Functional heterogeneity across structural MRI-based atrophy subtypes in Alzheimer's disease

Area of Science:

• Neuroscience
• Medical Imaging
• Neurology

Background:

• Alzheimer's disease (AD) is characterized by progressive brain atrophy.
• Identifying distinct structural atrophy patterns may reveal underlying functional differences.
• Understanding these subtypes is crucial for targeted therapeutic strategies.

Purpose of the Study:

• To investigate if different Alzheimer's disease (AD) structural atrophy subtypes exhibit unique functional connectivity profiles.
• To explore the relationship between MRI-derived atrophy patterns and resting-state functional MRI (rs-fMRI) and electroencephalography (EEG) measures.
• To determine if distinct AD subtypes have divergent functional network characteristics.

Main Methods:

• Cross-sectional multimodal study involving 116 AD patients and 74 controls.
• Structural MRI to classify AD patients into hippocampal-sparing (HpSp-MRI), typical (tAD-MRI), and limbic-predominant (LP-MRI) atrophy subtypes.
• Resting-state fMRI for functional connectivity analysis and EEG for spectral power and microstate dynamics.

Main Results:

• HpSp-MRI subtype showed reduced intranetwork connectivity in visual, somatomotor, and dorsal attention networks compared to other subtypes.
• LP-MRI and tAD-MRI subtypes exhibited differences in ventral attention network connectivity.
• LP-MRI subtype displayed stronger internetwork connectivity, and EEG suggested potential microstate transition differences between LP-MRI and tAD-MRI groups.

Conclusions:

• MRI-defined Alzheimer's disease (AD) atrophy subtypes possess distinct resting-state functional connectivity profiles.
• These findings offer a potential foundation for personalized, brain network-targeted interventions in AD.
• Subtype-specific functional characteristics highlight the heterogeneity of AD pathophysiology.