Longitudinal Relationship Between Brain Atrophy Patterns, Cognitive Decline, and Cerebrospinal Fluid Biomarkers in...

Area of Science:

• Neuroimaging
• Alzheimer's Disease Research
• Biomarker Analysis

Background:

• Longitudinal magnetic resonance imaging (MRI) is a key tool for tracking Alzheimer's disease (AD) progression via brain atrophy assessment.
• Identifying distinct patterns of brain atrophy is crucial for understanding AD's longitudinal trajectory.

Purpose of the Study:

• To detect and characterize brain atrophy patterns in Alzheimer's disease (AD) patients.
• To use these patterns as a longitudinal tracker for disease progression.
• To investigate associations between atrophy, cognitive changes, and AD biomarkers.

Main Methods:

• Utilized an refined orthonormal projective non-negative matrix factorization (OPNMF) method.
• Analyzed voxel-wise volume loss in 83 AD patients (ADNI3 cohort) and controls (ABIDE study).
• Validated findings in an independent ADNI2 dataset, comparing atrophy coefficients across patient groups and with CSF biomarkers.

Main Results:

• Identified six distinct, non-overlapping spatial components of gray matter volume loss, primarily in frontal, temporal, parietal, and cerebellar regions.
• Found strong cross-sectional and longitudinal correlations between regional atrophy and cognition, with medial temporal atrophy being most significant.
• Observed that elevated TAU/PTAU and lower Aβ42 levels were associated with a faster increase in atrophy.

Conclusions:

• Developed a transferable method to characterize AD-associated imaging changes using six distinct atrophy components.
• Correlated these atrophy patterns with cognitive changes and CSF biomarkers, offering insights into AD pathology.
• Demonstrated the potential of these atrophy patterns as biomarkers for AD progression and treatment monitoring.