhibited
             protection against oxidative and ischemic
             neuronal damage.




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BRAIN-E® DHA (K53/55/65)
                              PHYTO BRAIN-E® (K54)
               •         DHA
               •         EPA
               •         Phosphatidylcholine
               •         Sesame oil




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SMRAB09(06092011)BROCK.PPT                                For Nutritional Purposes Only   89
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Phosopholipids and Neuron
                               Structure




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Mitochondria
                                           Oxidative
                                        Phosphorylation


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Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10.
                    Mitochondrial decay in the brains of old rats:
             ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine.




           • To investigate the mitochondrial decay and
             oxidative damage resulting from aging, the
             kinetics of the mitochondrial complexes
             were examined in the brains of young and
             old rats as well as in old rats fed alpha-
             lipoic acid plus acetyl-L-carnitine.


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Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10.
                    Mitochondrial decay in the brains of old rats:
             ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine.




           • The brain mitochondria of old rats, compared
             with young rats, had significantly decreased
             endogenous antioxidants and superoxide
             dismutase activity; more oxidative damage to
             lipids and proteins; and decreased activities
             of complex I, IV, and V.


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Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10.
                    Mitochondrial decay in the brains of old rats:
             ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine.




           • Feeding LA/ALC to old rats partially restored
             age-associated mitochondrial dysfunction to
             the levels of the young rats.




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Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10.
                    Mitochondrial decay in the brains of old rats:
             ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine.




           • These results indicate that oxidative
             mitochondrial decay plays an important
             role in brain aging and that a combination
             of nutrients targeting mitochondria could
             ameliorate mitochondrial decay.



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J Neurosci Res. 2008 Aug 1;86(10):2339-52.
                        Age-related decreases in NAD(P)H and glutathione
                      cause redox declines before ATP loss during glutamate
                               treatment of hippocampal neurons.




           • We conclude that old-aged neurons consume
             more NADH and glutathione, leading to a
             catastrophic decline in redox ratio, leading to
             age-related glutamate excitotoxicity.



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Brain Res. 2006 May 23;1090(1):35-44. Epub 2006 May 2.
                Age-related changes in glutathione and glutathione-related
                                  enzymes in rat brain.


           • The most reliable and robust risk factor for
             some neurodegenerative diseases is aging.

           • It has been proposed that processes of aging
             are associated with the generation of
             reactive oxygen species and a disturbance of
             glutathione homeostasis in the brain.


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Brain Res. 2006 May 23;1090(1):35-44. Epub 2006 May 2.
                Age-related changes in glutathione and glutathione-related
                                  enzymes in rat brain.



           • The results suggested a significant age-
             related reduction of reduced glutathione
             (GSH) level in all brain regions examined,
             associated with an increase of GSH oxidation
             to glutathione disulfide (GSSG) and decrease
             of the GSH/GSSG ratio.


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GLUTATHIONE RECYCLER® (K57)
                  •      Cordyceps extract
                  •      Gotu Kola extract
                  •      Milk Thistle extract
                  •      N-Acetyl Cysteine
                  •      Alpha Lipoic Acid
                  •      L-Glutamine
                  •      Selenium


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N-Acetyl Cysteine
                                                          (Research Review)



           • Research has clearly demonstrated that
             N-Acetyl Cysteine is rapidly metabolized to
             intracellular glutathione.




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Alpha Lipoic Acid
                                                          (Research Review)


           • It directly recycles and extends the
             metabolic life spans of vitamin C,
             glutathione, and coenzyme Q10, and it
             indirectly renews vitamin E, all of which are
             necessary for glutathione recycling.



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L-Glutamine
                                                          (Research Review)

           • Research has demonstrated that glutamine
             is important for the generation of
             glutathione.

           • It is transported into the cell, converted to
             glutamate, and readily available for
             intracellular glutathione synthesis.


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Selenium
                                                          (Research Review)



           • Selenium is a trace element nutrient that
             serves as the essential cofactor for the
             enzyme glutathione peroxidase.




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Cordyceps
                                                          (Research Review)

           • It has been shown to activate glutathione
             peroxidase synthesis in the body.

           • Cordyceps research has demonstrated that
             it helps protect cells by engaging the
             glutathione enzyme cycle.



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Gotu Kola
                                                          (Research Review)



           • Research has clearly demonstrated that
             oral intake very rapidly and dramatically
             increases the activity and amount of
             glutathione perioxidase and the quantity
             of glutathione.


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Milk Thistle
                                                          (Research Review)



           • Administration of milk thistle has shown
             to significantly increase glutathione,
             increase superoxide dismutase activity,
             and have a positive influence in the ratios
             of reduced and oxidized glutathione.



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NEURO-PTX® (K47)
           •       N-Acetyl Cysteine
           •       N-Acetyl Carnitine
           •       Alpha Lipoic Acid
           •       Creatine Monohydrate
           •       Genistein
           •       Milk Thistle extract
           •       CoQ10
           •       Alpha Ketoglutarate
           •       d-alpha tocopherol succinate
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SMRAB09(06092011)BROCK.PPT                                For Nutritional Purposes Only   113
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Microglia
                             Neuroinflammation



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Brain on Fire




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Reactive Microgliosis




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NEUROFLAM™ (K46)
                   •       Apigenin
                   •       Luteolin
                   •       Baicalin
                   •       Rutin
                   •       Catechin
                   •       Curcumin (turmeric)



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Mol Nutr Food Res. 2008;52(4):427-38.
        Plant-derived polypheonls attenuate lipopolysaccharide-induced
               nitric oxide and tumour necrosis factor production
                      in murine microglia and macrophages.




           • Apigenin attenuated lipopolysaccharide
             induced nitric oxide and TNF production in
             microglia.




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J Neuroinflammation. 2008;25(5):41.
                      Apignin and luteolin modulate microglial activation via
                          inhibition of STAT-1 induced CD40 expression.




           • Apigenin and luteolin concentration-
             dependently suppressed IFN-gamma-
             induced CD40 expression of microglia.




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J Neuroinflammation. 2008;25(5):41.
                      Apignin and luteolin modulate microglial activation via
                          inhibition of STAT-1 induced CD40 expression.




           • Our findings provide further support that
             apigenin and luteolin's anti-inflammatory
             effects have neuroprotective properties in
             various neurodegenerative disorders.




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Neurosci Lett. 2008;448(2):175-179.
   Luteolin protects dopaminergic neurons from inflammation-induced
             injury through inhibition of microglial activation.




           • Luteolin also significantly inhibited LPS-
             induced activation of microglia.




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Neurosci Lett. 2008;448(2):175-179.
   Luteolin protects dopaminergic neurons from inflammation-induced
             injury through inhibition of microglial activation.




           • Our results demonstrate that luteolin may
             protect neurons by inhibiting microglia
             activation.




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Proc Natl Acad Sci USA. 2008;105(21):7534-7539.
                  Luteolin reduces IL-6 production in microglia by inhibiting
                         JNK phosphorylation and activation of AP-1.




           • Luteolin may be useful for mitigating
             microglia neuroinflammation.




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J Pharmacol Exp Ther. 2003;305(2):638-45.
                            Flavonoid baicalein attenuates activation-induced
                                      cell death of brain microglia.


           • Our current results suggest that baicalein
             selectively inhibits activated microglia.

           • Also, inhibiting effects of baicalein were
             specific for the inflammatory stimulus that
             activated microglia.



