Clinical prediction of Parkinson's disease: planning for the age of neuroprotection

As a chronic progressive disease, Parkinson's disease (PD) has a presymptomatic interval; that is, a period during which the pathological process has begun, but motor signs required for the clinical diagnosis are absent. The ability to identify this preclinical stage may be critical in the development and eventual use of neuroprotective therapy. Recently proposed staging systems of PD have suggested that degeneration may occur initially in areas outside the substantia nigra, suggesting that non-motor manifestations may be markers of presymptomatic PD. Decreased olfaction has recently been demonstrated to predict PD in prospective pathological studies, although the lead time may be relatively short, and the positive predictive value is low. Idiopathic RBD has a very high predictive value, with approximately 50% of affected individuals developing PD or dementia within 10 years. This implies that idiopathic RBD patients are ideal candidates to test potential preclinical markers. However, the specificity of symptom screens for RBD is not established, not all persons with PD develop RBD, and there are only limited ways to predict which RBD patients will develop PD. Other simple screens based upon autonomic symptoms, depression and personality changes, quantitative motor testing and other sleep disorders may also be useful markers, but have not been extensively tested. Other more expensive measures such as detailed autonomic testing, cardiac MIBG-scintigraphy, dopaminergic imaging and transcranial ultrasound may be especially useful in defining disease risk in those identified through primary screening.