Cortical Thickness and Microstructural White Matter Changes Detect Amnestic Mild Cognitive Impairment

Area of Science:

• Neuroimaging
• Neurodegeneration
• Genetics

Background:

• Apolipoprotein E (APOE) ɛ4 allele and amnestic mild cognitive impairment (aMCI) are established risk factors for Alzheimer's disease (AD).
• Understanding how APOE genotype influences brain structure changes in aMCI is crucial for early AD detection and intervention.

Purpose of the Study:

• To investigate whether APOE genotype modifies aMCI-related abnormalities in gray matter (GM) cortical thickness and white matter (WM) tracts integrity.
• To explore the relationship between WM integrity, parahippocampal atrophy, and cognitive performance in aMCI patients.

Main Methods:

• Multi-modal brain magnetic resonance imaging (MRI) scans were performed on 146 older adults (64 aMCI patients, 82 controls).
• Participants were stratified by aMCI status and APOE ɛ4 carrier status.
• Analyses included cortical thickness, WM integrity (mean diffusivity), and neuropsychological assessments, focusing on episodic memory.

Main Results:

• aMCI patients exhibited reduced parahippocampal gyrus cortical thickness and disrupted WM integrity in limbic tracts compared to controls.
• No significant effects of APOE genotype or diagnosis-by-genotype interaction were found on GM thickness or WM integrity.
• WM microstructural disruptions in limbic tracts correlated with parahippocampal atrophy and were significantly associated with poorer episodic memory performance in aMCI.

Conclusions:

• Early-stage AD, characterized by aMCI, involves WM microstructural disruptions in limbic tracts in an APOE-independent manner.
• These WM changes appear to occur progressively, alongside parahippocampal atrophy, and contribute to initial episodic memory impairment.