The impact of peripheral insulin resistance on systemic health is well-documented and its profound effects on brain function and cognition have gained increased attention in recent years The project will analyze the relevance of insulin-resistance (IR) and IR-associated metabolic dysbalances in the brain as key factors promoting cognitive impairment (CI) and unhealthy aging. A triple integrative approach will be implemented in the present study.

First, a retrospective analysis in a large EU cohort (Rotterdam Study) will determine the weight of life styles and nutritional habits (dietary fat and carbohydrates consumption) on IR-associated CI, focusing on the predictive value of metabolic plasma biomarkers, circulating neurotrophic and systemic inflammation factors and gut microbiome analysis.

Second, preclinical models of diet-induced obesity resulting in both IR and CI will provide insights on the molecular mechanisms of peripheral/brain IR, providing a comparison with the nutritional epidemiology study. 

Finally, a nutritional intervention in mild CI patients with dietary administration of insulin sensitizers/modulators (D-Pinitol or D-chiroinositol administration) will evaluate the effectiveness of IR-oriented interventions along a 2 year follow-up, where clinical records and plasma evaluation will incorporate monitoring of parameters identified in both retrospective and preclinical studies.

AI-based modeling will integrate all the information gathered to establish the value of preventive interventions of IR impacting on the risk of CI and dementia. The studies will focus on gender differences to provide the most accurate gender-adjusted solutions, and will be developed in tight association with patient’s organizations, health stakeholders and general citizens in an open science-based design.

The contribution of an EU SME specialized on the production of high quality nutritional ingredients is incorporated to guarantee a rapid translation to the market/citizens.