15/10/2018. A Functional Approach to Neurodegeneration. Functional Medicine for Alzheimer s Patients. Belinda Reynolds B.Sc.Nut.Diet.

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A Functional Approach to Neurodegeneration Belinda Reynolds B.Sc.Nut.Diet.

1 A Functional Approach to Neurodegeneration Belinda Reynolds B.Sc.Nut.Diet. (Hons) 1 Functional Medicine for Alzheimer s Patients Source: 2 High homocysteine Low vitamin D status Poor sleep Sedentary lifestyle Insulin resistance Genetics Cardiovascular disease Nutrient-deplete diet Mitochondrial dysfunction Poor gut health Inflammation and oxidative stress Emotional stress Hormonal imbalance Poor oral health COGNITIVE DECLINE 1

2 Example of a Personalised Intervention: 4 Depression a Predictor of Dementia? Normal Depression Normal Alzheimer s 5 These findings suggest that depressive symptoms precede memory decline consistent with the hypotheses that depression is a prodrome of dementia or a causal contributor to memory decline. Clinicians should be aware that depressive symptoms may represent an early indicator not only of dementia but also memory decline generally. 6 2

Brain Derived Neurotrophic Factor (BDNF) BDNF: brain derived neurotrophic factor promotes neurogenesis and increases cell survival BDNF promotes the survival and differentiation of 5-HT neurons

3 Brain Derived Neurotrophic Factor (BDNF) BDNF: brain derived neurotrophic factor promotes neurogenesis and increases cell survival BDNF promotes the survival and differentiation of 5-HT neurons Promotes Nrf2 BDNF levels are abnormally low in patients suffering major depressive disorder, and anxiety (particularly OCD) Higher serum BDNF levels may protect against future occurrence of dementia and Alzheimer s disease (AD) Suliman S, et al. Brain-Derived Neurotrophic Factor (BDNF) protein levels in anxiety disorders: systematic review and meta-regression analysis. Front Integr Neurosci. 2013;7:55. Weinstein G, et al. Serum brain-derived neurotrophic factor and the risk for dementia: the Framingham Heart Study. JAMA Neurol 2014;71(1): BDNF Promotion BDNF expression compromised by: inflammation and oxidative stress poor diet (e.g. high in sugar and bad fat) high glucocorticoids (due to chronic stress) genetic variants (SNPs) Interventions to increase BDNF expression: anti-inflammatory/antioxidant support (e.g. fish oil, turmeric) mitochondrial nutrients (e.g. CoQ10) exercise, calorie restriction, cognitive stimulation 8 Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry 2009;65(9): BDNF Promotion 9 3

BDNF Promotion 10 BDNF Promotion 11 Promote Neurogenesis

supplement if patient on statins - Consider NQO1 SNP

supplement (1-2g) if diet poor and signs of CVD Consider

coloured plant foods - If significant symptoms of

4 BDNF Promotion 10 BDNF Promotion 11 Promote Neurogenesis Ensure CoQ10 sufficiency - Consider ubiquinol mg supplement if patient on statins - Consider NQO1 SNP Recommend diet rich in essential fats - Consider fish oil supplement (1-2g) if diet poor and signs of CVD Consider zinc and magnesium Recommend diet rich in bright and dark coloured plant foods - If significant symptoms of inflammation recommend curcumin supplement Ensure healthy blood sugar control 12 4

Sleep deprivation: promotes inflammation suppresses neurogenesis disrupts sex hormones is linked to weight gain associated with insulin resistance 13 Encourage Healthy Sleeping Habits Aim for 8

