The neuroprotective effect of deep brain stimulation at nucleus basalis of Meynert in transgenic mice with Alzheimer's disease

2019 ◽  
Vol 12 (1) ◽  
pp. 161-174 ◽  
Author(s):  
Chuyi Huang ◽  
Heling Chu ◽  
Yu Ma ◽  
Zaiying Zhou ◽  
Chuanfu Dai ◽  
...  
2021 ◽  
pp. 1-18
Author(s):  
Yu-si Chen ◽  
Kai Shu ◽  
Hui-cong Kang

Alzheimer’s disease (AD) is becoming a prevalent disease in the elderly population. Past decades have witnessed the development of drug therapies with varying targets. However, all drugs with a single molecular target fail to reverse or ameliorate AD progression, which ultimately results in cortical and subcortical network dysregulation. Deep brain stimulation (DBS) has been proven effective for the treatment of Parkinson’s disease, essential tremor, and other neurological diseases. As such, DBS has also been gradually acknowledged as a potential therapy for AD. The current review focuses on DBS of the nucleus basalis of Meynert (NBM). As a critical component of the cerebral cholinergic system and the Papez circuit in the basal ganglia, the NBM plays an indispensable role in the subcortical regulation of memory, attention, and arousal state, which makes the NBM a promising target for modulation of neural network dysfunction and AD treatment. We summarized the intricate projection relations and functionality of the NBM, current approaches for stereotactic localization and evaluation of the NBM, and the therapeutic effects of NBM-DBS both in patients and animal models. Furthermore, the current shortcomings of NBM-DBS, such as variations in cortical blood flow, increased temperature in the target area, and stimulation-related neural damage, were presented.


2021 ◽  
Vol 15 ◽  
Author(s):  
Wei Zhang ◽  
Wei Liu ◽  
Bhavana Patel ◽  
Yingchuan Chen ◽  
Kailiang Wang ◽  
...  

Patients with advanced Alzheimer's disease (AD) experience cognitive impairment and physical disabilities in daily life. Currently, there are no treatments available to slow down the course of the disease, and limited treatments exist only to treat symptoms. However, deep brain stimulation of the nucleus basalis of Meynert (NBM-DBS) has been reported to improve cognitive function in individuals with AD. Here, we report the effects of NBM-DBS on cognitive function in a subject with severe AD. An 80-year-old male with severe AD (Clinical Dementia Rating scale: 3.0 points) underwent surgery for bilateral NBM-DBS electrode placement. After 10 weeks of stimulation, Mini-Mental State Examination (MMSE) assessment improved from a score of 5 to 9 points, and assessment using the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-cog) showed a marked reduction in total score from 43 to 33 points, suggesting cognitive benefits from NBM-DBS. The patient's postoperative course was complicated by a subdural effusion that occurred several days after surgery, with complete recovery. Interestingly, the subject also displayed abnormal thermoregulation with stimulation initiation and stimulation parameter modifications. NBM-DBS may serve as a potential therapy for severe AD patients.Clinical Trial Registration: ChiCTR1900022324.


2019 ◽  
Author(s):  
Philippos Koulousakis ◽  
Daniel van den Hove ◽  
Veerle Visser-Vandewalle ◽  
Thibaut Sesia

AbstractBackgroundDeep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has shown to have promising results in a pilot study with patients suffering from Alzheimer’s disease (AD). A recent study in aged monkeys shows a novel intermittent stimulation pattern to have superior cognitive benefits over continuous paradigms.Objective/HypothesisWe aimed at comparing the cognitive effects elicited by intermittent and continuous NBM stimulation paradigms in an animal model for AD (TgF344-AD rat line; TG), i.e. rats expressing mutant human amyloid precursor protein (APPsw) and presenilin 1 (PS1ΔE9) genes, each independent causes of early-onset familial AD.MethodsIn this exploratory study, aged APP/PS1 rats were tested pre-, and post implantation with several stimulation parameters, i.e. unilateral- or bilateral-intermittent, and bilateral-continuous, while performing various behavioral tasks (open field, novel object recognition, and modified Barnes maze).Results and ConclusionBilateral-intermittent NBM DBS allowed aged TG rats to perform better and maintain their performance longer in a spatial memory task, as compared to other conditions. These data support the notion that NBM DBS could be further refined in the clinic, thereby improving patient care.


2021 ◽  
pp. 1-13
Author(s):  
Saravanan Subramaniam ◽  
David T. Blake ◽  
Christos Constantinidis

Memory and cognitive impairment as sequelae of neurodegeneration in Alzheimer’s disease and age-related dementia are major health issues with increasing social and economic burden. Deep brain stimulation (DBS) has emerged as a potential treatment to slow or halt progression of the disease state. The selection of stimulation target is critical, and structures that have been targeted for memory and cognitive enhancement include the Papez circuit, structures projecting to the frontal lobe such as the ventral internal capsule, and the cholinergic forebrain. Recent human clinical and animal model results imply that DBS of the nucleus basalis of Meynert can induce a therapeutic modulation of neuronal activity. Benefits include enhanced activity across the cortical mantle, and potential for amelioration of neuropathological mechanisms associated with Alzheimer’s disease. The choice of stimulation parameters is also critical. High-frequency, continuous stimulation is used for movement disorders as a way of inhibiting their output; however, no overexcitation has been hypothesized in Alzheimer’s disease and lower stimulation frequency or intermittent patterns of stimulation (periods of stimulation interleaved with periods of no stimulation) are likely to be more effective for stimulation of the cholinergic forebrain. Efficacy and long-term tolerance in human patients remain open questions, though the cumulative experience gained by DBS for movement disorders provides assurance for the safety of the procedure.


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