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Neurosci Lett. 2008;441(1):16-20.
          Neuroprotective effect of baicalein against MPTP neurotoxicity:
            behavioral, biochemical and immunohistochemical profile.




           • The results suggest that baicalein possesses
             potent neuroprotective activity and has
             potential anti-Parkinson’s activity.




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Neuroreport. 2001;12(10):2199-202.
                       Baicalein protects cortical neurons from beta-amyloid
                                     (25-350 induced toxicity).




           • Baicalein protects lipoxygenase mediated
             pathways for micoroglia activated
             neuroinflammation associated with
             Alzheimer’s disease.




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Invest Opthalmol Vis Sci. 2008; Nov 14.
                                        Baicalein reduces inflammatory process
                                       in a rodent model of diabetic retinopathy.




           • Baicalein has demonstrated to ameliorate
             inflammatory processes of diabetic
             retinopathy and has inhibitory activity
             against neuron loss in diabetic retinas.




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Brain Res. 2008; Oct 18 [Epub ahead of print].
                    Baicalein protects rat brain mitochondria against
                chronic cerebral hypoperfusion-induced oxidative damage.



           • Baicalein has been found to protect neuronal
             mitochondria damage and swelling promoted
             by chronic cerebral hypoperfusion and has
             been suggested as a potential support agent
             for dementia caused by decreased blood flow
             to the brain.


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Neurochem Res. 2008;33(10):2044-53.
              Curcumin protects dopaminergic neuron against LPS induced
                   neurotoxicity in primary rat neuron/glia culture.




           • Curcumin has demonstrated the ability to
             protect dopaminergic neurons against
             lioppolysaccharide induced neurotoxicity in
             animal neurona/glia culture.




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Acta Pharmacol Sin. 2007;28(10):1645-51.
          Curcumin attenuates the release of pro-inflammatory cytokines
                 in lipopolysaccharide-stimulated BV2 microglia.




          • Curcumin has been found to have
            neuroprotective effects by blocking the
            production of pro-inflammatory and
            cytotoxic mediators by activated microglia.




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REPAIRVITE® (K60)
      •      L-Glutamine
      •      MSM
      •      Licorice extract
      •      Aloe Vera extract
      •      Marshmallow extract
      •      Slippery Elm extract
      •      Spanish Moss
      •      German Chamomile extract
      •      Marigold extract

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Cerebral Blood Flow



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Blood Flow = Function




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BMC Neurosci. 2010 Jun 24;11(1):78.
      Study of the nitric oxide system in the rat cerebellum during aging.


           • In the senescent cerebellum, inducible nitric
             oxide system activity results in an increase of
             the protein nitration.

           • These changes might be related to the
             oxidative damage detected with aging in the
             cerebellum.



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Brain Res. 2002 Nov 29;956(2):385-92.
            Age-related changes of the nitric oxide system in the rat brain.




           • Concerning age, in the cerebellum the eNOS
             expression decreased whereas iNOS
             increased.




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Biochim Biophys Acta. 1999 May 5;1411(2-3):415-36.
                                 Roles of nitric oxide in brain hypoxia-ischemia.




           • A large body of evidence has appeared over
             the last 6 years suggesting that nitric oxide
             biosynthesis is a key factor in the
             pathophysiological response of the brain to
             hypoxia-ischemia.



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Biochim Biophys Acta. 1999 May 5;1411(2-3):415-36.
                                 Roles of nitric oxide in brain hypoxia-ischemia.

           • In conclusion, it appears that activation of
             iNOS mediates ischemic brain damage.

           • However, there is a simultaneous
             compensatory response through eNOS
             activation within the endothelium of blood
             vessels, which mediates vasodilation and
             hence increases blood flow to the damaged
             brain area.

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NITRIC BALANCE® (K62)
             •      ATP
             •      Huperzine A
             •      Vinpocetine
             •      Alpha-GPC
             •      Alpha-Ketoglutaric Acid (AKG)
             •      Xanthinol Nicotinate
             •      Acetyl L-Carnitine


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NITRIC BALANCE® (K62)
           •            Provides compounds that are used to
                        support the expression of eNOS and nNOS,
                        while dampening the expression of iNOS.
                        Healthy balance of NO helps the body to:
                            1. Support tissue healing
                            2. Dampen tissue inflammation
                               and destruction
                            3. Modulate autoimmune reactions

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Adenosine
                                                          (Research Review)

              • Adenosine increases extracellular ATP,
                which has been found to activate eNOS
                and nNOS.

              • More importantly, it does not activate
                iNOS activity, and has even
                demonstrated suppressive iNOS activity.


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Huperzine A
                                                          (Research Review)


              •            Huperzine A is powerful compound for
                           ideal nitric oxide isomer expression
                           because it enhances acetylcholine
                           activity necessary for eNOS and nNOS,
                           and it has powerful iNOS inhibiting
                           properties.


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Huperzine A
                                                          (Research Review)



              • Huperzine is a potent natural
                acetylcholine esterase inhibitor leading
                to increased acetylcholine activity that is
                necessary for ideal eNOS and nNOS
                activity.



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Huperzine A
                                                          (Research Review)




                 • Not only does Huperzine A inhibit iNOS
                   activity directly, but it also suppresses
                   the same cytokines that stimulate iNOS.




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Vinpocetine
                                                          (Research Review)



                 • Vinpocetine is classified as selective
                   cyclic GMP phosphodiesterase (PDE)
                   inhibitor and modulates vascular tone
                   and nitric oxide release in system
                   circulation.



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Vinpocetine
                                                          (Research Review)



                 • The net effect of PDE inhibitors, such as
                   vinpocetine, is to increase eNOS activity
                   leading to vasodilation and increase
                   blood delivery to peripheral tissues for
                   recovery.



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Vinpocetine
                                                          (Research Review)


              • In addition to vinpocetine’s properties of
                eNOS activation, the compound has
                powerful influences on the
                neurotransmitter acetylcholine.

              • Acetylcholine activity is critical for ideal
                eNOS receptor site activity.


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Alpha-GPC
                                                          (Research Review)

                • Oral intake of Alpha GPC has been shown
                  to increase acetylcholine levels in the
                  body.

                • Acetylcholine activity promotes nitric
                  oxide synthase activity and nitric oxide
                  promotes acetylcholine activity that is
                  responsible for eNOS vascular dilation
                  and nNOS synaptic activity.
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Alpha-Ketoglutaric Acid (AKG)
                                                          (Research Review)



                        Alpha-Ketoglutaric Acid is a citric cycle
                        intermediate and can be used to help
                        produce nitric oxide via the urea cycle
                        and metabolize harmful nitrogen out of
                        the body.


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Alpha-Ketoglutaric Acid (AKG)
                                                          (Research Review)




            • AKG supplementation has been shown to
              have positive modulating activity on iNOS.




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Alpha-Ketoglutaric Acid (AKG)
                                                          (Research Review)



               • AKG supplementation has been shown to
                 help modulate nitrogen balance and
                 preserve protein synthesis after cell injury.




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Xanthinol Nicotinate
                                                          (Research Review)




                       It has demonstrated properties to
                       increase eNOS by its nicotinate
                       component activity on the acetylcholine
                       receptors.



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Xanthinol Nicotinate
                                                          (Research Review)

              • Clinical research has found that xanthinol
                nicotinate has antioxidant properties that
                may lead to decreased iNOS activities.

              • Several research studies have found it
                improves microcirculation and aids in
                healing.


