R01AG077489

Towards Precision Nutrition for Alzheimer's Dementia Prevention: A Prospective Study of Dietary Patterns, the Gut Microbiome, and Cognitive Function - Project Summary

This proposal directly addresses a high-priority research topic, "Enabling Precision Medicine for Alzheimer's Disease and Related Dementias through Deep Molecular Phenotyping," for PAR-19-070, Research on Current Topics in Alzheimer's Disease and its Related Dementias. The aim is to develop precision dietary approaches for Alzheimer's disease (AD) prevention by integrating multiple molecular data types.

The potential for healthy dietary patterns to maintain cognitive health is supported by cohort studies and a randomized trial. However, these healthy dietary patterns were developed based on population averages and may not be best suited for an individual. Preliminary data from our group and others support the rationale to study personalized approaches tailored to individual gut microbiomes to improve dietary prevention of AD. However, no study has examined the modifying and mediating roles of the gut microbiome in the diet-cognition association. The few human studies of the gut microbiome in AD were limited by small size, cross-sectional design, and lack of high-resolution microbial functional profiling.

This background supports our central hypotheses that 1) healthy dietary patterns contribute to cognitive health partly through modulating the gut microbiome, and 2) associations of the dietary patterns with cognitive function vary by individuals' gut microbial profiles. This proposal represents a highly cost-efficient, prospective study leveraging existing fecal samples/microbiome data and cognitive function assessments in three studies with complementary strengths in study design, and diet and outcome assessments: the Nurses' Health Study II (NHSII, N = 1,500) with decades-long repeated dietary assessments and extended follow-up, the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial with randomized dietary interventions (N = 604), and the ASPREE-XT study (N = 13,000) with adjudicated incident AD endpoints.

To gain more advanced mechanistic insights, we will take a multi-omic approach to combine shotgun metagenomics and metatranscriptomics to profile the microbial composition and enzymatic function, and fecal metabolomics to measure the microbiome metabolic activity. We will investigate roles of gut microbial composition and enzymatic function in the associations of the Mediterranean diet (MEDDIET) and the MIND diet with cognitive function (Aim 1) and examine the interrelationships among the two healthy dietary patterns, the metabolic activity of the gut microbiome, and cognitive function (Aim 2) in the NHSII. We will replicate findings from Aims 1 and 2 in ASPREE-XT and the MIND trial (Aim 3).

This project will generate reproducible, translational evidence on gut microbial and fecal metabolomic features that explain inter-individual heterogeneity in response to healthy dietary patterns. It will provide foundational knowledge for maximizing the benefits of dietary approaches, discovering novel predictive biomarkers, and ultimately contributing to precision prevention of AD.

Brigham & Womens Hospital

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Boston, Massachusetts 021155804 United States

Single Zip Code

Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) (PAR-19-070)

Amendment Since initial award the total obligations have increased 283% from $917,501 to $3,513,490.