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The Utility of Transcranial Doppler Ultrasound in the Detection of Preclinical Alzheimer's Disease

Mohammed Rasheed Alwatban, University of Nebraska - Lincoln


This dissertation describes the development and validation of a new biomarker, based on engineering biosignal analysis, to detect subjects in the asymptomatic stage of Alzheimer's disease (AD). A method to measure cerebrovascular reactivity (CVR), termed the breath-hold acceleration index (BHAI), is introduced and compared with a conventional method. A pilot study was conducted to evaluate the ability of the BHAI to detect subjects in the asymptomatic stage of AD, and to validate the BHAI with the gold standard (PET amyloid scan imaging). Results suggest that the BHAI is a promising tool that can be used to screen for asymptomatic AD. The conception of this new biomarker stems from the understanding, borne out by a large body of previously published evidence, that AD is strongly linked to cerebral hypo-perfusion. Cerebral hypo-perfusion is the primary trigger for neuronal dysfunction. Indeed, several studies using different imaging techniques have already linked hypo-perfusion to AD. CVR, which can be quantified in vivo using transcranial Doppler ultrasound (TCD), provides an early biomarker for cerebral hypo-perfusion. TCD is a non-invasive sensing modality that measures blood flow velocities in cerebral arteries and can evaluate CVR with high temporal resolution. It was hypothesized that impaired CVR precedes symptomatic AD, and this work aimed to determine the association of CVR with cognitive decline and the risk of dementia in subjects in the asymptomatic phase of AD. Beta-amyloid deposition in the brain is the central force and the primary trigger driving AD pathogenesis. Thus, Beta-amyloid biomarkers have been the gold standard of the asymptomatic stage. However, Beta-amyloid biomarkers are measured in cerebrospinal fluid or using beta amyloid imaging, which limits their applicability as screening tools for AD. Studies described here show that BHAI was able to significantly distinguish between normal aging and asymptomatic AD. To our knowledge this is the first study to show the utility of TCD to detect subjects in the asymptomatic stage of AD. The contribution of this dissertation is two-fold. First, the research proposed a novel biomarker to detect early AD. Second, the study enhanced the understanding of the association between brain hypoperfusion and AD.

Subject Area

Biomedical engineering

Recommended Citation

Alwatban, Mohammed Rasheed, "The Utility of Transcranial Doppler Ultrasound in the Detection of Preclinical Alzheimer's Disease" (2018). ETD collection for University of Nebraska-Lincoln. AAI10982473.