Structural MRI in frontotemporal dementia and Alzheimer's disease: stage-dependent atrophy patterns

Differentiating Alzheimer's disease (AD) from frontotemporal dementia (FTD) remains a major clinical challenge, particularly in early disease stages when phenotypic overlap is common and in later stages when cortical degeneration becomes widespread. Structural magnetic resonance imaging (MRI) provides a widely available, non-invasive framework for assessing region-specific brain atrophy patterns associated with these disorders. This narrative review synthesizes current evidence on MRI-based approaches for distinguishing FTD from AD across disease stages. FTD, particularly the behavioral variant, is characterized by early and prominent degeneration of frontal and anterior temporal networks, frequently with hemispheric asymmetry and early behavioral change, including apathy as a core feature. In contrast, AD typically demonstrates a posterior-predominant pattern, with medial temporal and temporoparietal atrophy reflecting a posterior-to-anterior trajectory, while frontal involvement emerges later except in atypical variants. Quantitative MRI techniques, including voxel-based morphometry, cortical thickness analysis, and asymmetry indices, together with validated visual rating scales, enhance the detection of these spatial patterns. Fluid-attenuated inversion recovery imaging supports interpretation by identifying vascular burden, and complementary biomarkers, including FDG-PET, cerebrospinal fluid, and blood-based markers, provide molecular and functional context in diagnostically ambiguous cases. The diagnostic specificity of frontal atrophy is greatest in early stages and decreases as AD and FTD converge anatomically in moderate to advanced disease. Accurate differential diagnosis, therefore, requires a stage-aware, integrative framework that combines structural MRI with longitudinal clinical assessment, neuropsychological profiling, and biomarker information. Structural MRI remains the cornerstone of differentiation, with regional atrophy patterns interpreted within a broader clinical and biological context rather than in isolation.