ABSTRACTBackgroundCurrent evidence suggests that there is a prodromal stage in Parkinson disease characterized by a variety of nonmotor symptoms.Methods and ResultsA 69‐year‐old man presented to our sleep center with isolated rapid eye movement sleep behavior disorder. During a 10‐year follow‐up period, longitudinal clinical and laboratory assessments indicated the development of hyposmia, depression, mild cognitive impairment, and constipation. Parkinsonism was absent, but dopamine transporter imaging showed subclinical substantia nigra damage. Postmortem examination demonstrated neuronal loss and Lewy body pathology in the peripheral autonomic nervous system (eg, cardiac and myenteric plexus), olfactory bulb, medulla, pons, substantia nigra pars compacta (estimated cell loss, 20%‐30%), nucleus basalis of Meynert, and amygdala, sparing the neocortex.ConclusionsOur observations indicate that nonmotor symptoms plus widespread peripheral and central nervous system pathological changes occur before parkinsonism and dementia onset in diseases associated with Lewy pathology. The current diagnostic criteria for Parkinson's disease miss these patients, who present only with nonmotor symptoms. © 2014 International Parkinson and Movement Disorder Society