Download
neurodegenerative disease n.
Skip this Video
Loading SlideShow in 5 Seconds..
Neurodegenerative Disease PowerPoint Presentation
Download Presentation
Neurodegenerative Disease

Neurodegenerative Disease

694 Vues Download Presentation
Télécharger la présentation

Neurodegenerative Disease

- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

  1. NeurodegenerativeDisease Dr Melvyn A Sydney-Smith. KGSJ. MBBS, PhD, Dip Gest Ther, Master Prac NLP, FACNEM. Australian College of Holistic Medicine Adjunct Professor, Nutrition Medicine RMIT University

  2. Neurodegenerative Disease Excludes known disease: vascular, toxic, metabolic,infective and autoimmune disease Progressive, nerve cell dysfunction & apoptosis  eventuating in CNS atrophy & death Affects specific brain systems implies selective regionalnerve cell vulnerability Pathogenesis is ill-defined is apparently multifactorial ~related to~ genetic, environmental, metabolic and other aging factors Abnormal protein accumulation ~e.g. amyloid B plaques M. Flint Beal, AC. Ludolph (2005). Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics, Cambridge University Press.

  3. Neurodegenerative Disease Dementia disordersAlzheimer’s DiseasePick’s Disease All share common characteristics Movement disordersParkinson’s DiseaseCerebellar AtaxiaMotor Neurone DiseaseMultiple System Atrophy Dementia + Movement disordersDiffuse Lewy Body Disease Alzheimer’s Disease Lewy Body variantHungtington’s Disease M. Flint Beal, AC. Ludolph (2005). Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics, Cambridge University Press.

  4. Neurodegenerative Disease Increased tissue oxidative damage Reduced mitochondrial and axonal transport Increased Tau protein phosphorylation Common characteristics Progressive cell atrophy & apoptosis Accumulation of abnormal protein fragments Increased inflammatory cytokine production Decreased neurotransmitter production Progressive cell atrophy & apoptosis Increased inflammatory lipid mediators Skovronsky et al. 2006. "NEURODEGENERATIVE DISEASES … Ann Rev Path Mech Dis. 1(1)

  5. Cognitive Disorder Dementia90 % sporadic10 % familial Pick’s disease ~more common below 60 yrs Alzheimer’s disease ~90% of dementia cases > 70 yrs Annual incidence Exponential increase with age 40 to 60 yrs ~ 2.4 / 100,000 80 yrs ~ 127 / 100,000 4th or 5th leading cause of death Amyloid-B-peptide Accumulation Insoluble amyloid plaques Tau protein hyperphosphorylation~ neurofibrillary tangles Thomas & Fenech. 2007. A review of genome mutation and Alzheimer's disease. Mutagenesis22(1): 15-33. Mendez et al. 2008. Psychopathology of Frontotemporal Dementia: J Neuropsychiatry Clin Neurosci 20(2)

  6. Alzheimer’s disease ~Classic dementia disorder& the commonestIncidence rises rapidly over 70 yrs age CVD is next commonest cause Neurofibrillary formation, Amyloid plaque deposition Lewy Bodies & Pick Bodies Insidious onset memory loss ~ progresses over 5~10 yrs impaired executive function, attentiveness, language, visual & motor processing and behaviour Neuronal Loss Brain Atrophy  Death Alzheimer’s Disease NormalAging Minati L, et al. 2008. Current Concepts in Alzheimer's Disease: A Multidisciplinary Review.. J Alzheimers Dis Other Demen.

  7. Early Onset Familial Alzheimer’s Disease ~ accounts for < 5% of all Alzheimer patients ~ generally onsets between 50 ~ 60 yrs age Clinical Picture rapid & unrelenting progressionof cognitive deterioration Genetic form of Alzheimer’s Disease ~ multiple polymorphisms on 3 genes ~ autosomal dominant inheritance presenilin 1 (PSEN1) ch-14, presenilin 2 (PSEN2) ch-1 Aβ precursor protein (APP) ch-21 Thomas & Fenech. 2007. A review of genome mutation and Alzheimer's disease. Mutagenesis22(1): 15-33.

  8. Increased risk with: • APO-E4 genotype  to 40~70% of cases • TNF-alpha polymorphism • Trisomy 21 Late Onset Alzheimer’s Disease 90% of all Alzheimer patientsabove age 70 yrsslow progressive disease • Risk Factors: • Aging, menopause • low education level • head trauma, • cerebral ischaemia • Risk Factors: • cardiovascular disease • obesity • diabetes • chronic inflammation Protective factors: anti-inflammatory drugs antioxidant agents oestrogen high educational level Minati L, et al. 2008. Current Concepts in Alzheimer's Disease: A Multidisciplinary Review..J Alzheimers Dis Other Demen.

  9. Alzheimer’s Disease 3 Major processes Oxidantstress InsulinResistance Inflammation Emerit, J., M. Edeas, et al. (2004). "Neurodegenerative diseases and oxidative stress." Biomedicine & Pharmacotherapy 58(1): 39-46.

