Neurodegenerative diseases (NDDs) remain among the most challenging disorders to treat, owing to their multifactorial pathology, limited drug delivery across the blood-brain barrier, and lack of effective disease-modifying therapies. Smart nanomedicines are emerging as powerful tools to overcome these challenges by enabling targeted delivery, controlled release, and enhanced bioavailability of therapeutics. In parallel, advances in molecular imaging, combined with machine learning (ML) and artificial intelligence (AI), are transforming the design, validation, and optimization of nanomedicines. This article integrates the rapidly evolving fields of nanomedicine and AI/ML-driven imaging to evaluate their synergistic potential toward NDD therapy. The capabilities of AI-aided imaging for mapping nanomedicine biodistribution, predicting therapeutic outcomes, guiding nanoparticle design, and ensuring quality control at preclinical and clinical stages in NDDs are discussed. This synergistic approach opens new avenues for precision medicine, enabling personalized and adaptive treatment strategies for Alzheimer's, Parkinson's, and other NDDs by linking smart nanocarriers with intelligent imaging analytics. Hence, this article presents a roadmap for translating AI-guided nanomedicine-integrated imaging platforms into clinically viable solutions, marking a paradigm shift in the diagnosis and treatment of NDDs.

AELIA Organization 9th Km Thessaloniki Thermi 57001 Thessaloniki Greece

Catalan Institute of Nanoscience and Nanotechnology Campus UAB 08193 Bellaterra Barcelona Spain

Chemical Engineering Department University of Tennessee Knoxville TN 37403 USA

Department of Medical Oncology Loannina University Hospital Loannina 45500 Greece

Department of Research and Innovation Medway NHS Foundation Trust Gillingham ME7 5NY UK

Division of Experimental Neurobiology Preclinical Research Program National Institute of Mental Health 250 67 Klecany Czechia

Faculty of Engineering and Science University of Greenwich London Chatham Maritime Kent ME4 4TB UK

Faculty of Life Sciences and Medicine School of Cancer and Pharmaceutical Sciences King's College London London WC2R 2LS UK

Faculty of Medicine Health and Social Care Canterbury Christ Church University Canterbury CT1 1QU UK

Faculty of Medicine School of Health Sciences University of Ioannina Loannina 45110 Greece

Faculty of Medicine Tbilisi State University 0177 Tbilisi Georgia

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