NMDC221 Session 17: Nervous System Disease Part IV. Endeavour College of Natural Health endeavour.edu.au 1

Transcription

1 NMDC221 Session 17: Nervous System Disease Part IV Endeavour College of Natural Health endeavour.edu.au 1

2 Recommended Reading Mahan, LK, & Raymond, JL (14th ed) 2016, Krause s food & the nutrition care process, 14th ed, Elsevier, St. Louis, MO. pp.835-8, Endeavour College of Natural Health endeavour.edu.au 2

3 Topic Summary Nervous System Disease: Part IV o Nutritional treatment and consideration of drug-nutrient interactions for: Dementia Alzheimer s disease Parkinson s disease Endeavour College of Natural Health endeavour.edu.au 3

4 Dementia Endeavour College of Natural Health endeavour.edu.au 4

5 What is Dementia? Dementia o Dementia is a clinical syndrome characterised by a cluster of symptoms and signs manifested by difficulties in memory, disturbances in language, psychological and psychiatric changes, and impairments in activities of daily living. Alzheimer s disease is a specific disease entity and is the commonest cause of dementia. (Burns, A 2009) o Common in the elderly (affecting > 15% of persons > 65 yr old and as many as 40% of persons > 80 yr old). o May occur at any age and can affect young people as the result of injury or hypoxia. (Kumar & Clark, 2009) o Burden of disease - About 12 million people worldwide have dementia, and this total is likely to increase to 25 million by 2040 (Burns A, 2009). Endeavour College of Natural Health endeavour.edu.au 5

6 Dementia Dementia is categorized into a few subtypes.:- Alzheimer s disease (AD) accounts for about half of the affected population Vascular dementia (VaD) (20 25%) Mixed dementia (5 10%), Parkinson s disease, Dementia with Lewy bodies Physical brain injury Huntington s disease Creutzfeldt Jacob disease Frontotemporal dementia/pick s disease Normal pressure hydrocephalus (Chen, Lin, Chen 2009) AD is also the most common neurodegenerative disorder and affects million individuals worldwide. AD has been further categorized into two forms according to its onset: sporadic cases (> 95%) with late-onset disease; and autosomal-dominant mutation cases (< 5%) with early onset. Endeavour College of Natural Health endeavour.edu.au 6

7 Risks Factors: Dementia o Several factors are related to dementia, e.g. age, ethnicity, sex, genetic factors (APOE gene for late onset AD & for early-onset cases, APP, preselin (PS)-1, and PS-2 genes appear most relevant) o Physical activity, smoking, drug use, education level, alcohol consumption, body mass index, comorbidity, and environmental factors (Chen, Lin, Chen 2009) Signs & symptoms: o Poor memory and disorientation o Cognitive impairment (aphasia, apraxia, agnosia, or a loss of executive functioning). Unfortunately, the appearance of clinical features suggest there is a substantial progression of the disease process. (Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 7

8 Dementia Causes of Dementia: o Cerebral atrophy - Alzheimer's disease accounts for over 65%. Other diseases implicated include Parkinson s disease, Huntington s disease o Diffuse vascular disease o Metabolic insufficiencies uraemia, liver failure o Nutritional deficiencies - vitamins B1, B3, B6 & Folate or B12 o Toxic damage alcohol, solvents, heavy metals o Head trauma & lesions o Infections HIV, neurosyphilis o Hypothyroidism, hypoparathyroidism (Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 8

9 Nutritional Treatment Aims Support Digestion: o Address nutritional deficiencies Dementia o Increase absorption (digestive enzymes or lemon water) o Maintain adequate protein, fibre, fluid intakes (assess hydration) o Maintain consistent blood glucose levels (eat every 3 hours) o Assess EFA and saturated fat intake o Correct any gut dysbiosis: prebiotics, probiotics, anti-microbials, repairing nutrients (Sarris & Wardle, 2010) Endeavour College of Natural Health endeavour.edu.au 9

