Sleep disorders and Parkinson's disease: is there a right direction?

In the last years, the hypothesis of a close relationship between sleep disorders (SDs) and Parkinson's disease (PD) has significantly strengthened. Whether this association is causal has been also highlighted by recent evidence demonstrating a neurobiological link between SDs and PD. Thus, the question is not whether these two chronic conditions are mutually connected, but rather how and when this relationship is expressed. Supporting this, not all SDs manifest with the same temporal sequence in PD patients. Indeed, SDs can precede or occur concomitantly with the onset of the clinical manifestation of PD. This review discusses the existing literature, putting under a magnifying glass the timing of occurrence of SDs in PD-neurodegeneration. Based on this, here, we propose two possible directions for studying the SDs-PD relationship: the first direction, from SDs to PD, considers SDs as potential biomarker/precursor of future PD-neurodegeneration; the second direction, from PD to SDs, considers SDs as concomitant symptoms in manifest PD, mainly related to primary PD-neuropathology and/or parkinsonian drugs. Furthermore, for each direction, we questioned SDs-PD relationship in terms of risk factors, neuronal circuits/mechanisms, and impact on the clinical phenotype and disease progression. Future research is needed to investigate whether targeting sleep may be the winning strategy to treat PD, in the context of a personalized precision medicine.