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Acetyl L-Carnitine (LAC)
                                                          (Research Review)



                • Research has shown that LAC mimics
                  acetylcholine activity, and has shown
                  effectiveness in acetylcholine-mediated
                  pathways.



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Acetyl L-Carnitine (LAC)
                                                          (Research Review)



              • Acetylcholine activity promotes nitric
                oxide synthase activity, and nitric oxide
                promotes acetycholine activity that is
                responsible for eNOS vascular dilation
                and nNOS synaptic activity.



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NEURO2™ (K45)
                •      Ginkgo Biloba
                •      Vinpocetine
                •      Butcher’s Broom
                •      Feverfew
                •      Cayenne (Capsaicin)




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Altered Methylation
                and Neurodegenerative
                       Disease


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Heijer, T, et al. 2002;1:170-175.
      Homocysteine and brain atrophy on MRI of non-demented elderly.




           • A study of 1077, non-demented people
             investigated the association between plasma
             homocysteine levels and severity of
             hippocampal, amygdalar, and global brain
             atrophy on MRI.



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Heijer, T, et al. 2002;1:170-175.
      Homocysteine and brain atrophy on MRI of non-demented elderly.




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Heijer, T, et al. 2002;1:170-175.
      Homocysteine and brain atrophy on MRI of non-demented elderly.




           • The results concluded higher plasma
             homocysteine levels are associated with
             more atrophy of the hippocampus and
             cortical regions in elderly at risk or
             Alzheimer’s disease.



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Heijer, T, et al. 2002;1:170-175.
      Homocysteine and brain atrophy on MRI of non-demented elderly.




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A study published in Neurology called the
               Rotterdam Scan Study with over 1,000 study
               subjects, demonstrated that homocysteine
               elevations were associated with silent brain
               infarcts and white matter lesions.




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METHYL-SP™ (K14)
         •       Folate 1200 mcg (300%)
         •       B-12 600 mcg (10,000 %)
         •       Choline 50 mg
         •       Trimethlyglycine 550 mg
         •       MSM 50 mg
         •       Beet (Root) 50 mg
         •       Betaine HCl 60 mg
         •       Magnesium 140 mg (35%)
         •       Vitamin C 50 mg (83%)
         •       Vitamin B6 10 mg (500%)
         •       Vitamin E 20 IU (66%)
         •       Riboflavin 10 mg (588%)
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SMRAB09(06092011)BROCK.PPT                                For Nutritional Purposes Only   174
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Autoimmunity
                                   in the Aging Brain



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Neuroreport. 1995 Jun 19;6(9):1274-6.
                                          Immune aging and Alzheimer’s disease.




          • The model thus emerging for sporadic
            Alzheimer's disease is that of a T-cell-
            mediated chronic autoimmune syndrome
            following the age-dependent loss of thymic
            function.



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Gerontology. 1997;43(1-2):79-94.
                                  Neuroautoimmunity: pathogenic implications
                                           for Alzheimer’s disease.



           • Immune factors such as cellular immunity,
             autoimmunity, and inflammation may play
             a pathogenic role in Alzheimer's disease
             (AD), a neurodegenerative disorder.




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Clin Rev Allergy Immunol. 2011 Jan 14.
                  Autoimmunity and autoantibodies in Parkinson’s disease.

          • Recent revelations of immune alterations in
            Parkinson's disease have led to the convergence
            that an autoimmune mechanism may play a role.

          • The presence of seven autoantibodies
            previously found to be associated with central
            nervous system manifestations, namely:
            antineuronal-cells, anti-brain lysate, anti-dsDNA,
            anti-phosphatidylserine, anti-cardiolipin, anti-
            serotonin, and anti-melanocytes antibodies.


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Clin Rev Allergy Immunol. 2011 Jan 14.
                  Autoimmunity and autoantibodies in Parkinson’s disease.




           • Clinical manifestations of Parkinson's
             disease, particularly dyskinesia and
             depression, were found to be associated
             with the presence of these autoantibodies.




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J Affect Disord. 2009 Aug;116(3):192-200.
                                            Anti-brain antibodies in adult patients
                                             with obsessive-compulsive disorder.


           • An autoimmune hypothesis has been
             suggested for a subtype of Obsessive-
             Compulsive Disorder (OCD) with childhood
             onset.

           • For a proportion of OCD patients,
             autoimmune reactions towards neuronal
             structures are present.

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Cyrex™ Labs
               Array 5 - Neuroautoimmunity Panel
                                                             Coming Soon




                                                          www.CyrexLabs.com

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                                                                              183
Putting It All Together



Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                          184
What State is the Neuron In?




Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                          185
What State is the Microglia In?




Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                          186
Earliest Signs of an Aging Brain
           • Fatigue promoted by brain activity – driving,
             reading, brain tasks

           • Depression – lack of healthy brain firing
             leads to depression

           • Poor Digestive Function – 90% of the brain’s
             output goes to the pontomedullary system


Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                             187
Moderate Signs of an Aging Brain
           • Inability to focus or concentrate
           • Difficulty learning new tasks
           • Chronic constipation, opportunistic intestinal
             overgrowth, digestive enzyme insufficiency
           • Increased sympathetic tone leading to:
              – increased blood pressure
              – increased resting heart rate
              – stress susceptibility
              – poor blood flow
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                              188
Significant Brain Aging
           • Inability to work professionally
           • Inability to appreciate life
           • Inability to perceive neurological loss
           • Early signs of neurological disease
              – tremors
              – inability to find directions
              – etc.

Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                                189
Severe Brain Aging
             • Neurodegenerative disease
             • Uncontrolled bladder tone
             • Bowel obstruction and inability to digest food
             • Inability to taste, smell, or develop social
               relationships
             • Dependency on family and medical staff for
               daily functions

Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                                    190
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                          191
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                          192
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                          For Nutritional Purposes Only   193
IMPORTANT & RELEVANT
                WEEKEND SEMINARS
                                                          DEVELOPED BY
                                                   DATIS KHARRAZIAN,
                               DC, DHSc, MS, MNeuroSci, FACFN, FABVR, FAACP,
                                        DACNB, DABCN, DIBAK, CNS




Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                                               194
FUNCTIONAL BLOOD CHEMISTRY
                              CEUs AVAILABLE. PLEASE INQUIRE FOR DETAILS.


    THIS WEEKEND COURSE IS DESIGNED TO HELP YOU:
    • Understand the differences between functional and pathological ranges on
      Lab Reports.
    • Understand the key principles of laboratory biochemistry.
    • Understand how to differentially evaluate blood chemistry patterns
         for nutritional purposes.
    • Identify nutritional and herbal compounds that can be used to
         support nutritional imbalances through a review of medical literature.


    RECOMMENDED COURSES (NOT REQUIRED) & CDs TO PREPARE FOR THIS
    WEEKEND COURSE:

    • CARDIO GI & IMMUNE AXIS (2-HOUR SEMINAR CD ALSO AVAILABLE WITH NOTES).

Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                                                  195
MASTERING THE THYROID
                                  CEUs AVAILABLE. PLEASE INQUIRE FOR DETAILS.


    This course will redefine and create the new standard for natural medicine support of thyroid
    imbalances. Dr. Kharrazian has meticulously organized a comprehensive and detailed three-day
    course to help clinicians master the concepts of thyroid physiology, assessment, and clinical
    applications.


