# Revision Supplement: Model-based cerebrovascular markers extracted from hemodynamic data for diagnosing MCI or AD and predicting disease progression

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $501,351

## Abstract

Urgent Competitive Revision Supplement to the multi-PI award RO1AG058162 entitled:
"Model-based cerebrovascular markers extracted from hemodynamic data for
non-invasive, portable and inexpensive diagnosis of MCI or mild AD and prediction of
disease progression"
PROJECT SUMMARY
The goal of the proposed Urgent Competitive Revision Supplement to the current multi-PI
award RO1AG058162 is to expand the scope of the current program to include aspects of
cardio-respiratory regulation of cerebral perfusion in a subset of volunteers from our current
cohort (30 AD patients, 30 MCI patients and 30 cognitively-normal controls) as well as in 30
newly recruited Covid-recovered patients in order to investigate the cardio-respiratory regulation
in MCI and AD patients, as well as the effect of Covid-19 on the regulation of cardio-respiratory
control and cerebral perfusion. The latter issue has attained urgent clinical importance during
the ongoing Covid-19 pandemic because of the observed dysfunction of the fundamental
cardio-respiratory chemoreflex that appeared unable to restore the homeostatic balance in
some severe cases of Covid-19 presenting very low blood oxygen saturation without the
normally expected tachypnea (termed tentatively “silent hypoxemia”).
This proposed expansion of the scope of the current multi-PI program will further enhance the
main objective regarding the potential utility of a new class of cerebrovascular markers for the
improved diagnosis and prediction of disease progression in Mild Cognitive Impairment (MCI)
and mild Alzheimer's Disease (AD). The means for obtaining these markers are non-invasive,
inexpensive and portable, so that they can be used for screening in a primary-care setting. The
scientific rationale for this new class of cerebrovascular markers is provided by recent promising
results of our group and the mounting evidence of a strong correlation between MCI/AD and
cerebrovascular dysregulation in the work of many others, which suggest that cerebrovascular
dysregulation is the earliest and strongest pathologic factor associated with AD
progression, corroborating the hypothesis of cerebrovascular dysregulation.
The current research program and the proposed expansion of its scope will achieve reliable
quantification of cerebrovascular dysregulation through our novel integrative approach of
predictive dynamic modeling that analyzes the cerebral hemodynamics and cardio-respiratory
regulation through the use of input-output predictive models of the dynamic relationships
between changes in beat-to-beat cerebral blood flow velocity or cerebral tissue oxygenation in
response to changes in arterial blood pressure, end-tidal CO2 data, blood oxygen saturation,
heart rate and (with the expanded scope of the proposed Revision Supplement) changes in
respiratory rate, ventilation and inhaled gases (O2 and CO2). The obtained data-based models
are subsequently used to compute markers of the dynamics of cerebrovascular regulation.
These mod...

## Key facts

- **NIH application ID:** 10242469
- **Project number:** 3R01AG058162-03S1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Sandra A Billinger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $501,351
- **Award type:** 3
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242469

## Citation

> US National Institutes of Health, RePORTER application 10242469, Revision Supplement: Model-based cerebrovascular markers extracted from hemodynamic data for diagnosing MCI or AD and predicting disease progression (3R01AG058162-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242469. Licensed CC0.

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