Structural and microstructural changes in white and gray matter across the Alzheimer's disease continuum

Area of Science:

• Neuroimaging
• Neurodegenerative Diseases
• Biomarker Development

Background:

• Alzheimer's disease (AD) is characterized by progressive brain atrophy affecting gray matter (GM) and white matter (WM).
• Understanding volumetric changes across the AD continuum (preclinical, subjective cognitive decline, MCI, dementia) is crucial for diagnosis and treatment.

Purpose of the Study:

• To review neuroimaging features of brain volumetric changes in Alzheimer's disease (AD).
• To explore the clinical implications and prognostic value of these changes across the AD continuum.
• To propose a unified model of AD neuroanatomy integrating GM and WM pathology.

Main Methods:

• Review of neuroimaging studies focusing on brain volumetric changes in Alzheimer's disease (AD).
• Analysis of structural alterations in gray matter (GM) and white matter (WM) across different clinical phases of AD.
• Identification of specific white matter (WM) tracts with prognostic value.

Main Results:

• White matter (WM) volume loss is an active contributor to clinical decline in Alzheimer's disease (AD), not just a consequence of gray matter (GM) degeneration.
• Specific white matter (WM) tracts show atrophy rates that provide prognostic information beyond hippocampal volume.
• A unified model of AD neuroanatomy is proposed, highlighting the interplay between GM and WM pathology.

Conclusions:

• The spatiotemporal pattern of white matter (WM) loss is a significant factor in Alzheimer's disease (AD) progression.
• Refined understanding of AD neuroanatomy, integrating GM and WM interactions, is essential for next-generation biomarker development.
• Artificial intelligence (AI) and multi-omics data integration are vital for future personalized predictive models in AD.