White matter integrity and key structures affected in Alzheimer's disease characterized by diffusion tensor imaging

Area of Science:

• Neuroimaging
• Neurology
• Biomedical Engineering

Background:

• White matter (WM) integrity is implicated in early Alzheimer's disease (AD) detection.
• Specific brain circuitry affected by WM degeneration in AD remains unclear.
• Diffusion tensor imaging (DTI) offers insights into WM microstructural changes.

Purpose of the Study:

• To investigate the association between DTI measures of WM tract integrity and AD diagnosis.
• To identify key WM substrates predictive of AD.
• To explore correlations between WM changes, cognitive function, and AD.

Main Methods:

• Analyzed DTI measures (mean diffusivity, fractional anisotropy, radial diffusivity, axial diffusivity) of 18 WM tracts.
• Included 84 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset.
• Utilized multivariable general linear models and variable cluster analysis, adjusting for age, gender, and education.

Main Results:

• Significant differences in DTI measures were observed between AD patients and controls.
• Increased mean diffusivity, radial diffusivity, and axial diffusivity were noted in several WM tracts (e.g., corpus callosum, fornix, cingulum hippocampus).
• Decreased fractional anisotropy was found in the splenium of the corpus callosum and fornix.
• Hippocampus volume, MMSE scores, and specific WM tracts (cingulate gyrus/hippocampus, inferior fronto-occipital fasciculus, uncinate fasciculus) showed strong correlations with mean diffusivity.

Conclusions:

• WM degeneration, particularly in the right cingulum gyrus and right uncinate fasciculus, is significantly associated with AD.
• These affected WM tracts correlate with cognitive test performance (MMSE), suggesting their role in AD progression.
• Age is a significant risk factor for AD, whereas gender and education are not.
• The identified WM regions may serve as crucial biomarkers for AD staging and therapeutic targeting.