Associations between structural neuroimaging markers and neuropathology of Alzheimer's Disease

Area of Science:

• Neurology
• Neuroimaging
• Pathology

Background:

• Structural magnetic resonance imaging (MRI) is crucial for tracking Alzheimer's disease (AD) progression.
• Postmortem pathological examination is the definitive method for diagnosing AD.
• Validating MRI markers against neuropathology is essential for clinical trial applications.

Purpose of the Study:

• To investigate the association between structural MRI markers and Alzheimer's disease neuropathology.
• To compare the efficacy of aggregate atrophy indices versus single-region measures.
• To evaluate MRI markers for their utility in Alzheimer's disease clinical trials.

Main Methods:

• Analysis of structural MRI data from 805 individuals with detailed neuropathological data.
• Measurement of medial temporal lobe (MTL) and whole-brain atrophy markers.
• Calculation of aggregate indices for AD-related atrophy (FSAD) and brain aging (brainageR).
• Statistical analysis using ordinal logistic regression to correlate MRI markers with AD neuropathologic change (ADNC).

Main Results:

• High ADNC was strongly associated with reduced MTL volume and higher FSAD scores.
• Adjusted analyses showed significantly increased odds of high ADNC with low MTL volume (OR=5.0) and high FSAD (OR=11.0).
• MRI markers showed stronger correlations with tau pathology than amyloid beta pathology.
• Atrophy patterns linked to AD neuropathology differed from normal aging, with prominent MTL involvement.

Conclusions:

• Aggregate indices of AD-related atrophy, like FSAD, are more robust indicators of neuropathology than single-region atrophy.
• Structural MRI markers, especially aggregate indices, show significant correlation with AD neuropathology.
• These findings support the use of aggregate MRI atrophy indices for sample enrichment and outcome measures in AD clinical trials.