  10. Inflammation Present at cellular level ~brain microglia activation ~ not systemic inflammation Increased cytokine production TNF-alphaIL-1 Exacerbated by*cerebral iron & copper* Vascular endothelial disease* APO E4 gene* Insulin Resistance Increased lipidmediators: Leukotrienes Reduced DHAimpairs Neuronal signalling Tan, Z. S., A. S. Beiser, et al. (2007). "Inflammatory markers and the risk of Alzheimer disease: The Framingham Study." Neurology68(22): 1902-1908. Lukiw, W. J. (2009). "Docosahexaenoic acid and Amyloid-beta Peptide Signaling in Alzheimer's Disease." World Rev Nutr Diet99: 55-70.

  11. Oxidant Stressderives from EFA imbalanceomega-3-FA insufficiency InflammationAPO e4 gene TNF-alpha polymorphism Chronic inflammatory disease Low antioxidant status Ascorbate Bioflavonoids proanthocyanidins Environmental oxidant exposure Smoking Air pollution Heavy metals ~ Hg, Mn Insulin Resistance Cardiovascular Disease Diabetes Heavy metal overloadiron, coppermercury Yan, S. D., X. Chen, et al. (1996). "RAGE and amyloid-[beta] peptide neurotoxicity in Alzheimer's disease." Nature382(6593): 685-691. Emerit, J., M. Edeas, et al. (2004). "Neurodegenerative diseases and oxidative stress." Biomedicine & Pharmacotherapy 58(1): 39-46.

  12. InsulinResistance Omega-3-EFA deficiencyinadequate intake of Fish & fish oils Obesity andOverweight • Mineral Depletion • Zinc • Magnesium • Chromium DIET High Carbohydrate intake High saturated fat intake Carbohydrate-responsive Gene PolymorphismsPPARS SREBP ChREBP ChronicInflammation Lack ofEXERCISE Sabayan, B., F. Foroughinia, et al. (2008). "Role of Insulin Metabolism Disturbances in the Development of Alzheimer Disease: Mini Review." American Journal of Alzheimer's Disease and Other Dementias23(2): 192-199.

  13. Alzheimer’s Disease Causal Factors NutrientDepletion Heavy metal toxicity Oxidative damage Inflammatorycytokinerelease Mitochondrial dysfunction ObesityAdipokineproduction Reduced ATP genesis Neurotransmitterimbalance InsulinResistance InflammatoryLipidMediators NMDA- receptoractivation Glutamate toxicity Glucosetoxicity

  14. Alzheimer’s Disease Useful Tests Cigarette Smoking APO E genotype Check Alcoholconsumption Full Blood Count & ESR High sensitivity CRPand ESR Glucose Tolerance Testwith insulin & cortisol Nutrient statusVit C, E & D Urinary MineralAnalysisCa, Mg, Zn Iron studyand ferritin Food Antibodiesboth IgG and IgE Red cell EFA analysis Neurotransmitterbalance Antioxidant Status& Co-Q10 Urinary Metabolite Analysis Bowel Dysbiosismarkers Hormone BalanceDHEA, OestrogenTestosterone DNA Oxidative damage Faecal Bacterial Analysismicrobial culture&/or DNA analysis Test for Heavy Metal Load Hair Analysis or Urinary Mercury Provocation

  15. Alzheimer’s Disease TREATMENT DIGESTIVE SUPPORTGastric acid and Digestive enzymes DIETLow-allergy & Low Glycemic LoadHigh protein & vegetable intake Consider Paleolithic or ketogenic diet Primary Antioxidant TherapyVitamin C ~ mixed mineral ascorbatesMixed tocopherols & TocotrienolsMixed bioflavonoids Phytonutrient TherapyBlueberries Green tea Resveratrol Curcumin Pomegranate Essential Fatty Acid SupplementsDHA-rich omega-3-FAsalpha-Linolenic acid

  16. Alzheimer’s Disease TREATMENT Toxic Mineral Removal Natural chelators N-acetylcysteine Garlic extracts Alpha-lipoic acid Green tea extract Pharmaceutical chelating agents EDTA chelation Clioquinol Desferrioxamine DMSA Mineral therapyCalcium Magnesium Selenium Chromium Zinc Vitamin therapyHigh dose: ActivatedB-Complex Folate & B12 Pyridoxal-5-phosphate NADH Neuronal stimulation Citicholine Phosphatidylserine L-arginine Adaptogenic Herbs Ginkgo biloba Korean GinsengAshagarwan

  17. Alzheimer’s Disease THERAPY NEEDS TO BE Multimodal & Integrated~ targeting identified metabolic dysfunctions Initiated at earliest sign of cognitive dysfunction Persistent ~ long-term administration of therapeutic agents Clinically Monitored ~ on an ongoing basis

  18. Thank you • for your • care and attention

  19. REFERENCES: Samuel, T. H. (2004). "High carbohydrate diets and Alzheimer's disease." Medical hypotheses 62(5): 689-700. Van der Auwera, I., S. Wera, et al. (2005). "A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease." Nutr Metab (Lond). Sabayan, B., F. Foroughinia, et al. (2008). "Role of Insulin Metabolism Disturbances in the Development of Alzheimer Disease: Mini Review." American Journal of Alzheimer's Disease and Other Dementias 23(2): 192-199. Mosconi, L., A. Pupi, et al. (2008). "Brain glucose hypometabolism and oxidative stress in preclinical Alzheimer's disease." Ann N Y Acad Sci1147: 180-95. Freund-Levi, Y., M. Eriksdotter-Jonhagen, et al. (2006). "{omega}-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial." Arch Neurol63(10): 1402-1408. Nurk, E., C. A. Drevon, et al. (2007). "Cognitive performance among the elderly and dietary fish intake: the Hordaland Health Study." Am J Clin Nutr86(5): 1470-1478. Lukiw, W. J. (2009). "Docosahexaenoic acid and Amyloid-beta Peptide Signaling in Alzheimer's Disease." World Rev Nutr Diet 99: 55-70. Yehuda, S., S. Rabinovtz, et al. (1996). "Essential Fatty Acids Preparation (Sr-3) Improves Alzheimer's Patients Quality of Life." International Journal of Neuroscience87(3): 141-149.

  20. REFERENCES • Bowman, G. L., H. Dodge, et al. (2009). "Ascorbic Acid and rates of cognitive decline in Alzheimer's disease." J Alzheimers Dis 16(1): 93-8. • Morris, M. C., D. A. Evans, et al. (2005). "Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change." Am J Clin Nutr 81(2): 508-514. • Chandan K. Sen, S. K. S. R. (2004). "Tocotrienol: The Natural Vitamin E to Defend the Nervous System?" Annals of the New York Academy of Sciences 1031(Vitamin E and Health): 127-142. • Maczurek, A., K. Hager, et al. (2008). "Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer's disease." Adv Drug Deliv Rev 60(13-14): 1463-70. • Abdul, H. M. and D. A. Butterfield (2007). "Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by cotreatment of acetyl-L-carnitine and alpha-lipoic acid against HNE-mediated oxidative stress and neurotoxicity: implications for Alzheimer's disease." Free Radic Biol Med 42(3): 371-84. • Holmquist, L., G. Stuchbury, et al. (2007). "Lipoic acid as a novel treatment for Alzheimer's disease and related dementias." Pharmacol Ther113(1): 154-64. • Maczurek, A., K. Hager, et al. (2008). "Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer's disease." Adv Drug Deliv Rev60(13-14): 1463-70. • Bruce N. Ames, J. L. (2004). "Delaying the Mitochondrial Decay of Aging with Acetylcarnitine." Annals of the New York Academy of Sciences1033(Carnitine The Science behind a Conditionally Essential Nutrient): 108-116.

  21. REFERENCES Orly, W., M. Silvia, et al. (2004). "Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases." The Journal of nutritional biochemistry15(9): 506-516. Rezai-Zadeh, K., D. Shytle, et al. (2005). "Green Tea Epigallocatechin-3-Gallate (EGCG) Modulates Amyloid Precursor Protein Cleavage and Reduces Cerebral Amyloidosis in Alzheimer Transgenic Mice." J. Neurosci.25(38): 8807-8814. Vingtdeux, V., U. Dreses-Werringloer, et al. (2008). "Therapeutic potential of resveratrol in Alzheimer's disease." BMC Neurosci9 Suppl 2: S6. Zhu, Y., P. C. Bickford, et al. (2008). "Blueberry Opposes ß-Amyloid Peptide-Induced Microglial Activation Via Inhibition of p44/42 Mitogen-Activation Protein Kinase." Rejuvenation Research11(5): 891-901. Papandreou, M. A., A. Dimakopoulou, et al. (2008). "Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity." Behavioural Brain Research. Francis, C. L., S.-H. Barbara, et al. (2005). "The beneficial effects of fruit polyphenols on brain aging." Neurobiology of aging26(1): 128-132. Hartman, R. E., A. Shah, et al. (2006). "Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease." Neurobiology of Disease24(3): 506-515.

  22. REFERENCES Isingrini, E., T. Desmidt, et al. (2009). "Endothelial dysfunction: A potential therapeutic target for geriatric depression and brain amyloid deposition in Alzheimer's disease?" Curr Opin Investig Drugs10(1): 46-55. Monnet-Tschudi, F., M. G. Zurich, et al. (2006). "Involvement of environmental mercury and lead in the etiology of neurodegenerative diseases." Rev Environ Health 21(2): 105-17. Mutter, J., J. Naumann, et al. (2004). "Alzheimer disease: mercury as pathogenetic factor and apolipoprotein E as a moderator." Neuro Endocrinol Lett25(5): 331–339. Bush,A.I. (2002) Metal complexing agents as therapies for Alzheimer’s disease. Neurobiol. Aging, 23, 1031–1038. Chen, D., Q. C. Cui, et al. (2007). "Clioquinol, a Therapeutic Agent for Alzheimer's Disease, Has Proteasome-Inhibitory, Androgen Receptor-Suppressing, Apoptosis-Inducing, and Antitumor Activities in Human Prostate Cancer Cells and Xenografts." Cancer Res67(4): 1636-1644.