Reviewing novel dietary strategies to delay or prevent Alzheimer s disease. Dr David Vauzour

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1 Reviewing novel dietary strategies to delay or prevent Alzheimer s disease Dr David Vauzour

2 Populations are getting older x 2.5 United Nations 2012

3 Ageing and dementia

4 Global impact of dementia World Alzheimer Report 2015: The Global Impact of Dementia

5 Risk factors and brain vulnerability Modifiable risk factors Unhealthy diet Physical inactivity Tobacco/alcohol/drugs Stress Intermediate risk factors Cardiovascular disease Obesity Diabetes Pulmonary disease Mental Illness Non modifiable risk factors Age Family history Genetics

6 Lexical cluster analysis Terms: cognitive+decline+diet Database: PubMed Nutrition and the ageing brain It is becoming widely accepted that lifestyle changes are the best protection against dementia, creating a massive opportunity for nutritional products Keith Wesnes, Exeter University

7 A diverse array of brain nutritional bioactives Omega-3 (Fish, flaxseed) Flavonoids (Fruits, Veg) Curcumin (Turmeric) B Vitamins - Folic acid (Vit B9) - Cyanocobalamin (Vit B12) - Pyridoxine (Vit B6)

8 Omega-3 intervention studies Effect on specific cognitive domains in cognitively impaired participants Not in healthy or demented participants

9 Works better in non APOE4 carriers 9

10 Fish oil intake and cognitive decline/ad: RCTs Alzheimer s Disease Co-operation Study (ADCS)(Quinn et al., 2010) DHA 2g/d vs. placebo, 18m 10

11 B vitamins protect cognition

12 Omega-3 status influences response to B-vitamins

13 Low selenium levels associated with poor cognitive functions

14 Multinutrient intervention

15 falters in clinical trial

16 Polyphenols, friends for the brain PAQUID study, France, West South 1367 subjects > 65 yrs, 5yrs follow up Dementia incidence : Flavonoids < 11 mg/d RR = 1 Flavonoids > 11 mg/d RR = 0.55 Commenges et al, Eur J Epidemiol, 2000,16: Suvimax 2 Study : 2135 subjects, 13 years after Suvimax : Suvimax 1 middle-aged volunteers became "seniors" Total and specific polyphenols intakes in middle-life are associated with cognitive function measured 12 yrs later Kesse-Guyot et al, J Nutr 2012,142(1):76-83

17 Adherence to Mediteranean (MeDi) diet reduces risk of cognitive decline Reduced risk of develpping MCI Reduced risk of converting from MCI to AD Multi ethnic community study in northern Manhattan New-York cognitively normal participants (77 yrs). 275 developed MCI during follow-up of 4.5 years. Scarmeas, Arch Neur. 2009

18 Impact of flavanols on cognitive performance

19 Executive Function (Z Score) Episodic Memory (Z-Score) Flavanol intervention acutely (2h) improves executive function and episodic memory Executive Function z-score from 5 tests Episodic memory z-score from 4 tests 0.25 p < p < Low Flavanol High Flavanol -2.5 Low Flavanol High Flavanol Saunders C et al, AJCN submitted

20 Cerebrovascular blood flow and cognition ASL: arterial spin labelling - measuring cerebral blood flow (CBF) in vivo fmri: functional MRI - haemodynamic response (change in blood flow) related to neural activity in the brain

21 Acute cognitive improvements induced by flavanols (450 mg) are linked to changes in blood flow % FMD Total Plasma Flavanols (nm) Hg) mean CBF (ml/100g/min) Flavanol effects of peripheral vascular response 10 Control High Flavanol *** A *** Control High Flavanol ** 8 *** Baseline 2h 4h B -100 Low Flavonoid High Flavonoid h 4h 10 * * 5 *

22 Time-series analysis on resting state ASL dataflavanol vs. control intervention (axial slices) Middle frontal gyrus Pre-central gyrus Lateral occipital cortex

23 Flavanols increase angiogenesis Control Epicatechin Lectin-stained vessels Pseudocolor mask van Praag H et al. J. Neurosci. 2007;27:

24 Neurogenesis Neurogenesis 24

25 Neurogenesis in the adult hippocampus The genesis of new cells, including neurons, in the adult human brain has not yet been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the adult human brain, in regions previously identified as neurogenic in adult rodents and monkeys. Human brain tissue was obtained postmortem from patients... We demonstrate that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans. Our results further indicate that the human hippocampus retains its ability to generate neurons throughout life.

26 Flavanols enhance dentate gyrus functions Brickman AM et al Nat Neurosci. 2014

27 Summary Miquel S et al. ILSI Europe Nutrition and Mental Performance Task Force. Poor cognitive ageing: Vulnerabilities, mechanisms and the impact of nutritional Interventions. Ageing Research Reviews In revision

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29 Acknowledgements Nutritional Sciences Pr. Jeremy Spencer Dr. Manal Abd El Mohsen Dr. Giulia Corona Dr. Catarina Rendeiro Dr. Ana Rodriguez-Mateos Psychology Dr. Laurie Butler Dr. Claire Williams GESVAB Pr. Jean Michel Mérillon Dr. Pierre Waffo-Téguo Dr Tristan Richard