Parkinson's at risk syndrome: can Parkinson's disease be predicted?

The treatment of Parkinson's disease (PD) has revolved around pharmacologic interventions that primarily treat the cardinal (dopaminergic) manifestations of tremor, rigidity, and bradykinesia; yet, we now know that the pathology of PD is widespread, accounting for more disabling symptoms such as cognitive impairment, autonomic problems, and postural instability. Further, attempts at modifying PD may be hampered as much by the imperfection of therapeutic interventions as by the extent of neuronal damage that exists even in early PD, when most putative neuroprotective agents are tried. Our approach to PD must therefore evolve and include strategies for detecting PD earlier in its course and, eventually, intervening when the disease process is in its nascent stages. Parkinson's associated risk syndrome (PARS) is the term we have coined to describe patients at risk for developing PD. These patients may have genetic risk factors or may have subtle, early non-motor symptoms including abnormalities in olfaction, gastrointestinal function, cardiac imaging, vision, behavior, and cognition. Changes in neuroimaging modalities can predict the emergence of neurologic signs and symptoms within several years. The PARS study is now underway to determine the feasibility of screening a large cohort of subjects to identify those at highest risk for developing PD. If successful, we will have the tools to identify cohorts for clinical trials of PD prevention or, at the very least, delay of disease onset, and long-term disability. Further, our concept of PD risk will change the nosology of PD as those now considered "at-risk" may ultimately be considered to already have the disease.