Quantifying the longitudinal effects of Alzheimer's disease upon myelin content in gray matter.

Abstract

Because the cortical tissue of Alzheimer's disease (AD) patients undergoes demyelination far earlier than disease onset, monitoring this phenomenon could yield new AD risk biomarkers (Fornari et al, 2012). The ratio R of T1 -to-T2 -weighted magnetic resonance image (MRI) intensities is proportional to cortical myelin content (Glasser et al, 2012), such that the time change ΔR can reveal demyelination progression. Currently, quantifying ΔR is difficult due to spatial inhomogeneity differences across MRI timepoints and to harmonization challenges. By charting how ΔR varies, we illustrate AD's impact on cortical demyelination. T1 and T2 MRIs were acquired from AD patients (N = 41, age μ = 73.64; σ = 8.33) and from age- and sex-matched healthy controls (HCs, N = 68, age μ = 73.83; σ = 2.93) at two points less than a year apart. Longitudinal volume co-alignment of T1 and T2 MRIs was performed in 3D Slicer using BRAINSfit with modified parameters to increase registration fidelity, whilst segmentation was undertaken in FreeSurfer using joint processing of T1 and T2 volumes to improve skull stripping, pial surface reconstruction, tissue classification and surface topology estimation. SPM12 was used with default parameters to correct bias fields and reduce spurious variations in myelin sensitivity across MRIs. The T1 /T2 intensity ratio R and its time difference ΔR was calculated at each cortical location. The null hypothesis of no group difference in the mean value of ΔR was tested for each cortical location at α = 0.05. Compared to HCs, AD showed significantly greater decrease in ΔR in the inferior frontal, medial superior frontal, and orbital gyri, and in both calcarine and central sulci (p < 0.05). In all other cortex areas, ΔR did not differ significantly from HCs. In AD, 51% of the cortex showed more negative differences in myelination across time. As expected, AD patients exhibit faster demyelination than HCs in regions responsible for visuomotor acuity, memory, and executive function. Future research should chart long-term demyelination and include MCI patients to better understand how this phenomenon is related to cognitive decline.