Smell the smoke before one sees the fire—The oligosymptomatic prodromal phase of neurodegenerative diseases

Background: With the increasing development of disease-modifying causative treatment, the importance of early diagnosis and detection of asymptomatic or oligosymptomatic early stages of neurodegenerative diseases is increasing. Objective: Presentation of early stages of neurodegenerative diseases, diagnostic procedures for the early detection and possible treatment consequences. Material and methods: Selective literature search, discussion of basic research and expert recommendations. Results: Many neurodegenerative diseases have a prodromal phase preceding the manifest disease that can be diagnosed with current criteria. In this prodromal phase, those affected are often oligosymptomatic but in some cases can already be identified using biomarkers. These developments are already taken into account in diagnostic criteria for some of these prodromal phases. The prodromal phase, in turn, is preceded by an asymptomatic phase which, however, already shows molecular changes and can be identified by biomarkers in some diseases. The early identification and stratification of patients is particularly important when planning studies for disease-modifying treatment, and biomarkers are already being used in clinical trials for this purpose. Discussion: Biomarker-based identification of individuals in the prodromal phase of neurodegenerative diseases is already possible for some entities. People who show the first signs of a neurodegenerative disease can be referred to centers for clinical trials and observational studies.