Detection of gray matter microstructural changes in Alzheimer’s disease continuum using fiber orientation

BACKGROUND: This study aimed to investigate feasible gray matter microstructural biomarkers with high sensitivity for early Alzheimer’s disease (AD) detection. We propose a diffusion tensor imaging (DTI) measure, “radiality”, as an early AD biomarker. It is the dot product of the normal vector of the cortical surface and primary diffusion direction, which reflects the fiber orientation within the cortical column. METHODS: We analyzed neuroimages from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, including images from 78 cognitively normal (CN), 50 early mild cognitive impairment (EMCI), 34 late mild cognitive impairment (LMCI), and 39 AD patients. We then evaluated the cortical thickness (CTh), mean diffusivity (MD), which are conventional AD magnetic resonance imaging (MRI) biomarkers, and the amount of accumulated amyloid and tau using positron emission tomography (PET). Radiality was projected on the gray matter surface to compare and validate the changes with different stages alongside other neuroimage biomarkers. RESULTS: The results revealed decreased radiality primarily in the entorhinal, insula, frontal, and temporal cortex with further progression of disease. In particular, radiality could delineate the difference between the CN and EMCI groups, while the other biomarkers could not. We examined the relationship between radiality and other biomarkers to validate its pathological evidence in AD. Overall, radiality showed a high association with conventional biomarkers. Additional ROI analysis revealed the dynamics of AD-related changes as stages onward. CONCLUSION: Radiality in cortical gray matter showed AD-specific changes and relevance with other conventional AD biomarkers with high sensitivity. Moreover, radiality could identify the group differences seen in EMCI, representative of changes in early AD, which supports its superiority in early diagnosis compared to that possible with conventional biomarkers. We provide evidence of structural changes with cognitive impairment and suggest radiality as a sensitive biomarker for identifying early AD.