Serendipitous Stimulation of Nucleus Basalis of Meynert—The Effect of Unintentional, Long-Term High-Frequency Stimulation on Cognition in Parkinson’s Disease

Bogdan, I Daria; Oterdoom, D L Marinus; Laar, Teus van; Huitema, Rients B.; Odekerken, Vincent J.J.; Boel, Judith A.; Bie, Rob M.A. de; Dijk, J. Marc C. van; Group, On Behalf Of The Nstaps Study

doi:10.3390/jcm11020337

Cited by 4 publications

(3 citation statements)

References 38 publications

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“… 40 If so, cell grafting designed to restore the cholinergic innervation to these cortical regions will ultimately fail. Such cortical changes could explain why the clinical response to cholinesterase inhibitors is so variable 41 and may also explain why attempts to use deep brain stimulation to stimulate the BF cholinergic neurons to improve cognition so far have failed to yield consistent long-term benefits, 42 , 43 possibly because of early synaptic loss in the BF cholinergic system preventing it from being able to induce an increase in acetylcholine release. Nevertheless, the experience gained from the successful use of cholinesterase inhibitors to treat some of the PD-related cognitive impairments 44 provides support for the idea that transplant-induced restoration of cholinergic transmission can be beneficial and lead to a change in the natural history of PD by alleviating its cognitive problems, albeit without curing it.…”

Section: Role Of the Basal Forebrain Cholinergic System In Parkinson’...mentioning

confidence: 99%

The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease

Björklund,

Barker

2024

Brain

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In recent years there has been a renewed interest in the basal forebrain (BF) cholinergic system as a target for the treatment of cognitive impairments in patients with Parkinson´s disease (PD), due in part to the need to explore novel approaches to treat the cognitive symptoms of the disease, and in part to the development of more refined imaging tools that have made it possible to monitor the progressive changes in the structure and function of the BF system as they evolve over time. In parallel, emerging technologies allowing the derivation of authentic BF cholinergic neurons from human pluripotent stem cells are providing new powerful tools for the exploration of cholinergic neuron replacement in animal models of PD-like cognitive decline. In this review, we discuss the rationale for cholinergic cell replacement as a potential therapeutic strategy in PD and how this approach can be explored in rodent models of PD-like cognitive decline, building on insights gained from the extensive animal experimental work that was performed in rodent and primate models in the 1980s and 90 s. Although therapies targeting the cholinergic system has so far been focused mainly on patients with Alzheimer´s disease, PD with dementia may be a more relevant condition. In PD with dementia the BF system undergoes progressive degeneration, and the magnitude of cholinergic cell loss has been shown to correlate with the level of cognitive impairment. Thus, cell therapy aimed to replace the lost BF cholinergic neurons represents an interesting strategy to combat some of the major cognitive impairments in patients with PD dementia.

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Section: Role Of the Basal Forebrain Cholinergic System In Parkinson’...mentioning

confidence: 99%

The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease

Björklund,

Barker

2024

Brain

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“…In a few recent studies ( Table 1 ), human patients were implanted with electrodes that allowed stimulation of the nucleus basalis of Meynert, among other targets [ 76 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ]. Implantation and stimulation pulses in the range of 20 Hz (and higher) were safe and well tolerated, and adverse effects were comparable to those of movement disorders.…”

Section: Potential For Human Interventionmentioning

confidence: 99%

“…Human clinical studies targeting the nucleus basalis of Meynert (NB)[76,[113][114][115][116][117][118][119][120].…”

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confidence: 99%

Improving Visual Working Memory with Cholinergic Deep Brain Stimulation

et al. 2023

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Acetylcholine is a critical modulatory neurotransmitter for cognitive function. Cholinergic drugs improve cognitive performance and enhance neuronal activity in the sensory and association cortices. An alternative means of improving cognitive function is through the use of deep brain stimulation. Prior animal studies have demonstrated that stimulation of the nucleus basalis of Meynert through DBS improves cognitive performance on a visual working memory task to the same degree as cholinesterase inhibitors. Additionally, unlike current pharmacological treatments for neurocognitive disorders, DBS does not lose efficacy over time and adverse effects are rare. These findings suggest that DBS may be a promising alternative for treating cognitive impairments in neurodegenerative disorders such as Alzheimer’s disease. Thus, further research and human trials should be considered to assess the potential of DBS as a therapeutic treatment for these disorders.

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Cholinergic Basal Forebrain Integrity and Cognition in Parkinson's Disease: A Reappraisal of Magnetic Resonance Imaging Evidence

Slater,

Melzer,

Myall

et al. 2024

Movement Disorders

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Cognitive impairment is a well‐recognized and debilitating symptom of Parkinson's disease (PD). Degradation in the cortical cholinergic system is thought to be a key contributor. Both postmortem and in vivo cholinergic positron emission tomography (PET) studies have provided valuable evidence of cholinergic system changes in PD, which are pronounced in PD dementia (PDD). A growing body of literature has employed magnetic resonance imaging (MRI), a noninvasive, more cost‐effective alternative to PET, to examine cholinergic system structural changes in PD. This review provides a comprehensive discussion of the methodologies and findings of studies that have focused on the relationship between cholinergic basal forebrain (cBF) integrity, based on T1‐ and diffusion‐weighted MRI, and cognitive function in PD. Nucleus basalis of Meynert (Ch4) volume has been consistently reduced in cognitively impaired PD samples and has shown potential utility as a prognostic indicator for future cognitive decline. However, the extent of structural changes in Ch4, especially in early stages of cognitive decline in PD, remains unclear. In addition, evidence for structural change in anterior cBF regions in PD has not been well established. This review underscores the importance of continued cross‐sectional and longitudinal research to elucidate the role of cholinergic dysfunction in the cognitive manifestations of PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Serendipitous Stimulation of Nucleus Basalis of Meynert—The Effect of Unintentional, Long-Term High-Frequency Stimulation on Cognition in Parkinson’s Disease

Cited by 4 publications

References 38 publications

The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease

The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease

Improving Visual Working Memory with Cholinergic Deep Brain Stimulation

Cholinergic Basal Forebrain Integrity and Cognition in Parkinson's Disease: A Reappraisal of Magnetic Resonance Imaging Evidence

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