RecruitingNCT05934188

Exploring the Gut-Brain Axis in Ageing and Neurodegeneration

Role of the Gut-microbiota on Ageing and Neurodegeneration: a Clinical and Brain Imaging Study


Sponsor

IRCCS San Camillo, Venezia, Italy

Enrollment

200 participants

Start Date

May 1, 2023

Study Type

OBSERVATIONAL

Conditions

Summary

Neurodegenerative diseases are a major health concern due to their growing societal implications and economic costs. The identification of early markers of pathogenic mechanisms is one of the current main challenges. The gut-brain axis has become a primary target because of its transversal role across the neurodegenerative spectrum and its effect on cognition. However, despite recent progress, how changes in the gut-microbiota composition can affect the human brain is still unclear. The goal of this observational study is to characterise the gut-microbiota composition associated with alterations in brain structure and function during the ageing process and across neurodegenerative disorders. This is based on recent studies showing that changes in the human brain and in the microbiota composition, can indicate very sensitively and in a predictive way pathological development and, consequently, be used as markers of neurodegenerative diseases. The main questions it aims to answer are: * How variation in the gut-microbiota composition correlates with the normal brain ageing trajectory? * How dysregulation in the gut-microbiota correlates with pathological changes in brain regions in specific neurodegenerative disorders? * Can the impact of the gut-microbiota on the brain be modulated by blood biomarkers? The investigators will recruit 40 young healthy participants, 40 old healthy participants, 40 participants with prodromal Alzheimer's Disease, 40 participants with Parkinson's Disease and 40 participants with Multiple Sclerosis. Participants will undergo the following examinations: * Magnetic Resonance Imaging * Analysis of a stool sample * Analysis of a blood sample * Neuropsychological assessment * Questionnaires on eating habits


Eligibility

Min Age: 20 YearsMax Age: 90 Years

Inclusion Criteria20

  • Healthy Young and Old Subjects:
  • or 60-90 years old
  • Cognitively healthy (Mini-Mental State examination ≥ 26)
  • Absence of significant neurological disorders
  • Patients with prodromal Alzheimer's Disease:
  • Subjective cognitive complaint (corroborated by the informant)
  • Episodic memory deficit on neuropsychological testing
  • Clinical Dementia Rating = 0.5
  • Mini-Mental State Examination (MMSE) \> 23
  • Independently functioning in activities of daily living
  • Patients with Parkinson's Disease:
  • Recent diagnosis of Parkinson's Disease
  • Mild-moderate score at the Unified Parkinson's Disease Rating Scale (UPDRS)
  • Cognitively healthy (Mini-Mental State examination ≥ 26)
  • In case of taking medications for Parkinson's Disease: stable dosage for at least 6 months
  • Patients with Multiple Sclerosis:
  • Recent diagnosis of relapsing-remitting Multiple Sclerosis
  • Expanded Disability Status Scale score ≤ 4.0
  • Cognitively healthy (Mini-Mental State examination ≥ 26)
  • In case of taking medications for Multiple Sclerosis: stable dosage for at least 6 months.

Exclusion Criteria4

  • For both healthy participants and patients:
  • Contraindications to magnetic resonance imaging (metal implant in body, known claustrophobia, pacemakers)
  • Severe comorbidities
  • Antibiotics treatments over the last 3 months

Interventions

DIAGNOSTIC_TESTMagnetic Resonance Imaging

The Magnetic Resonance Imaging protocol will comprise both structural and functional sequences.

BEHAVIORALNeuropsychological protocol

Neuropsychological tests will be administered to participants to assess general cognitive state and a range of high-level cognitive functions (memory, executive, language). In addition, disease-specific tests will be administered to patients to investigate disease staging and the level of disability and autonomy.

BEHAVIORALEating habits

Information on eating habits will be derived from food questionnaires.

DIAGNOSTIC_TESTMicrobiome analyses

The Microbiome analyses will be derived from a stool sample (16S rRNA sequencing targeted metagenomic analyses).

DIAGNOSTIC_TESTInflammatory markers

Inflammatory markers will be evaluated in terms RNA expression level in plasma blood sample.

DIAGNOSTIC_TESTAlzheimer's Disease biomarkers

The Alzheimer's Disease biomarkers will be measured in the plasma of prodromal Alzheimer's Disease patients.


Locations(3)

IRCCS San Camillo

Venice-Lido, Venice, Italy

IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli

Brescia, Italy

Università Ca' Foscari Venezia

Venice, Italy

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NCT05934188


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