10 Nutritional Treatment Aims Dementia Support anti-oxidant status o Increased consumption of antioxidant foods o Minimise environmental chemical & toxin contact o Assess homocysteine levels support B12 & folate Support neuronal activity o Support phospholipid maintenance lecithin, EPA/DHA o Support the endogenous production of Dopamine, Serotonin, GABA and Acetylcholine (Sarris & Wardle, 2010) Endeavour College of Natural Health endeavour.edu.au 10

11 Dementia Nutritional Treatment Aims Support liver detoxification & heavy metal chelation o Assess heavy metal exposure: lead, mercury, aluminum o Green leafy vegetables, cruciferous vegetables, soluble fiber, dandelion and other bitter vegetables o Glycine, cysteine and glutamine for glutathione production Support cellular metabolism & energy Improve circulation (Sarris & Wardle, 2010) Endeavour College of Natural Health endeavour.edu.au 11

12 Alzheimer's Disease Endeavour College of Natural Health endeavour.edu.au 12

13 Alzheimer's Disease o A common, progressive form of Dementia (50% - 70% of all cases) that usually occurs during middle age or later. o Exact cause of Alzheimer s Disease has not yet been determined and is difficult to diagnose. However, there is a strong genetic link ( o On autopsy a progressive, loss of cognitive function associated with an excessive number of senile plaques in the cerebral cortex and subcortical grey matter, which also contains beta-amyloid and neurofibrillary tangles. Signs & Symptoms o Dementia, poor memory, mood, depression, language impairment, seizures later in disease. (Bryant & Knights, 2011; Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 13

14 Alzheimer's Disease Risk factors : o Age. Also some studies on parental age at birth, but still inconclusive. o Sex - AD higher in women compared with men at ages >85 years (Chen, Lin, Chen 2009) o Positive family history o Presence of APO-E4 gene significant (later AD). A Swedish twin study has reported that 60 80% of AD is attributable to genetic effects (Gatz M, Fratiglioni L, Johansson B, et al 2005) o Inflammation - recent studies have shown that polymorphisms of one of the inflammatory genes alone or in combination have comparable effects on AD risk to those for the APOEe4 allele (Chen, Lin, Chen 2009). Endeavour College of Natural Health endeavour.edu.au 14

15 AD Risk Factors Continued: Smoking Trisomy 21 (Down s syndrome) can develop pathological brain changes after yrs age, indistinguishable from Alzheimer s Low Physical Activity (PA) - physical activity is associated positively with cognitive function among older people. Other studies have found that physical activity is associated with a reduction of 30 50% in cognitive decline (Chen, Lin, Chen 2009) Trauma to the head Heavy metal toxicity particularly Aluminium Oxidative damage to brain tissue low antioxidants, vascular issues Hyper-inflammation Circulation disorders due to impaired vascular integrity (Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 15

16 o Drugs AD Risk Factors cont. Benzodiazepine's increase the risk of AD. However - the following appeared to reduce the risk: Statins HRT antihypertensive drugs NDAID s (Chen. Lin, Chen 2009) o Alcohol Alcohol drinking may be protective for AD and dementia, but not for VaD and cognitive decline (Peters R, Peters J, Warner J, et al. 2008) Endeavour College of Natural Health endeavour.edu.au 16

17 Therapeutic Actions Homocysteine Alzheimer's Disease o Recently, a few studies have linked increased levels of plasma Homocysteine with increased risk of AD and increased rate of progression. (Paulionis, Kane, & Meckling, 2005) o Malouf & Evans (2008) found that group of healthy elderly people with high homocysteine levels, 800 mcg/day folic acid supplementation over three years was associated with significant benefit in terms of global functioning memory storage and informationprocessing speed. Endeavour College of Natural Health endeavour.edu.au 17

