Brain Health & the Microbiome

Study Overview
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Brief Summary
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The GW SMHS supports research in complementary and integrative approaches to treatment of sickness and disease and for health promotion. Sometimes, research may involve asking questions of patients, students, and health providers. In this study, individuals are being asked to participate in this study as either 1) a healthy volunteer, 2) a person with Mild Cognitive Impairment (MCI), or 3) a person with early Alzheimer's disease (eAD). We are trying to learn more about if the gut microbiome (the microbes that live in our digestive tract) of individuals with eAD, MCI, and healthy controls are altered following lifestyle changes. This research will provide the pilot data to begin to understand if these changes in the gut microbiome are beneficial to health and/or may slow or halt the progression of MCI or early Alzheimer's.

Detailed Description
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AD is, in a word, devastating. The massive psychological and physical trauma experienced by people with dementia and their loved ones is catastrophic and incapable of overestimation. It is incumbent upon researchers and clinicians to not only better understand the etiology of this disease, but also to translate this knowledge into actionable evidence to facilitate clinical care and prevention. The MGBA serves as a major etiological factor, in both cause and potentiation of the disease process, that possesses great potential for intervention. Interventions have the greatest opportunity for success earlier in the disease pathogenesis; therefore, MCI is an ideal target for intervention to prevent progression to AD. To effectively apply knowledge of this bidirectional relationship, a clearer picture of dysbiosis relevant to cognitive decline must be identified. The inclusion of HC, MCI, and early AD allows for the detection of a dose-response relationship, which is one of Bradford Hill's criteria for causality. 1 This means we will begin to investigate causality (using one of Hill's eight criteria) in addition to association in this proof-of-concept study. Most previous research has been done at too high a phylogenetic level to be truly informative in terms of interventions-in other words the data is too low resolution. The microbiome field was launched at the phylum/genus level for many reasons including the need to start somewhere in such a complex system. To put this in perspective, comparing a genus, such as Lactobacillus, would be akin to comparing a compilation or average of all species of the genus Homo: H. sapiens, H. habilis, H. errectus, H. heigelbergensis, H. neanderthalensis, and H. naledi. The diversity in Homo sapiens alone is staggering. How could we possibly think this is specific or high resolution enough to be clinically meaningful? Well, the research has shown that it is not. This coupled with advancements in technology (qPCR to 16S to shotgun metagenomics) has changed the landscape of the microbiome field. However, such advanced testing and understanding has yet to make it to the clinic and has largely not been applied to MCI or AD populations to date. The sum of the evidence suggests that restoration of the gut microbiome may serve to prevent, slow, or even reverse MCI/AD. Whether this entails the use of diet, supplements, medications, etc. or some combination thereof remains to be discovered. Before an intervention can be designed, a firm grasp of the specific alterations to the gut microbiome must be identified using higher resolution than simply genus alone-we must understand species level at least, ideally strain level in many cases. Once we understand the species-level alterations, therapeutic interventions may then be implemented to determine the effect size of said interventions.

Official Title
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Brain Health & the Microbiome: A Proof-of-Concept Study in Patients With Mild Cognitive Impairment

Conditions
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Mild Cognitive Impairment, Mild Dementia, Alzheimer Disease 1

Intervention / Treatment
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* Other: Gut Microbiome Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50-90 Early Alzheimer's Disease (eAD) Mild Cognitive Impairment (MCI) Healthy Control (no eAD or MCI) Exclusion Criteria: Criteria or pathology that may affect the outcomes of the study or the risk/benefit ratio as determined by the study team

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Controls<br>Healthy males and females, ages 50-90 | Other: Gut Microbiome Testing<br>* Stool microbiome testing using shotgun metagenomic sequencing<br>|
| Mild Cognitive Impairment<br>Males and females with mild cognitive impairment, ages 50-90 | Other: Gut Microbiome Testing<br>* Stool microbiome testing using shotgun metagenomic sequencing<br>|
| Early Alzheimer's Disease<br>Males and females with early Alzheimer's disease, ages 50-90 | Other: Gut Microbiome Testing<br>* Stool microbiome testing using shotgun metagenomic sequencing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut Microbiome Composition | To compare the gut microbiomes of patients with early Alzheimer's disease, mild cognitive impairment, and healthy controls using diversity as well as genus, species, and strain level differences in composition (shotgun metagenomics). | 3- and 6-months | 
| Gut Microbiome Function | To compare the gut microbiomes of patients with early Alzheimer's disease, mild cognitive impairment, and healthy controls using diversity as well as genus, species, and strain level differences in function (shotgun metagenomics). | 3- and 6-months | 
| Document microbiome changes following lifestyle changes in subjects with early Alzheimer's disease, mild cognitive impairment, and healthy controls for future study design. | Observationally collect gut microbiome and lifestyle changes to inform the design of a trial to study lifestyle interventions. | 3- and 6-months |