Biomarkers of Nonmotor Symptoms in Parkinson's Disease

Biomarkers are helpful for early diagnosis, assessment of disorder severity, prognosis, and prediction of response to therapy. Given that early therapeutic intervention may be useful in forestalling or slowing neurodegenerative conditions, employing reliable biomarkers to identify asymptomatic individuals who are destined to develop clinical Parkinson's disease (PD) is critical. Two important observations have been repeatedly found in persons who eventually develop clinical PD: (1) significant neuronal loss occurs in the substantia nigra and (2) the presence of nonmotor symptoms (NMS). Each of these findings occurs prior to the development of motor signs and symptoms, often preceding the clinical diagnosis of PD by a decade or more. As such, NMS themselves, and factors associated with their development may be useful clinical biomarkers for predicting future development of motor PD. Recently, research criteria for prodromal PD, defined as presence of motor and/or NMS, but not yet fulfilling the classic PD diagnosis, have been proposed by the International Parkinson and Movement Disorder Society Task Force. Although there are a small number of biomarkers associated with NMS of PD, in this chapter, discussion follows concerning the expanding literature associated with clinical, biochemical, imaging, and genetic biomarkers of NMS in patients with PD.