帕金森疾病预防

Conceptual Framework of Prodromal PD: What is Meant, How to Diagnose, and When to Treat Whom (A) Gives a schematic overview of our current understanding of the neurodegenerative process in PD and illustrates that the prodromal phase can be divided into 3 stages. Notably, these are hypothetical frameworks only—the specific elements represented and the timeframes specified are not proven. These stages do not need to be evident in all individuals, may have different durations, and can even occur simultaneously (e.g., individuals with mild motor abnormalities may become hyposmic at the same time the motor changes become obvious). In (B), markers for the specific phases are suggested. (C) Provides examples of specific cohorts (Who?) for clinical trials dependent on the stage and accompanying markers. Pharmacologic trials in all cohorts can only be justified when PD-specific pathology is proven—by demonstrating either α-synuclein pathology or involvement of the nigrostriatal system (early motor). Conversely, low-threshold interventions (e.g., exercise) may be applied at all stages even if pathology cannot be proven. The choice of intervention (What?) may differ, depending on the clinical subtype (Who?) and the specificity of biomarkers, that is, endpoints for clinical studies (How?). PD = Parkinson disease; SN = substantia nigra.