Microbiome and Dementia
Microbiome and Dementia
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.
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.
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