18 Therapeutic Actions Vitamin B3 Alzheimer s Disease o Mild to severe Alzheimer s patients were given 10mg of NADH. There was a 240% increase in NADH activity within 2 weeks. This improved mental function, alertness & memory with increases in dopamine & norepinephrine. o Global deterioration scale ratings conducted before and after NADH treatment confirmed significant improvement. (Demarin et.al 2004) o Green et.al. (2008) found that nicotinamide was indicated for early or mild stages of Alzheimer s disease. Endeavour College of Natural Health endeavour.edu.au 18

19 Therapeutic Actions Turmeric Alzheimer s Disease o The incidence of Alzheimer disease has been found to be lower in India and areas with a high traditional consumption of turmeric. o The therapeutic effect of turmeric is thought to be associated with decreased beta-amyloid plaques, delayed degradation of neurons, metal-chelation, anti-inflammatory, antioxidant and decreased microglia formation. o Rodent study found turmeric significantly reduced levels of soluble and insoluble beta amyloid as well as phosphorylated Tau protein. Extract 82% curcuminoids dosage 5mg/mouse/day. (Mishra, S, & Palanivelu, K, 2008, Potter, 2010, Shytle RD et al, 2012) Endeavour College of Natural Health endeavour.edu.au 19

20 Dementia & Alzheimer s Nutritional Treatment Aims Support Digestion: o Address nutritional deficiencies o Increase absorption (digestive enzymes or lemon water) o Maintain adequate protein, fibre, fluid intakes (assess hydration) o Maintain consistent blood glucose levels (eat every 3 hours) o Assess EFA and saturated fat intake o Correct any gut dysbiosis: prebiotics, probiotics, antimicrobials, repairing nutrients (Sarris & Wardle, 2010) Endeavour College of Natural Health endeavour.edu.au 20

21 Dementia & Alzheimer s Nutritional Treatment Aims Support anti-oxidant status o Increased consumption of antioxidant foods o Minimise environmental chemical & toxin contact o Assess homocysteine levels: elevated in brain tissue of Alzheimer s. Support with B12 & folate Support neuronal activity o Support phospholipid maintenance lecithin, EPA/DHA o Support the endogenous production of Dopamine, Serotonin, GABA and Acetylcholine. (Sarris & Wardle, 2010) Endeavour College of Natural Health endeavour.edu.au 21

22 Dementia & Alzheimer s Nutritional Treatment Aims Support liver detoxification & heavy metal chelation o Assess heavy metal exposure: lead, mercury, aluminum o Green leafy vegetables, cruciferous vegetables, soluble fiber, dandelion and other bitter vegetables o Glycine, cysteine and glutamine for glutathione production Support cellular metabolism & energy Improve circulation (Sarris & Wardle, 2010) Endeavour College of Natural Health endeavour.edu.au 22

23 Dementia & Alzheimer s Nutrient Dosage Therapeutic Actions 5-HTP Tryptophan Tyrosine Phenylalanine 300-4,000mg mg up to 6,000mg) mg Inositol ,000mg ACL - Acetyl-L- Carnitine Phosphatidylcholine Phosphatidylserine 500-6,000mg mg mg Depression associated with dementia Dopamine, Adrenaline, Noradrenaline. Alzheimer s disease patients have sub-optimal production (Spagnoli et al. 1991; Fugh-Berman & Cott, 1999; Farber et al. 2000; Hager et al. 2001;Huang et al. 2001; Suzuki et al. 2001) Secondary messenger for noradrenaline, serotonin and cholinergic receptors Improves neuronal energetics. Antioxidant for brain cells. Enhances or mimics acetylcholine function. Acetylcholine substrate. Found to be broken down faster in AD Boosts Acetylcholine levels Main phospholipid found in brain. Increases cell membrane fluidity. Endeavour College of Natural Health endeavour.edu.au 23

