Screening and Targeting Risk Factors for Prodromal Synucleinopathy: Taking Steps toward a Prescriptive Multi-modal Framework

As the prevalence of Parkinson’s disease (PD) grows, so too does the population at-risk of developing PD, those in the so-called prodromal period. This period can span from those experiencing subtle motor deficits yet not meeting full diagnostic criteria or those with physiologic markers of disease alone. Several disease-modifying therapies have failed to show a neuroprotective effect. A common criticism is that neurodegeneration, even in the early motor stages, has advanced too far for neuro-restoration-based interventions to be effective. Therefore, identifying this early population is essential. Once identified, these patients could then potentially benefit from sweeping lifestyle modifications to alter their disease trajectory. Herein, we review the literature on risk factors for, and prodromal symptoms of, PD with an emphasis on ones which may be modifiable in the earliest possible stages. We propose a process for identifying this population and speculate on some strategies which may modulate disease trajectory. Ultimately, this proposal warrants prospective studies.