NIH awards US$9.5M for groundbreaking research on polyphenols role in Alzheimer’s prevention

08 Aug 2024 --- The US National Institutes of Health (NIH), with support from the Science Foundation Ireland and Public Health Agency Health & Social Care, awarded the University of California, Los Angeles (UCLA) Health researchers US$9.5M to study the effects of polyphenols on cognitive health and the gut-brain axis.

“Right now we are in the process of setting up the study, getting regulatory approvals, coordinating acquisition and study protocols between the different study sites,” Aparna Church, Ph.D. and co-director of the UCLA Goodman-Luskin Microbiome Center and principal investigator, tells Nutrition Insight. 

“Globally, populations are aging, increasing the prevalence of Alzheimer’s disease (AD) due to lack of effective treatments. By 2050 it is estimated that more than two billion people will be over 60 years. This demographic shift will be accompanied by increases in prevalence of cognitive dysfunction ranging from mild cognitive impairment to dementia including AD and health related costs to exceed US$305 billion to US$1 trillion.” 

“Therefore adequate treatments and prevention strategies are needed. In fact, in order to reduce the risk of developing dementia and to formulate preventive interventions, the World Health Organization has highlighted the need to understand lifestyle factors, including diet underlying this trend. Studies have shown that the traditional Mediterranean diet, can help prevent or delay cognitive dysfunction and preserve healthy brain structure and function.”

The proposal, named Maeve, stands for “Microbiota mediated flavonoid metabolites for cognitive health.” Researchers will investigate the impact of dietary polyphenol supplements on 300 older adults at risk for Alzheimer’s disease. 

Three-pronged approach
The five-year study will explore the relationship between polyphenols, cognitive function and brain health through four project aims in adults over 50 with an enhanced risk for Alzheimer’s. 

“Health promoting effects of the Mediterranean diet have been attributed to specific plant based components such as polyphenols. Polyphenols are classified as flavonoids, specifically flavanols, anthocyanins and flavonoid polymers are important mediators of these Mediterranean-based diet effects. Therefore, we are specifically looking at the effect of polyphenols on delaying cognitive decline,” Church explains.

The researchers will assess the protective effects of dietary polyphenol supplementation on the brain using multimodal magnetic resonance imaging and cognitive parameters. They will then analyze microbiome metabolites, inflammatory markers and Alzheimer’s disease biomarkers related to polyphenol intake. 

Once completed, they will use bioinformatics and machine learning approaches to explore the associations between polyphenol intake and gut microbial metabolites, inflammatory and Alzheimer’s disease markers, brain parameters and cognitive function. 

The researchers will use a reverse translational approach, in which stool transplants from high-risk individuals on the polyphenol diet supplementation are used in mouse models to better understand the underlying mechanisms.

“Studies have shown that healthy nutrition can prevent and slow cognitive decline. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) reported that counseling and nutritional guidance improve or maintain cognitive functioning in at-risk older adults,” says Church. 

“The Mediterranean-Dietary Approaches to Stop Hypertension Interventions for Neurodegenerative Delay (MIND) indicate protective effects on cognitive decline and AD risk. The Framingham study demonstrated that high polyphenol intake was associated with lower AD risk.” 

“A recent meta-analysis on polyphenol intervention studies, has reported a significant positive effect on working and episodic memory, impairments of which increased risk of developing dementia. Despite all this preliminary data out there, few studies have actually identified the mechanisms underlying these diet-related benefits on cognitive health,” she says.

It’s a multicenter, longitudinal and translational intervention study designed so the researchers can look at the mechanisms and pathways involved in cognitive decline. They are 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.

Delaying cognitive decline
Polyphenols, found in berries, grapes, green tea and cocoa, are a vital component of Mediterranean diets. They delay cognitive decline by preserving brain function and structure through gut microbiome metabolites. They do this by altering the physiology of the host’s secondary bile acids, which is why they have the potential to prevent Alzheimer’s disease.

“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 will help us better understand the ameliorative properties of a polyphenol-rich diet and whether we need diet interventions and regimes to delay the onset and progression of cognitive decline.”

The interdisciplinary and multicenter study is funded through the Tripartite US-Ireland Research & Development Partnership Program. 

Earlier this year, the US National Institute of General Medical Science, part of the NIH, awarded a US$1.9 million five-year research grant to help understand how complex communities of microbes impact human health. 

In addition, the NIH awarded plant cell technology company Ayana Bio US$300,000, which it will use to support its research into the neuroprotective benefits of saffron for Huntington’s disease and other neurological and age-related diseases.

By Inga de Jong