24 Dementia & Alzheimer s Nutrient Dosage Therapeutic Actions Lipoic acid EPA/DHA ,000mg mg Recycles anti-oxidants, Improves ATP synthesis neuronal energetics, Detoxifies heavy metals, Improves ageing-related cellular processes mitochondrial function Cell membrane, supports circulation. Supports neuronal activity. Low DHA levels have been linked to an increased risk of developing Alzheimer s disease Vitamin E iu Retards the progression of Alzheimer s disease by 25% (clinical trials). Treatment of cultured (test-tube) neurons with vitamin E protects them from beta-amyloid (implicated in Alzheimer s disease) toxicity. Carnitine 500-6,000mg Improves neuronal energetics (Fugh-Berman & Cott, 1999; Morris, 2004; Malouf & Evans, 2008) Endeavour College of Natural Health endeavour.edu.au 24

25 Dementia & Alzheimer s Nutrient Dosage Therapeutic Actions Vitamin B mg Cofactor for ACh (most depleted in Alzheimer s) & fatty acid synthesis. Cellular energetics. Deficiency causes dementia like symptoms Vitamin B mg Cofactor. Activation of B6. Conversion of folate to its coenzymes; conversion to Tryptophan to niacin & support of antioxidant activity through FAD & reduced glutathione. Cellular energetics Vitamin B mg Cofactor. Stimulates GABA without binding to the receptor sites, an effect likened to that of benzodiazepines. Cellular energetics. Deficiency causes dementia like symptoms. Memory enhancer (Farber et al. 2000; Demarin et.al. 2004; Morris, 2004; Green, 2008 ; Malouf & Evans 2008) Endeavour College of Natural Health endeavour.edu.au 25

26 Dementia & Alzheimer s Nutrient Dosage Therapeutic Actions Vitamin B5 Vitamin B6 Folate Vitamin B mg mg mcg mcg Synthesis of acetylcholine. Deficiency causes dementia like symptoms Methylation. Deficiency causes dementia like symptoms. Lowers high serum homocysteine levels - increased risk of AD & accelerated progression. Selenium mcg Neural Anti-Oxidant. Deficiencies present with low cognitive function Taurine mg Neuroactive Neurotransmitters. Alzheimer s disease patients have depleted levels of taurine in their cerebrospinal fluid. (Spagnoli et al. 1991; Fugh-Berman & Cott, 1999; Hager et al. 2001; Louzada et.al. 2004; Morris, 2004; Gao et al. 2007) Endeavour College of Natural Health endeavour.edu.au 26

27 Dementia & Alzheimer s Drug Action Side Effects Interactions Acetylcholinesterase Inhibitors: Donepezil, Rivastigmine, Galantamine Inhibit acetylcholinesterase thereby reducing ACh breakdown at nicotinic & muscarinic receptor sites. Delays cognitive decline in the initial stages, the disease will progress. Increased muscle activity in the eyes (pupil constriction), bradycardia, diarrhoea, muscle twitching, bronchoconstriction. Also hypotension, increased lacrimation & sweating None listed (Romi et.al, 2005; Auchus, 2007;; Bullock et.al. 2007; Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 27

28 Dementia & Alzheimer s Drug Action Side Effects Interactions NMDA (N-methyld-aspartate) Antagonist: Memantine Selectively blocks glutamate receptors (N-methyl-daspartate receptor) to reduce overstimulation (characteristic of Alzheimer s). Slows the progression of the disease. Headache, dizziness, agitation. Drowsiness, insomnia. GIT disturbance Coughing None listed (Auchus, 2007; Bullock et.al. 2007) Endeavour College of Natural Health endeavour.edu.au 28

29 Parkinson s Disease Endeavour College of Natural Health endeavour.edu.au 29

30 Parkinson s Disease Chronic disease affecting the basal ganglia of the brain, with degeneration of dopaminergic receptors in the substantia nigra. Age is usually 40 yrs+ (can be earlier). Risk Factors include: o Neurotoxins o Poor antioxidant status and high free radical production oxidising myelin sheaths o Impaired function of the mitochondria is closely associated with the progression of Parkinson s Disease as seen with significant damage to the mitochondrial DNA. (Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 30

31 Parkinson s Disease Signs & symptoms: o Loss of smell (early warning sign) o Restlessness and tremors of the hands mainly at rest. Movement reduced symptoms. o Feeling of sluggishness o Gait is shuffling and stumbling due to loss of centre of gravity. o Rigidity of skeletal muscles and facial muscles (mask-like appearance) (Kumar & Clark, 2009) Endeavour College of Natural Health endeavour.edu.au 31

32 Parkinson s Disease Therapeutic Nutritional Considerations: Folate o Folate deficiency and hyperhomocysteinemia may contribute to Parkinson s disease pathogenesis, decrease dopaminergic neurons and induced profound motor dysfunctions (Chen et. al, 2004, p. 373) Vitamin B3 o NADH administration (1.4 mg/kg) has been useful in PD patients. An antioxidant, that can stimulate the production of L-dopa in vivo and dopamine in PC-12 cells, a dopaminergic cell line as well as ATP. (Prasad et.al. 1999) Endeavour College of Natural Health endeavour.edu.au 32

33 Parkinson s Disease Therapeutic Actions Vitamin C & Vitamin E o Prasad et.al. (1999) found that a large community-based study in the Netherlands has reported that vitamin E consumption was significantly lower among patients with PD than among controls. (p. 414) o Also supplemental vitamin E (3,000IU/day) and vitamin C (3,000 mg/day) increased the time interval for requiring L-dopa therapy by about 2 to 4 years in 75% of patients when compared to historical controls. (Prasad et.al. 1999, p. 418) Endeavour College of Natural Health endeavour.edu.au 33

34 Parkinson s Disease Nutritional Treatment Aims o Support Digestive system o Support the Liver and heavy metal chelation increase sulphur containing foods (e.g. garlic, onions, eggs) to aid in phase II sulphation pathways. Sulphate conjugation has been implicated in disease pathogenesis o Support anti-oxidant status o Support cellular energetics o Support circulation o Assess hydration levels (Pizzorno & Murray 2006; Sarris & Wardle, 2010) Endeavour College of Natural Health endeavour.edu.au 34

35 Parkinson s Disease Nutritional Treatment Aims Support neurotransmitter synthesis o Maintain a protein status of 0.8g/kg to aid in dopamine production. o Note: high amino acid levels can compete with levodopa across the blood brain barrier, reducing efficacy. o Fava (Broad) beans have been shown to be high in natural levodopa 100g serving = 250mg levodopa) (Pizzorno & Murray 2006; Sarris & Wardle, 2010) Endeavour College of Natural Health endeavour.edu.au 35

36 Parkinson s Disease Nutrient Dosage Therapeutic Actions Vitamin B mg Mitochondrial Support, acetylcholine & fatty acid synthesis Vitamin B (up to 3000mg) Vitamin B ,000mcg Vitamin C Up to 5,000mg Mitochondrial Support Cofactor and memory enhancer Nerve support. Elevated Homocysteine contributes to the development of Parkinson s Disease. NTM Cofactor adrenal NTM. In combination with vitamin E has been found to slow progression of Parkinson s disease Vitamin E iu Antioxidant, commonly deficient in Parkinson s disease. Selenium mcg Cofactor of glutathione peroxidase, antioxidant (Prasad et.al. 1999; Chen et.al. 2004; Demarin et.al. 2004; Green, 2008; Malouf & Evans, 2008) Endeavour College of Natural Health endeavour.edu.au 36

37 Parkinson s Disease Nutrient Dosage Therapeutic Actions EFA s ,000mg Folic Acid mcg (up to 5000mcg) Parkinson's Disease occurs when the Myelin Sheaths of Neurons are damaged by Oxidation Reduce homocysteine levels, implicated in Parkinson s exacerbation Tyrosine mg Tyrosine elevated dopamine (precursor) in the CNS of patients with Parkinson Disease Phenylalanine mg Dopamine precursor Phosphatidylserine mg Main phospholipid found in brain. Increases cell membrane fluidity. Glutathione mg Antioxidant, commonly low in Parkinson s patients (Fugh-Berman & Cott, 1999; Fernstrom, 2000; Suzuki et al. 2001; Chen et.al. 2004; Pizzorno & Murray, 2006; Malouf et.al. 2008) Endeavour College of Natural Health endeavour.edu.au 37

