UCLA Health researchers, in collaboration with teams from the Republic of Ireland and Northern Ireland, have been awarded a $9.5 million grant to study the potential effects of polyphenols on cognitive health. This significant funding comes from the National Institutes of Health (NIH), with additional support from European agencies such as the Science Foundation Ireland (SFI) and the Public Health Agency Health & Social Care (HSC). The ambitious study aims to explore the complex relationship between dietary polyphenols, Alzheimer’s prevention, and the brain-gut-microbiome system.
The study, named MAEVE—short for “Microbiota mediated flavonoid metabolites for cognitive health”—is part of an interdisciplinary and multicenter effort funded by the Tripartite US-Ireland Research & Development Partnership Program. Researchers will investigate how dietary polyphenol supplements affect 300 older adults who are at risk for Alzheimer’s disease. Polyphenols, known for their abundance in Mediterranean diets and found in foods like berries, grapes, green tea, and cocoa, may play a crucial role in delaying cognitive decline. The research will focus on how these compounds preserve brain function and structure through gut microbiome metabolites by altering the physiology of the host’s secondary bile acids, underscoring their potential in Alzheimer’s prevention.
Arpana Church, PhD, co-director of the UCLA Goodman-Luskin Microbiome Center and the contact principal investigator, describes the study as “a multicenter, longitudinal, and translational intervention designed to explore the mechanisms and pathways involved in cognitive decline.” She emphasizes the comprehensive nature of the research, stating, “We’re looking at multiple markers such as cognitive functioning, brain structure and function, the microbiome and microbial polyphenol metabolites, inflammatory markers like interleukins, and Alzheimer’s disease-specific plasma markers such as tau proteins ptau181 and ptau217.”
This five-year study involves several key investigators, including Dr. Emeran Mayer, co-principal investigator and founding director of the Goodman-Luskin Microbiome Center. Together, they aim to delve into the relationship between polyphenols, cognitive function, and brain health in adults over 50 who are at increased risk for Alzheimer’s disease. The research will be conducted through four primary project aims:
- Assessing Protective Effects: The team will evaluate how dietary polyphenol supplementation impacts brain health using multimodal MRI and other cognitive parameters.
- Analyzing Metabolites and Markers: Researchers will study microbiome metabolites, inflammatory markers, and Alzheimer’s disease biomarkers associated with polyphenol intake.
- Utilizing Bioinformatics and Machine Learning: Advanced computational approaches will explore the links between polyphenol intake and gut microbial metabolites, inflammatory and Alzheimer’s disease markers, brain parameters, and cognitive function.
- Reverse Translational Approach: The study will involve stool transplants from high-risk individuals on a polyphenol diet into mouse models to uncover underlying mechanisms.
“We’re hoping to better understand the role of dietary polyphenols in slowing the development of cognitive decline and how this is all influenced by the brain and gut microbiome,” Church explains. This research aims to shed light on the beneficial properties of a polyphenol-rich diet and its potential for developing dietary interventions to delay the onset and progression of cognitive decline. This groundbreaking study represents a significant step forward in understanding the intricate relationship between diet, cognitive health, and the gut microbiome. If successful, it could pave the way for new strategies to prevent or delay the onset of Alzheimer’s disease, offering hope to millions at risk worldwide.
