# Longitudinal Study of MRI, Clinical, and Genetic Biomarkers of Cognitive Impairment and Alzheimer's Disease in Elderly American Indians

> **NIH NIH U54** · UNIVERSITY OF COLORADO DENVER · 2021 · $364,768

## Abstract

ABSTRACT
Precision medicine is the emerging practice of delivering healthcare tailored to patients on the basis of specific
factors that contribute to disease risk, prognosis, and treatment response. The prospect of applying precision
medicine to neurodegenerative disorders such as Alzheimer's disease (AD) is especially promising. Genetic
markers, most notably variation in the apolipoprotein E gene, and measures of vascular brain injury and
cerebral atrophy assessed by MRI have emerged as useful biomarkers of preclinical AD and risk of clinical
disease. More than 3 million American Indians (AIs), Alaska Natives, Blacks, Latinos, and Asians suffer from
AD, and experience earlier onset of cognitive impairment and AD than Whites. The few studies of AD in AIs
are limited by small, single-community samples. We will use data from the Strong Heart Study (SHS) and
ancillary Cerebrovascular Disease and its Consequences in American Indians (CDCAI) study to evaluate
cognitive function, AD risk factors, and MRI-defined biomarkers of AD in older AIs. The SHS collected data
from 4,549 AIs aged 45-74 years from tribes in the Southwest, Southern Plains, and Northern Plains in 3
phases from 1988 to 2000. The CDCAI study assessed cognitive function and MRI-defined vascular brain
injury in 818 surviving SHS participants in 2010-2013 and is reassessing surviving participants with the same
MRI and cognitive tests. We will use statistical mapping software to reprocess MRIs from both the original and
follow-up CDCAI examinations and will create 3-dimensional brain maps for older AIs. We will quantify cerebral
atrophy in brain regions preferentially affected by AD such as the hippocampus, parahippocampal, medial
temporal, and parietal regions, and the posterior cingulate cortex. We will compare structural patterns on MRI
at both CDCAI time points with normative data on AD patients from other populations. We will define probable
AD cases by assessing change in MRI-defined loss in regions selectively affected by AD, in combination with
AD-related cognitive test performance and activities of daily living; and examine associations of probable AD
with risk factors and functional outcomes. Our Specific Aims are to: 1) establish AI-specific normative values
of MRI atrophy in brain regions selectively affected by AD, and evaluate AD-related regional atrophy in
combination with cognitive and behavioral changes to calculate prevalence of probable AD; 2) use genetic,
sociodemographic, and clinical data on risk factors for AD observed in other populations to identify correlates
of probable AD in elderly AIs; and 3) estimate associations of MRI markers of probable AD with measures of
cognitive and physical function, independent of the effects of vascular brain injury. AD is the leading cause of
dementia and of death in the US. The CDCAI sample is the only population-based cohort of AIs with MRI data
and genetic biomarkers relevant to AD. We will leverage these unique data to address...

## Key facts

- **NIH application ID:** 10164621
- **Project number:** 5U54MD000507-19
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** DEDRA S BUCHWALD
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $364,768
- **Award type:** 5
- **Project period:** 2003-09-30 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164621

## Citation

> US National Institutes of Health, RePORTER application 10164621, Longitudinal Study of MRI, Clinical, and Genetic Biomarkers of Cognitive Impairment and Alzheimer's Disease in Elderly American Indians (5U54MD000507-19). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10164621. Licensed CC0.

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