    The following tools and concepts will give you insight into this unique approach:
    • Thyroid-Immune-Nervous System-Endocrine crosstalk and its clinical implications
    • The impact of thyroid hormones on every major physiological process
    • A step-by-step approach to conducting a thyroid physical examination
    • A complete review of the literature on natural supplements that supports or disrupts thyroid function
    • Identify 24 common and newly highlighted patterns that lead to thyroid imbalances on lab tests

    RECOMMENDED COURSES (NOT REQUIRED) & CDs TO PREPARE FOR THIS WEEKEND COURSE:
    • THYROID-BRAIN-IMMUNE PHYSIOLOGICAL CROSSTALK
    • AUTOIMMUNE THYROID RESEARCH AND PRACTICE UPDATES (2-HOUR SEMINAR OR CD ALSO
       AVAILABLE WITH NOTES)
    • THYROID PRINCIPLES AND CASE STUDIES (2-HOUR SEMINAR OR CD ALSO AVAILABLE
       WITH NOTES)
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                                                                              196
NEUROTRANSMITTERS & BRAIN
                             CEUs AVAILABLE. PLEASE INQUIRE FOR DETAILS.

   Dr. Kharrazian reviews physiological interactions among neurotransmitters,
   hormones, and the immune system. Clinical applications regarding questionnaire
   forms, laboratory tests, and nutritional supplements will be emphasized
   in the course.
   A complete review of the literature that pertains to natural supplements
   that support neurotransmitters, hormones, and the immune system will be provided
   in the course book. Numerous clinical pearls and case studies will be presented to
   provide information that can be used effectively by the practicing clinician.

   TAKE YOUR PRACTICE AND CLIENTS’ HEALTH TO THE NEXT LEVEL WITH
   THIS COURSE!
   RECOMMENDED COURSES (NOT REQUIRED) & CDs TO PREPARE FOR THIS
   WEEKEND COURSE:
   • INTRODUCTION TO NEUROCHEMISTRY (2-HOUR SEMINAR)
   • FUNCTIONAL BLOOD CHEMISTRY & FUNCTIONAL ENDOCRINOLOGY
     (CEU-APPROVED WEEKEND COURSES)
Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                                                    197
For dates and additional information:
                             PLEASE LOOK FOR OUR
              WEEKEND & 2-HOUR COURSE
                    SCHEDULE!
                                    www.apexseminars.com


Copyright © 2011 Datis Kharrazian. All Rights Reserved.
SMRAB09(06092011)BROCK.PPT
                                                           198

