The present Reprint explores the rapidly evolving landscape of cognitive disorder diagnosis, moving beyond traditional symptom-based paradigms toward integrated, multidimensional frameworks. As global populations age, clinicians face increasing diagnostic complexity at the intersection of neurological, systemic, and environmental influences. The contributed articles illustrate how systemic conditions, such as pulmonary disease and perioperative stress, impact cognitive outcomes, while also highlighting the role of detailed neuropsychological profiling in differentiating overlapping syndromes. Furthermore, this Reprint examines the transformative potential of biomarkers, genomics, and artificial intelligence to enhance diagnostic precision and support clinician decision-making. By synthesizing clinical expertise with technological innovation, these studies advocate for a data-informed and patient-centered model of care across the lifespan.