Nonmotor Symptoms and Natural History of Parkinson's Disease: Evidence From Cognitive Dysfunction and Role of Noninvasive Interventions

Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor and nonmotor symptoms (NMS). Several subsequent studies substantiate the great functional burden related to NMS, their progression, and negative effect on quality of life in PD. Additional evidence indicates interesting relationships between striatal dopaminergic function and NMS. The basal ganglia are implicated in the modulation and integration of sensory information and pain, bladder function is under control of both inhibitory (D1) and facilitatory (D2) dopaminergic inputs, finally reduced dopaminergic activity in the mesocortical and mesolimbic pathways is involved in the development of several NMS including mood, motivational, and cognitive alterations. Some NMS fluctuate in response to dopaminergic treatment and are relieved by dopamine replacement therapy, other are insensitive to current therapeutic strategies. The relation among the overall disease complications, perhaps the most important for PD patients and family members\u2019 well-being and functionality is dementia that affects most PD patients over the course of disease. Specific pharmacological treatment is lacking, and alternative approaches have been implemented to improve everyday functionality and quality of life. The state of the art suggests that cognitive rehabilitation in PD is possible and may either increase performance or preserve cognitive level over the time. However, it is also evident that cognitive abnormalities in PD are heterogeneous and we still do not have biomarkers to detect early patients at risk for dementia. Cognitive dysfunction is one the most prevalent NMS and is a clinically and functionally important disease milestone. Given the available clinical and imaging evidence it is possible to use cognition to model NMS progression and design nonpharmacological interventions. In this chapter we will address the use of cognitive rehabilitation and noninvasive brain stimulation techniques to modulate cognitive performance and rescue connectivity in affected brain circuitry