# Genetic risk for trajectories of cognitive decline and progression to dementia among Mexican Americans and non-Hispanic whites

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $439,550

## Abstract

PROJECT SUMMARY/ABSTRACT
Cognitive function, such as perception, memory, attention, language, etc., varies among individuals in the
population, and declines across the continuum from normal brain aging to dementia. Heritable factors play an
important role in determining such variation. Large-scale population-based studies have been conducted to
understand the contribution of genetic variation to cognitive function primarily in the populations of European
ancestry. Hispanics make up the largest ethnic minority group in the US. Epidemiological data have shown that
US Hispanics have a higher risk of cognitive impairment and dementia than non-Hispanic whites that cannot be
fully explained by their diverse historical, cultural, or socio-economic factors, suggesting an ethnicity-specific role
that heritable factors may play, which, however, is poorly understood. Leveraging the multi-ethnic Texas
Alzheimer’s Research and Care Consortium research cohort with extensively collected longitudinal cognitive and
genetic data, we aim to explore the effects of genetic variations on the trajectories of cognitive decline and
progression to dementia in Mexican Americans and non-Hispanic whites. We anticipate that the genetic
architecture of cognitive function is heterogeneous between the two ethnic groups. Specifically, in Aim 1, we will
assess ethnicity-specific genetic association with global cognition, memory, and executive function at baseline
and over time, and with progression to Alzheimer’s disease (AD) via genome-wide association analysis; we will
then evaluate the ability of an individual’s genetic profile to predict the risk of cognitive impairment and dementia
using the polygenic risk score approach in Hispanics. In Aim 2, we will explore possible underlying mechanisms
of the genetic association with cognitive function, trajectories of cognitive decline, and progression to AD by
incorporating a variety of functional annotation sources and multi-layered human molecular (omics) data via
bioinformatics, network and systems approaches. In summary, Hispanics remain severely underrepresented in
existing genetic studies, which is likely to further exacerbate existing health disparities by limiting clinical
applications of genetic research, such as risk prediction and tailored interventions. Our exploratory effort will lay
the foundation for future larger and more comprehensive investigations, which may have the potential to guide
AD risk prediction, to enhance detection of asymptomatic individuals with preclinical AD, to optimize clinical trial
design, and to foster targeted interventions in high-risk subgroups. Further coupling the findings with multi-omics
data will help uncover the underlying molecular pathways of the observed genetic association, which may
ultimately lead to novel therapeutic target discoveries.

## Key facts

- **NIH application ID:** 10525544
- **Project number:** 1R21AG075791-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** XUEQIU JIAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $439,550
- **Award type:** 1
- **Project period:** 2022-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525544

## Citation

> US National Institutes of Health, RePORTER application 10525544, Genetic risk for trajectories of cognitive decline and progression to dementia among Mexican Americans and non-Hispanic whites (1R21AG075791-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10525544. Licensed CC0.

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