Lifestyle Interventions to Prevent Cognitive Deficits in Subjects With Depressive Symptoms: From Mechanisms to Clinical Practice

The goal of this clinical study is to investigate if lifestyle changes can help prevent cognitive decline and reduce depressive symptoms in people between the ages of 50 and 80 with depressive symptoms or a diagnosis of major depression, but without signs of cognitive decline. The main questions it aims to answer are: * Does regular physical activity improve mood and memory in people who are depressed or have depressive symptoms? * Does cognitive training help prevent mental difficulties in people at risk of cognitive decline? * Do changes in diet and lifestyle alter the composition of the gut microbiota and immuno-related infiammatory factors? Researchers will compare three different treatment groups to see which intervention is most effective in improving mental and cognitive health. The participants: * Will take part to online sessions on healthy eating based on the Mediterranean diet * Some will do regular exercise, supervised by a personal trainer * Others will do weekly cognitive training in small groups at the hospital * They will provide blood and fecal samples and complete cognitive tests and clinical questionnaires at the beginning, at the end of the treatment (12 weeks), and after 3 months.

NCT Number	NCT07009223
Lead Sponsor	IRCCS Centro San Giovanni di Dio Fatebenefratelli Collaborators: Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC), University of Milan, China Medical University, China, University College Cork, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
Conditions	Major Depressive Disorder (MDD), Physical Activity, Inflammation, Metabolome, Gut Microbiota, Depressive Symptoms
Enrollment	120 participants
Start Date	2025-10-01
Primary Completion	2026-08 (estimated)
Study Completion	2028-03 (estimated)
Updated on ClinicalTrials.gov	2026-02-11