Location: Nutrition, Food Safety/Quality
Project Number: 0500-00117-001-007-A
Project Type: Cooperative Agreement
Start Date: Aug 1, 2026
End Date: Jul 31, 2029
Objective:
The lack of effective therapies for Alzheimer’s disease and related dementias (ADRD) underscores the critical need for prevention strategies targeting modifiable risk factors such as diet. Peanuts are rich in unsaturated fats, plant protein, fiber, and bioactive compounds that may influence inflammatory, vascular, and metabolic pathways relevant to brain health; however, the biological mechanisms linking peanut intake to cognitive outcomes remain poorly understood. This proposed study aims to determine the impact of peanut consumption on cognitive health and underlying biological pathways.
To achieve this aim, the study will integrate three complementary approaches: (1) longitudinal analyses of the Chicago Health and Aging Project (CHAP) to evaluate associations between habitual peanut intake and cognitive and neuroimaging outcomes; (2) analysis of the MIND trial to assess the effects of peanut consumption within a structured dietary pattern on gut microbiome and metabolomics; and (3) a pragmatic randomized controlled trial to test the impact of substituting peanuts for typical snack foods on neuroinflammatory biomarkers and the gut microbiome.
The significance of the project is heightened by the focus on an affordable, widely accessible food source (i.e., peanuts). The innovation of this proposal lies in the integration of multi-omics and the use of plasma extracellular vesicles (EVs) to serve as a functional snapshot of peanut-induced changes, integrating host and microbiome response. Feasibility is ensured by utilizing established cohorts (Aims 1 & 2) and the study team’s success in conducting dietary clinical trials and the proposed biological readouts (Aim 3).
Approach:
We aim to address key gaps in understanding the relationship between peanut intake and brain health by integrating longitudinal epidemiology, multi-omics analyses, and a pragmatic randomized trial.
Aim 1: Longitudinal Cohort Analysis (Chicago Health and Aging Project [CHAP])
Hypothesis: Higher peanut and peanut butter intake is associated with slower cognitive decline and reduced vascular and neurodegenerative brain pathology.
Using the Chicago Health and Aging Project (CHAP), a longitudinal cohort of older adults (n=10,802), we will examine associations between peanut intake and cognitive trajectories, total brain volume, and white matter hyperintensity burden. Dietary intake was assessed by FFQ (n=6,603), cognition every 3 years (n=10,354), and MRI data are available in a subset (n=845). Linear mixed models and multivariable regression will evaluate associations adjusting for demographic, lifestyle, dietary, and APOE4 factors.
Aim 2: Multi-Omics Signatures of Peanut Intake within the MIND Trial
Hypothesis: Higher peanut and peanut butter intake is associated with a distinct multi-omic signature linked to better cognitive performance.
We will leverage data from the 3-year MIND Trial (n=604), a randomized dietary intervention in older adults at risk for Alzheimer’s disease. Repeated cognitive assessments, FFQs, neuroinflammatory biomarkers, metabolomics, and microbiome profiling are available in subsets of participants. Integrative analyses combining stool metagenomics, serum/stool metabolomics, and cognition will determine whether peanut-associated biological signatures are linked to cognitive outcomes and potential mechanisms.
Aim 3: Mechanistic Peanut Intervention in At-Risk Older Adults
Hypothesis: Daily peanut intake will lead to favorable changes in neuroinflammatory, neurovascular and neurodegenrative biomarker profiles compared with control.
We will conduct a 16-week single-blind pragmatic randomized trial in 70 adults aged =60 years at elevated AD risk. Following a 2-week nut-free run-in, participants will be randomized to consume either 56 g/day roasted low salt peanuts replacing usual snacks or maintain their habitual diet without nuts.
All participants will be instructed to avoid consumption of other nuts and nut products during the study. Study foods will be distributed biweekly. Participants will complete daily logs documenting diet, health status changes, and medication use. Study staff will conduct biweekly check-ins to assess adherence. Both groups will have equal contact with study personnel.
Dietary intake will be assessed using food frequency questionnaires (FFQ) at baseline and week 16, and three 24-hour dietary recalls collected at baseline, week 8, and week 16. Diet quality (e.g., MIND score) and caloric intake will be derived from these measures.
Biospecimens will be collected at baseline and week 16. Blood samples will be collected onsite, and stool samples will be self-collected by participants using standardized collection kits (as we routinely do in other studies). All samples will be stored at -80 °C and batch-analyzed after completion of the study.