# Validation and Mechanistic Interrogation of Metabolism Targeting for AD

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $705,280

## Abstract

PROJECT SUMMARY
 We hypothesize manipulating brain energy metabolism through a ketogenic diet (KD) will benefit
Alzheimer's disease (AD) patients. To test this hypothesis, we designed the “Therapeutics Diet in Alzheimer's
Disease (TDAD)” trial, a single blind, randomized, controlled study of a KD in AD participants. The TDAD will
evenly randomize 80 AD participants to a three-month KD or a Therapeutic Lifestyles Changes (TLC) diet
intervention. Aim 1 focuses on the clinical hypothesis and its primary endpoint analysis compares the mean
change in KD participant pre and post-diet ADASCog11 scores to the mean change in the TLC diet participant
pre and post-diet ADASCog11 scores. Secondary Aim 1 clinical outcomes include pre and post-intervention
changes in Clinical Dementia Rating (CDR) scale sum of the boxes (SOB), mini-mental state exam (MMSE),
logical memory test (LMT), and Stroop test scores. Aim 2 determines how a KD affects human physiology,
and includes a biomarker-based assessment of depth of ketosis, mitochondrial function, insulin and insulin
signaling, lipid homeostasis, and inflammation. We will further co-analyze the Aim 1 and Aim 2 data to identify
relationships between physiologic parameters and cognitive performance.
 In Aim 1, comparing the magnitude of change in cognitive test and functional assessment scores between
the two groups will determine whether a high fat, low carbohydrate, ketone body-inducing KD truly and
uniquely benefits AD symptoms. The Aim 2 assessments will provide mechanistic insight into KDs, immediate
target engagement feedback, and over the long term help guide the development of future metabolism-based
AD interventions.

## Key facts

- **NIH application ID:** 9857524
- **Project number:** 5R01AG060733-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** DEBRA K SULLIVAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $705,280
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857524

## Citation

> US National Institutes of Health, RePORTER application 9857524, Validation and Mechanistic Interrogation of Metabolism Targeting for AD (5R01AG060733-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857524. Licensed CC0.

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