Introduction: The neuro-anatomical and neurochemical substrates underlying most of the non-motor symptoms (NMS) of Parkinson's disease (PD) are not understood in depth.
Aim: To review the current knowledge on the pathophysiology of the different NMS of PD based on recent studies.
Development: In most of the NMS the pathophysiological foundation is complex. In addition to the dopaminergic dysfunction, the degeneration of non-dopaminergic (i.e. noradrenergic, serotoninergic and cholinergic) cellular systems is thought to underlie the development of most of the NMS and can be applied in dementia, depression, sleep disorders and vegetative disorders. Dementia, moreover, is essentially caused by different alterations that take place with the cerebral cortex. Dysfunction of the ventral striatum and of the mesolimbic projections exerts a crucial influence in impulsive-compulsive spectrum disorder. Loss of the sense of smell appears to be due to the neuronal degeneration of the olfactory bulb and the pain has an extremely varied pathogenetic basis and may be musculoskeletal, dystonic, radicular or central.
Conclusions: Despite the fact that a huge amount of progress has been made in research on the pathophysiology of the NMS of PD, further clinicopathological and pathobiochemical comparative studies are needed to explain the pathophysiological bases of PD and to provide a broader foundation for future therapeutic strategies to treat NMS.