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 dataset.
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 fMRI data, in order to probe cerebrovascular function and dysfunction. We aim to apply the RIPTiDe analysis method retrospectively to resting state acquisitions in the OASIS dataset, in order to examine how these parameters are affected by Alzheimer?s Disease (AD) and other dementias, relative to healthy comparison subjects. We will also examine how these quantities change with disease progression longitudinally in patients with AD and compare our results to standard blood flow measurements (ASL).
