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

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.

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.

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.