# Diversity Supplement for Jenny Lutshumba

> **NIH NIH RF1** · UNIVERSITY OF KENTUCKY · 2024 · $302,626

## Abstract

Abstract
There is a sex-based difference in the etiology of Alzheimer’s disease (AD) and Vascular
contribution to cognitive impairment and dementia (VCID), the two most common forms of
dementia. Females have a higher incidence of Alzheimer’s disease and related dementias
(ADRD), as well as sex-based differences in cardiovascular risk factors for dementia. In a
subgroup of participants from the risk reduction for Alzheimer’s disease (rrAD; NCT02913664)
clinical trial at baseline, we found a sex difference in plasma AD biomarkers. Females had
higher levels of total tau and total tau/Ab42 while pTau181 was higher in males, with no
difference found in the Ab42/40 ratio. VCID biomarkers also show no sex-based differences.
There was however a sex-based difference in the association between AD and VCID
biomarkers. In females, VEGF-D associated with total Tau, while in males VEGF-D associated
with pTau181 and pTau181/Ab42, and bFGF associated with Tau/Ab42. These preliminary
findings support a sex-based difference of biomarkers in the pathogenesis of VCID and AD in
cognitively healthy older adults. However, there is still a reluctance in human studies to stratify
cohorts by sex. Moreover, there is great appreciation for the importance of the crosstalk
between the systemic immune system and the brain pathologies in ADRDs. However, the role of
systemic inflammation in the pathogenesis of ADRDs remains under-explored. The purpose of
the proposed supplement is to investigate the sex effects of independent and combined effects
of Intensive pharmacological Reduction of Vascular Risk factors (IRVR) i.e. hypertension and
dyslipidemia and aerobic Exercise (Ex) on inflammation and cognitive function. Here, we will
test the hypothesis that females in IRVR+Ex will ameliorate AD/VCID-associated biomarkers
and pro-inflammatory cytokines and associate with better cognitive function by testing the
following aims: Aim1: To determine whether there is a sex difference in inflammatory cytokines
and injury markers in the plasma between IRVR+Ex and IRVR or Ex and their association with
AD/VCID biomarkers. Aim2: To determine whether there is a sex-mediated amelioration in
alteration in peripheral immune cells in IRVR+Ex compared to IRVR or Ex.
The long-term goal of this project is to identify inflammatory biomarkers that will be predictive of
ADRD in males and females.

## Key facts

- **NIH application ID:** 11062866
- **Project number:** 3RF1AG084134-01S1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** DWIGHT C. German
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $302,626
- **Award type:** 3
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11062866

## Citation

> US National Institutes of Health, RePORTER application 11062866, Diversity Supplement for Jenny Lutshumba (3RF1AG084134-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11062866. Licensed CC0.

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