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)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 285
- 试验地点
- 1
- 主要终点
- The changes of gut microbiome in the spectrum of AD
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)≥
- •AD dementia group:
- •meet the criteria for dementia and have impaired daily functional activities;
- •episodic memory deficit; 3) Clinical Dementia Rating (CDR) ≥ 1.
排除标准
- •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
结局指标
主要结局
The changes of gut microbiome in the spectrum of AD
时间窗: 5 year
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.
The changes of SCFAs in the spectrum of AD
时间窗: 5 year
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.
Multi-omics biomarkers associated with conversion to cognitive impairment for SCD subjects
时间窗: 5 years
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.
次要结局
- The interaction mechanisms of "gut microbiota-SCFAs-brain networks"(5 years)
研究者
Can Sheng
Professor
Jining Medical University