Gray & white matter tissue contrast differentiates Mild Cognitive Impairment converters from non-converters

Abstract

The clinical relevance of gray/white matter contrast ratio (GWR) in mild cognitive impairment (MCI) remains unknown. This study examined baseline GWR and 3-year follow-up diagnostic status in MCI. Alzheimer's Disease Neuroimaging Initiative MCI participants with baseline 1.5 T MRI and 3-year follow-up clinical data were included. Participants were categorized into two groups based on 3-year follow-up diagnoses: 1) non-converters (n = 69, 75 ± 7, 26 % female), and 2) converters (i.e., dementia at follow-up; n = 69, 75 ± 7, 30 % female) who were matched on baseline age and Mini-Mental State Examination scores. Groups were compared on FreeSurfer generated baseline GWR from structural images in which higher values represent greater tissue contrast. A general linear model, adjusting for APOE-status, scanner type, hippocampal volume, and cortical thickness, revealed that converters evidenced lower GWR values than non-converters (i.e., more degradation in tissue contrast; p = 0.03). Individuals with MCI who convert to dementia have lower baseline GWR values than individuals who remain diagnostically stable over a 3-year period, statistically independent of cortical thickness or hippocampal volume.

Figure 1. Illustration of GWR Protocol

(a) Non-converter (76 year old man, MMSE=24) and (b) Converter (76 year old man, MMSE=24). Orange line=gray/white boundary; green line=white matter surface, generated 1mm below the gray/white boundary; red line=outer pial surface; blue line=gray matter surface, generated 35% of the way from gray/white boundary to pial outer boundary.

Figure 2. GWR Differences for Converters and Non-converters

Top images in each panel represent lateral view. Panel a: Converters showed areas of lower GWR compared to non-converters when the model adjusted for scanner type, APOE4 status, ICV-corrected hippocampal volume and cortical thickness. Panel b: GWR differences when comparing converters to non-converters corrected for multiple comparisons by running n iterations of Monte Carlo simulations with a cluster-wise and vertex-wise threshold of p<0.05 where converters showed areas of lower GWR compared to non-converters when the model adjusted for scanner type, APOE4 status, and ICV-corrected hippocampal volume.