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

Jining Medical University285 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

285

Conditions

Alzheimer Disease Gut Microbiota Metabonomics Magnetic Resonance Imaging

Interventions

Eligibility

Sex: ALLMin age: 60 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 5 years

Secondary Outcomes

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

The gut microbiome, SCFAs and multi-modal MRI techniques will be combined to elucidate potential interaction mechanisms of "gut microbiota-SCFAs-brain networks".