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

Loading in 2 Seconds...

play fullscreen
1 / 22

Neurodegenerative Disease - PowerPoint PPT Presentation


  • 410 Views
  • Uploaded on

Neurodegenerative Disease. 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. Neurodegenerative Disease.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Neurodegenerative Disease' - Olivia


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
neurodegenerative disease

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

neurodegenerative disease2
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.

slide3

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.

neurodegenerative disease4
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)

slide5

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)

slide6

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.

slide7

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.

slide8

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.

slide9

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.

slide10

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.

slide11

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.

slide12

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.

slide13

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

slide14

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

slide15

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

slide16

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

slide17

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

slide18
Thank you
  • for your
  • care and attention
slide19

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.

slide20
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.
slide21

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.

slide22

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.