38 Drug Management Parkinson s Disease o Parkinson s Disease symptoms present as a depletion of dopamine. This NT works in equilibrium with acetylcholine to maintain proper motor function o Goal of drug therapy is to restore the balance between dopaminergic and cholinergic function o This can be accomplished in different ways, including: Increasing dopamine levels Augmenting dopamine levels with drugs that mimic dopamine activity Suppression of cholinergic activity (reduced ACh). (Bullock et.al. 2007; Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 38

39 Parkinson s Disease Drug Action Side Effects Interactions Levodopa L-dopa L-dopa crosses the blood-brain-barrier & then converted to dopamine raising brain levels. Dopamine can t cross the BBB. Dopa decarboxylase (Ldopa to dopamine conversion) is present in peripheral tissue = only 1% of levodopa reaches the brain. Peripheral conversion of levodopa is responsible for most of the adverse effects associated with the drug = nausea, vomiting, cardiac arrhythmias, postural hypotension. Vitamin B6: increases peripheral conversion of levodopa (co-factor) = less to cross BBB & increase the peripheral adverse effects Calcium, magnesium iron & zinc: forms insoluble complex = reduced drug absorption. Separate by 2 hours Tyrosine: L-dopa competes with tyrosine for BBB uptake. Avoid (Braun & Cohen 2010; Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 39

40 Parkinson s Disease Drug Action Side Effects Interactions Carbidopa; Sinemet Levodopa + carbidopa Combined with levodopa prevents peripheral conversion to dopamine (increased L-dopa crosses BBB). Lowers required dose of L- dopa & reduced drug adverse effects. Peripheral symptoms: Nausea, vomiting, cardiac arrhythmias, postural hypotension. Vitamin B6: (50-100mg/day) does not increase extra-cerebral conversion, thus drug efficacy is maintained Iron: binds to form insoluble complexes. Reduced drug bioavailability (emims, 2010; Braun & Cohen 2010; Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 40

41 Parkinson s Disease Drug Action Side Effects Interactions Selegiline Used in combination with levodopa in the late stages of the disease, selegiline inhibits the activity of the enzyme monoamine oxidase B (MAO-B), thereby delaying the breakdown of naturally occurring dopamine and dopamine derived from levodopa. Nausea, vomiting, stomach pain Insomnia, dizziness, mood alteration, dyskinesia. None listed (Bullock et.al. 2007; Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 41

42 Parkinson s Disease Drug Action Side Effects Interactions Dopamine Agonists: Bromocriptine, Pergolide, Cabergoline Directly stimulate the CNS dopamine (D 2 ) receptors providing symptomatic relief. Used as adjuncts to levodopa therapy to prolong effectiveness, stabilize responses of and increase tolerance to levodopa. Nausea, vomiting, cardiac arrhythmias, postural hypotension. None listed (Bullock et.al. 2007; Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 42

43 Parkinson s Disease Drug Action Side Effects Interactions Anticholinergics Biperiden, Benztropine Block the action of acetylcholine, thereby helping to restore the balance between cholinergic and dopaminergic activity. Used in the early stages of the disease. Nausea, vomiting, constipation Dry skin, dry mouth Drowsiness Irritability None listed (Bullock et.al. 2007; Bryant & Knights, 2011) Endeavour College of Natural Health endeavour.edu.au 43

44 Parkinson s Disease Drug Interaction Considerations o Natural therapies may be supportive in Parkinson s disease, but are not indicated as stand-alone therapies, given the nature of the disease o Currently, the only reported integrative interactions relate to L-dopa, however care should be taken when prescribing any natural therapies in Parkinson s disease. o All nutritional therapies that act on catecholamines, especially dopamine or acetylcholine pathways, may theoretically lead to an interaction with the anti- Parkinson s drug therapies Endeavour College of Natural Health endeavour.edu.au 44

