88-91 Although human studies are missing, subthalamic nucleus DBS in animals has demonstrated significant neuroprotective and neuroplastic properties. Thus, the initiation of DBS earlier in the course of PD has been suggested.92 This is assumed to provide added neuroprotective benefits in addition to symptomatic relief. Currently, several studies are under way exploring the neuroprotective Inhibitors,research,lifescience,medical potential of early DBS in PD (ClinicalTrials.gov identifier: NCT00282152, NCT01274832, NCT00354133). Results from these studies will be important for the discussion of an early intervention in other diseases, for example in depression. Overall, deep brain

stimulation has contributed to a novel view of depression — away from a synaptocentric view to a conceptualization of dysfunctional brain networks for the processing of emotions.93 It has become evident that several neuropsychiatric disorders might be associated with network dysfunctions.94 Initial

studies have demonstrated a positive effect Inhibitors,research,lifescience,medical of DBS on neuroplasticity and neuroprotection. Future studies are required to explore long-term effects of DBS on neuroneogenesis and neuroprotection. Aging and dementia AD is the most common neurodegenerative disease featuring progressive impairments in memory, cognition, Inhibitors,research,lifescience,medical and behaviour, and half of the cases of dementia are caused by AD. The neurodegenerative hallmarks of AD include the accumulation amyloid-β, the deposition of amyloid plaques and the formation of neurofibrillary tangles.95 Similar to the monoamine theory on depression, the cholinergic hypothesis of dementia was proposed in 1982 by Bartus et al who believed that Inhibitors,research,lifescience,medical functional disturbances in cholinergic activity occurred in the brains of healthy older adults and demented patients.96,97

This hypothesis has been supported by positive effects of cholinesterase inhibitors on cognition in patients suffering from AD.98 Although much clinical development research Inhibitors,research,lifescience,medical on cholinergic agents has followed, the clinical effects are limited99 and no therapeutic strategy for AD has demonstrated Resveratrol long-term efficacy to date.100 Thus, new concepts and therapeutic approaches are required. The role of inflammation (eg, cytokines) and SB216763 telomerase activity, which leads to neuronal degeneration94,98 have also been suggested in the neurogenesis theory of depression. These factors lead to a dysregulation of brain networks.99 It is unclear whether amyloid-β itself by its ability to alter synaptic (glutamatergic) transmission and to impair the induction of long-term potentiation.99 A disruption of the connectivity of memory networks have been observable in early AD and asymptomatic individuals with high amyloid burden.100 Novel concepts of aging and dementia as a dysfunction of neuronal networks led to the application of deep brain stimulation in patients suffering from AD.