Ageing Gut Brain Interactions

This research project will address a desperate need for evidence on how diet could be used to treat and improve symptoms of Alzheimer's disease (AD). It has been estimated that 36 million people have dementia worldwide, and in older people Alzheimer's disease accounts for 60-70% of all dementia. Research supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, which opens new avenues for prevention or modification of disease.

The concept that inspires this proposal 'Ageing-Gut-Brain Interactions study' is that the gut microbiota impact upon the gut-brain axis and thereby on behaviour, including challenging behaviours often associated with dementia. In the absence of available cures for Alzheimer's disease, diet is an important modifiable component but knowledge about the role of diet in clinical symptoms of dementia is currently very limited. A recent study from Ireland from the European Union funded Nu-Age cohort reported that the gut microbiota profile in the elderly was different between community-living and institutionalized individuals, with specific microbiome profiles correlating with frailty and poor health.

Changes in dietary composition and diversity were considered the main drivers of the shifts in gut bacteria profile. In this multi-disciplinary research study, the investigators will assess the gut microbiota composition in people with Alzheimer's dementia with and without challenging behaviours; test the feasibility of recruitment; and provide initial data to support a future grant application involving a dietary intervention study in patients with Alzheimer's disease.

The investigators will test the hypothesis that the gut-brain axis promotes behavioural changes in Alzheimer's dementia and is responsive to changes in gut microbiota profile, by comparing the gut microbiota profile between three participant groups (1) Alzheimer's dementia with challenging behaviour, (2) Alzheimer's dementia without challenging behaviour, and (3) a control group of healthy age-matched elderly. The investigators will also carry out a survey of care homes to assess willingness to participate in a future dietary supplementation study.

Introduction

Healthy life expectancy is a key area of research. It has been estimated that 36 million people have dementia worldwide and that there are 4.6 million new cases of dementia every year. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, opening new avenues for prevention. Alzheimer's disease is the commonest cause of dementia in older people, accounting for 60-70% of all dementia cases when using traditional diagnostic criteria for dementia subtypes.

There are no available cures for AD, but an alternative approach is to use strategies that delay disease progression at an early stage. Optimal brain function results from highly complex interactions between numerous genetic and environmental factors, including food intake, physical activity, age and stress. Diet in particular has become the object of intense research in relation to cognitive aging and neurodegenerative diseases.

The gut microbiota is a large, diverse collection of microbes, collectively containing 100 times more genes than the host. It is host-specific, contains heritable components, can be modified by diet, surgery or antibiotics, and in its absence nearly all aspects of host physiology are affected. It is now realised that the human microbiota is a previously overlooked system that makes a significant contribution to human biology and development.There is a new and exciting field of research with limited published data in the elderly, that could provide a basis for the design of novel, microbiota-targeted, therapies to improve care of older people suffering from Alzheimer's dementia.

There is increasing evidence that identifies the gut microbiota as a key conduit between nutrition and brain function. Reduction in the frequency of genes encoding short chain fatty acid (SCFA) production was prominent among institutionalized older adults, as were increases in circulating pro-inflammatory cytokines tumour necrosis factor-alpha, interleukins-6 and -8, and C-reactive protein.

Rationale for Study

Hypothesis: The composition and/or diversity of the gut microbiota is different between healthy elderly and those with Alzheimer's dementia, who do or do not exhibit behaviour(s) that are challenging.

The concept that inspires Ageing-GB is that our gut microbiota impact upon the gut-brain axis and thereby on behaviour. There is a need to understand the nature of that impact, the underlying mechanisms, and how changes in diet can reprogram our gut microbiota-brain axis to resolve or reduce clinical symptoms associated with Alzheimer's dementia.

However, to the investigator's knowledge, there has been no published work to examine the gut microbiota profile in patients with Alzheimer's disease. Consequently, the investigators first need to demonstrate the differences in microbiota profile between AD patients with or without behaviours that are more challenging to manage. This work is anticipated to provide fundamental evidence to support dietary modification or supplementation as cost-effective and safe avenues for alleviating signs and symptoms of dementia in this vulnerable group and thus reduce the carer burden.

This study will require the co-operation of care home managers and staff, and investigators will thus simultaneously assess the feasibility of performing a nutritional intervention study in this group of individuals, in this setting.

Eligibility Criteria:
Inclusion Criteria:

* Resident in a care home

Exclusion Criteria:

* Use of antibiotics in last 8 weeks
* Active gastrointestinal disease
* Unable to provide informed consent