Grey Matter Loss at Different Stages of Cognitive Decline: A Role for the Thalamus in Developing Alzheimer's Disease

Abstract

Background: Alzheimer's disease (AD) is characterized by cognitive impairment and large loss of grey matter volume and is the most prevalent form of dementia worldwide. Mild cognitive impairment (MCI) is the stage that precedes the AD dementia stage, but individuals with MCI do not always convert to the AD dementia stage, and it remains unclear why.

Objective: We aimed to assess grey matter loss across the brain at different stages of the clinical continuum of AD to gain a better understanding of disease progression.

Methods: In this large-cohort study (N = 1,386) using neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative, voxel-based morphometry analyses were performed between healthy controls, individuals with early and late and AD dementia stage.

Results: Clear patterns of grey matter loss in mostly hippocampal and temporal regions were found across clinical stages, though not yet in early MCI. In contrast, thalamic volume loss seems one of the first signs of cognitive decline already during early MCI, whereas this volume loss does not further progress from late MCI to AD dementia stage. AD dementia stage converters already show grey matter loss in hippocampal and mid-temporal areas as well as the posterior thalamus (pulvinar) and angular gyrus at baseline.

Conclusion: This study confirms the role of temporal brain regions in AD development and suggests additional involvement of the thalamus/pulvinar and angular gyrus that may be linked to visuospatial, attentional, and memory related problems in both early MCI and AD dementia stage conversion.

Keywords: Alzheimer’s disease; angular gyrus; grey matter; hippocampus; neuroimaging; thalamus.

Fig. 1

Visualization of grey matter volume reductions in EMCI < CN. Reductions centered around the bilateral ventrolateral thalamus, orbitofrontal cortex, anterior cingulate cortex and cerebellum. MNI coordinate along the x-axis indicated in white. Lighter colors indicate higher t-values (see Table 2).

Fig. 2

Visualization of GM volume reduction cluster (yellow/orange) in EMCI < CN located in the bilateral ventrolateral thalamus (green/purple) and globus pallidus (blue) according to the Talairach and Harvard-Oxford structural atlas.

Fig. 3

Widespread grey matter volume reductions in LMCI < EMCI. The largest cluster centered around the bilateral mediotemporal gyri, hippocampus, and entire thalamus (see Table 3).

Fig. 4

Additional grey matter volume reductions centered mostly around temporal areas in AD dementia < LMCI (see Table 4).

Fig. 5

GM volume reductions in temporal, frontal, parietal and cerebellar areas in AD dementia < CN (see Table 5).

Fig. 6

GM volume reductions in temporal areas, posterior thalamus, left angular gyrus and more in 2-year AD dementia converters < AD dementia non converters (see Table 6).

Fig. 7

Visualization of GM volume reduction cluster (red) in AD dementia converters located in the bilateral hippocampus and left (purple) and right (yellow) posterior thalamus/pulvinar according to the Talairach structural atlas.