5 Sleep deprivation: promotes inflammation suppresses neurogenesis disrupts sex hormones is linked to weight gain associated with insulin resistance 13 Encourage Healthy Sleeping Habits Aim for 8 hours/night - Reduce caffeine in the hours close to bed - Reduce alcohol before to bed Alcohol disturbs sleep - Reduce short-wavelength blue light exposure close to bed time - Reduce processed carbohydrates close to bed time Leave 3 hours between eating and sleep 14 BDNF and Exercise Physical exercise has been identified as useful for increasing neuroplasticity via rises in BDNF Animal studies have noted that physical exercise increased BDNF, which correlated with cognitive improvements Human studies have observed improvements in cerebral blood flow and neurogenesis as a result of physical activity (150mins/week of walking) Gomez-Pinilla F, et al. The influence of exercise on cognitive abilities. Compr Physiol 2013;3(1): Lautenschlager NT, et al. The influence of exercise on brain aging and dementia. Biochim Biophys Acta 2012;1822(3):

Exercise, Cognition and Wellbeing People who undertake physical activity while listening to music performed better on some measures of cognition

au/nsw/news/the-benefits-of-physical-activity-and-exercise-forpeople-living-with-dementia Satoh M, et al.

PLOS one 2014;9(4):E95230 16 The Influence of Exercise on Cognitive Abilities Gomez-Pinilla F, et al.

17 Sarcopenia and Insulin Resistance: Risk Factors for Cognitive Decline A systemic review and meta-analysis found that sarcopenia was independently

6 Exercise, Cognition and Wellbeing People who undertake physical activity while listening to music performed better on some measures of cognition than those who exercised without music creation of stronger social connections and better community engagement Source: Satoh M, et al. The effects of physical exercise with music on cognitive function of elderly people: Mihamo-Kiho project. PLOS one 2014;9(4):E The Influence of Exercise on Cognitive Abilities Gomez-Pinilla F, et al. The influence of exercise on cognitive abilities. Compr Physiol 2013;3(1): Sarcopenia and Insulin Resistance: Risk Factors for Cognitive Decline A systemic review and meta-analysis found that sarcopenia was independently associated with cognitive impairment Insulin resistance is related to subsequent poorer cognitive performance and greater cognitive decline among patients with cardiovascular disease Chang KV, et al. Association Between Sarcopenia and Cognitive Impairment: A Systematic Review and Meta-Analysis. J Am Med Dir Assoc. 2016;17(12):1164.e e

Sarcopenia 19 Osteosarcopenic Obesity and Insulin Resistance Source: http://link.springer.com/article/10.1007/s13539-014-0146-x 20 Supplementation with whey protein (22g), essential amino acids (10.

7 Sarcopenia 19 Osteosarcopenic Obesity and Insulin Resistance Source: 20 Supplementation with whey protein (22g), essential amino acids (10.9g) and vitamin D (2.5mcg/100IU), in conjunction with ageappropriate exercise, not only boosts fat-free mass and strength but also enhances other aspects that contribute to wellbeing in sarcopenic elderly. 21 7

8 Fish Oil Supports Muscle and Metabolic Health Dietary fish oil-derived n-3 PUFA (1.86g EPA, 1.5g DHA) supplementation can increase muscle mass, reduce oxygen demand during physical activity, and improve physical function (muscle strength and power, and endurance) in people. Fish oil-derived n-3 PUFA therapy slows the normal decline in muscle mass and function in older adults and should be considered a therapeutic approach for preventing sarcopenia and maintaining physical independence in older adults. Consider FADS1 and PEMT SNPs Effect of dietary n-3 PUFA supplementation on the muscle transcriptome in older adults. Physiol Rep. 2016;4(11). Yoshino J, et al. Fish oil-derived n-3 PUFA therapy increases muscle mass and function in healthy older adults. Am J Clin Nutr 2015;102(1): Encourage Physical Activity and Prevent Sarcopenia Aim for 150mins/week of exercise - Exercise with music - Exercise with others (e.g. dancing, aquaaerobics) - Start small (e.g. walk around the clothes line or the block) Consume 25g protein/meal (aim for 1g/kg body weight per day) - Consider whey protein supplement or similar Consider vitamin D and fish oil as support if indicated 23 Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions. NB: These new findings confirm that vitamin D levels above 50 nmol/l are most strongly associated with good brain health. 24 8

Vitamin D deficient individuals had a 63% increased risk of developing dementia in comparison to those who were vitamin D sufficient.

