A Longitudinal Study to Explore the Impact of Gut Microbiome on Brain Health in Alzheimer's Disease

NCT06837272 | Recruiting

• 1 other identifier: JiningMU_Shc1
• Study Type: observational
• Target: 285
• Locations: 1 country
• Sites: 1

Brief Summary

Gut microbiota dysfunction is associated with Alzheimer's disease (AD). However, the potential modulatory mechanism remains unclear. Previous studies have shown that gut-derived metabolites short-chain fatty acids (SCFAs) may be the key mediators between gut microbiota and brain, participating in the modulatory pathway "gut microbiota-SCFAs-brain networks". In this project, high-throughput targeted metabolomics technique will be used to explore the differences of SCFAs in the spectrum of AD, including cognitively normal individuals, subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD dementia. Then, the gut microbiome and multi-modal MRI techniques will be combined to elucidate potential interaction mechanisms of "gut microbiota-SCFAs-brain networks". Finally, based on multi-omics features extracted from gut microbiome, metabolomics, and neuroimaging after five years, the diagnostic model of SCD due to preclinical AD will be established using machine learning methods.

Conditions

Alzheimer Disease; Gut Microbiota; Metabonomics; Magnetic Resonance Imaging

Keywords

Subjective cognitive decline; Multi-omics

Outcome Measures

Primary Outcomes (3)

• The changes of gut microbiome in the spectrum of AD

  Using the 16S rRNA Illumina Miseq sequencing technique, the diversity and compositions of gut microbiome will be compared in different stages of AD, including cognitively normal individuals, SCD, MCI and AD dementia.

  5 year

• The changes of SCFAs in the spectrum of AD

  Using the high-throughput target metabolomics technique, SCFAs will be compared in different stages of AD, including cognitively normal individuals, SCD, MCI and AD dementia.

  5 year

• Multi-omics biomarkers associated with conversion to cognitive impairment for SCD subjects

  SCD subjects will be followed for five years. The investigators aim to characterize those who convert to MCI or AD dementia during the follow-up, and further find the multi-omics features associated with the progression of AD. Based on multi-omics features extracted from clinical data, gut microbiome, metabolomics, and multi-modal MRI, the diagnostic model of SCD due to preclinical AD will be established.

  5 years

Secondary Outcomes (1)

• The interaction mechanisms of "gut microbiota-SCFAs-brain networks"

  5 years

Study Arms (4)

Cognitively normal group

(1) normal performance on standardized cognitive tests; (2) with no cognitive complaints or any concerns (worries).

Subjective cognitive decline (SCD) group

(1) self-experienced persistent decline in memory, rather than other domains of cognition; (2) normal performance on standardized cognitive tests; (3) failure to meet the criteria for MCI or dementia; (4) age at onset of SCD ≥ 60 years old; (5) onset of SCD within the last 5 years; (6) concerns (worries) associated with SCD; (7) feeling of worse performance than others of the same age group.

Diagnostic Test: Multi-omics features extraction

Mild cognitive impairment (MCI) group

(1) having impaired scores on both measures in at least one cognitive domain (memory, language, or speed/executive function); (2) having impaired scores in each of the three cognitive domains (memory, language, or speed/executive function); (3) the Functional Activities Questionnaire (FAQ)≥9.

AD dementia group

(1) meet the criteria for dementia and have impaired daily functional activities; (2) episodic memory deficit; 3) Clinical Dementia Rating (CDR) ≥ 1.

Interventions

Multi-omics features extraction DIAGNOSTIC_TEST

Based on multi-omics features extracted from clinical data, gut microbiome, metabolomics, and multi-modal MRI, the diagnostic model of SCD due to preclinical AD will be established.

Subjective cognitive decline (SCD) group

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Volunteers recruited from both clinical and communities, and signed up with informed consent.

You may qualify if:

• Cognitively normal group:
• normal performance on standardized cognitive tests;
• with no cognitive complaints or any concerns (worries).
• SCD group:
• self-experienced persistent decline in memory, rather than other domains of cognition;
• normal performance on standardized cognitive tests;
• failure to meet the criteria for MCI or dementia;
• age at onset of SCD ≥ 60 years old;
• onset of SCD within the last 5 years;
• concerns (worries) associated with SCD;
• feeling of worse performance than others of the same age group.
• MCI group:
• having impaired scores on both measures in at least one cognitive domain (memory, language, or speed/executive function);
• having impaired scores in each of the three cognitive domains (memory, language, or speed/executive function);
• the Functional Activities Questionnaire (FAQ)≥9.

You may not qualify if:

• a history of stroke;
• major depression and anxiety;
• other central nervous system disorders that may cause cognitive impairment, such as Parkinson's disease, tumors, encephalitis, and epilepsy;
• cognitive impairment caused by traumatic brain injury;
• systemic diseases, such as thyroid dysfunction, syphilis and HIV;
• psychosis or congenital mental developmental delay;
• a history of using antibiotics, probiotics, prebiotics, or synbiotics within 3 months;
• the use of corticosteroid, immune stimulating medications, and immunosuppressive agents;
• major gastrointestinal tract surgery in past 5 years;
• severe gastrointestinal diseases, such as irritable bowel syndrome, infammatory bowel disease, severe gastritis, other dysfunction in digestion and absorption, which has been reported to infuence gut microbiota

Sponsors & Collaborators

• Jining Medical University: lead
• Xuanwu Hospital, Beijing: collaborator

Study Sites (1)

Department of Neurolgy, the Affiliated Hospital of Jining Medical University

Jining, Shandong, 272029, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

In this project, the investigators will test ApoE genotype.

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Can Sheng, PhD

  Jining Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Can Sheng, PhD

CONTACT

86-18701257298; canyeweiwu2013@163.com

Yun Guo, Master

CONTACT

86-18863030588; yun125985@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 15, 2025
• First Posted: February 20, 2025
• Study Start: January 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 20, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: When summary data are published or starting 12 months after publication.
• Access Criteria: When summary data are published or starting 12 months after publication.

Locations

CN (1)