Biomarkers

Area of Science:

• Neuroimaging
• Neuropathology
• Vascular Neurology

Background:

• Atherosclerosis of the Circle of Willis (ACW) frequently co-occurs with Alzheimer's disease (AD).
• Understanding ACW's influence on AD-related neurodegeneration is crucial for developing effective treatments.
• Investigating ACW's impact on cortical microstructural changes can refine diagnostic precision for combined pathologies.

Purpose of the Study:

• To assess the impact of ACW severity on cortical microstructural changes in individuals with Alzheimer's disease neuropathologic change (ADNC).
• To identify potential cortical patterns indicative of combined vascular and neurodegenerative pathologies.
• To explore the utility of diffusion MRI metrics in differentiating AD patients based on ACW severity.

Main Methods:

• Structural and diffusion MRI data from 58 participants with intermediate/severe ADNC were analyzed.
• Participants were grouped by ACW severity (none/mild vs. moderate/severe).
• Cortical diffusivity metrics (ParlPD, PerpPD+) were compared between groups using linear models, adjusted for relevant covariates and corrected for multiple comparisons.

Main Results:

• Participants with moderate/severe ACW showed significantly lower ParlPD in temporal and occipital regions.
• Lower PerpPD+ values were observed in the left occipital regions of participants with higher ACW severity.
• No significant differences were found in demographic, clinical, or macrostructural MRI data between ACW groups.

Conclusions:

• Cortical diffusivity metrics reveal distinct microstructural changes associated with varying ACW severity in AD patients.
• These findings support the use of cortical diffusivity for patient stratification in AD clinical practice and trials.
• This approach may enhance the precision of therapeutic targeting for individuals with comorbid ACW and AD.