Gray matter microstructural changes as an early neuroimaging biomarker for Alzheimer's disease

Abstract

Alzheimer’s disease (AD) is notorious for its long preclinical period, and there is an increasing interest to early detection in order to prevent or delay the onset of cognitive decline. The progress of dementia accompanies with accumulation of molecular pathology followed by inexorable neuronal damage. At present, it is impossible to reverse neurodegeneration but be more successful by preventing. With the aim of facilitating the early detection of AD, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) subdivided mild cognitive impairment (MCI) to two stages based on the Wechsler memory performance: early (EMCI) and late MCI (LMCI). With diffusion tensor imaging (DTI), we sought to find feasible gray matter microstructure biomarker.

At first, we targeted early hippocampus changes in terms of surface atrophy and microstructure. With simultaneous analysis of morphology and microstructure changes, we expected to understand the diffusivity measure and its properties. The results delineate that regional surface atrophy accompanies with microstructural changes with diffusivity increase. Furthermore, the regional diffusivity differences showed progressive changes that suit with disease progression model.

Next, we sought to find better microstructure measure. We move on to cortex microstructure and propose DTI measure, radiality, for early AD biomarker. It is a dot product between cortical surface normal vector and primary diffusion direction, which reflect fiber orientation. Overall, radiality in cortical gray matter showed AD specific changes and relevance with other conventional AD biomarkers. Besides, it could show group differences in early AD changes from EMCI which show advantage for early diagnosis than using conventional biomarkers. We provide the evidence of structure changes with cognitive impairment and suggest radiality as sensitive AD biomarker.