• Improvement of Montreal cognitive assessment (MoCA) [ Time Frame: Three months ]
  After intervention for three months, the investigators first aim to compare cognitive changes of Montreal cognitive assessment (MoCA) among three groups, in order to investigate the therapeutic effectiveness of probiotic supplementation and functional foods.
• Improvement of Auditory Verbal Learning Test (AVLT) [ Time Frame: Three months ]
  After intervention for three months, the investigators will then compare cognitive changes of Auditory Verbal Learning Test (AVLT) among three groups, in order to investigate the therapeutic effectiveness of probiotic supplementation and functional foods.
• Changes of intestinal microbial flora diversity [ Time Frame: Three months ]
  After intervention for three months, the investigators will further compare the diversity changes of intestinal microbial flora, such as Lactobacteria species, Bifidobacterium, Enterococci, Propionobacteria, Peptostreptococci, etc., among three groups.

• Structural MRI-based brain network changes [ Time Frame: Three months ]
  After intervention for three months, the investigators will compare the structural changes of brain network among three groups (e.g., efficiency, clustering, modularity) in order to reveal the regulatory mechanism of intestinal microorganism in intervening aMCI.
• Functional MRI-based brain network changes [ Time Frame: Three months ]
  After intervention for three months, the investigators will compare the functional changes of brain network among three groups (e.g., functional connectivity, hub) in order to reveal the regulatory mechanism of intestinal microorganism in intervening aMCI.
• FNIRS-based brain network changes [ Time Frame: Three months ]
  After intervention for three months, the investigators will compare the functional changes of brain network among three groups (e.g., functional connectivity, small word, efficiency) in order to reveal the regulatory mechanism of intestinal microorganism in intervening aMCI.

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.

• Gut Microbiota
• Mild Cognitive Impairment
• Dementia, Alzheimer Type
• Neuroimaging

• Dietary Supplement: Probiotic supplemented intervention
  In this project, taking the method of random, double blindness and control, the probiotic supplemented group with aMCI will take Bifidobacterium for three months. After that, cognitive changes will be test to investigate the effectiveness of probiotic supplementation.
• Dietary Supplement: Placebo
  In this project, taking the method of random, double blindness and control, the placebo group with aMCI will take placebo for three months. After that, cognitive changes will be test.

• Experimental: Probiotic supplemented group with aMCI
  Thirty participants in this group will take Bifidobacterium for three months.
  Intervention: Dietary Supplement: Probiotic supplemented intervention
• Placebo Comparator: Placebo group with aMCI
  Thirty participants in this group will take placebo for three months.
  Intervention: Dietary Supplement: Placebo

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.

• First Hospital of Tsinghua University
• Beijing Normal University