In vivo detection of changes related to cortical columnar organization across the AD continuum

Abstract

AbstractBackgroundRecent studies have suggested intriguing biphasic trajectories of cortical structural changes in both sporadic and autosomal‐dominant Alzheimer’s disease (AD), namely decreased mean diffusivity (MD) and increased cortical thickness in cognitively normal, amyloid positive individuals, ahead of increases and decreases, respectively, in these parameters in cognitively impaired stages of the disease. To better understand these observations, we assessed novel diffusion tensor imaging (DTI) metrics that are correlated with disruption of cortical minicolumns ‐ the units of cortical microstructure. These have previously been shown to be associated with protein deposition and synaptic and neuronal loss. Such cytoarchitectural changes offer potential pathological markers before alterations at the macrostructural level.MethodTwenty‐four amyloid‐negative controls (CN‐), 28 amyloid‐positive controls (CN+), 46 amyloid‐positive subjects with Mild cognitive Impairment (MCI+) and 22 amyloid‐positive subjects with Alzheimer’s disease from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were used. 3DT1 and DTI scans at 2 timepoints (baseline and 24‐month follow‐up) were used to calculate the cortical MD and three novel cortical diffusivity measures, namely: the angle between the radial minicolumnar direction and the principal diffusion direction (AngleR); the diffusion components perpendicular to the minicolumns (PerpPD), and the principal diffusion component parallel with the minicolumns (ParlPD). Mixed effect models were used to investigate cross‐sectional and longitudinal differences.ResultAt a whole‐brain level, the mixed effects models revealed a significant effect of diagnostic group in all the measures (all p‐values<0.001). The pairwise (Figure 1) comparisons showed AngleR differed between CN‐ and CN+ (p<0.005), between CN+ and MCI+ (p<0.005) and between CN+ and AD+ (p<0.001). PerpPD values were significantly different between CN‐ and MCI+ (p<0.05) and AD+ groups (p<0.001), CN+ and MCI+ (p<0.005) and AD+ groups (p<0.001) while differences between CN‐ and CN+ were not significant. No significant difference was found between the timepoints for any measures, although the direction of change indicated progression between the first and second assessments.ConclusionCortical diffusivity parameters reflecting cortical minicolumnar organization may provide a more sensitive and biologically interpretable measurement of cortex quality and microstructure across the AD continuum.