Gut Microbiome and Blood Indices in Patients With AD and Their Spousal Caregivers

Study Overview
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Brief Summary
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Spousal caregivers of Alzheimer's Dementia (AD) patients have an elevated risk of developing AD in the future. Past studies have shown the presence of serum indicators correlated with gut biome dysfunction in AD patients. We hypothesize that the same gut biome dysfunction may be present in spousal caregivers of AD patients.

Detailed Description
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Patients with Alzheimer's disease (AD) have gut dysbiosis. Short-chain fatty acids (SCFAs) are products of the gut microbiome. Among them, Acetate and valeric acid were positively correlated with the Aβ plaque load detected by amyloid PET in participants with or without AD. However, the levels of SCFAs in the blood of patients with AD have not been defined. Also, the usefulness of indices of inflammation and neuropathology in the blood as biomarkers for cognitive impairment in patients with AD is elusive. Importantly, spousal caregivers of patients with dementia have a higher risk of developing dementia later in life than those whose spouses do not have dementia. The spousal caregivers have an accelerated cognitive decline. The mechanisms for these phenomena are not known. We hypothesize that spousal caregivers of patients with AD have gut microbiome and levels of blood SCFAs similar to those of patients with AD, that these spouses have increased inflammatory cytokines and indices of AD-like neuropathology in the blood, and that there is a correlation between the cognition and various indices in the blood among patients with AD, their spouses, and age-matched controls. To address these hypotheses, we will recruit three groups of participants: Patients with AD, their spousal caregivers, and controls that are age-matched with the caregivers. Their gut microbiome and indices of neuroinflammation and neuropathology in the blood will be determined. Their cognition will be assessed. The correction of cognition with gut microbiome genera or indices in the blood will be analyzed. Our studies may represent the first study to determine whether the gut microbiome and SCFAs may play a role in the cognitive impairment in the spousal caregivers of patients with AD. These studies may also identify biomarkers for cognitive impairment in these caregivers and patients with AD. These findings may ultimately help the care of patients with AD and reduce the cognitive declines in spousal caregivers of patients with AD.

Official Title
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Gut Microbiome and Blood Indices in Patients With AD and Their Spousal Caregivers

Conditions
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Alzheimer Disease, Gut Biome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with AD whose clinical dementia rating (CDR) is > 1 Spouses of Patients in the above group Or Healthy adult unrelated to groups 1 and 2, with no history of dementia And Regardless of the grouping, the prospective subject must be between 65 and 90 years old Exclusion Criteria: Familial Alzheimer's Disease (AD) Severe cardiovascular disease Severe respiratory system disease Severe liver disease Severe kidney disease Severe central nervous system diseases Having a lifespan of fewer than 3 months History of psychiatric illness Major neurological diseases other than AD Current use of corticosteroids, antibiotics, or bowel motility modification agents Any history of Alcoholism or illicit drug dependence Previous inclusion in this study Difficulty with follow-up or poor compliance Severe hearing impairment Severe vision impairment

Ages Eligible for Study
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Minimum Age: 65 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 |
| --- | --- |
| Alzheimer's Patient<br>patients with AD whose clinical dementia rating (CDR) is > 1 Age 65-90 with none of the criteria below: Familial Alzheimer's Disease (AD) Severe cardiovascular disease Severe respiratory system disease Severe liver disease Severe kidney disease Severe central nervous system diseases Having a lifespan of fewer than 3 months History of psychiatric illness Major neurological diseases other than AD Current use of corticosteroids, antibiotics, or bowel motility modification agents Any history of Alcoholism or illicit drug dependence Previous inclusion in this study Difficulty with follow-up or poor compliance Severe hearing impairment Severe vision impairment | |
| Spousal Caregiver to Alzheimer's Patient<br>Spousal Caregiver to Alzheimer's Patient group, Age 65-90 with none of the criteria below: Familial Alzheimer's Disease (AD) Severe cardiovascular disease Severe respiratory system disease Severe liver disease Severe kidney disease Severe central nervous system diseases Having a lifespan of fewer than 3 months History of psychiatric illness Major neurological diseases other than AD Current use of corticosteroids, antibiotics, or bowel motility modification agents Any history of Alcoholism or illicit drug dependence Previous inclusion in this study Difficulty with follow-up or poor compliance Severe hearing impairment Severe vision impairment | |
| Healthy adult control<br>Age-matched to Spousal Caregiver to Alzheimer's Patient group Age 65-90 with none of the criteria below: Familial Alzheimer's Disease (AD) Severe cardiovascular disease Severe respiratory system disease Severe liver disease Severe kidney disease Severe central nervous system diseases Having a lifespan of fewer than 3 months History of psychiatric illness Major neurological diseases other than AD Current use of corticosteroids, antibiotics, or bowel motility modification agents Any history of Alcoholism or illicit drug dependence Previous inclusion in this study Difficulty with follow-up or poor compliance Severe hearing impairment Severe vision impairment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammation related biomarkers | interleukin (IL)-1β, IL-6, IL-10, IL-17, complement 3 (C3,) and YKL-40 | one day | 
| amyloid biomarker | amyloid beta (Aβ)1-42 | one day | 
| ratio of Aβ1-42 and Aβ1-40 |  | one day | 
| total tau biomarker |  | one day | 
| phospho-tau at 181 or 217 biomarker |  | one day | 
| neurodegeneration related biomarkers | neurofilament light chain (NFL) and neurogranin | one day | 
| serum short chain fatty acids | acetic acid, propionic acid, isobutyric acid, butyric acid, valeric acid and hexanic acid | one day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimers, biome