Cognitive decline is physiologically associated with ageing, however it is also characterizing younger individuals affected by mental diseases, such as Major Depressive Disorder (MDD). Although several studies have investigated how non-pharmacological interventions, such as exercise and diet have a positive effect on depressive symptoms, only few studies focused on cognition. Also, little is known about the possible biological substrates that could mediate the effect of these non-pharmacological interventions on cognition and no biological predictors of cognitive deficits or of improvement of cognitive performances have been identified yet. POWER is a multidisciplinary project characterized by interlinked research activities built up on already available clinical cohorts together with already collected biosamples and data from preclinical models for innovative mechanistic research, and high-throughput experimental multi-omic approaches. POWER will identify specific immune-metabolic and nutritional signatures associated with cognitive impairment both in physiological ageing and in MDD, with the goal of identifying possible targets for preventive interventions and improving patient care. POWER will exploit data already collected in non-pharmacological interventions-based studies in MDD populations to identify how the modulation of inflammation and of nutrients/metabolites associated with these interventions can have effects on brain functioning. Here we will test immune markers, metabolites and diet nutrients in association with changes in cognition and depressive symptoms. Moreover, in subjects with obesity, where patients show cognitive deficits and depressive symptoms and are also characterized by inflammatory and metabolic dysfunctions, we will evaluate whether inflammatory and metabolomic changes induced by bariatric surgery can improve depressive symptomatology and cognition. POWER will then upscale a multilevel pilot intervention trial aimed at lowering the risk of functional and cognitive impairment in patients with depression and will demonstrate the role of gut microbiota (GMB) in mediating the effect of diet, physical activity and brain training on cognition. For this purpose, changes in inflammatory/immune markers, metabolites, nutrients and GMB profiles will be evaluated in relation to cognitive outcomes and depressive symptoms. Finally, POWER will also demonstrate causality by performing faecal microbiota transplantation experiments in animal models. Overall, POWER will demonstrate the beneficial effect of non-pharmacological intervention in depressed patients at risk of developing cognitive impairment.
