Cortical microstructure in young onset Alzheimer's disease using neurite orientation dispersion and density imaging

Abstract

Alzheimer's disease (AD) is associated with extensive alterations in grey matter microstructure, but our ability to quantify this in vivo is limited. Neurite orientation dispersion and density imaging (NODDI) is a multi-shell diffusion MRI technique that estimates neuritic microstructure in the form of orientation dispersion and neurite density indices (ODI/NDI). Mean values for cortical thickness, ODI, and NDI were extracted from predefined regions of interest in the cortical grey matter of 38 patients with young onset AD and 22 healthy controls. Five cortical regions associated with early atrophy in AD (entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, fusiform gyrus, and precuneus) and one region relatively spared from atrophy in AD (precentral gyrus) were investigated. ODI, NDI, and cortical thickness values were compared between controls and patients for each region, and their associations with MMSE score were assessed. NDI values of all regions were significantly lower in patients. Cortical thickness measurements were significantly lower in patients in regions associated with early atrophy in AD, but not in the precentral gyrus. Decreased ODI was evident in patients in the inferior and middle temporal gyri, fusiform gyrus, and precuneus. The majority of AD-related decreases in cortical ODI and NDI persisted following adjustment for cortical thickness, as well as each other. There was evidence in the patient group that cortical NDI was associated with MMSE performance. These data suggest distinct differences in cortical NDI and ODI occur in AD and these metrics provide pathologically relevant information beyond that of cortical thinning.

Keywords: Alzheimer's disease; dementia; diffusion MRI; grey matter; neurite orientation dispersion and density imaging; neurodegenerative disorders.

Figure 1

Steps involved in surface‐based region of interest cortical analysis of NODDI maps. (a) Reconstruction of structural imaging, (b) NODDI maps registered to structural imaging, (c) neocortical midpoint values from ODI/NDI maps projected to inflated surface, and (d) mean ODI/NDI values at each neocortical midpoint extracted for each ROI from Desikan atlas. Key: GM = grey matter; WM = white matter; CSF = cerebrospinal fluid; ODI = orientation dispersion index; NDI = neurite density index; ROI = region of interest [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Box plots ‐ cortical thickness, NDI, and ODI in healthy controls and young onset Alzheimer's disease in a priori cortical regions‐of‐interest (NDI = neurite density index; ODI = orientation dispersion index): * p < .05 **p < .008. Bonferroni corrected threshold: p = .05 divided by 6 (total number of regions of interest) [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Scatter plots showing relationship between MMSE score (MMSE = mini mental state examination) and orientation dispersion index (ODI)/neurite density index (NDI)/cortical thickness in YOAD patients only: *p < .05, **p < .008. Bonferroni corrected threshold: p = .05 divided by 6 (total number of regions of interest) [Color figure can be viewed at http://wileyonlinelibrary.com]