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Renewing the Aging Brain

  • 1. sponsored by apexenergetics RENEWING THE AGING BRAIN Presented by BRANDON BROCK, RN, BSN, MSN/FNP, DC, DACNB, FACFN, FABES, FABVR, FICC, RNCST, CNCT Written by DATIS KHARRAZIAN, DC, DHSc, MS, MNeuroSci, Associate Professor of Clinical Neurology - Carrick Institute Fellow of the American College of Functional Neurology Fellow of the American Board of Vestibular Rehabilitation Fellow of the American Academy of Chiropractic Physicians Diplomate of the American Board of Clinical Nutrition Diplomate of the Board of Nutrition Specialists Diplomate of the International Board of Applied Kinesiology Diplomate of the American Board of Chiropractic Neurology Copyright © 2011 Datis Kharrazian. All Rights Reserved. Copyright © 2011, Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 1
  • 2. INTENDED USE STATEMENT The content of this course is intended for informational purposes only. The medical information in this course is intended as general information only and should not be used in any way to diagnose, treat, cure, or prevent any disease. The goal of this course is to present and highlight nutritionally significant information, and offer suggestions and protocols for nutritional support and health maintenance. Homeopathic protocols are intended for use in symptom relief and OTC indications only. It is the sole responsibility of the user of this information to comply with all local and federal laws regarding the use of such information, as it relates to the scope and type of user’s practice. The nutritional protocols and suggestions presented in this course are based on the presenter’s clinical experience and research and are not intended to represent any claims regarding product performance or benefits by the manufacturer, its distributors, or the sponsors of this seminar. Statements regarding nutritional products in this seminar have not been evaluated by the Food and Drug Administration. Nutritional products presented in this seminar are not intended to diagnose, treat, cure, or prevent any disease. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 2
  • 3. DISCLAIMER AND NOTICES The information and recommendations outlined in this presentation are not intended as a substitute for personalized medical advice. The presentation proposes certain theoretical methods of nutrition, not necessarily mainstream. It is left to the discretion, and it is the sole responsibility of the user of the information indicated in the presentation, to determine if procedures and recommendations described are appropriate for a patient. Neither the authors nor the sponsors (such as Apex Energetics) of this information can be held responsible for the information or any inadvertent errors or omissions of the information. The information in this presentation should not be construed as a claim or representation that any procedure or product mentioned constitutes a specific cure, palliative or ameliorative. Procedures and products described should be considered as adjunctive to other accepted conventional procedures deemed necessary by the attending licensed doctor. It is the concern of the Department of Health and Human Services that no homeopathic and nutritional supplements be used to replace established, conventional medical approaches, especially in cases of emergencies, serious or life threatening diseases or conditions. We share in this concern, as replacing conventional treatment with such remedies, especially in serious cases, may deprive the patient of necessary treatment and thereby cause harm as well as potentially pose a major legal liability for the health professional involved. Apex formulas should not be used as replacements for conventional medical treatment. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 3
  • 4. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 4
  • 5. The Glia System Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 5
  • 6. Healthy and Unhealthy Neurons Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 6
  • 7. How Old is Your Brain? Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 7
  • 8. Atrophy of the Memory Centers Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 8
  • 9. The Aging Brain Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 9
  • 10. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 10
  • 11. Questions to Ask • Is it too late? • Is it permanent? • What changes can be made? • Will it get worse? Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 11
  • 12. What are the Earliest Signs of an Aging Brain? Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 12
  • 13. Earliest Signs of an Aging Brain • Fatigue promoted by brain activity – driving, reading, brain tasks • Depression – lack of healthy brain firing leads to depression • Poor Digestive Function – 90% of the brain’s output goes to the pontomedullary system Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 13
  • 14. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 14
  • 15. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 15
  • 16. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 16
  • 17. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 17
  • 18. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 18
  • 19. Autonomic Nervous System Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 19
  • 20. Moderate Signs of Aging Brain • Inability to focus or concentrate • Difficulty learning new tasks • Chronic constipation, opportunistic intestinal overgrowth, digestive enzyme insufficiency • Increased sympathetic tone leading to: – Increased blood pressure – Increased resting heart rate – Stress susceptibility – Poor blood flow Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 20
  • 21. Significant Brain Aging • Inability to work professionally • Inability to appreciate life • Inability to perceive neurological loss • Early signs of neurological disease – tremors – inability to find directions – etc. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 21
  • 22. Severe Brain Aging • Neurodegenerative disease • Uncontrolled bladder tone • Bowel obstruction and inability to digest food • Inability to taste, smell, or develop social relationships • Dependency on family and medical staff for daily functions Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 22
  • 23. Where are you? Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 23
  • 24. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 24
  • 25. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 25
  • 26. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 26
  • 27. What are the Mechanisms for Poor Brain Aging? Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 27
  • 28. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 28
  • 29. Brain Aging of the Memory System Dementia and Alzheimer’s Disease Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 29
  • 30. The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD. Memory and the aging brain. • Studies that look at only the healthiest elderly tend to find minimal cognitive decline even into the ninth decade. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 30
  • 31. The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD. Memory and the aging brain. • It is clear that significant cognitive decline is not an inevitable consequence of advanced age. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 31
  • 32. The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD. Memory and the aging brain. • More than 4 million Americans have dementia, and the number is projected to grow to 14 million in the next 50 years. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 32
  • 33. The University of Iowa – Steven Anderson, PhD and Thomas Graboski, MD. Memory and the aging brain. • Currently there is no cure for dementia. • All people are at risk for dementia, with the greatest risk factor being increased age. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 33
  • 34. • Are you getting older? • Do you have the earliest signs of dementia? • Are you taking this seriously? Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 34
  • 35. Earliest Signs of Dementia • Poor short-term memory • Difficulty learning • Difficulty with directions • Decreased brain endurance If you have the symptoms, when did they start and how fast are they going? Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 35
  • 36. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 36
  • 37. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 37
  • 38. Papez Circuit Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 38
  • 39. Acetylcholine Pathways Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 39
  • 40. Early Alzheimer’s Disease Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 40
  • 41. Progressed Alzheimer’s Disease Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 41
  • 42. Healthy Neuron Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 43
  • 43. Beta-Amyloid Being Cleaved Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 44
  • 44. Beta-Amyloid Plaque Formation Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 45
  • 45. Tau Proteins Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 46
  • 46. Neurofibrillary Tangles Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 47
  • 47. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 48
  • 48. Clock Drawing Test Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 49
  • 49. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 50
  • 50. Acetylcholine Pathways Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 51
  • 51. Brain Affected Areas in Alzheimer’s Disease Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 52
  • 52. Symptoms of Cholinergic Pathways Degeneration • Loss of photographic memory • Difficulty with sense of directions • Poor memory • Memory lapses • Poor verbal memory • Slow mental speed Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 53
  • 53. Signs of Cholinergic Pathways Degeneration • Constantly losing keys, phone, etc. • Constantly forget where car is parked • Dependency on navigations system for directions • Must write everything down • Constantly forgetting appointments, tasks, etc. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 54
  • 54. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 55
  • 55. ACETYL-CH® ACTIVE (K40) • Huperzine A • Alpha-GPC • N-Acetyl L-Carnitine • Pantothenic Acid Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 56
  • 56. Brain Aging of the GABAergic System Anxiety, Restlessness, Panic Attacks Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 57
  • 57. GABAergic Pathways Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 58
  • 58. Symptoms of GABAergic Pathway Degeneration • Feelings of anxiety or panic for reasons • Difficulty shutting mind off • Feelings of being overwhelmed for no reason • Disorganized attention • Feelings of restlessness Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 59
