Grant: Catalyst Grant: Secondary Analysis of Neuroimaging Databases

Alzheimer's disease (AD) is the most common type of dementia and is the result of accumulating beta-amyloid plaques and tau protein tangles, regional loss of brain tissue and a myriad of cognitive symptoms. Diagnostic magnetic resonance imaging (MRI) can be used to quantify the brain tissue lost due to AD, but this structural information provides only one perspective on the disease. Functional and perfusion MRI approaches can also be used to understand the effects of AD, by providing physiological information that pertains to the blood vessels, an important consideration given that cerebrovascular dysfunction is common in AD. In this proposal we will capitalize on the AD Neuroimaging Initiative (ADNI) and attempt to establish the value of functional and perfusion dataset, for their ability to provide biomarker information of cerebrovascular dysfunction in the progression of AD. The objectives of this proposal are to: 1) use resting state fMRI to isolate cardiac pulsatility effects in white matter as a global measure of cerebrovascular dysfunction and 2) use arterial spin labeling perfusion images to establish an optimized analysis approach that yields the sensitivity to detect the progression from mild cognitive impairment to AD. A secondary objective will be to investigate the role of a genetic marker known to be implicated in AD pathology, the APOE e4 allele, in exacerbating cerebrovascular dysfunction. To carry out this research we propose to implement our unique analysis approaches on over one hundred resting-state fMRI and over three hundred arterial spin labeling datasets currently available in ADNI. This research will advance AD research by developing novel non-invasive imaging biomarkers. A positive outcome this proposal could lead to rapid implementation of these imaging-based tools into the neurodegenerative research currently being conducted at the research institutes represented by the applicants.