45 References o Auchus A. (2007). Dementia. Merk manual online for healthcare professionals. Retrieved 13 January 2011 from: 1 #sec16-ch213-ch213c-99 o Burns, Alistair. (2009). Dementia. Brit Med J, 2009; 338. o Braun, L., & Cohen, M. (2015). Herbs & natural supplements: An evidencebased guide (4th ed.). Chatswood, NSW: Elsevier. o Bryant, B. J., & Knights, K. M. (2015). Pharmacology for health professionals (4th ed.). Chatswood, NSW: Elsevier. o Bullock, S., Manias, E. & Galbraith, A. (2007). Fundamentals of pharmacology. 5 th ed. Pearson, NSW. o Chen, J., Lin, K., & Chen, Y. (2009). Review Article: Risk Factors for Dementia. Journal Of The Formosan Medical Association, doi: /s (09) o Chen, H., Zhang, S. M., Schwarzschild, M. A., Hernán, M. A., Logroscino, G., Willett, W. C., & Ascherio, A. (2004). Folate intake and risk of Parkinson's disease. American Journal Of Epidemiology, 160(4), Endeavour College of Natural Health endeavour.edu.au 45

46 o o o o o References Demarin, V., Podobnik, S.S., Storga-Tomic, D. & Kay, G. (2004). Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. Drugs under experimental and clinical research. Vol. 30, 1, p Retrieved 24 January from: Douglas Shytle, R., Tan, J., Bickford, P. C., Rezai-zadeh, K., Hou, L., Zeng, J., Roschek, B. (2012). Optimized Turmeric Extract Reduces β- Amyloid and Phosphorylated Tau Protein Burden in Alzheimer s Transgenic Mice. Current Alzheimer Research, 9(4), Farber, S.A., Slack, B.E. & Blusztajn, J.K. (2000). Acceleration of phosphatidylcholine synthesis and breakdown by inhibitors of mitochondrial function in neuronal cells: a model of the membrane defect of Alzheimer s disease. Journal of the federation of American societies for experimental biology. Vol. 14, p Retrieved 24 January 2011 from: Fernstrom, J.D. (2000). Can nutrient supplements modify brain function? American journal of clinical nutrition. 71, 6, 1669s-1673s. Fugh-Berman, A & Cott, JM 1(999). Dietary supplements and natural products as psychotherapeutic agents. Psychosomatic medicine, Vol. 61, No. 5, pp Endeavour College of Natural Health endeavour.edu.au 46

47 References o Gao, S., Jin, Y., Hall, K.S., Liang, C., Unverzagt, F.W., Ji, R., Murrell et al. (2007). Selenium Level and Cognitive Function in Rural Elderly Chinese. American journal of epidemiology. Vol Iss. 8, p Viewed 29 March 2018 from: o o o Gatz, M., Fratiglioni, L., Johansson, B., Berg, S., Mortimer, J. A., Reynolds, C. A., & Pedersen, N. L. (2005). Complete ascertainment of dementia in the Swedish Twin Registry: the HARMONY study. Neurobiology Of Aging, 26(4), Green, K. N., Steffan, J. S., Martinez-Coria, H., Sun, X., Schreiber, S. S., Thompson, L. M., & LaFerla, F. M. (2008). Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau. The Journal Of Neuroscience: The Official Journal Of The Society For Neuroscience, 28(45), doi: /jneurosci Hager, K., Kenklies, M., & McAfoose, J. (2008). Alpha-lipoic acid as a new treatment option for Alzheimer's disease--a 48 months follow-up analysis. Alternative Medicine Review, (1), 74. Endeavour College of Natural Health endeavour.edu.au 47

