Multimodal Magnetic Resonance Imaging in Alzheimer's Disease Patients at Prodromal Stage

Abstract

One objective of modern neuroimaging is to identify markers that can aid in diagnosis, monitor disease progression, and impact long-term drug analysis. In this study, physiopathological modifications in seven subcortical structures of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) were characterized by simultaneously measuring quantitative magnetic resonance parameters that are sensitive to complementary tissue characteristics (e.g., volume atrophy, shape changes, microstructural damage, and iron deposition). Fourteen MCI patients and fourteen matched, healthy subjects underwent 3T-magnetic resonance imaging with whole-brain, T1-weighted, T2*-weighted, and diffusion-tensor imaging scans. Volume, shape, mean R2*, mean diffusivity (MD), and mean fractional anisotropy (FA) in the thalamus, hippocampus, putamen, amygdala, caudate nucleus, pallidum, and accumbens were compared between MCI patients and healthy subjects. Comparisons were then performed using voxel-based analyses of R2*, MD, FA maps, and voxel-based morphometry to determine which subregions showed the greatest difference for each parameter. With respect to the micro- and macro-structural patterns of damage, our results suggest that different and distinct physiopathological processes are present in the prodromal phase of AD. MCI patients had significant atrophy and microstructural changes within their hippocampi and amygdalae, which are known to be affected in the prodromal stage of AD. This suggests that the amygdala is affected in the same, direct physiopathological process as the hippocampus. Conversely, atrophy alone was observed within the thalamus and putamen, which are not directly involved in AD pathogenesis. This latter result may reflect another mechanism, whereby atrophy is linked to indirect physiopathological processes.

Keywords: Alzheimer’s disease; brain; diffusion tensor imaging; iron; magnetic resonance imaging; mild cognitive impairment; multimodal; shape; subcortical structures; volumetry.

Fig.1

Shape modifications between MCI-due-to-AD patients and healthy controls in dorsal and ventral views. Areas in orange represent localization with significant shape modification (p <  0.05 corrected for multiple comparisons).

Fig.2

Voxel-based analysis of mean diffusivity with mask composed of both thalami, both hippocampi, both putamen, and both amygdala with threshold of significance of p <  0.05 and threshold-free cluster enhancement corrected in MCI-due-to-AD patients versus healthy controls (A, anterior; I, inferior; L, left; P, posterior; R, right; S, superior).

Fig.3

Voxel-based morphometry in MCI-due-to-AD patients versus healthy controls corrected for multiple comparison (p <  0.05) (A, anterior; I, inferior; L, left; P, posterior; R, right; S, superior)