# Probing cerebral hemodynamics in Alzheimer's Disease using novel retrospective delay analysis

> **NIH NIH R21** · MCLEAN HOSPITAL · 2020 · $410,000

## Abstract

Summary:
Alzheimer’s Disease (AD) is a progressive disease, which to date cannot be cured, prevented or slowed. The
disease remains one of the top ten leading causes of death in the US (1). In most patients, with the late-onset
type of the disease, clinical symptoms start around the early to mid 60s. However the disease process may begin
two decades or more prior to clinical symptoms (2), with patients rarely being able to recognize early cognitive
decline (3). In America, more than 5 million people above the age of 65 years are living with AD (4). With
increasing age as the most important known risk factor this number will only grow (5). Finding the biomarkers
leading to AD is critical. Recent work with the large Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset
has shown that vascular deficits might be one of the earliest biomarkers in AD (6) as it is highly predictive of
rapid cognitive decline in older people (7). Numerous SPECT (8-10), FDG-PET (8, 10), DSCMRI (11-13), and
ASL (14-19) studies have found profound regional circulatory changes early on in the disease.
We have developed a novel analysis method (Regressor Interpolation of Progressive Time Delays – RIPTiDe)
to extract detailed maps of hemodynamic parameters, including blood arrival time delay, cerebrovascular
reactivity (CVR) magnitude and CVR delay, correlation strength (a proxy for rCBV), and mean transit time (MTT),
from retrospective analysis of resting state data, in order to probe cerebrovascular function and dysfunction. We
have shown that these metrics are sensitive to both macrovascular (large artery) and microvascular changes,
and can be used as a sensitive probe for circulatory dysfunction (20). This technique is extremely well suited to
studying the circulatory changes associated with the progression of AD and related dementias.
RIPTiDe analysis offers a unique way to measure brain perfusion, especially capillary circulation, which is of
particular interest in AD (13) and is not well visualized with other MR methods. RIPTiDe can probe these regional
vascular disturbances that accompany, and in fact may precede, neuronal damage in AD and other related
dementias, from resting state fMRI data alone. Moreover, the ability to derive these metrics retrospectively from
existing public datasets will allow us to leverage the Open Access Series of Imaging Studies (OASIS) (21)
dataset to study a large number of existing cross-sectional and longitudinal data.
We aim to apply the RIPTiDe analysis method retrospectively to resting state fMRI datasets in the OASIS
dataset, in order to examine how blood arrival time delay, correlation strength (a proxy for rCBV), and mean
transit time (MTT) differ between subjects with AD, subjects with other dementias, and healthy comparison
subjects. We will also examine how these quantities change with disease progression longitudinally in patients
with AD and compare our results to the standard blood flow measurements (ASL) also in the dat...

## Key facts

- **NIH application ID:** 10105704
- **Project number:** 1R21AG070383-01
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** LIA MARIA HOCKE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105704

## Citation

> US National Institutes of Health, RePORTER application 10105704, Probing cerebral hemodynamics in Alzheimer's Disease using novel retrospective delay analysis (1R21AG070383-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10105704. Licensed CC0.

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