# Implications of metabolism on healthy aging in African and Caucasian Americans: the Health ABC study

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $236,412

## Abstract

Alzheimer-type (AD) and non-AD dementias and neurocognitive impairment have origins in dysregulated me-
tabolism, leading to consideration of dementia as a “type 3 diabetes” phenotype. A wide array of basic labora-
tory, model systems-based, and human investigations around identifying precise metabolic defects as the core
of AD/non-AD dementias have emerged. A critical feature of studies attempting to identify a metabolic basis of
neurocognitive dysfunction is the application of a broad assessment of metabolism to a well phenotyped hu-
man cohort with dementia and related outcomes. As part of R01AG059729, Drs. Shah, Newman, Murthy and
Clish have been performing metabolite profiling in a biracial subsample of the Healthy Aging and Body Com-
position Study (Health ABC) to identify metabolic pathways relevant to healthy aging. While the parent study
includes some neurocognitive measures, it only assays a subsample within Health ABC for lipid and lipid me-
diators, the key metabolites felt to be relevant to AD and related dementias. Based on data suggesting the
emerging importance of inflammation and lipid abnormalities in AD, the study team is requesting supplemental
funds as part of this application to complete lipid and lipid intermediate metabolite profiling to facilitate (1) wider
scientific discovery in AD and AD-related phenotypes and (2) integration with other metabolite modes already
completed in Health ABC to provide a wider description of the metabolic abnormalities important in the life-
course of neurocognitive dysfunction and AD. We hypothesize that lipid and lipid mediators will be associated
with phenotypes and phenotypic groups central to AD and may facilitate discovery of potentially intervenable
pathways at the heart of AD and AD-related neurocognitive dysfunction. To address this hypothesis, we will
perform metabolite profiling in a wider sample size in Health ABC for lipid (C8 positive) and lipid mediators
(C18 negative) to identify metabolites and encoded pathways associated with clinical and imaging-based de-
mentia endpoints. In Aim 1, we will identify lipid and lipid mediator metabolite signatures associated with sub-
sequent cognitive decline, preclinical AD phenotypes, and dementia. In Aim 2, we will identify association of
lipid and lipid mediators with selected MRI markers of dementia previously reported. In Aim 3, we will test how
metabolic pathways linked to dementia differ by race and sex and how these metabolite signatures are related
to diet, fitness, activity, and adiposity, key modifiable lifestyle features linked to improved neurocognitive func-
tion. This supplement is unique in that it has been conceived and constructed in full collaboration with the Na-
tional Institutes of Aging (Dr. Luigi Ferrucci and Qu Tian), experts in aging and AD and substantially augments
the sample size for metabolite profiling covered by the parent R01 grant, while leveraging its substantial re-
sources. Completion would afford the sc...

## Key facts

- **NIH application ID:** 10118476
- **Project number:** 3R01AG059729-03S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Venkatesh Locharla Murthy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $236,412
- **Award type:** 3
- **Project period:** 2018-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118476

## Citation

> US National Institutes of Health, RePORTER application 10118476, Implications of metabolism on healthy aging in African and Caucasian Americans: the Health ABC study (3R01AG059729-03S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10118476. Licensed CC0.

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