Can you reduce dementia risk through diet? Margaret P Rayman Professor of Nutritional Medicine University of Surrey
Dietary Factors That May Protect Against Cognitive Decline and Alzheimer s Disease Antioxidants vitamin C, vitamin E (foods not supplements), selenium Polyphenols B vitamins folate, B12, B6 Fish and fish oil Monounsaturated fatty acids Vitamin D Dietary patterns, e.g. Mediterranean diet MIND diet
Polyphenols (including the large and complex class of flavonoids) Widely available in foodstuffs such as fruits, vegetables, cereals, tea and wine Interventions with polyphenol-rich foods and beverages derived from grapes, cocoa, tea and blueberries, have demonstrated beneficial effects on memory and learning. Rendeiro et al. Proc Nutr Soc 2012
Chocolate, Wine, Tea and Cognitive Performance 2031 Norwegians, aged 70-74 y, from the Hordaland Health Study Their habitual food intake over the previous year was assessed. They were given six cognitive tests. Maximum benefit was seen at intake: 10 g/d, for chocolate approximately 75-100 ml/d, for wine 200 ml/d or more, for tea Nurk et al. J Nutr 2009
Berry Intake can Delay Cognitive Ageing by up to 2.5 yr 16,010 participants from the US Nurses' Health Study filled in a food frequency questionnaire every four years. Cognitive function was measured using six cognitive tests in those aged 70 years and follow-up assessments were conducted twice. Greater intakes of blueberries and strawberries were associated with significantly slower rates of cognitive decline Strawberries and blueberries have high levels of anthocyanidins, a sub-class of flavonoids, which are associated with significantly slower rates of cognitive decline. Berry-derived anthocyanidins are uniquely capable of both crossing the blood-brain barrier and localizing in brain regions involved in learning and memory. Benefits were seen at: blueberries strawberries 1 serving/wk vs. <1/mth 2 servings/wk vs. <1/wk Devore et al. Ann Neurol. 2012; 72:135-43.
B vitamins, Homocysteine and Brain Health Three B vitamins regulate the level of homocysteine; homocysteine is deleterious to brain health SH CH 2 CH 2 CH COOH increases risk of Cognitive decline Alzheimer s Disease Vascular dementia Brain damage/atrophy NH 2 Homocysteine Slide courtesy of Prof David Smith Department of Pharmacology University of Oxford
The Methionine Cycle: How Homocysteine is Removed Methionine S-adenosylmethionine (SAM) Deficiency related to brain atrophy Protein Brain fats Neurotransmitters Methylation S-adenosylhomocysteine Methylated Proteins Brain fats Neurotransmitters Folate Methylation B12 Homocysteine B 6 Cystathionine B 6 Cysteine Slide courtesy of Prof David Smith Department of Pharmacology University of Oxford
VITACOG Trial 266 participants with mild cognitive impairment (MCI), aged 70 y, were randomly assigned to receive a daily dose of 800 µg folic acid, 500 µg vitamin B12 and 20 mg vitamin B6 or placebo for 2 y. Plasma homocysteine fell by 30% in those treated with B vitamins. 168 participants had MRI scans at baseline and 2 y Rate of brain atrophy per year was 30% less in the B-vitamin group than in the placebo group [OR (95% CI)]: 0.76% (0.63-0.90) in the B vitamin group 1.08% (0.94-1.22) in the placebo group B vit. vs. placebo, P=0.001 Placebo B vitamins Smith et al. PLoS ONE 2010 Sep 8;5(9):e12244
Vitamin B12 Deficiency B12 deficiency is very common in the elderly, e.g. > 20% in people over 65 Much of this is due to malabsorption (10 30% of older adults): atrophic gastritis causes loss of HCl in stomach, hence food-bound B12 not released Helicobacter pylori infection long-term medication use e.g. - proton pump inhibitors (Omeprazole, Lansoprazole) - H2-receptor antagonists (Tagamet, Zantac) - metformin (diabetes) The US IOM recommends that adults > 50 y obtain most of their vitamin B12 from vitamin supplements or fortified foods. http://ods.od.nih.gov/factsheets/vitaminb12-healthprofessional/
Sources of B12 for those able to absorb it Data from 6000 subjects from the Hordaland Homocysteine Study Plasma B12 was associated with increasing intake of B12 from dairy products or fish (P for trend <0.001 for both) but not with intake from meat or eggs. However, vitamin B12 appears to be most bioavailable from dairy products. Vogiatzoglu et al. AJCN, 2009.
