Identification of dietary modulators of cognitive aging & brain plasticity and proof of concept of efficacy for preventing/reversing cognitive decline

Lead Research Organisation: King's College London
Department Name: Neuroscience

Abstract

Understanding how diet modifies cognitive ageing represents the next frontiers for developing prevention strategies. A key may rely on elucidating the exact combination of nutrient capable of modulating cognitive decline via the ability of the brain to be plastic and produce new nerve cells and connections. Another important question is the particular population(s) in which such nutritional intervention should be undertaken. We think that a combination of nutients capable of modulating cognition and brain plasticity exists, and that the influence of diet on the brain starts in early in life and occurs throughout life and that we should consider exposure to stress/genetic predisposition as vulnerability factors. We propose a project across the field of nutrition, epidemiology, and neuroscience using human data/serum samples and mouse models and employing innovative approaches assessing dietary exposure, the ability of the brain to make new neurons and modelling cognitive ageing.

On completion of this project we will have (i) identified and validated an optimum combination of dietary compounds providing protective effect against cognitive ageing and brain plasticity alteration, (ii) identified vulnerable populations responding to the impact of diet on cognitive decline, (iii) provided evidence of brain plasticity as targets of choice for nutrients intervention to prevent/slowdown cognitive decline and (iv) provided a proof-of-principle life-long dietary intervention for preventing/rescuing cognitive decline. It is expected that the nutrients identified and validated will lead to dietary interventions and recommendations for cognitive decline prevention.

Technical Summary

There is a need to uncover the exact dietary bioactives that underlie an individual's risk and resilience to cognitive decline associated with ageing. Furthermore, the roles of dietary modulators must be understood at the neurobiological level to effectively exploit the protective bioactives identified, in order to develop targeted dietary interventions for the prevention and slowing down of cognitive decline.

We hypothesize that (i) there exists a combination of dietary bioactives capable of modulating cognition and brain plasticity, (ii) dietary modulation of brain plasticity and cognition starts in early-life and occurs throughout life and (iii) exposure to stress/genetic predisposition are vulnerability factors to consider. We propose a translational project across nutrition, epidemiology, and neurosciences leveraging human data/serum samples and mouse models and using innovative approaches of: (i) dietary exposure assessment (the food metabolome), (ii) human brain plasticity (in vitro parabiosis to assess neurogenesis and microglial function, lipidomics to assess neuronal integrity), and (iii) cognitive ageing modeling (early-life stress mouse model).

D-CogPlast will start with a discovery stage in humans, aimed at identifying a set of dietary bioactives from the food metabolome associated with cognitive decline, along with vulnerable populations, in 200 individuals with accelerated cognitive decline over 13+ years against 200 individuals with preserved cognition. This will be further validated in 400 participants from a separate cohort. The second stage will be to investigate the ability of the identified set of bioactives predictive of cognitive decline to modulate brain plasticity and neuronal integrity. The third stage will consist in a proof-of-principle dietary intervention with identified bioactives in a mouse model of cognitive decline.

Planned Impact

Impact overview:
D-CogPlast will provide the scientific foundations for evidence-based recommendations for optimal nutrition/new nutritional targets that incorporate long-term health outcomes, focusing here on cognitive ageing.

It is expected that the bioactives identified and validated will lead to dietary interventions and recommendations for cognitive decline prevention and have societal impact across all ages.

D-CogPlast expects to further its impact through dissemination, knowledge exchange, data sharing, and future commercial collaboration and exploitations as highlighted below:

Dissemination:
D-CogPlast is committed to communicating, creating dialogue and promoting the use of results of the project among target groups and stakeholders within Europe and internationally.

Aside from dissemination at scientific meetings and via publications by all partners, D-CogPlast -via Dr. Thuret- will be part of the organizing committee of the July 2016 EU-ILSI Nutrition and Cognitive Ageing workshop which will be open to the scientific community, policy-makers, opinion-leaders, health care professionals and their associations, the food and beverage industry, consumer organizations and Non-Government Organizations.

At the local level, all partners will involve the general public through their networks and national funders and via press offices of their institution. Across the partners' institutions yearly open days, 'Public-days' and 'Scientific cafes' occurs during which public contact and exchange occurs.

Knowledge exchange:
D-CogPlast will foster exchange of scientific know-how between project partners via local and mobility training in order to enhance and support career development of participating young researchers. By providing exchange opportunities, participating researchers will complement their expertise with critical and emerging technologies. This will strengthen the employability of participating researchers, contribute to the attractiveness of positions offered by consortium members and promote European excellence in this field of research.

Data/material sharing:
Data will be available via published articles in open access journals. It is envisaged that the datasets will be available as appropriate 6 months following the end of the project and maintained for a period of at least 10 years. We will also deposit data as appropriate onto the JPI-HDHL Meta Database.

Publications

10 25 50
 
Title Narrating Plasticity: A collaboration bewteen Neurosciences and the Plastic Arts 
Description Art and Humanity PhD student Benjamin Dalton approached the Thuret lab for thier work on neurogenesis with the idea that contemporary conceptions of neuroplasticity - the mutability of the human brain - borrow their thinking of plasticity from sculpture and the plastic arts; this project aimed to explore the artistic, clinical, and philosophical cross-fertilizations that might result from a reconnection of current neuroscience with its artistic and sculptural roots. In order to catalyse these dialogues, this project united a plastic artist -ceramist Amanda Doidge- and Neuroscientists -Thuret lab members- over the course of four workshops. Two of these workshops were help in the artist's studio, and two were held in the lab. The project culminated in an exhibition showcasing the art work produced in the encounter, as well as a panel discussion opening dialogues between the neurosciences, philosophy, and the plastic arts. Further, the project will seek to question how these cross-fertilizations might have an impact on clinical practice. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2018 
Impact Please see a film available here: https://www.youtube.com/watch?time_continue=5&v=5P7scLUiHrw 
URL https://narratingplasticity.wordpress.com/2018/02/04/narrating-plasticity-the-exhibition/
 
Description International Life Sciences Institute (ILSI) NUTRITION AND MENTAL PERFORMANCE TASK FORCE Scientific Advisor
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
URL http://ilsi.eu/about-us/
 
Description EU Joint Programming Initiative D-CogPlast 
Organisation French National Institute of Agricultural Research
Country France 
Sector Public 
PI Contribution I am the consortium leader of D-CogPlast which is an EU Joint Programming Initiative funded research programme investigating dietary modulators of cognitive ageing and brain plasticity. This MRC award is funding part of this the research programme.
Collaborator Contribution D-CogPlast is a research consortium investigating dietary modulators of cognitive ageing and brain plasticity. It is among Five transnational research consortia including 26 research groups from 9 European countries to have been awarded funding under the umbrella of the European Union's H2020 funded JPI HDHL Joint Call "Nutrition and Cognitive Function". D-CogPlast is a multidisciplinary consortium bringing expertise in nutrition, cognition, ageing, brain plasticity and cutting edge technology such as metabolomics, lipidomics and new methodologies such as in vitro parabiosis. The translational nature of D-CogPlast is demonstrated by bringing together basic scientists and epidemiologists, gathering all the necessary skills to successfully conduct this study. D-CogPlast makes synergistic usage of existing data, a community-based cohort, biomaterial and developed animal models, collectively adding value to -and building on- independent work for a greater impact on cognitive decline understanding and prevention via nutrition.
Impact No output/outcome yet.
Start Year 2016
 
Description EU Joint Programming Initiative D-CogPlast 
Organisation National Institute of Health and Medical Research (INSERM)
Country France 
Sector Public 
PI Contribution I am the consortium leader of D-CogPlast which is an EU Joint Programming Initiative funded research programme investigating dietary modulators of cognitive ageing and brain plasticity. This MRC award is funding part of this the research programme.
Collaborator Contribution D-CogPlast is a research consortium investigating dietary modulators of cognitive ageing and brain plasticity. It is among Five transnational research consortia including 26 research groups from 9 European countries to have been awarded funding under the umbrella of the European Union's H2020 funded JPI HDHL Joint Call "Nutrition and Cognitive Function". D-CogPlast is a multidisciplinary consortium bringing expertise in nutrition, cognition, ageing, brain plasticity and cutting edge technology such as metabolomics, lipidomics and new methodologies such as in vitro parabiosis. The translational nature of D-CogPlast is demonstrated by bringing together basic scientists and epidemiologists, gathering all the necessary skills to successfully conduct this study. D-CogPlast makes synergistic usage of existing data, a community-based cohort, biomaterial and developed animal models, collectively adding value to -and building on- independent work for a greater impact on cognitive decline understanding and prevention via nutrition.
Impact No output/outcome yet.
Start Year 2016
 
Description EU Joint Programming Initiative D-CogPlast 
Organisation Paracelsus Private Medical University of Salzburg
Country Austria 
Sector Academic/University 
PI Contribution I am the consortium leader of D-CogPlast which is an EU Joint Programming Initiative funded research programme investigating dietary modulators of cognitive ageing and brain plasticity. This MRC award is funding part of this the research programme.
Collaborator Contribution D-CogPlast is a research consortium investigating dietary modulators of cognitive ageing and brain plasticity. It is among Five transnational research consortia including 26 research groups from 9 European countries to have been awarded funding under the umbrella of the European Union's H2020 funded JPI HDHL Joint Call "Nutrition and Cognitive Function". D-CogPlast is a multidisciplinary consortium bringing expertise in nutrition, cognition, ageing, brain plasticity and cutting edge technology such as metabolomics, lipidomics and new methodologies such as in vitro parabiosis. The translational nature of D-CogPlast is demonstrated by bringing together basic scientists and epidemiologists, gathering all the necessary skills to successfully conduct this study. D-CogPlast makes synergistic usage of existing data, a community-based cohort, biomaterial and developed animal models, collectively adding value to -and building on- independent work for a greater impact on cognitive decline understanding and prevention via nutrition.
Impact No output/outcome yet.
Start Year 2016
 
