Deep brain stimulation of the nucleus basalis of Meynert modulates hippocampal-frontoparietal networks in patients with advanced Alzheimer’s disease

Background:Deep brain stimulation(DBS)of the nucleus basalis of Meynert(NBM)has shown potential for the treatment of mild-to-moderate Alzheimer’s disease(AD).However,there is little evidence of whether NBM-DBS can improve cognitive functioning in patients with advanced AD.In addition,the mechanisms underlying the modulation of brain networks remain unclear.This study was aimed to assess the cognitive function and the resting-state connectivity following NBM-DBS in patients with advanced AD.Methods:Eight patients with advanced AD underwent bilateral NBM-DBS and were followed up for 12 months.Clinical outcomes were assessed by neuropsychological examinations using the Mini-Mental State Examination(MMSE)and Alzheimer’s Disease Assessment Scale.Resting-state functional magnetic resonance imaging and positron emis-sion tomography data were also collected.Results:The cognitive functioning of AD patients did not change from baseline to the 12-month follow-up.Interestingly,the MMSE score indicated clinical efficacy at 1 month of follow-up.At this time point,the connectivity between the hippocampal network and frontoparietal network tended to increase in the DBS-on state compared to the DBS-off state.Additionally,the increased functional connectivity between the parahippocampal gyrus(PHG)and the parietal cortex was associated with cognitive improvement.Further dynamic functional network analysis showed that NBM-DBS increased the proportion of the PHG-related connections,which was related to improved cognitive performance.Conclusion:The results indicated that NBM-DBS improves short-term cognitive performance in patients with advanced AD,which may be related to the modulation of multi-network connectivity patterns,and the hippocampus plays an important role within these networks.

Transplantation of cholinergic neural stem cells in a mouse model of (Alzheimer’s) disease

It is believed that the degeneration of cholinergic cells in the nucleus basalis of Meynert (NBM) and the loss of cortical cholinergic innervation (cause dementia) of Alzheimer’s disease (AD).~1 (Currently available) therapeutic interventions are mainly aimed at alleviating the cholinergic deficits. Unfortunately, these strategies do not prevent the disease, but instead offer limited symptomatic improvement.~2 A recent study demonstrated that transplantation of in vitro expanded neural stem cells (NSCs) in an animal model of Parkinson’s disease (PD) resulted in functional recovery of the animals to some extent,~2 suggesting that such neural precursors might offer a useful future therapy for AD. In this study, we tried to find whether mouse embryonic stem (ES) cell derived cholinergic NSCs grafted in the prefrontal and parietal cortex have effects on the disruption of spatial memory following development of lesion in NBM.