A milk-based smoothie is an excellent source of vitamin B12 as are molluscs (e.g. mussels, scallops)
Fish/Seafood Intake and Risk ofad: Prospective Epidemiologic Studies Rotterdam Kalmijn 1997 Three-City Barberger-Gateau 2007 CHCS Huang 2005 PAQUID Barberger-Gateau 2002 Framingham Schaefer 2006 CHAP Morris 2003 1 fish meal/wk* 2-3 fish meals/wk* 2 fish meals/wk* 1 fish meal/wk* 3 fish meals/wk* 1 fish meal/wk* *vs little/none 0 0.2 0.4 0.6 0.8 1.0 Odds Ratio 1.2 Morris et al. Proc Nutr Soc 2012
Dietary Patterns & Brain Protection Beneficial dietary patterns appear to reduce the risk of dementia more than single nutrients. Examples are: The Mediterranean Diet The MIND Diet http://oldwayspt.org/resources/heritage-pyramids/mediterranean-pyramid/overview Morris MC et al. Alzheimers Dement. 2015 Feb 11. pii: S1552-5260(15)00017-5.
The MIND Diet High intake of plantbased foods High consumption of berries High consumption of green leafy vegetables One fish meal per week Limited intake of animal foods & foods high in saturated fat Morris MC et al. Alzheimers Dement. 2015 Feb 11. pii: S1552-5260(15)00017-5.
Comparison between effectiveness of the Mediterranean diet & the MIND Diet Participants who adhered well (t3) or moderately well (t2) to the MIND diet had a significantly lower risk of developing AD, by 53% and 35%, respectively. Participants who adhered well to the Mediterranean diet (t3) had a significantly lower risk of developing AD, by 54%, but those who only adhered moderately well did not have a significantly reduced risk of developing AD. This suggests that green leafy veg and berries may be more important than lots of fruit or fish. MIND MEDITERRANEAN Morris MC et al. Alzheimers Dement. 2015 Feb 11. pii: S1552-5260(15)00017-5.
Increased risk Increased risk Decreased risk Decreased risk Decreased risk Prospective Studies of Fats & Cognitive Decline STUDY Exposure Outcome SAT TRANS MUFA PUFA U/S Okereke, 2012 WHS Diet Global - - Devore, 2009 NHS Diet Global - Eskelinen, 2008 Finland Diet Global - - - Beydoun, 2007 ARIC Plasma Global - Morris, 2006 CHAP Diet Global Solfrizzi, 2006 ILSA Diet MMSE - Heude, 2003 EVA Erythro MMSE - - Bowman, 2012 Oregon Plasma Global Roberts, 2012 MAYO Diet MCI - - - Vercambre, 2010 WACS Diet Global - - Naqvi, 2011 WHI Diet Global - - Morris & Tangney, Neurobiol Aging 2014; 35: 559-564 U/S=unsat:sat
Evidence-Based Dietary Advice Ensure adequate intake of vitamin E from foods, not supplements (i.e. mixed tocopherols) Eat polyphenol sources: red wine/grapes soya products tea & coffee cocoa/dark chocolate berries citrus fruits Ensure adequate intake of folate, B12, B6 if over 50 y, take a B-complex supplement Eat fish at least once a week Use olive oil Adopt a protective dietary pattern Mediterranean diet MIND diet easier to adhere to, therefore more successful For extensive reference list see: www.surrey.ac.uk/diet-and-dementia
Relative risk of AD by level of intake of -3 fatty acids Fatty acid Increasing intake 1 2 3 4 5 P for trend Total -3 1.0 1.2 0.6 0.7 0.4 0.01* -Linolenic (18:3n-3) 1.0 1.8 0.8 0.9 0.7 0.1 EPA (20:5n-3) 1.0-1.1 0.5 0.9 0.4 DHA (22:6n-3) 1.0 0.8 0.4 0.2 0.3 0.02* *Significant protection (P<0.05) People with the highest intake of -3 fatty acids had a 60% reduction in risk compared with those with the lowest intake. DHA intake was even more protective than total -3 fatty acid intake, with statistically significant 70-80% reductions in risk for the upper two categories of intake. Trials of fish oil have not shown reduced risk but recruitment was not restricted to no-fish or low-fish consumers. Morris et al. Arch Neurol. 2003