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

Abstract

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.

Figure 1.

The Parkinson’s disease At-Risk Syndrome (PARS) pyramid. In this conceptual schema, four stages precede clinically manifest PD: pre-physiological, pre-clinical, pre-motor and pre-diagnostic. The prodromal period includes the middle categories where there is evidence of disease activity but there is no fulfillment of the PD diagnostic criteria.

Figure 2.

Flow diagram depicting proposed method of referral to wellness clinic for patients at risk. Automatic referrals would come through sleep medicine or neurology clinics. The next group would come from geriatrics or internal medicine clinics following a short or long screen. PSG: polysomnogram; RBD: REM Behavior Disorder; MCI: mild cognitive impairment; B-SIT: Brief smell identification test; RBD1Q: RBD single question screen; BP: blood pressure; PTSD: Post-traumatic Stress Disorder. The wellness clinic practitioners can then create a personalized intervention strategy based on tables 1 and 2.