Background: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is an emerging target to potentially treat cognitive dysfunction. Objectives: The aim of this study is to achieve feasibility and safety of globus pallidus pars interna (GPi) and NBM DBS in advanced PD with cognitive impairment. Methods: We performed a phase-II double-blind crossover pilot trial in six participants to assess safety and cognitive measures, the acute effect of NBM stimulation on attention, motor and neuropsychological data at one year, and neuroimaging biomarkers of NBM stimulation. Results: NBM DBS was well tolerated but did not improve cognition. GPi DBS improved dyskinesia and motor fluctuations (P = 0.04) at one year. NBM stimulation was associated with reduced right frontal and parietal glucose metabolism (P < 0.01) and increased low-and high-frequency power and functional connectivity. Volume of tissue activated in the left NBM was associated with stable cognition (P < 0.05). Conclusions: Simultaneous GPi and NBM stimulation is safe and improves motor complications. NBM stimulation altered neuroimaging biomarkers but without lasting cognitive improvement.
Parkinson’s disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) “Parkinson disease”; “Delirium,” “Dementia,” “Amnestic,” “Cognitive disorders,” and “Parkinson disease”; “depression,” “major depressive disorder,” “drug therapy.” We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs.
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