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

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive brain atrophy, with pathological progression accompanied by significant structural alterations in both gray matter (GM) and white matter (WM). This review summarizes the neuroimaging features and clinical implications of brain volumetric changes across distinct the clinical phases of the AD continuum [preclinical phase, subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia phase]. Our analysis reveals a key conceptual advance: the spatiotemporal pattern of WM volume loss is not merely a consequence of GM degeneration but an active and complementary contributor to clinical decline. We identify specific, underappreciated WM tracts whose atrophy rates offer unique prognostic value beyond hippocampal volume. The primary contribution of this work is a unified model of AD neuroanatomy, which challenges the isolated view of GM and WM pathology. This refined understanding is critical for developing the next generation of biomarkers and underscores the imperative to leverage artificial intelligence for analyzing these complex, multi-tissue interactions. Future research should further integrate artificial intelligence and multi-omics data to refine personalized predictive models.