Clinical trial NCT03991195: Intervention of Intestinal Microorganism in Mild Cognitive Impairment
Official title: Regulatory Mechanism of Intestinal Microorganism in Intervening Mild Cognitive Impairment Based on Multi-modal Neuroimaging Techniques
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gut Microbiota
Mild Cognitive Impairment
Dementia, Alzheimer Type
Neuroimaging
Keywords: mild cognitive impairment
intestinal microorganism
regulation
magnetic resonance imaging
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: First Hospital of Tsinghua University
name: Beijing Normal University
First posted: 2019-06-19
Enrollment: 90
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Alzheimer's disease (AD) is the most common form of neurodegenerative disorders leading to dementia. Currently, there has been no effective drugs targeting this disease. Dysbiosis of the gut microbiota is considered to be associated with AD, and probiotic supplementation may positively affect cognitive function. However, there are few studies involving the relationship between intestinal microorganism and amnestic mild cognitive impairment (aMCI). In this project, taking the method of random, double blindness and control, the probiotic supplemented group with aMCI will take certain Bifidobacterium for a certain time. After that, the investigators aim to investigate the improvement of cognitive function and changes of intestinal microbial flora diversity via combining neuropsychological tests and 16S recombinant deoxyribonucleic acid (rDNA) high-throughput sequencing technique. Furthermore, based on the multi-modal neuroimaging techniques, the regulatory mechanism of intestinal microorganism in intervening aMCI will be revealed from the perspective of brain networks. In conclusion, these results are beneficial for understanding the therapeutic effect of gut microbiota as a non-drug treatment for early AD and further elucidating the potential brain mechanism, which are of great values in solving scientific and clinical practice issues.

Detailed description: Dysbiosis of the gut microbiota is considered to be associated with Alzheimer's disease (AD), and probiotic supplementation may positively affect cognitive function for patients with AD. However, there are few existing studies involving the role of gut microbiota in possible intervention for amnestic mild cognitive impairment (aMCI).

In this project, taking the method of random, double blindness and control, the probiotic supplemented group with aMCI will take Bifidobacterium for three months. The control group with aMCI will take placebo. After that, the investigators aim to investigate the differences of cognitive function between these two groups and changes of intestinal microbial flora diversity via combining neuropsychological tests and 16S rDNA high-throughput sequencing technique. Furthermore, based on the multi-modal neuroimaging techniques, including structural magnetic resonance imaging (sMRI）, functional MRI, diffusion tensor imaging (DTI)， functional near-infrared spectroscopy (fNIRS), the regulatory mechanism of intestinal microorganism in intervening aMCI will be revealed from the perspective of brain networks.

In conclusion, these results are beneficial for understanding the therapeutic effect of gut microbiome as a non-drug treatment for early AD and further elucidating the potential brain mechanism, which are of great values in solving scientific and clinical practice issues.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of patients with aMCI: memory loss complaint confirmed by an informant; objective cognitive impairment in single or multiple domains, adjusted for age and education; preserved general cognitive function; failure to meet the criteria for dementia; the clinical dementia rating (CDR) score is 0.5.
* Clinical diagnosis of patients with subjective cognitive decline (SCD): presence of self-perceived continuous cognitive decline compared to previous normal status and unrelated to an acute event; failure to meet the following criteria for MCI.
* Clinical diagnosis of the control group: no complaint of memory loss; CDR score is 0; no severe visual or auditory impairment.

Exclusion Criteria:

* a history of stroke;
* major depression (Hamilton Depression Rating Scale score \> 24 points);
* other central nervous system diseases 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;
* a history of psychosis or congenital mental growth retardation.

Primary outcomes:
measure: Improvement of Montreal cognitive assessment (MoCA)
timeFrame: Three months
measure: Improvement of Auditory Verbal Learning Test (AVLT)
timeFrame: Three months
measure: Changes of intestinal microbial flora diversity
timeFrame: Three months
Secondary outcomes:
measure: Structural MRI-based brain network changes
timeFrame: Three months
measure: Functional MRI-based brain network changes
timeFrame: Three months
measure: FNIRS-based brain network changes
timeFrame: Three months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Neurolgy, Xuanwu Hospital of Capital Medical University
state: Beijing
Study officials:
affiliation: Xuanwu Hospital of Capital Medical University
name: Ying Han, PhD
role: PRINCIPAL_INVESTIGATOR
References: