Investigating changes in cerebral blood flow response to local neural stimulation in Alzheimer disease retina as a potential mechanism for early diagnosis

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Alzheimer’s disease (AD) is a brain disorder and is the sixth leading cause of death in the United States. AD cannot be slowed or cured should the disease proceed to cognitive decline. Early detection would favor timely intervention to avoid brain cell loss and improve life quality of patients. The main goal of this project is to establish a viable and cost-effective strategy for early detection of AD through a set of relatively simple eye imaging procedures. New optical technologies will be developed to measure changes in eye and brain blood flow associated with AD. Machine learning tools will be deployed to predict the trajectory of the disease. In addition, this project will provide a training opportunity for engineering students to learn about AD and use their engineering skills to contribute to the collective effort of combating this devastating condition.Neural degeneration and loss of connectivity in AD leads to morphological and metabolic changes in the brain that can be visualized in magnetic resonance or positron emission tomography images. However, these brain imaging methods, as diagnostic tools, are neither cost effective nor readily available to large populations. Since the eye is accessible for noninvasive imaging, several procedures have been proposed for detection of AD via ophthalmological examinations and retinal imaging. Unfortunately, none of these tests have proven to be effective indicators of AD at early stages of the disease. This project seeks to explore a promising alternative by studying changes in retinal hemodynamics for early AD detection. There is experimental evidence suggesting that AD-associated changes in specific features of retinal hemodynamics appear in the pre-symptomatic phase of AD making these features superior indicators for early diagnosis. In this project, advanced technologies including multi-photon microscopy, optical coherence tomography, and optogenetic neural stimulation will be developed and employed with biochemical and immunohistochemistry lab techniques, to study the correlation between the state and progression of AD in the brain and retina. Specifically, the relationship between changes in the resting-state cerebral and retinal blood flow and disruption of functional hyperemia under AD will be explored. In this project, the research team will test the analytical validity and potential clinical viability of these features for noninvasive early detection of AD.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.