Nutrition and the Ageing Brain: can specific foods and nutrients help to preserve better cognition in older adults?
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1 Nutrition and the Ageing Brain: can specific foods and nutrients help to preserve better cognition in older adults? Helene McNulty PhD RD MRIA Director of the Nutrition Innovation Centre for Food and Health (NICHE) ulster.ac.uk
2 Presentation Outline Nutrition and cognitive health in later life Results from the TUDA study (island of Ireland) Future directions and impact
3 Dementia: the predictions
4 Cognitive Health Cognitive Impairment Spectrum COGNITIVE FUNCTION Dementia Cases: Expected to reach 50% > 131 million by 2050 Trillion dollar disease TIME (Years) 85 NORMAL AGEING MILD COGNITIVE IMPAIRMENT DEMENTIA
5 Dementia: The Costs UK 850, billion ROI 74, billion Connolly et al. (2014) Dementia 13(1): Pierce et al.(2014) Genio Report
6 1. Smith, Food Nutr Bull 2008; 29, 2, S Stahl et al., Am J Psychiatry 2008; 171, 5, Gallagher et al.; J. Affect Disord 2016; 190; Kennedy, Nutrients 2016; 8(2), 68
7 Foods and Brain Health 1-6 Mediterranean diet ( fruit, vegetables, wholegrains, olive oil and fish) Observational evidence Protects cognition function Protective against depressive symptoms Limited data from intervention studies in older adults Moore et al. (2018) Proc Nutr Soc 77,
8 Specific nutrients and brain health Vitamin D Moore et al. (2018) Proc Nutr Soc 77,
9 Potential Mechanisms - One Carbon Metabolism B6 c B12 B2 B6 B6 c B2
10 B-vitamins and Cognitive Function: RCTs Author Dose (mg/d) Findings McMahon 2006 B12 (0.5), FA (1) and B6 (10) for 2 years n=253 No effect Durga 2007 Kwok 2010 Walker 2012 VITACOG Study Smith 2010 De Jager 2012 Douaud 2013 Jernerén 2015 Van der Zwaluw 2014 FA (0.8) for 3 years n=836 B12 (1) and FA (5) for 2 years n=140 B12 (0.1) and FA (0.4) for 2 years n=900 B12 (0.5), FA (0.8) and B6 (20) for 2 year n=266 B12 (0.5), FA (0.4) and D3 (0.15) for 2 years n=856 Improved cognition No effect Improved cognition Improved cognition MRI: grey matter brain atrophy by 30% No effect
11 Anthropometric details Measures of frailty Physical self maintenance, daily living activities, mobility Demographic details Lifestyle variables Smoking, alcohol, dietary habits, sun exposure The Trinity Ulster Department of Agriculture (TUDA) Ageing Study n = 5,186 Medications, supplements, fortified foods Medical history, Heart disease, stroke, diabetes, hypertension, falls, anxiety, depression Clinical parameters BP, liver function, kidney function, haematology, lipids, electrolytes
12 Cognitive Assessment Mini-Mental State Examination (MMSE) Quick method for global cognition; widely used <24 mild cognitive impairment; <20 dementia Repeatable Battery for Neuropsychological Assessment (RBANS) Screening battery for attention, language, constructional abilities, immediate and delayed memory <80 cognitive impairment Frontal Assessment Battery (FAB) Designed to test frontal lobe function <15 cognitive impairment
13 Trinity Ulster Department of Agriculture (TUDA) Cohort Study 1 2 3
14 TUDA Study - General Characteristics Males n 1699 Females n 3487 P value Age (years) 73.4± ± Educations (years) 16.0± ± BMI (kg/m 2 ) 28.5± ±5.8 <0.001 FA Fortified Food Consumer (%) B-vitamin Supplement user (%) <0.001 Hypertension (%) <0.001 Diabetes (%) <0.001 Stroke (%) <0.001 Data presented as mean ± SD unless otherwise indicated. Differences assessed using an independent t test and chisquare analysis p<0.05 considered significant.
15 B-Vitamin Status by B-Vitamin Intake Non consumers Consumer of B-vitamin Fortified Food (FF) B-vitamin supplement users Portions/week (0) (1-4) (5-7) (8+) (±FF) n RBC folate (nmol/l) 692 a 802 b 909 c 1139 d 1475 e Serum Vit B12 (pmol/l) Plasma PLP (nmol/l) Riboflavin (EGRac) 238 a 243 a 260 a 271 b 299 c 47.0 a 54.1 b 60.8 c 70.3 d 67.6 d 1.35 a 1.32 b 1.28 c 1.28 c 1.24 d Data presented as median. ANOVA and post-hoc comparisons using the Tukey. Values in the same row with different superscript letters are significantly different, P < 0.05
16 TUDA 5+ Study Aim: Examine role of baseline folate and related B-vitamins as predictors of subsequent cognitive decline in ageing Hypothesis Suboptimal status of B-vitamins will be associated with a greater rate of cognitive decline over a five year follow-up period.
