Neuroimaging in the era of biologically defined Alzheimer's disease and disease-modifying therapy.

Abstract

Disease-modifying therapies and biomarker-based diagnostic frameworks will fundamentally altered the clinical diagnosis and management of Alzheimer's disease. Diagnosis is increasingly anchored in the biological evidence of pathology rather than clinical presentation alone, with implications for treatment eligibility, prognosis, and monitoring. In clinical practice, patients with memory complaints can present with complex mixed pathologies that develop across the lifespan. Brain imaging, particularly MRI and PET, plays a crucial role in visualising these cumulative abnormalities. With Alzheimer's disease-specific therapies now available in many regions of the world, amyloid PET plays a central role in establishing Alzheimer's disease diagnosis, determining eligibility for amyloid-targeting therapies, and quantifying treatment-related amyloid clearance. In settings where available, tau PET informs biological stage, prognosis, and clinical heterogeneity. MRI remains indispensable for differential diagnosis, the assessment of comorbid and vascular pathology, and monitoring for complications, particularly amyloid-related imaging abnormalities. Technological advances-including quantitative imaging, artificial intelligence, accelerated acquisition, and workflow optimisation-are improving reliability, efficiency, and access to these tools. Neuroimaging is now a cornerstone of Alzheimer's disease care and a crucial discriminator tool for characterising brain injury across the lifespan. With emerging fluid biomarkers, neuroimaging supports accurate diagnosis, prognosis, and treatment monitoring.