Exploring the Gut-Brain Axis in Ageing and Neurodegeneration

Recent studies show that alterations in the microbiota profile has been observed in the ageing process and across neurodegenerative disorders and it has been associated with cognitive decline and disease-specific clinical symptoms. The objective of this multicenter observational cross-sectional cohort study is to characterise how changes in the gut-microbiota profile may affect brain changes during the physiological ageing processes and across neurodegenerative disorders with different etiopathogenesis. The investigators will combine novel magnetic resonance imaging and biological techniques to test these hypotheses: 1. Specific functional and structural changes, which reflect unsuccessful compensatory mechanisms to counteract ageing, are associated with changes in the gut-microbiota composition. 2. Neurodegenerative disorders (prodromal Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis) show unique changes in the gut-microbiome profile, associated with specific structural and functional brain changes. 3. The microbiota profile characterizing the unsuccessful ageing and different neurodegenerative diseases is associated with alterations in blood biomarkers. For this study the investigators plan to recruit 80 healthy subjects divided into two groups (40 subjects aged 20-50 years and 40 subjects aged 60-90 years) and 120 patients divided into three groups (40 patients with prodromal Alzheimer's Disease, 40 patients with Parkinson's Disease and 40 patients with Multiple Sclerosis). All participants will undergo a multimodal Magnetic Resonance Imaging protocol to study the brain structure and function and a detailed neuropsychological protocol to assess cognitive functioning. In addition, stool and blood samples will be collected to investigate the gut-microbiota composition and the presence of inflammatory markers, respectively. Participants will also be asked to fill out questionnaires on eating habits. There are no known risks or long-term side effects related to Magnetic Resonance Imaging. The performance of the examination does not involve physical or mental impairment. The study does not directly benefit the participant. However, participation in the study will increase knowledge in the area of the relationship between the gut microbiota and the brain, providing potential new knowledge useful for preventing the risk of developing neurodegenerative processes. The study takes place at San Camillo IRCCS S.r.l. (70 Alberoni street, Lido VE, 30126, Italy IT). The study started on 01/05/2023 and the end is planned for 30/04/2026. The submitted study is funded by the Ministry of Health through a finalized research call won by Principal Investigator, Dr. Nicola Filippini, and approved by Ethics Committee for Clinical Trials of the Province of Venice and IRCCS San Camillo, Azienda ULSS 3 Serenissima.