Gray matter atrophy and structural connectivity in Posterior Cortical Atrophy: A voxel-based meta-analysis

Area of Science:

• Neuroscience
• Radiology
• Neurology

Background:

• Posterior Cortical Atrophy (PCA) is a neurodegenerative syndrome often linked to Alzheimer's disease, causing progressive visuospatial and visuoperceptual deficits.
• Existing voxel-based morphometry studies show gray matter loss in PCA, but a comprehensive meta-analysis and understanding of structural connectivity alterations are lacking.

Purpose of the Study:

• To conduct a systematic review and coordinate-based meta-analysis of voxel-based morphometry studies in Posterior Cortical Atrophy (PCA).
• To investigate structural connectivity alterations associated with gray matter atrophy in PCA using diffusion MRI tractography.
• To provide a statistically robust characterization of brain alterations in PCA following consensus diagnostic criteria.

Main Methods:

• Systematic review and voxel-based meta-analysis of 18 studies (339 PCA patients; 577 controls) using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI).
• Meta-regression analyses to explore the influence of demographic and clinical variables on atrophy patterns.
• Deterministic tractography on a normative diffusion MRI template, using meta-analytic gray matter clusters as seeds to assess white matter integrity.

Main Results:

• Meta-analysis identified significant bilateral gray matter atrophy in the lateral occipital cortex, inferior parietal lobule, precuneus, and ventral occipitotemporal regions in PCA patients.
• Meta-regression revealed an interaction between age and disease duration impacting atrophy in the left superior temporal gyrus and right thalamus.
• Tractography showed affected gray matter clusters were part of major white matter pathways, including the superior/inferior longitudinal fasciculi, vertical occipital fasciculi, and parietal aslant tract.

Conclusions:

• This study provides the first comprehensive meta-analysis of PCA brain alterations post-consensus criteria, detailing gray matter atrophy patterns.
• Structural connectivity analysis highlights PCA's impact on key long-range white matter tracts.
• Findings offer potential imaging biomarkers for PCA diagnosis and therapeutic target identification.