9 Available data indicates that lower vitamin D status may be associated with increased risk of developing AD and dementia. Vitamin D deficiency (<50 nmol/l) was associated with an increased risk of developing AD by 21% in comparison to those who were sufficient. Vitamin D deficient individuals had a 63% increased risk of developing dementia in comparison to those who were vitamin D sufficient. 25 Check vitamin D status (25(OH)D) Aim for >50-100nmol/L If low, supplement with 4000IU/day Assess for specific gene SNPs which impact vitamin D status e.g. DHCR7, GC 26 Homocysteine Many cross-sectional and prospective studies have shown that raised levels of plasma total homocysteine (thcy) are associated with cognitive impairment, AD, or vascular dementia 27 9

progression to dementia can be prevented.

(fasting blood) B12 status Folate status

10 Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjects with high homocysteine levels are warranted to see if progression to dementia can be prevented. 28 Recommend measurement of: Homocysteine (fasting blood) B12 status Folate status Suggested intervention: B mcg/day Folate mcg/day B6 20mg/day 29 Supporting Healthy Methylation 30 10

Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment Consider PEMT SNP and others impacting methylation Oulhaj A, et al.

11 Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment Consider PEMT SNP and others impacting methylation Oulhaj A, et al. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment. J Alzheimers Dis 2016;50(2): Forgetting to Eat and Difficulties with Preparation Alarm clock as a reminder at meal times Healthy snacks that are easily seen and available - Look to options that don t require refrigeration and that require little-to-no preparation Meals-on-wheels if suitable Pre-prepared meals or foods requiring less preparation (e.g. frozen vegetables) Cook large batches of foods and freeze meal portions Make meals a social occasion where possible 32 Checklist for Assessing Opportunities for Intervention A Summary 33 11

12 Optimising Cognitive Health Check List Check-up with GP: - HbA1c, fasting insulin - Blood lipids and blood pressure (BP) to determine vascular health For elevated trigs, LDL, BP and low HDL recommend 2g fish oil or 2g krill oil - Homocysteine, B12 and folate status - Thyroid function (e.g. TSH) - 25(OH)D to determine vitamin D status (aim for >50-100nmol/L) Generalised pain associated with deficiency, and muscle wasting 4000IU vitamin D3 daily required to correct deficiency Check for medication use known to increase risk of specific deficiencies - Metformin Recommend vitamin B mcg/day - Statin Recommend 100mg/day ubiquinol Consider vitamin K2 180mcg (warnings with Warfarin) 34 Optimising Cognitive Health Check List (contd.) Assess for sarcopenia - Muscle wasting may not be visually evident in early stages, ask questions around strength and balance - Encourage greater protein intake (e.g. 25g/meal) or whey protein supplement plus vitamin D - Emphasise the importance of exercise (especially resistance exercise) Sleep: encourage 8 hours/night Exercise: aim for 150mins/week (with music, and as part of a group is ideal) - NB: Not realistic for all, simply increasing incidental exercise is useful, or short walks around the block that gradually increase in length Reduce inflammation if present with curcumin (e.g mg highly bioavailable form) and fish oil (2-4g/day) - Signs of inflammation include joint pain/back pain, generalised pain, inflammatory skin conditions, depressive symptoms - Encourage more vegetables and fruit in the diet, less processed/refined carbohydrates - Eat more fibre, protein and good fats Oral health: encourage dentist check-up 35 12

Dr. Jonathan Spages D.C.

17 Natural Ways to Lower Cholesterol Dr. Jonathan Spages D.C. Copyright 2017 All Rights Reserved No part of this book may be reproduced in any form or by any electronic or mechanical means including information