Microbiome in Aging of Gut and Brain

Microbiome in Aging Gut and Brain (MiaGB) Study

The Microbiome in Aging Gut and Brain (MiaGB) Study is an observational study designed to examine whether differences in the microorganisms living in the gut and mouth are associated with cognitive health and cognitive decline.

The study includes young healthy adults, cognitively healthy older adults, older adults with mild cognitive impairment (MCI), and older adults with Alzheimer's disease or related dementia. At the baseline visit, participants complete assessments of medical history, cognitive function, physical function, and diet and provide biological samples that may include stool, saliva, oral swabs, blood, and urine.

Researchers will study the gut and oral microbiome and related biological factors, including metabolites and markers of intestinal permeability and inflammation, to determine whether these measures differ according to cognitive status.

Young healthy adults, cognitively healthy older adults, and participants with MCI will be followed annually for up to 5 years to evaluate changes in the microbiome and cognitive function over time. Participants with Alzheimer's disease or related dementia will participate in the baseline assessment only.

No drug, treatment, or other research intervention is assigned as part of this study.

The Microbiome in Aging Gut and Brain (MiaGB) Study is a multisite observational study investigating relationships among the gut and oral microbiome, cognitive function, microbial metabolites, intestinal permeability, inflammation, and other biological characteristics associated with aging and cognitive impairment.

The study consists of two interconnected phases.

Phase 1 is a baseline cross-sectional assessment. A total of 700 participants are planned, including 100 young healthy adults, 300 cognitively healthy older adults, 200 older adults with mild cognitive impairment (MCI), and 100 older adults with Alzheimer's disease or related dementia. Baseline assessments include demographic and medical history information, cognitive function, dietary information, and selected physical function assessments. Biological samples may include stool, oral swabs, saliva, blood, and urine.

Laboratory analyses may include characterization of the gut and oral microbiome, metabolomics, markers of intestinal permeability and inflammation, proteomics, transcriptomics, genetic analyses, mitochondrial function, immunophenotyping, and other protocol-specified biological assessments. These data will be examined to determine whether microbial and biological patterns differ among participants with different levels of cognitive function.

Phase 2 is a prospective longitudinal follow-up. Young healthy adults, cognitively healthy older adults, and participants with MCI will be reassessed approximately annually for up to 5 years. Longitudinal assessments will be used to evaluate whether changes in the microbiome and related biological measures are associated with changes in cognitive function and whether these measures may help identify individuals at increased risk of cognitive decline. Participants with Alzheimer's disease or related dementia will undergo baseline assessment only and will not participate in the 5-year longitudinal follow-up.

This is an observational study. Participants are not assigned to a drug, biological product, behavioral treatment, or other research intervention.

Inclusion Criteria:

Age 18-60 years for young healthy participants, or age 60 years and older for older adult participants.

Participants meeting one of the following cognitive categories:

Normal cognitive function Mild cognitive impairment (MCI) Alzheimer's disease or Alzheimer's disease-related dementia Able to participate in the informed consent process as applicable. For participants unable to provide informed consent because of cognitive impairment, consent may be obtained from a legally authorized representative (LAR) according to the approved protocol.

Exclusion Criteria:

History of brain or gastrointestinal surgery within the past 5 years. History of cancer and/or cancer treatment within the past 5 years, except non-melanoma skin cancer.

History of systemic cancer treatment within the past 5 years. Neurological disorders including epilepsy, Parkinson's disease, or amyotrophic lateral sclerosis.

Antibiotic use within the past 30 days. Diarrhea, vomiting, and/or food poisoning within the past 30 days. History of inflammatory bowel disease. Body mass index (BMI) greater than 45 kg/m² or less than 18 kg/m². Weight loss of more than 10 pounds within the past 2 weeks.