Individuals with or at increased risk of Alzheimer’s disease (AD) have an altered community of microbes(microbiome) within the intestinal tract. Through the production of inflammatory and neurotoxic metabolites, this microbial population may negatively contribute to cognitive decline and early dementia risk. Lifestyle interventions, such as diet and exercise, have been shown to alter the gut microbiome beneficially and therefore may be useful strategies in the prevention of AD and related dementias.

Our objectives are to establish the role of the gut microbiome in facilitating the beneficial effects of exercise and/or a brain-healthy diet on cognitive function among people living with subjective cognitive decline. Specifically, we want to know if: 1) our lifestyle interventions can beneficially alter the intestinal microbiome (e.g., which microbes are present and what metabolites they produce) and blood inflammatory and neuroprotective factors, and 2) these microbial changes are related to improvements in cognition.

Individuals with subjective cognitive decline (SCD) enrolled in a 6-month trial to evaluate lifestyle interventions(exercise and/or diet), administered virtually, on cognition. Fecal and blood samples will be collected at 0, 3 and 6months, and the microbiota composition and their metabolites, and blood markers of inflammation and neuroprotection, will be measured. This is the first study to evaluate the microbiota as a contributor to the effects of diet/exercise on cognition in people with SCD.

It is expected that diet and exercise, and more so their combination, will beneficially improve the microbiome, resulting in increased production of anti-inflammatory factors which will improve cognition. If alterations in the microbiota explain the cognitive effects of these interventions, the microbiome and associated metabolites could be a valuable biomarker to monitor intervention effectiveness and inform personalized therapeutic approaches to disease prevention.

Delaying dementia by 2 years could reduce dementia cases by 1/3 over 30 years. People with SCD are not generally managed within the healthcare system due to the absence of notable deficits. Therefore, reducing risk by improving the gut microbiome through lifestyle interventions led by community exercise professionals and dietitians may be an ideal approach to reducing dementia risk in this group.