  • 59. Signs of GABAergic Pathway Degeneration • Anxiety episodes • Cannot initiate projects due to constant distractions • Startled easily and difficulty calming down afterwards • Severely sensitive to light and sound • Increased resting heart rate Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 60
  • 60. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 61
  • 61. GABATONE® ACTIVE (K39) • Valerian Root extract • Lithium Orotate • Passion Flower extract • L-Theanine • L-Taurine • Pyridoxal-5-Phosphate • Manganese Succinate • Zinc Glycinate • Magnesium Succinate Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 62
  • 62. Brain Aging of the Serotonergic System Depression, Loss of Joy, Poor Focus, Sense of Self and Purpose Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 63
  • 63. Serotonergic Pathways Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 64
  • 64. Symptoms of Serotonergic Pathway Degeneration • Guilty depression • Inability to feel joy from hobbies, friends, music, food, etc. • Depressed with overcast weather or chronic lack of sunlight • Loss of interest in life Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 65
  • 65. Signs of Serotonergic Pathway Degeneration • Social isolation with unwillingness to go out • Depression • Cravings and overeating of carbohydrates and sugars • Slowed reflexes and coordination Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 66
  • 66. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 67
  • 67. SEROTONE® ACTIVE (K38) • 5-Hydroxytryptophan • St. John’s Wort • SAMe • Pyridoxal 5 Phosphate • Niacinamide • Magnesium Citrate • Methylcobalamin • Calcium Folinate Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 68
  • 68. Brain Aging of the Dopaminergic System Depression, Loss of Motivation, Inability to Finish Tasks, Slow Movements, Slow Mind Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 69
  • 69. Dopaminergic Pathways Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 70
  • 70. Dopamine Receptors in the Brain Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 71
  • 71. Areas of the Brain in Depression Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 72
  • 72. Symptoms of Dopaminergic Pathway Degeneration • Feelings of hopelessness and worthlessness • Inability to handle stress • Unable to self-motivate to start or finish tasks • Need to consume caffeine to stay focused • Depression Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 73
  • 73. Signs of Dopaminergic Pathway Degeneration • Depression • Isolation • Quick to snap at every little thing • Poor compliance with healthcare, exercise, etc. • Anger episodes • Hypokinesia (slow and diminished movements) • Constipation with diminished smell or taste perception Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 74
  • 74. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 75
  • 75. DOPATONE® ACTIVE (K41) • Mucuna Pruriens • Beta-Phenylethylamine • Blueberry extract • D,L – Phenylalanine • N-Acetyl L-Tyrosine • Pyridoxal 5 Phosphate • Alpha Lipoic Acid • Selenium • N-Acetyl L-Cysteine Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 76
  • 76. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 77
  • 77. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 78
  • 78. Phosopholipid Integrity 60% of the Brain is Made Up of Phosopholipids Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 79
  • 79. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 80
  • 80. Phosopholipids and Neuron Structure Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 81
  • 81. Neuroscience. 1999;94(1):305-14. Age-related changes in synaptic function: analysis of the role of dietary supplementation. • DHA is used to enhance cell fluidity, neuronal signaling, neuronal dendrite growth, and brain function, as well as reduce inflammation, and decrease the incidence of neurodegenerative conditions. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 82
  • 82. Int. J Neurosci. 1996 Nove;87(3-4):141-9. Essential fatty acids preparation (SR-3) improves Alzheimer’s patient’s quality of life. • DHA intake has demonstrated the ability to boost brain function, improve quality of life, and reduce the incidence of neurodegenerative conditions. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 83
  • 83. Current Enzyme Inhibition. 2005;1:11-20. Sesamin and sesamolin: nature’s therapeutic lignans. • Sesamin and Sesamolin found in sesame seed oil and have exhibited properties to protect neurons and modulate microglia neuroinflammatory properties. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 84
  • 84. Int J of Biomed Sci. 2006:2:284-288. Neuroprotective effects of sesamin and sesamolin on gerbil brain in cerebral ischemia. • Sesamin and sesamolin have the ability to attenuate excess generation of oxidative stress stimulated by microglia and to reduce infarct size by approximately 50% when compared with the control group in a cerebral artery occlusion study. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 85
  • 85. Biochem J. 1982;208(3):631-40. Influence of dietary fat on lipid composition of rat brain synaptosomal and microsomal membranes. • Phosphatidylcholine (PC) plays a crucial role in the formation and structural integrity of neurons and brain architecture. • PC supports cell-membrane integrity, fluidizing the membranes, and it supports intracellular communication. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 86
  • 86. Artif Cells Blood Substit Immobil Biotechnol. 1994;22(1):83-9. Effects of lecithin-emulsified perflurochemical compounds in ischemic brain injury. • Dietary supplementation with Phosphatidylcholine has exhibited protection against oxidative and ischemic neuronal damage. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 87
  • 87. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 88
  • 88. BRAIN-E® DHA (K53/55/65) PHYTO BRAIN-E® (K54) • DHA • EPA • Phosphatidylcholine • Sesame oil Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 89
  • 89. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 90
  • 90. Phosopholipids and Neuron Structure Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 91
  • 91. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 92
  • 92. Mitochondria Oxidative Phosphorylation Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 93
  • 93. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 94
  • 94. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 95
  • 95. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 96
  • 96. Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10. Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine. • To investigate the mitochondrial decay and oxidative damage resulting from aging, the kinetics of the mitochondrial complexes were examined in the brains of young and old rats as well as in old rats fed alpha- lipoic acid plus acetyl-L-carnitine. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 97
  • 97. Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10. Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine. • The brain mitochondria of old rats, compared with young rats, had significantly decreased endogenous antioxidants and superoxide dismutase activity; more oxidative damage to lipids and proteins; and decreased activities of complex I, IV, and V. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 98
  • 98. Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10. Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine. • Feeding LA/ALC to old rats partially restored age-associated mitochondrial dysfunction to the levels of the young rats. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 99
  • 99. Neurochem Res. 2009 Apr;34(4):755-63. Epub 2008 Oct 10. Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine. • These results indicate that oxidative mitochondrial decay plays an important role in brain aging and that a combination of nutrients targeting mitochondria could ameliorate mitochondrial decay. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 100
  • 100. J Neurosci Res. 2008 Aug 1;86(10):2339-52. Age-related decreases in NAD(P)H and glutathione cause redox declines before ATP loss during glutamate treatment of hippocampal neurons. • We conclude that old-aged neurons consume more NADH and glutathione, leading to a catastrophic decline in redox ratio, leading to age-related glutamate excitotoxicity. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 101
  • 101. Brain Res. 2006 May 23;1090(1):35-44. Epub 2006 May 2. Age-related changes in glutathione and glutathione-related enzymes in rat brain. • The most reliable and robust risk factor for some neurodegenerative diseases is aging. • It has been proposed that processes of aging are associated with the generation of reactive oxygen species and a disturbance of glutathione homeostasis in the brain. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 102
  • 102. Brain Res. 2006 May 23;1090(1):35-44. Epub 2006 May 2. Age-related changes in glutathione and glutathione-related enzymes in rat brain. • The results suggested a significant age- related reduction of reduced glutathione (GSH) level in all brain regions examined, associated with an increase of GSH oxidation to glutathione disulfide (GSSG) and decrease of the GSH/GSSG ratio. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 103
  • 103. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 104
  • 104. GLUTATHIONE RECYCLER® (K57) • Cordyceps extract • Gotu Kola extract • Milk Thistle extract • N-Acetyl Cysteine • Alpha Lipoic Acid • L-Glutamine • Selenium Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 105
  • 105. N-Acetyl Cysteine (Research Review) • Research has clearly demonstrated that N-Acetyl Cysteine is rapidly metabolized to intracellular glutathione. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 106
  • 106. Alpha Lipoic Acid (Research Review) • It directly recycles and extends the metabolic life spans of vitamin C, glutathione, and coenzyme Q10, and it indirectly renews vitamin E, all of which are necessary for glutathione recycling. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 107
  • 107. L-Glutamine (Research Review) • Research has demonstrated that glutamine is important for the generation of glutathione. • It is transported into the cell, converted to glutamate, and readily available for intracellular glutathione synthesis. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 108
  • 108. Selenium (Research Review) • Selenium is a trace element nutrient that serves as the essential cofactor for the enzyme glutathione peroxidase. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 109
  • 109. Cordyceps (Research Review) • It has been shown to activate glutathione peroxidase synthesis in the body. • Cordyceps research has demonstrated that it helps protect cells by engaging the glutathione enzyme cycle. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 110
  • 110. Gotu Kola (Research Review) • Research has clearly demonstrated that oral intake very rapidly and dramatically increases the activity and amount of glutathione perioxidase and the quantity of glutathione. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 111
  • 111. Milk Thistle (Research Review) • Administration of milk thistle has shown to significantly increase glutathione, increase superoxide dismutase activity, and have a positive influence in the ratios of reduced and oxidized glutathione. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 112
  • 112. NEURO-PTX® (K47) • N-Acetyl Cysteine • N-Acetyl Carnitine • Alpha Lipoic Acid • Creatine Monohydrate • Genistein • Milk Thistle extract • CoQ10 • Alpha Ketoglutarate • d-alpha tocopherol succinate Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 113
  • 113. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 114
  • 114. Microglia Neuroinflammation Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 115
  • 115. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 116
  • 116. Brain on Fire Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 117
  • 117. Reactive Microgliosis Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 118
  • 118. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 119
  • 119. NEUROFLAM™ (K46) • Apigenin • Luteolin • Baicalin • Rutin • Catechin • Curcumin (turmeric) Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 120
  • 120. Mol Nutr Food Res. 2008;52(4):427-38. Plant-derived polypheonls attenuate lipopolysaccharide-induced nitric oxide and tumour necrosis factor production in murine microglia and macrophages. • Apigenin attenuated lipopolysaccharide induced nitric oxide and TNF production in microglia. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 121
  • 121. J Neuroinflammation. 2008;25(5):41. Apignin and luteolin modulate microglial activation via inhibition of STAT-1 induced CD40 expression. • Apigenin and luteolin concentration- dependently suppressed IFN-gamma- induced CD40 expression of microglia. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 122
  • 122. J Neuroinflammation. 2008;25(5):41. Apignin and luteolin modulate microglial activation via inhibition of STAT-1 induced CD40 expression. • Our findings provide further support that apigenin and luteolin's anti-inflammatory effects have neuroprotective properties in various neurodegenerative disorders. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 123
  • 123. Neurosci Lett. 2008;448(2):175-179. Luteolin protects dopaminergic neurons from inflammation-induced injury through inhibition of microglial activation. • Luteolin also significantly inhibited LPS- induced activation of microglia. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 124
  • 124. Neurosci Lett. 2008;448(2):175-179. Luteolin protects dopaminergic neurons from inflammation-induced injury through inhibition of microglial activation. • Our results demonstrate that luteolin may protect neurons by inhibiting microglia activation. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 125
  • 125. Proc Natl Acad Sci USA. 2008;105(21):7534-7539. Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. • Luteolin may be useful for mitigating microglia neuroinflammation. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 126
  • 126. J Pharmacol Exp Ther. 2003;305(2):638-45. Flavonoid baicalein attenuates activation-induced cell death of brain microglia. • Our current results suggest that baicalein selectively inhibits activated microglia. • Also, inhibiting effects of baicalein were specific for the inflammatory stimulus that activated microglia. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 127
  • 127. Neurosci Lett. 2008;441(1):16-20. Neuroprotective effect of baicalein against MPTP neurotoxicity: behavioral, biochemical and immunohistochemical profile. • The results suggest that baicalein possesses potent neuroprotective activity and has potential anti-Parkinson’s activity. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 128
  • 128. Neuroreport. 2001;12(10):2199-202. Baicalein protects cortical neurons from beta-amyloid (25-350 induced toxicity). • Baicalein protects lipoxygenase mediated pathways for micoroglia activated neuroinflammation associated with Alzheimer’s disease. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 129
  • 129. Invest Opthalmol Vis Sci. 2008; Nov 14. Baicalein reduces inflammatory process in a rodent model of diabetic retinopathy. • Baicalein has demonstrated to ameliorate inflammatory processes of diabetic retinopathy and has inhibitory activity against neuron loss in diabetic retinas. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 130
  • 130. Brain Res. 2008; Oct 18 [Epub ahead of print]. Baicalein protects rat brain mitochondria against chronic cerebral hypoperfusion-induced oxidative damage. • Baicalein has been found to protect neuronal mitochondria damage and swelling promoted by chronic cerebral hypoperfusion and has been suggested as a potential support agent for dementia caused by decreased blood flow to the brain. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 131
  • 131. Neurochem Res. 2008;33(10):2044-53. Curcumin protects dopaminergic neuron against LPS induced neurotoxicity in primary rat neuron/glia culture. • Curcumin has demonstrated the ability to protect dopaminergic neurons against lioppolysaccharide induced neurotoxicity in animal neurona/glia culture. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 132
  • 132. Acta Pharmacol Sin. 2007;28(10):1645-51. Curcumin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated BV2 microglia. • Curcumin has been found to have neuroprotective effects by blocking the production of pro-inflammatory and cytotoxic mediators by activated microglia. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 133
  • 133. REPAIRVITE® (K60) • L-Glutamine • MSM • Licorice extract • Aloe Vera extract • Marshmallow extract • Slippery Elm extract • Spanish Moss • German Chamomile extract • Marigold extract Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 134
  • 134. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 135
  • 135. Cerebral Blood Flow Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 136
  • 136. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 137
  • 137. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 138
  • 138. Blood Flow = Function Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 139
  • 139. BMC Neurosci. 2010 Jun 24;11(1):78. Study of the nitric oxide system in the rat cerebellum during aging. • In the senescent cerebellum, inducible nitric oxide system activity results in an increase of the protein nitration. • These changes might be related to the oxidative damage detected with aging in the cerebellum. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 140
  • 140. Brain Res. 2002 Nov 29;956(2):385-92. Age-related changes of the nitric oxide system in the rat brain. • Concerning age, in the cerebellum the eNOS expression decreased whereas iNOS increased. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 141
  • 141. Biochim Biophys Acta. 1999 May 5;1411(2-3):415-36. Roles of nitric oxide in brain hypoxia-ischemia. • A large body of evidence has appeared over the last 6 years suggesting that nitric oxide biosynthesis is a key factor in the pathophysiological response of the brain to hypoxia-ischemia. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 142
  • 142. Biochim Biophys Acta. 1999 May 5;1411(2-3):415-36. Roles of nitric oxide in brain hypoxia-ischemia. • In conclusion, it appears that activation of iNOS mediates ischemic brain damage. • However, there is a simultaneous compensatory response through eNOS activation within the endothelium of blood vessels, which mediates vasodilation and hence increases blood flow to the damaged brain area. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 143
  • 143. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 144
  • 144. NITRIC BALANCE® (K62) • ATP • Huperzine A • Vinpocetine • Alpha-GPC • Alpha-Ketoglutaric Acid (AKG) • Xanthinol Nicotinate • Acetyl L-Carnitine Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 145
  • 145. NITRIC BALANCE® (K62) • Provides compounds that are used to support the expression of eNOS and nNOS, while dampening the expression of iNOS. Healthy balance of NO helps the body to: 1. Support tissue healing 2. Dampen tissue inflammation and destruction 3. Modulate autoimmune reactions Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 146
  • 146. Adenosine (Research Review) • Adenosine increases extracellular ATP, which has been found to activate eNOS and nNOS. • More importantly, it does not activate iNOS activity, and has even demonstrated suppressive iNOS activity. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 147
  • 147. Huperzine A (Research Review) • Huperzine A is powerful compound for ideal nitric oxide isomer expression because it enhances acetylcholine activity necessary for eNOS and nNOS, and it has powerful iNOS inhibiting properties. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 148
  • 148. Huperzine A (Research Review) • Huperzine is a potent natural acetylcholine esterase inhibitor leading to increased acetylcholine activity that is necessary for ideal eNOS and nNOS activity. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 149
  • 149. Huperzine A (Research Review) • Not only does Huperzine A inhibit iNOS activity directly, but it also suppresses the same cytokines that stimulate iNOS. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 150
  • 150. Vinpocetine (Research Review) • Vinpocetine is classified as selective cyclic GMP phosphodiesterase (PDE) inhibitor and modulates vascular tone and nitric oxide release in system circulation. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 151
  • 151. Vinpocetine (Research Review) • The net effect of PDE inhibitors, such as vinpocetine, is to increase eNOS activity leading to vasodilation and increase blood delivery to peripheral tissues for recovery. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 152
  • 152. Vinpocetine (Research Review) • In addition to vinpocetine’s properties of eNOS activation, the compound has powerful influences on the neurotransmitter acetylcholine. • Acetylcholine activity is critical for ideal eNOS receptor site activity. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 153
  • 153. Alpha-GPC (Research Review) • Oral intake of Alpha GPC has been shown to increase acetylcholine levels in the body. • Acetylcholine activity promotes nitric oxide synthase activity and nitric oxide promotes acetylcholine activity that is responsible for eNOS vascular dilation and nNOS synaptic activity. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 154
  • 154. Alpha-Ketoglutaric Acid (AKG) (Research Review) Alpha-Ketoglutaric Acid is a citric cycle intermediate and can be used to help produce nitric oxide via the urea cycle and metabolize harmful nitrogen out of the body. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 155
  • 155. Alpha-Ketoglutaric Acid (AKG) (Research Review) • AKG supplementation has been shown to have positive modulating activity on iNOS. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 156
