The Role of Clinical Assessment in the Era of Biomarkers.

Hippocratic Medicine revolved around the three main principles of patient, disease, and physician and promoted the systematic observation of patients, rational reasoning, and interpretation of collected information. Although these remain the cardinal features of clinical assessment today, Medicine has evolved from a more physician-centered to a more patient-centered approach. Clinical assessment allows physicians to encounter, observe, evaluate, and connect with patients. This establishes the patient-physician relationship and facilitates a better understanding of the patient-disease relationship, as the ultimate goal is to diagnose, prognosticate, and treat. Biomarkers are at the core of the more disease-centered approach that is currently revolutionizing Medicine as they provide insight into the underlying disease pathomechanisms and biological changes. Genetic, biochemical, radiographic, and clinical biomarkers are currently used. Here, we define a seven-level theoretical construct for the utility of biomarkers in neurodegenerative diseases. Level 1-3 biomarkers are considered supportive of clinical assessment, capable of detecting susceptibility or risk factors, non-specific neurodegeneration or dysfunction, and/or changes at the individual level which help increase clinical diagnostic accuracy and confidence. Level 4-7 biomarkers have the potential to surpass the utility of clinical assessment through detection of early disease stages and prediction of underlying pathology. In neurodegenerative diseases, biomarkers can potentiate, but cannot substitute, clinical assessment. In this current era, aside from adding to the discovery, evaluation/validation, and implementation of more biomarkers, clinical assessment remains crucial to maintaining the personal, humanistic, and sociocultural aspects of patient care. We would argue that clinical assessment is a custom that should never go obsolete.