48 o o o o o o References Huang, W., Alexander, G.E., Chang, L., Shetty, H.U., Krasuski, J.S., Rapoport, S.I. & Schapiro, M.B. (2001). Brain metabolite concentration and dementia severity in Alzheimer s disease. Neurology. 57, 4, Kumar, P. & Clark, M. (2009). Clinical medicine (7th ed). Edinburgh, Scotland: Saunders Elsevier. Healthnotes Releases A -Z Guide to Drug-Herb-Vitamin Interactions, A Comprehensive Reference for Consumers. (2000) PR Newswire. Lininger SW (1999). A-Z Guide to Drug-Herb-Vitamin Interactions. Healthnotes. Three Rivers Press. New York Louzada, P. R., Paula Lima, A. C., Mendonca-Silva, D. L., Noël, F., De Mello, F. G., & Ferreira, S. T. (2004). Taurine prevents the neurotoxicity of beta-amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer's disease and other neurological disorders. FASEB Journal: Official Publication Of The Federation Of American Societies For Experimental Biology, 18(3), Luchsinger JA, Tang MX, Siddiqui M, et al (2004). Alcohol intake and risk of dementia. J Am Geriatr Soc, vol 52: Endeavour College of Natural Health endeavour.edu.au 48

49 o o o o o o o References Malouf, R. & Grimley Evans, J. (2008). Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane database of systemic reviews. Retrieved 24 January 2011 from: Mishra, S., & Palanivelu, K. (2008). The effect of curcumin (turmeric) on Alzheimer's disease: An overview. Annals Of Indian Academy Of Neurology, (1). Morris, M.C. (2004). Diet & Alzheimer s disease: what the evidence shows. Medscape general medicine. Vol. 6, No. 1. Retrieved 24 January 2011 from: Mukamal KJ, Kuller LH, Fitzpatrick AL (2003). Prospective study of alcohol consumption and risk of dementia in older adults. 2003;289: Osiecki, H. (2014). The Nutrient Bible (7th ed.). Eagle Farm, QLD: Bioconcepts Publishing. Peters R, Peters J, Warner J (2008). Alcohol, dementia and cognitive decline in the elderly: a systematic review. Age Ageing. 37: Pizzorno, J., & Murray, M. (2006). Textbook of Natural Medicine (3rd ed). St. Louis, MO: Churchill Livingstone. Endeavour College of Natural Health endeavour.edu.au 49

50 References o o o o o Potter, P.E. (2010). Investigational medications for treatment of patients with Alzheimer disease. Journal of the American osteopathic association. Vol. 110, Iss. 9, Suppl. 8, p Retrieved 11 January 2011 from: file:///c:/users/staff/desktop/working/research/alzeimers%20parkinsons/inve stigations%20in%20ad.htm Prasad, K.N., Cole, W.C. & Kumar, B. (1999). Multiple antioxidants in the prevention and treatment of Parkinson's disease. Journal of the American college of nutrition, Vol. 18, No. 5, p viewed 26/01/11: Romi, F., Gilhus, N. E., & Aarli, J. A. (2005). Myasthenia gravis: clinical, immunological, and therapeutic advances. Acta Neurologica Scandinavica, 111(2), Reuben, D. B., Judd-Hamilton, L., Harris, T. B., & Seeman, T. E. (2003). The associations between physical activity and inflammatory markers in highfunctioning older persons: MacArthur Studies of Successful Aging. Journal Of The American Geriatrics Society, 51(8), Sarris, J & Wardle, J (2010) Clinical naturopathy. Churchill Livingstone Elsevier, Chatswood, NSW. Endeavour College of Natural Health endeavour.edu.au 50

51 References o Spagnoli, A., Lucca, U., Menasce, G., Bandera, L., Cizza, G., Forloni et al. (1999). Long term acetyl L carnitine treatment in Alzheimer's disease Neurology. Vol. 41, Iss. 11, p Retrieved from: o Suzuki, S., Yamatoya, H., Sakai, H., Kataoka, A., Furushiro, M. & Kudo, S. (2001). Oral administration of soybean lecithin transphosphatidylated phosphatidylserine improves memory impairment in aged rats. Journal of nutrition. Vol. 131, p Viewed 24/01/11: Endeavour College of Natural Health endeavour.edu.au 51

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