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.

Hypertension With High Homocysteine Is Associated With Default Network Gray Matter Loss

“…Nevertheless, we found that the MMSE scores were correlated with almost all the significant clusters, thereby suggesting the role of these regions in global cognition. This finding is in line with many studies investigating the brain anatomical correlates with global cognition (25)(26)(27)(28)(29)(30). The precuneus is a core of the DMN, and this result is also in line with other published reports on vascular cognitive impairment (51)(52)(53).…”

“…These silent lesions represent physical dysconnectivity, compromised coordination between interconnected gray matter regions, and progressive atrophy itself. We know that cortical gray matter integrity is the neuroanatomical basis of large-scale brain networks that support human behaviors and cognition, and mounting evidence links gray matter atrophy to cognitive impairment (25)(26)(27)(28)(29)(30). However, it is unclear that whether and to what extent HHT may affect the DMN gray matter morphometry.…”

Focal thalamus pathology in frontotemporal dementia: Phenotype-associated thalamic profiles

“…The distinction between AD and early FTD can also be challenging on clinical grounds. There is evidence of relatively selective thalamic nuclei involvement along the clinical continuum of AD [76]. Post-mortem studies have shown preferential involvement of the anterior thalamic nuclei with relative sparing of the medial dorsal nuclei even in the later stages [77], which is particularly interesting given our contrary finding of mediodorsal nuclei atrophy in FTD.…”

Automated High-Definition MRI Processing Routine Robustly Detects Longitudinal Morphometry Changes in Alzheimer’s Disease Patients

“…Cross-sectional studies have shown that cognitive decline at different stages of the Alzheimer’s disease (AD) correlate with gray matter loss ( Van de Mortel et al, 2021 ; Wu et al, 2021 ). At late stages of AD, a widespread reduction in brain volume was consistently found in the hippocampus, temporal pole, medial- and inferior temporal cortex, precuneus, parietal lobe and cerebellum ( Chapleau et al, 2016 ; Dicks et al, 2019 ; Kang et al, 2019 ; Kunst et al, 2019 ).…”