# Neurovascular calcification, Alzheimer’s disease and related dementias in two Native South American populations

> **NIH NIH RF1** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $2,452,559

## Abstract

PROJECT SUMMARY
Neurovascular calcification is associated with cerebrovascular disease, with mild cognitive impairment (MCI),
Alzheimer’s disease and related dementias (ADRD), but mechanisms are uncertain. To clarify how calcification
harms neurocognitive functions, we focus on the relationship between regional brain volume and calcification of
intracranial internal carotid arteries (iICAs), which are among the blood vessels with strongest ADRD
involvement. Although both medial and intimal iICACs predict disease, how iICAC relates to age-related regional
brain volume trajectories, MCI, and ADRD is unknown. We propose CT studies of iICAC in two native South
American populations with high iICAC prevalence: the Tsimane/Moseten people of Bolivia. These forager-farmer
populations with a non-industrial lifestyle have higher iICAC prevalence than US/EU populations, but far less
brain volume decline with age. Tsimane lifestyle approximates that of our preindustrial past, whereas Moseten
have partial exposure to the industrialized world and are thus closer to the US/EU along the industrialization
continuum. In our first aim, we will develop automated, clinician-validated methods to segment, characterize and
quantify iICAC. We will (1) distinguish medial from intimal iICAC, (2) calculate iICAC volumetrics & morphology,
and (3) perform validation using gold-standard manual segmentations supervised by clinicians. In our second
aim, we will determine how medial vs. intimal iICAC modifies age-dependent gray matter volume trajectory. We
will segment gyri/sulci from head CT at resolutions approaching that of MRI. We will relate iICAC to gyral/sulcal
volumes as a function of age and sex. In our third aim, we will quantify how medial/intimal iICAC acts on regional
brain volumes to influence MCI and ADRD. The extent to which medial vs. intimal iICACs are associated with
regional brain atrophy that reflects MCI/ADRD will be quantified in Tsimane/Moseten (N > 1200) and the
Alzheimer’s Disease Neuroimaging Initiative (ADNI, N > 800). Establishing the relationships linking iICAC to
regional atrophy and to cognitive impairment status can help to understand the etiology and pathways whereby
vascular disease risk operates on the risk of MCI and ADRD through brain atrophy. This project will also inform
public health strategies to recommend preventive behaviors: should blood biomarkers of disease risk predict
iICAC, this would help to establish how such biomarkers associate with ADRD. Proposed approaches could
augment clinicians’ diagnostic armamentarium by providing information with predictive value on cognitive
trajectories leading to ADRD. This is a unique opportunity as findings may generalize to other populations. CT
methods will help to further the study of brain aging and ADRD in underprivileged populations with limited access
to MRI. Project findings should also help to inform the high ADRD morbidity of US Native American populations.

## Key facts

- **NIH application ID:** 10662151
- **Project number:** 1RF1AG082201-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Andrei Irimia
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,452,559
- **Award type:** 1
- **Project period:** 2023-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10662151

## Citation

> US National Institutes of Health, RePORTER application 10662151, Neurovascular calcification, Alzheimer’s disease and related dementias in two Native South American populations (1RF1AG082201-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10662151. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*