Microbiome and Dementia

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

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.

Study Overview

• Status: Completed
• Conditions: Dementia

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 43

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with dementia and age matched healthy controls

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
dementia; patients with dementia
control; healthy control

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical University of Graz

Publications and helpful links

General Publications

• Stadlbauer V, Engertsberger L, Komarova I, Feldbacher N, Leber B, Pichler G, Fink N, Scarpatetti M, Schippinger W, Schmidt R, Horvath A. Dysbiosis, gut barrier dysfunction and inflammation in dementia: a pilot study. BMC Geriatr. 2020 Jul 20;20(1):248. doi: 10.1186/s12877-020-01644-2.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2017
• Primary Completion (Actual): July 2, 2018
• Study Completion (Actual): July 16, 2020

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 24, 2017
• First Posted (Actual): May 30, 2017

Study Record Updates

• Last Update Posted (Actual): July 17, 2020
• Last Update Submitted That Met QC Criteria: July 16, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Dementia
• Other Study ID Numbers: Demenz

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO