1. Diet and Alzheimer’s disease Andy Smith School of Psychology Cardiff University

2. How my interest in Alzheimer’s disease has developed 1. Immune suppression in carers of Alzheimer’s patients

3. Factors influencing cognitive function Environmental factors e.g. noise Infections e.g. influenza Health-related behaviours e.g. Food and drink In all areas the approach now involves looking across the lifespan “From the cradle to the grave”

4. Methods Acute effects on cognitive function Neurotransmitter challenge Simulations of real-life activities Longer interventions Epidemiology – children, young adults, representative samples, the elderly – mental health; health and safety at work

5. Interventions Manipulation of diet is potentially the simplest and most cost-effective way to influence cognition on a large scale This will need to be done as dementia currently affects 700,000 in the UK and this will double over the next 25 years Dementia costs £17 billion, making it the largest healthcare challenge in the UK

6. Evidence for effects of diet on cognition in the elderly and dementia Cognitive function in the elderly is predicted by the level of plasma IGF-I in mid-life and this in turn is influenced by dietary factors in early life, such as intake of milk. People with elevated serum cholesterol are at increased risk of Alzheimer's disease (AD), stroke and vascular dementia. Epidemiological data and animal studies suggest that increased intake of docosahexaenoic acid (DHA) reduces the risk of AD and vascular dementia.

7. Diet and dementia (contd) The neurodegenerative changes in AD result from the accumulation of excessive amounts of Aβ, synthesis and degradation of which occurs to a large extent within lipid rafts. Raft formation depends on the relative amounts of cholesterol and DHA within the plasma membrane and influences not only Aβ metabolism but also receptor proteins for glutamate and other transmitters, which have central roles in memory, cognition, response to ischaemia and development of dementia.

8. Food/Drink and Alzheimer’s Caffeine Anti-oxidants Toxins in the gut Omega-3-fatty acids

9. Gut microbiota and cognitive decline in the elderly “Good bacteria” (e.g. bifidobacteria) lead to the production of SCFAs which provide energy to the muscles and improve brain metabolism (?). Studies have shown a reduction in these bacteria in the elderly. “Bad bacteria” (e.g. clostridia) lead to production of (neuro)toxins.

10. Anti-oxidants/anti-inflammatory polyphenols Fruit and veg Especially berries Shukitt-Hale et al. (2008)- Berry fruit supplementation lowers oxidative stress and inflammation

11. Mechanisms Alters: Signalling involved in neuronal connections Calcium buffering Neuroprotective stress shock proteins Plasticity Stress signalling pathways

12. Evidence Epidemiology – nutritional anti- oxidants may forestall the onset of dementia (Solfrizzi et al., 2003) Flavanoids (anthocyanins) lead to benefits in animal models of dementia.

13. Caffeine/Coffee Epidemiology and animal models Some of the effects could be due to anti-oxidant properties of coffee. But effects of caffeine look stronger.

14. Effects of caffeine on cognition Substantial literature on effects of caffeine on cognitive function in animals and humans (both young adults and elderly). Mechanism – effects on adenosine receptors that lead to down-stream changes in neurotransmitters.

15. Neurotransmitters and caffeine 1. Central noradrenaline – a model for the effects observed in fatigued individuals.

17. Caffeine, speed of encoding, - cholinergic effects – observed in even alert individuals

19. A rabbit model of Alzheimer’s Chen et al. (2008) Alzheimer’s due to the breakdown of the blood brain barrier (BBB) Can be induced by a high cholesterol diet Can effect on BBB be eliminated by 3mg caffeine a day in drinking water?

20. Results Caffeine: Blocked BBB leakage Decreased expression of endothelial cell tight junction proteins Increased activation of astrocytes Increased microglia density

21. What I’d like to do Collaboration in epidemiological studies of Alzheimer’s. Collaboration in studies using animal models. Human intervention studies.