  • 156. Alpha-Ketoglutaric Acid (AKG) (Research Review) • AKG supplementation has been shown to help modulate nitrogen balance and preserve protein synthesis after cell injury. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 157
  • 157. Xanthinol Nicotinate (Research Review) It has demonstrated properties to increase eNOS by its nicotinate component activity on the acetylcholine receptors. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 158
  • 158. Xanthinol Nicotinate (Research Review) • Clinical research has found that xanthinol nicotinate has antioxidant properties that may lead to decreased iNOS activities. • Several research studies have found it improves microcirculation and aids in healing. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 159
  • 159. Acetyl L-Carnitine (LAC) (Research Review) • Research has shown that LAC mimics acetylcholine activity, and has shown effectiveness in acetylcholine-mediated pathways. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 160
  • 160. Acetyl L-Carnitine (LAC) (Research Review) • Acetylcholine activity promotes nitric oxide synthase activity, and nitric oxide promotes acetycholine activity that is responsible for eNOS vascular dilation and nNOS synaptic activity. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes only 161
  • 161. NEURO2™ (K45) • Ginkgo Biloba • Vinpocetine • Butcher’s Broom • Feverfew • Cayenne (Capsaicin) Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 162
  • 162. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 163
  • 163. Altered Methylation and Neurodegenerative Disease Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 164
  • 164. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 165
  • 165. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 166
  • 166. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 167
  • 167. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 168
  • 168. Heijer, T, et al. 2002;1:170-175. Homocysteine and brain atrophy on MRI of non-demented elderly. • A study of 1077, non-demented people investigated the association between plasma homocysteine levels and severity of hippocampal, amygdalar, and global brain atrophy on MRI. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 169
  • 169. Heijer, T, et al. 2002;1:170-175. Homocysteine and brain atrophy on MRI of non-demented elderly. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 170
  • 170. Heijer, T, et al. 2002;1:170-175. Homocysteine and brain atrophy on MRI of non-demented elderly. • The results concluded higher plasma homocysteine levels are associated with more atrophy of the hippocampus and cortical regions in elderly at risk or Alzheimer’s disease. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 171
  • 171. Heijer, T, et al. 2002;1:170-175. Homocysteine and brain atrophy on MRI of non-demented elderly. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 172
  • 172. A study published in Neurology called the Rotterdam Scan Study with over 1,000 study subjects, demonstrated that homocysteine elevations were associated with silent brain infarcts and white matter lesions. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 173
  • 173. METHYL-SP™ (K14) • Folate 1200 mcg (300%) • B-12 600 mcg (10,000 %) • Choline 50 mg • Trimethlyglycine 550 mg • MSM 50 mg • Beet (Root) 50 mg • Betaine HCl 60 mg • Magnesium 140 mg (35%) • Vitamin C 50 mg (83%) • Vitamin B6 10 mg (500%) • Vitamin E 20 IU (66%) • Riboflavin 10 mg (588%) Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 174
  • 174. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 175
  • 175. Autoimmunity in the Aging Brain Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 176
  • 176. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 177
  • 177. Neuroreport. 1995 Jun 19;6(9):1274-6. Immune aging and Alzheimer’s disease. • The model thus emerging for sporadic Alzheimer's disease is that of a T-cell- mediated chronic autoimmune syndrome following the age-dependent loss of thymic function. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 178
  • 178. Gerontology. 1997;43(1-2):79-94. Neuroautoimmunity: pathogenic implications for Alzheimer’s disease. • Immune factors such as cellular immunity, autoimmunity, and inflammation may play a pathogenic role in Alzheimer's disease (AD), a neurodegenerative disorder. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 179
  • 179. Clin Rev Allergy Immunol. 2011 Jan 14. Autoimmunity and autoantibodies in Parkinson’s disease. • Recent revelations of immune alterations in Parkinson's disease have led to the convergence that an autoimmune mechanism may play a role. • The presence of seven autoantibodies previously found to be associated with central nervous system manifestations, namely: antineuronal-cells, anti-brain lysate, anti-dsDNA, anti-phosphatidylserine, anti-cardiolipin, anti- serotonin, and anti-melanocytes antibodies. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 180
  • 180. Clin Rev Allergy Immunol. 2011 Jan 14. Autoimmunity and autoantibodies in Parkinson’s disease. • Clinical manifestations of Parkinson's disease, particularly dyskinesia and depression, were found to be associated with the presence of these autoantibodies. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 181
  • 181. J Affect Disord. 2009 Aug;116(3):192-200. Anti-brain antibodies in adult patients with obsessive-compulsive disorder. • An autoimmune hypothesis has been suggested for a subtype of Obsessive- Compulsive Disorder (OCD) with childhood onset. • For a proportion of OCD patients, autoimmune reactions towards neuronal structures are present. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 182
  • 182. Cyrex™ Labs Array 5 - Neuroautoimmunity Panel Coming Soon www.CyrexLabs.com Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 183
  • 183. Putting It All Together Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 184
  • 184. What State is the Neuron In? Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 185
  • 185. What State is the Microglia In? Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 186
  • 186. Earliest Signs of an Aging Brain • Fatigue promoted by brain activity – driving, reading, brain tasks • Depression – lack of healthy brain firing leads to depression • Poor Digestive Function – 90% of the brain’s output goes to the pontomedullary system Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 187
  • 187. Moderate Signs of an Aging Brain • Inability to focus or concentrate • Difficulty learning new tasks • Chronic constipation, opportunistic intestinal overgrowth, digestive enzyme insufficiency • Increased sympathetic tone leading to: – increased blood pressure – increased resting heart rate – stress susceptibility – poor blood flow Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 188
  • 188. Significant Brain Aging • Inability to work professionally • Inability to appreciate life • Inability to perceive neurological loss • Early signs of neurological disease – tremors – inability to find directions – etc. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 189
  • 189. Severe Brain Aging • Neurodegenerative disease • Uncontrolled bladder tone • Bowel obstruction and inability to digest food • Inability to taste, smell, or develop social relationships • Dependency on family and medical staff for daily functions Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 190
  • 190. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 191
  • 191. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 192
  • 192. Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT For Nutritional Purposes Only 193
  • 193. IMPORTANT & RELEVANT WEEKEND SEMINARS DEVELOPED BY DATIS KHARRAZIAN, DC, DHSc, MS, MNeuroSci, FACFN, FABVR, FAACP, DACNB, DABCN, DIBAK, CNS Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 194
  • 194. FUNCTIONAL BLOOD CHEMISTRY CEUs AVAILABLE. PLEASE INQUIRE FOR DETAILS. THIS WEEKEND COURSE IS DESIGNED TO HELP YOU: • Understand the differences between functional and pathological ranges on Lab Reports. • Understand the key principles of laboratory biochemistry. • Understand how to differentially evaluate blood chemistry patterns for nutritional purposes. • Identify nutritional and herbal compounds that can be used to support nutritional imbalances through a review of medical literature. RECOMMENDED COURSES (NOT REQUIRED) & CDs TO PREPARE FOR THIS WEEKEND COURSE: • CARDIO GI & IMMUNE AXIS (2-HOUR SEMINAR CD ALSO AVAILABLE WITH NOTES). Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 195
  • 195. MASTERING THE THYROID CEUs AVAILABLE. PLEASE INQUIRE FOR DETAILS. This course will redefine and create the new standard for natural medicine support of thyroid imbalances. Dr. Kharrazian has meticulously organized a comprehensive and detailed three-day course to help clinicians master the concepts of thyroid physiology, assessment, and clinical applications. The following tools and concepts will give you insight into this unique approach: • Thyroid-Immune-Nervous System-Endocrine crosstalk and its clinical implications • The impact of thyroid hormones on every major physiological process • A step-by-step approach to conducting a thyroid physical examination • A complete review of the literature on natural supplements that supports or disrupts thyroid function • Identify 24 common and newly highlighted patterns that lead to thyroid imbalances on lab tests RECOMMENDED COURSES (NOT REQUIRED) & CDs TO PREPARE FOR THIS WEEKEND COURSE: • THYROID-BRAIN-IMMUNE PHYSIOLOGICAL CROSSTALK • AUTOIMMUNE THYROID RESEARCH AND PRACTICE UPDATES (2-HOUR SEMINAR OR CD ALSO AVAILABLE WITH NOTES) • THYROID PRINCIPLES AND CASE STUDIES (2-HOUR SEMINAR OR CD ALSO AVAILABLE WITH NOTES) Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 196
  • 196. NEUROTRANSMITTERS & BRAIN CEUs AVAILABLE. PLEASE INQUIRE FOR DETAILS. Dr. Kharrazian reviews physiological interactions among neurotransmitters, hormones, and the immune system. Clinical applications regarding questionnaire forms, laboratory tests, and nutritional supplements will be emphasized in the course. A complete review of the literature that pertains to natural supplements that support neurotransmitters, hormones, and the immune system will be provided in the course book. Numerous clinical pearls and case studies will be presented to provide information that can be used effectively by the practicing clinician. TAKE YOUR PRACTICE AND CLIENTS’ HEALTH TO THE NEXT LEVEL WITH THIS COURSE! RECOMMENDED COURSES (NOT REQUIRED) & CDs TO PREPARE FOR THIS WEEKEND COURSE: • INTRODUCTION TO NEUROCHEMISTRY (2-HOUR SEMINAR) • FUNCTIONAL BLOOD CHEMISTRY & FUNCTIONAL ENDOCRINOLOGY (CEU-APPROVED WEEKEND COURSES) Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 197
  • 197. For dates and additional information: PLEASE LOOK FOR OUR WEEKEND & 2-HOUR COURSE SCHEDULE! www.apexseminars.com Copyright © 2011 Datis Kharrazian. All Rights Reserved. SMRAB09(06092011)BROCK.PPT 198