Efstratios Karavasilis ^1* Vasileios Balomenos ^2,3 Foteini Christidi ^4,5 Georgios Velonakis ³ Georgia Angelopoulou ⁴ Mary Yannakoulia ⁶ Eirini Mamalaki ⁶ Archontoula Drouka ⁶ Dora Brikou ⁶ Angeliki Tsapanou ^4,7 Yian Gu ⁷ Nikolaos Scarmeas ^4,7

• ¹ Medical School, Democritus University of Thrace, Alexandroupolis, Greece
• ² Department of Imaging and Interventional Radiology, ‘Sotiria’ General and Chest Diseases Hospital of Athens, Athens, Greece
• ³ Research Unit of Radiology and Medical Imaging, 2nd Department of Radiology, Attikon General University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
• ⁴ First Department of Neurology, Aeginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
• ⁵ Computational Neuroimaging Group (CNG), School of Medicine, Trinity College Dublin, Dublin, Ireland
• ⁶ Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece
• ⁷ Taub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center, Columbia University, New York, United States

Adjustable lifestyle factors, such as diet, are associated with cognitive functions, structural and functional brain measures, but the association between the functional connectivity (FC) and the Mediterranean Diet (Medicine) in population without dementia is yet to be explored. The association between MeDi and brain FC in 105 individuals without dementia aged 63 (SD±8.72) years old who underwent brain MRI including resting-state (rs) functional MRI (fMRI) was examined. Dietary intake was evaluated through four 24-h recalls using the multiple-pass method and adherence to the MeDi was estimated using the MedDietScore, with higher values indicating greater adherence to MeDi. Multivariable linear regression models were used to investigate the associations between FC (both positive and negative associations) and MedDietScore. Rs-fMRI analysis revealed significant associations between FC and MedDietScore. The FC between the medial prefrontal cortex and a cluster located in left postcentral gyrus and in the left supramarginal gyrus was positively associated with MedDietScore. On the other hand, the FC between medial visual and right posterior division of both middle and superior temporal gyrus was negatively associated with MedDietScore. Of note, a temporal negative correlation was detected between above-mentioned FC networks. The FC between superior temporal gyrus and occipital regions was associated with participants' attention, executive functions, and memory scores. Furthermore, the associations for attention and executive functions were pronounced in participants with high adherence to MeDi compared to those with low adherence to MeDi. In conclusion, our study documented an association between higher adherence to MeDi and rs-FC in fronto-parietal and temporo-occipital regions, particularly in areas that are involved in cognitive processes altered across normal and pathological aging. From a clinical point of view, our findings support a favorable role of MeDi on FC which may have significant clinical implications in the rapidly aging population. Rs-fMRI is also proposed as a useful tool in the emerging field of nutritional neuroscience and a candidate non-invasive biomarker of brain aging.