Abstract
Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that may benefit from early diagnosis and intervention. Therefore, there is a need to identify early biomarkers of AD using non-invasive techniques such as functional magnetic resonance imaging (fMRI). Recently, novel approaches to the analysis of resting-state fMRI data have been developed that focus on the moment-to-moment variability in the blood oxygen level dependent (BOLD) signal. The objective of the current study was to investigate BOLD variability as a novel early biomarker of AD and its associated psychophysiological correlates.Method: Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 2 database from 19 participants with AD and 19 similarly aged controls. For each participant, a map of BOLD signal variability (SDBOLD) was computed as the standard deviation of the BOLD timeseries at each voxel. Group comparisons were performed to examine global differences in resting state SDBOLD in AD versus healthy controls. Correlations were then examined between participant SDBOLD maps and (1) ADNI-derived composite scores of memory and executive function and (2) neuroimaging markers of cerebrovascular status.Results: Between-group comparisons revealed significant (p < 0.05) increases in SDBOLD in patients with AD relative to healthy controls in right-lateralized frontal regions. Lower memory scores and higher WMH burden were associated with greater SDBOLD in the healthy control group (p < 0.1), but not individuals with AD.Conclusion: The current study provides proof of concept of a novel resting state fMRI analysis technique that is non-invasive, easily accessible, and clinically compatible. To further explore the potential of SDBOLD as a biomarker of AD, additional studies in larger, longitudinal samples are needed to better understand the changes in SDBOLD that characterize earlier stages of disease progression and their underlying psychophysiological correlates.
Highlights
Alzheimer’s disease is a progressive, neurocognitive disorder characterized by impairments in memory, as well as other cognitive domains, including language, visuospatial skills, and executive functions (Alzheimer’s Association, 2016)
Relations between blood oxygen level dependent (BOLD) Variability and Cerebrovascular Status (WM Lesion Volumes) To derive a measure of cerebrovascular status, we identified participant white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery (FLAIR) images and determined total WM lesion burden for each participant
We observed significant increases in standard deviation of the functional magnetic resonance imaging (fMRI) BOLD signal (SDBOLD) in patients with Alzheimer’s disease (AD) in a number of gray matter (GM) and WM frontal regions, including portions of the superior frontal and precentral gyri, the superior longitudinal fasciculus, and widespread regions of the corona radiata (Table 3)
Summary
Alzheimer’s disease is a progressive, neurocognitive disorder characterized by impairments in memory, as well as other cognitive domains, including language, visuospatial skills, and executive functions (Alzheimer’s Association, 2016). A number of factors have been associated with the development of AD, epidemiological evidence suggests that the strongest risk factor for AD is age. Available treatment options are limited and focus primarily on delaying the progression of symptoms (Wilkinson, 2012; Alzheimer’s Association, 2016). While there is limited evidence to support the use of mass cognitive screens due to their unclear benefits, improving the identification of high-risk groups will be imperative in order to deliver targeted treatment. This points to an everincreasing need for the identification of reliable, early biomarkers for AD. The objective of the current study was to investigate BOLD variability as a novel early biomarker of AD and its associated psychophysiological correlates
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