There is a lack of effective treatment for dementia, the way forward is the rigorous investigation of modifiable preventive factors such as diet that impact brain aging and disease. Diet plays a pivotal role in the regulation of systemic inflammation and oxidative stress, two causal pathways leading to dementia. The Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet can be modified to eating patterns across the world and is designed to investigate as a brain healthy diet rich in anti-inflammatory/anti-oxidative dietary factors in relation to neurodegenerative disease outcomes. However, these findings do not give us information at the individual level. Therefore, we will use the personalized nutrition framework to test the effect of omics signatures of the MIND diet on the brain. This is the first study to investigate omics signatures of the MIND diet in relation positron-emission tomography (PET)-imaging biomarkers of Alzheimer’s disease dementia (AD) and incident all- cause dementia and AD. We aim to conduct (1a) metabolic profiling (using metabolomics) to identify (individual and composite score) metabolic signatures of the MIND diet among participants in the Offspring (GEN2, n~2300) and Generation 3 (GEN3, n~1220) cohorts of the Framingham Heart Study (FHS); (1b) biological pathway over representation analysis of the omics signatures of the MIND diet; (1c) and we will investigate genetic determinants associated with the newly identified omics biomarkers associated with the MIND diet. Secondly, we will investigate (2a) the MIND diet in relation to amyloid (i.e. precuneus and fronto-lateral-retrosplenial), and tau PET-imaging (i.e. entorhinal, inferotemporal and rhinal cortex, global weighted averaged and global cortical composites weighted averaged) among participants in FHS GEN2 and GEN3 (n=350); (2b) We will investigate the newly identified omics signatures of the MIND diet individually and as a score in relation to incident all-cause dementia and AD (n~800), and PET-imaging markers of AD (n~200); (2c) We will investigate the associations among subgroups (sex differences, Apolipoprotein e4 carriers vs. non-carriers, and age). Sample for aim 1 will include GEN2 (exams 5, 8 or 9) and GEN3 (exam 2) participants who have plasma metabolomic levels, filled out the FFQ, and have covariate data. Sample for aim 2 will include GEN2 (exams 5 up to 9) and GEN3 (exams 1 up to 4) participants who have plasma metabolomic levels, filled out the FFQ, who underwent beta-amyloid and Tau PET scans (GEN2 between exams 9 and 10; GEN3 between exams 3 and 4), who have dementia surveillance and covariate data. We will relate the metabolomic signatures of the MIND diet to the MIND diet as well as PET-imaging biomarkers of AD using multivariable linear regression and incident all-cause dementia and AD using Cox proportional hazard models. When significant associations are found (Aim 2), we will perform stratified analyses to investigate subgro...