Parkinson's disease risk score: moving to a premotor diagnosis

Early pre-motor symptoms (also frequently termed "non-motor" symptoms) in Parkinson's disease (PD), which precede the onset of motor symptoms, are being increasingly recognized by clinicians. Non-motor symptoms in the pre-motor phase of PD include impaired olfaction (hyposmia), sleep disturbances (i.e., radid eye movement sleep behavior disorder, daytime sleepiness), behavioral/emotional dysfunction (i.e., change of personality or change of core personal characteristics), dysautonomia (i.e., constipation, urinary dysfunction, orthostatic hypotension), depressive symptoms (i.e., fatigue, apathy, anxiety), and chronic pain (joint and muscle). The pre-motor phase of PD is based on current pathophysiological concepts that relate these symptoms to early structural changes within lower brainstem nuclei and the peripheral nervous system including the autonomic and enteric ganglia. The perspective to identify these symptoms as early as possible will enable neurologists to make a diagnosis at the pre-motor stage of PD. Thus, the development of a PD risk score will be the first means to identify individuals at risk who are most likely to develop the prototypical motor symptoms of PD later in life. More importantly, these individuals at risk will be the first to benefit from disease-modifying strategies. In this workshop report, the elements of a PD risk score are proposed, including the stepwise sequence of escalating diagnostic measures to diagnose the pre-motor stage in PD.