Description EU Joint Programming Initiative D-CogPlast 
Organisation University of Amsterdam
Country Netherlands 
Sector Academic/University 
PI Contribution I am the consortium leader of D-CogPlast which is an EU Joint Programming Initiative funded research programme investigating dietary modulators of cognitive ageing and brain plasticity. This MRC award is funding part of this the research programme.
Collaborator Contribution D-CogPlast is a research consortium investigating dietary modulators of cognitive ageing and brain plasticity. It is among Five transnational research consortia including 26 research groups from 9 European countries to have been awarded funding under the umbrella of the European Union's H2020 funded JPI HDHL Joint Call "Nutrition and Cognitive Function". D-CogPlast is a multidisciplinary consortium bringing expertise in nutrition, cognition, ageing, brain plasticity and cutting edge technology such as metabolomics, lipidomics and new methodologies such as in vitro parabiosis. The translational nature of D-CogPlast is demonstrated by bringing together basic scientists and epidemiologists, gathering all the necessary skills to successfully conduct this study. D-CogPlast makes synergistic usage of existing data, a community-based cohort, biomaterial and developed animal models, collectively adding value to -and building on- independent work for a greater impact on cognitive decline understanding and prevention via nutrition.
Impact No output/outcome yet.
Start Year 2016
 
Description EU Joint Programming Initiative D-CogPlast 
Organisation University of Barcelona
Country Spain 
Sector Academic/University 
PI Contribution I am the consortium leader of D-CogPlast which is an EU Joint Programming Initiative funded research programme investigating dietary modulators of cognitive ageing and brain plasticity. This MRC award is funding part of this the research programme.
Collaborator Contribution D-CogPlast is a research consortium investigating dietary modulators of cognitive ageing and brain plasticity. It is among Five transnational research consortia including 26 research groups from 9 European countries to have been awarded funding under the umbrella of the European Union's H2020 funded JPI HDHL Joint Call "Nutrition and Cognitive Function". D-CogPlast is a multidisciplinary consortium bringing expertise in nutrition, cognition, ageing, brain plasticity and cutting edge technology such as metabolomics, lipidomics and new methodologies such as in vitro parabiosis. The translational nature of D-CogPlast is demonstrated by bringing together basic scientists and epidemiologists, gathering all the necessary skills to successfully conduct this study. D-CogPlast makes synergistic usage of existing data, a community-based cohort, biomaterial and developed animal models, collectively adding value to -and building on- independent work for a greater impact on cognitive decline understanding and prevention via nutrition.
Impact No output/outcome yet.
Start Year 2016
 
Description BBC 1 Documentary: Food: Truth or Scare 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Dr. Thuret contributed as an expert in diet and impact in the brain/cognition/mood for this BBC1 programme where hosts Gloria Hunniford and Chris Bavin present a series that cuts through confusion and conflicting headlines about Britain's favourite foods. Dr. Thureat clarified myths versus actual scientific data.
Year(s) Of Engagement Activity 2017
URL http://www.bbc.co.uk/programmes/b08f066n
 
Description BBC 1 documentatry: Holding back the years 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Dr Thuret contributed as an expert on diet and cognition/brain ageing for BBC 1 programme on "Holding back the years' Hosted by Bill Turnbull, Fiona Phillips and Dr Rangan Chatterjee, Holding Back the Years looks at how to stay well, live longer and be healthy - whatever age you are.
Year(s) Of Engagement Activity 2018
URL http://www.bbc.co.uk/programmes/b08l66cx
 
Description BBC Radio 4: All in the Mind 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Dr. Sandrine Thuret was invited on BBC Radio 4 by Claudia Hammond to discuss her latest research on the neurogenic theory of depression. The role of diet was also discussed. It is now a podcast.
Year(s) Of Engagement Activity 2017
URL http://www.bbc.co.uk/programmes/b08v09y4
 
Description PodCast: How to Grow New Brain Cells with Dr Sandrine Thuret by Dr. Rangan Chatterjee / January 9, 2019 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Guest for pod cast " 'Feel Better, Live More with Dr Rangan Chatterjee"

#1 health podcast on itune

How to Grow New Brain Cells with Dr Sandrine Thuret
by Dr. Rangan Chatterjee / January 9, 2019

https://drchatterjee.com/grow-new-brain-cells-dr-sandrine-thuret/

https://itunes.apple.com/gb/podcast/feel-better-live-more-with-dr-rangan-chatterjee/id1333552422?mt=2
(pod cast #44)
Year(s) Of Engagement Activity 2019
URL https://drchatterjee.com/grow-new-brain-cells-dr-sandrine-thuret/
 
Description School outreach 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact PhD students Chiara De Lucia and Alish Palmos and research technician Curie Kim from the Neurogenesis and Mental Health Lab visited Lyndhurst Primary school during their Science Week in June and delivered three enging talks and worskhops on brain anatomy and function for children in year 2 and year 4. Pupils enganed fully particularly understanding the role of nutriton in brain development and the later impact in adult life and for healthy ageing. The school would like this to be a yearly recurring event.
Year(s) Of Engagement Activity 2017
URL https://www.kcl.ac.uk/ioppn/depts/bcn/newsevents/records/Adult-Neurogenesis-and-Mental-Health-Lab-vi...