17 B-vitamin biomarkers and risk of cognitive decline (Porter et al unpublished) B-vitamin status RBANS Odds Ratio 95% CI P Elevated homocysteine Low folate status Low vitamin B12 status Low vitamin B6 status Low riboflavin status Binary logistic regression with adjustment for age, education, gender, depression and baseline cognitive score.
18 Summary of TUDA study Findings (so far) Older adults who do not consume fortified foods or supplements have sub-optimal B vitamin status. In relation to cognition: Findings add to emerging evidence supporting role of B-vitamins in maintaining cognitive health in ageing. They show: Suboptimal status of vitamin B6 or riboflavin are each associated with an increased risk of accelerated cognitive decline. Vitamin B6 and riboflavin may be much more important than previously appreciated for cognition in ageing (yet overlooked in most studies).
19 Public Health Impact of findings Optimising B-vitamin status may offer a public health strategy for maintaining cognition in ageing B-vitamin intake Biomarker status Rate of cognitive decline Potential to decrease health care costs and disease burden
20 BrainHOP Trial n 328 Placebo (n 165) B-vitamin Supplement (n 163) MEG (n 24) MEG (n 24)
21 Measuring outcomes in nutrition and brain research Investigating cognitive health outcomes: Validated questionnaire-based assessments Most common means of investigating cognitive and mental health outcomes Most informative as regards the effect of nutrition on behaviour 1 Brain imaging techniques in recent years provide an objective and highly robust means of assessing brain function and response to nutrition intervention 2 1.Macready et al. Nutrition Review 2010; 23: de Jager and Kovatcheva Nutrition Reviews 2010; 68: S53-S58 3.de Jager et al Nutrition Reviews 2010; 72:
22 Use of novel technologies in nutrition and brain research 1 EEG Electroencephalography Electric activity of the brain at the scalp Improved memory & functional connectivity in the delta band; response to a nutritional supplement in cognitively impaired patients. fmri Functional MRI Blood O 2 level dependent, changes in blood flow show areas of neural activity Demonstrated higher brain activation in specific regions in those who consumed a nutritionally balanced breakfast. MRI Magnetic resonance imaging Pictures Gray and white matter, blood vessels and bone Confirm the beneficial effects of B-vitamins on cognition in older adults. Moore et al. Proc Nutr Soc. (2018) in press
23 The VITACOG Study A: Placebo Rate of Atrophy: 2.5% per year B: B Vitamins Rate of Atrophy: 0.46% per year Significantly greater loss in Grey Matter Volume in the placebo group Smith et al., Plos One 2010; 5(9):e1224 Douaud et al., Proc of Natl Acad Sci of USA 2013; 110(23):
24 Magnetoencephalography (MEG) MEG maps brain activity by measuring the magnetic fields produced by neuronal activity with sub-millisecond precision. Preliminary results suggest that better B-vitamin status is associated with improved neuronal functioning Lopez et al American Aging Association 2014
25 INDIVIDUAL Diet Behaviours Age Related Changes Genetics Diseases Healthy Ageing SOCIOECONOMIC Education Income Family/Friends support Community safety ENVIRONMENT Housing Transport Social Poverty MENTAL HEALTH Relationships Discrimination Physical Health Community World Health Organization and Calouste Gulbenkian Foundation. Social determinants of mental health., WHO, Tod AM, Lusambili A, Homer C, et al. BMJ Open 2012;2:e doi: /bmjopen
26 Map showing the distribution of TUDA participants from (A) NI and (B) RoI GREEN - Least deprived 20% of areas; RED - Most deprived 20% of areas
27 The TUDA Study reports that older adults (n=5186) living in the most deprived areas of NI and ROI had 40% higher risk of cognitive dysfunction; less formal education; higher rates of smoking and alcohol consumption; higher rates if obesity; higher blood pressure; higher risk of diabetes.
28 Public health challenge Preventing or delaying the onset of cognitive impairment should be a major public health priority Delay onset by 5 years DEMENTIA Reduce incidence of dementia by 50%
29 Life-course model of contribution of modifiable risk factors to dementia
30 Take Home Messages Certain foods and nutrients may be beneficial for the ageing brain The evidence at this time is strongest in the case of B vitamins B vitamins may have important impacts on cognitive function Early results from the BrainHop RCT at this Centre show beneficial effects of B vitamin intervention on visuospatial cognition and potentially better neuronal functioning (via MEG) If confirmed, supplementation or food fortification with B-vitamins may offer effective, low cost options to promote better brain health in ageing Future work Further well-designed RCTs are required to confirm these effects targeted at those who can benefit Ideally incorporating imaging technologies
31 My thanks to co-investigators, collaborators and funders NICHE Mary Ward Sean Strain Kristina Pentieva Leane Hoey Catherine Hughes Katie Moore Our Collaborators in TCD and St James Hospital John Scott Anne Molloy Conal Cunningham Miriam Casey TUDA project teams at Ulster, TCD and SJH Dublin PhD students Clinical Collaborators Geraldine Horigan (2006) Catherine Hughes (2010) Carol Wilson (2010) Rosie Reilly (2014) Amy McMahon (2017) Kirsty porter (2017) Katie Moore (2018) Maurice O Kane Fergal Tracey John Purvis Tom Trouton Local General Practitioners
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