Background: Alzheimer's disease (AD) is associated with impairment of large-scale brain networks, disruption in structural connections, and functional disconnection between distant brain regions. Although decreased functional connectivity has been thoroughly investigated and reported by existing functional neuroimaging literature, this study investigated network-based differences due to the structural changes in white matter pathways in AD patients. We hypothesize that diffusion metrics of disrupted tracts that go through cognitive networks related with intrinsic awareness, motor movement, and executive control can be utilized as biomarkers to distinguish prodromal stage from AD stage. Methods: Diffusion MRI data of a total 154 subjects, including patients with clinical AD (n = 47) and patients with mild cognitive impairment (MCI) (n = 107) was used. To study structural changes associated with white matter fiber pathways voxel-averaged diffusion metrics and fiber density metrics were calculated. Results: Study revealed that AD patients exhibit disruptions in intrahemispheric tracts and projection fiber tracts as suggested by diffusion indices. Our whole brain analysis revealed that network differences within default mode network (DMN), sensory motor network, and frontoparietal networks are associated with disruption in inferior fronto-occipital fasciculus (IFOF), corticospinal tract, and superior longitudinal fasciculus. Global function revealed by Mini Mental State Examination correlate with those fiber pathways that form reciprocal connections within networks associated with motor movement and executive control. Conclusion: Diffusion metrics appear to be more sensitive than fiber density metrics in differentiating the structural changes in the white matter. Decreased fractional anisotropy along with increased mean diffusivity and radial diffusivity in forceps minor, corticospinal tract, and IFOF as an imaging biomarker would be ideal to distinguish AD patients from MCI patients. Difference of DMN, sensory motor network, and frontal parietal network in our study reveals that AD patients may suffer from poor motor movement and degraded executive control.
Keywords: default mode network; diffusion metrics; fiber density metrics; white matter.