Structural Changes in Thalamic Nuclei Across Prodromal and Clinical Alzheimer's Disease

Abstract

Background: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer's disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum.

Objective: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS).

Methods: MPRAGE data from the ADNI database were used in this study (n = 540). Healthy control (n = 125), early MCI (n = 212), late MCI (n = 114), and AD subjects (n = 89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA.

Results: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects.

Conclusion: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes.

Keywords: Alzheimer’s disease; Alzheimer’s disease neuroimaging initiative; Papez circuit; THOMAS; mild cognitive impairment; thalamic nuclei; thalamus; thalamus optimized multi-atlas segmentation.