Lifestyle interventions targeting modifiable risk hold great potential in reducing the risk of cognitive decline and dementia. To use this potential, we need to understand the optimal combination of lifestyle factors and specific nutrients, identify the individuals who benefit most, and reveal the underlying mechanisms. We propose a multidisciplinary project encompassing lifestyle, nutrition, epidemiology, neuroscience, human and animal research. COGNILIFT has three phases: A Trial phase: A 6-month randomised controlled trial (RCT) in Israeli older adults 60+ (n=200), testing a multidomain lifestyle intervention with/without polyphenol supplement (MemophenolTM) for cognitive decline.

 Based on the successful Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study, it includes physical activity, cognitive training, diet, social activities, and cardiovascular management. Participants will be divided into four groups, receiving either the full multidomain lifestyle intervention or general lifestyle advice, with or without the polyphenol supplement. We will assess cognitive functions, brain activity via electroencephalogram (EEG), blood metabolome, cytokine profiles, and faecal microbiome at baseline, 6 months (post-intervention), and 12-months (follow-up). A Validation phase: Testing the identified biomarkers in other international multidomain lifestyle intervention trials within the Worldwide-FINGERS network.

A Mechanistic phase: Using a mouse model of cognitive decline to explore (neuro)biological mechanisms of interventions. The project’s significance lies in its potential to develop a FINGER-based multidomain lifestyle intervention tailored for Israeli communities. It also aims to identify internationally validated biomarker signatures for cognitive health and unravel neurobiological mechanisms behind cognitive status, decline and intervention success.