Clinical trial NCT06837272: A Longitudinal Study to Explore the Impact of Gut Microbiome on Brain Health in Alzheimer's Disease
Official title: A Longitudinal Study to Explore the Impact of Gut Microbiome on Brain Health in Alzheimer's Disease: China Healthy Brain and Gut Microbiome Study (CHBGMS)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Alzheimer Disease
Gut Microbiota
Metabonomics
Magnetic Resonance Imaging
Keywords: Subjective cognitive decline
Multi-omics
Lead sponsor: Jining Medical University
Sponsor class: OTHER
Collaborators: name: Xuanwu Hospital, Beijing
First posted: 2025-02-20
Enrollment: 285
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Volunteers recruited from both clinical and communities, and signed up with informed consent.

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.


Eligibility criteria: Inclusion Criteria:

* Cognitively normal group:

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

Exclusion Criteria:

* 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

Primary outcomes:
measure: The changes of gut microbiome in the spectrum of AD
timeFrame: 5 year
measure: The changes of SCFAs in the spectrum of AD
timeFrame: 5 year
measure: Multi-omics biomarkers associated with conversion to cognitive impairment for SCD subjects
timeFrame: 5 years
Secondary outcomes:
measure: The interaction mechanisms of "gut microbiota-SCFAs-brain networks"
timeFrame: 5 years
Other outcomes:
Locations:
city: Jining
country: China
facility: Department of Neurolgy, the Affiliated Hospital of Jining Medical University
state: Shandong
Study officials:
affiliation: The Affiliated Hospital of Jining Medical University
name: Can Sheng, PhD
role: PRINCIPAL_INVESTIGATOR
References: