ILSI Europe Satellite Workshop on Nutrition for the Ageing Brain: Towards Evidence for an Optimal Diet

Transcription

1 ILSI Europe Satellite Workshop on Nutrition for the Ageing Brain: Towards Evidence for an Optimal Diet July 2014, Milan, Italy Nutritional effects on cognitive ageing Trial data Dr. Ir. Ondine van de Rest Division of Human Nutrition, WUR Organised by The ILSI Europe Nutrition and Mental Performance Task Force

2 Adequate nutrition... for the brain?

3 Evidence for brain foods or nutrients?

4 The evidence pyramid Review/meta-analysis Strength of evidence RCT Prospective studies Cross-sectional human studies Basic science: animal studies; mechanistic studies

5 Which nutrients or foods? Omega-3 fatty acids B-vitamins Vitamin D Antioxidants Alcohol Coffee Ginkgo biloba Mediterranean diet

6 Omega-3 fatty acids (PUFA): sources Vegetable fatty acids: 18:3 n-3 (ALA) Fish fatty acids: 20:5 n-3 (EPA) 22:6 n-3 (DHA)

7 Omega-3 PUFA: mechanisms Cardiovascular and cerebrovascular protection Reduction of cytokine synthesis ( brain inflammation) DHA key component of phospholipid cell membranes Modulation of amyloid precursor protein ( β amyloid) Nutrition and dementia report, ADI 2014

8 Omega-3 PUFA: observational studies 9 cross-sectional: 6 beneficial association 28 prospective: 21 beneficial association Majority showed beneficial associations Review Van de Rest et al, Ann Nutr Met 2012

9 Omega-3 PUFA: intervention studies (1) Cochrane Database of Systematic Reviews Sydenham et al, 2012 Only included trials: in non-demented duration of >6 months 3 trials (n=3,536) no effect on cognition

10 Omega-3 PUFA: intervention studies (2) Meta-analysis of 10 RCTs Effect on specific cognitive domains in cognitively impaired participants Not in healthy or demented participants Mazereeuw et al. Neurobiol Aging, 2013

11 Omega-3 PUFA: brain MRI 6 observational studies: all beneficial RCT 26 weeks (n=65): executive functioning (p=0.023) gray matter atrophy white matter microstructural integrity Witte et al. Cereb. Cortex 2013

12 B-vitamins: sources Folate Vitamin B12

13 Vitamin B12 deficiency in 25-40% of elderly people Main cause: malabsorption Food bound Intrinsic factor deficiency Van Asselt, AJCN 1998

14 B-vitamins: mechanisms Essential for remethylation of homocysteine (Hcy), else Hcy: amyloid and tau and neuronal death apoptosis and neurotoxicity platelet activation (white matter lesions, vascular injury, stroke)

15 B-vitamins: observational studies 35 cohort studies N=14,235, mean n= of good quality -> 7 significant associations Specific markers of B12 status (MMA, holotc) : consistent associations ADI report, Nutrition and dementia, 2014: New studies: 4 extra cohort studies All protective

16 B-vitamins: intervention studies Meta-analysis: 19 trials in individuals with (n=6) or without (n=13) cognitive impairment No effect of B-vitamin supplementation 3 extra trials (Hankey 2013, Douad 2013, Walker 2012) B-proof trial Ford, Journal of Alz Dis 2012

17 B vitamin treatment slows the mean rates of brain atrophy RCT 24 months in MCI, >70y Smith, PloSONE 2010

18 Vitamin D: sources 50-80% of elderly people vitamin D deficient! Source: Dutch Health Council 2008, 2012

19 Vitamin D: mechanisms With courtesy to Elske Brouwer-Brolsma

20 Vitamin D: observational studies Low vitamin D status associated with poorer cognitive function and higher AD risk. GR 2012: Not sufficiently proven that suppletion improves cognition Balion, Neurology 2012

21 Specific nutrients rate limit neuronal membrane and synapse formation The Kennedy pathway for biosynthesis neuronal membrane Uridine Phospholipids Choline Phosphocholine CDP - choline B Folate, - vitamins B6, B12 DHA Omega - 3 fatty EPA acids Phospholipids are main constituents of synapses dendritic spine Synapse Phosphatidylcholine Nerve cell neurite Vit C, E Se New neuronal membrane Prof Richard Wurtman, MIT, Boston, USA

22 Multi-nutrient interventions

23 Souvenaid Clinical Trial Program SMI due to AD amci due to AD Mild AD Moderate AD S-Connect Souvenir I Souvenir II Open Label MEG study MRS study ADAS-cog MMSE 14-24, stable on AD drugs WMS-r & ADAS-cog MMSE 20-26, drug-naïve NTB + EEG MMSE 20, drug-naïve Safety + Compliance + NTB MEG + EEG +NTB MMSE 20, drug-naïve 31P and 1H-MRS MMSE 20, drug-naïve LipiDiDiet FDG-PET NTB + MRI / CSF MMSE 24, drug-naïve FDG-PET + EEG MMSE 24, drug-naïve

24 Significant effect on memory domain during 24 weeks (p=0.023) Scheltens et al J Alz Dis 2012;31:225-36

25 In summary Omega-3 PUFA Epidemiology Protective RCT Only on atrophy + cognition (MCI) Vitamin D Protective Sparse B-vitamins Mixed results Multi-nutrient - MRI promising Only on atrophy, cognition (MCI, high Hcy) Souvenaid (3 studies so far) Within or on top of guidelines?

26 Limitations of past intervention trials Trial duration Target groups Dose Outcome measures (sensitivity and diversity)

27 Future perspectives Long intervention periods At risk groups (but not too late) Harmonize cognitive test battery Include biomarkers and/or imaging Multi-nutrient/food pattern approach Multi-domain interventions Align with mechanisms

28 Thank you for your attention! Acknowledgements: Agnes Berendsen Elske Brouwer-Brolsma Nikita van der Zwaluw