Microbiome and Dementia

Study Overview
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Brief Summary
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From this study, it is hoped to learn if and how the gut microbiome composition, gut permeability and inflammation in patients with dementia are associated with each other. Dysbiosis may lead to an increased gut permeability, bacterial translocation and inflammation which may influence pathogenesis and progression of dementia. The novel aspect of the study will be to understand the association between gut microbiome composition, gut permeability and the presence of dementia. This will help to better understand the pathogenesis of dementia and lead to the development of novel therapeutic strategies. If this hypothesis holds true, the study will be the basis to develop new treatment options for dementia.

Detailed Description
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Dementia is a disease that presents with deterioration in memory, thinking, behaviour and the ability to perform everyday activities. Worldwide 47.5 million people are affected and incidence of dementia is increasing. Dementia leads to disability and dependency among older people worldwide and thereby has a huge physical, psychological, social and economic impact on caregivers, families and society. Alzheimers disease (AD) is the most common form of dementia accounting for 60-70% of the cases; other forms include Lewy body dementia, frontotemporal dementia, vascular dementia and Parkinsons disease with dementia. In AD, pathologic protein aggregates of amyloid beta and hyperphosphorylated tangles of tau-protein which deposit as neurofibrillary tangles are typical features. This leads to neuroinflammation, mainly mediated by the innate immune system. The most important cells in this process are microglia cells, which represent the resident macrophages of the brain. Although microglia is able to remove extracellular amyloid beta, in later stages of the disease cells remain in a dystrophic state and cannot exert their beneficial functions. Microglia maturation and function is critically dependent on short-chain fatty acids produced by the gut microbiome and therefore highlights the microbiome as a potential diagnostic and therapeutic target in dementia. The role of the commensal microbial population of the human body - especially the intestinal microbiome - in various diseases is emerging due to the development of advanced analysis techniques. Recently the concept of the gut brain-axis has been established. Several pathways including the autonomic nervous system, the enteric nervous system, the neuroendocrine system and the immune system allow a communication between gut and brain but may also be involved in disease development. During ageing, the gut microbiome composition undergoes changes. A decrease in diversity, a loss of beneficial taxa and an increase of facultative pathogens has been described. Diet and the place of residence play an important role in the shaping of the microbiome. Aging is also associated with inflammation - often termed as inflammaging associated with an increase in gut permeability, mucosal inflammation and bacterial translocation. Since the main risk factor for developing dementia, especially AD, is aging, it is very likely that the gut-brain axis is critically involved in dementia development. Animal studies so far suggest that AD is associated with changes in the gut microbiome composition with a decrease in beneficial, anti-inflammatory genera. Furthermore, genetic alterations in amyloid genes can influence microbiome composition in mice, pointing towards a vicious cycle in AD development. In humans, so far no studies on the gut microbiome composition in patients with dementia have been published. However, there is evidence that the composition of the microbiome in subgingival plaques is altered in dementia and associated with cognitive function.

Official Title
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The Gut-Brain Axis in Dementia: Biomarker and Novel Intervention Strategies

Conditions
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Dementia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18y Dementia (Alzheimer type and mixed type) Informed consent signed by the patient or his legal representative Mini Mental State Examination ≤ 26 Exclusion Criteria: Other forms of dementia Inflammatory bowel diseases Liver cirrhosis Antibiotic treatment within the last 14 days Any other condition or circumstance, which, in the opinion of the investigator, would affect the patient's ability to participate in the protocol Healthy controls Age >18y Informed consent No known acute or chronic illness

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| dementia<br>patients with dementia | |
| control<br>healthy control | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alpha diversity | Chao1 index | single measurement at baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gut permeability | zonulin | single measurement at baseline | 
| bacterial translocation | serum biomarker of bacterial translocation | single measurement at baseline | 
| inflammation | serum biomarker of inflammation | single measurement at baseline |