The rationale for deep brain stimulation in Alzheimer’s disease

Mirzadeh, Zaman; Bari, Ausaf; Lozano, Andrés M.

doi:10.1007/s00702-015-1462-9

Cited by 30 publications

(25 citation statements)

References 60 publications

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“…This proposed therapeutic effect of brain stimulation using external modalities of stimulation is discussed below in relation to AD in six cases (one focused on diagnostics) but also one other work related to dysphagia. Finally, at the end of this section, a discussion on deep brain stimulation (DBS) applied to AD is examined [ 89 ]. DBS, although clearly not a modality of external stimulation, is certainly related to the general paradigm of brain stimulation for clinical effect and has relevance in deepening the knowledge of the area.…”

Section: Review Of Gamma Band Stimulatory and Related Studiesmentioning

confidence: 99%

“…The details in this table may aid selection of stimuli and protocols in future work in the area. Further insights into the harnessing of brain stimulation to elicit therapeutic effect is seen in the review of Mirzadeh et al relating to the use of DBS in AD [ 89 ]. AD is modelled by the authors as a neural circuit disorder (in addition to the typical neurodegenerative model) with circuits serving memory and cognition seen as having high levels of dysfunctionality.…”

Section: Review Of Gamma Band Stimulatory and Related Studiesmentioning

confidence: 99%

“…AD is modelled by the authors as a neural circuit disorder (in addition to the typical neurodegenerative model) with circuits serving memory and cognition seen as having high levels of dysfunctionality. A target for DBS was the nucleus basalis of Meynert (NBM) which features atrophy in AD with consequent effects on cholinergic innervation of areas such as the hippocampus [ 89 ]. DBS of the NBM was found to improve cognitive function in a single patient with Parkinson’s disease dementia [ 89, 112 ] but did not have a significant effect when trialed on AD patients (though some evidence of a slowing of disease progression was reported) [ 89, 113 ].…”

Section: Review Of Gamma Band Stimulatory and Related Studiesmentioning

confidence: 99%

“…A target for DBS was the nucleus basalis of Meynert (NBM) which features atrophy in AD with consequent effects on cholinergic innervation of areas such as the hippocampus [ 89 ]. DBS of the NBM was found to improve cognitive function in a single patient with Parkinson’s disease dementia [ 89, 112 ] but did not have a significant effect when trialed on AD patients (though some evidence of a slowing of disease progression was reported) [ 89, 113 ]. However, what was found, and had been noted before [ 84, 109 ] was that glucose metabolism was elevated as a result of DBS as measured by FDG-PET indicating an increase in the metabolism, and hence activity, of the neural tissue as a result of the treatment [ 89, 113 ].…”

Section: Review Of Gamma Band Stimulatory and Related Studiesmentioning

confidence: 99%

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Gamma Band Neural Stimulation in Humans and the Promise of a New Modality to Prevent and Treat Alzheimer’s Disease

McDermott

Porter

Hughes

et al. 2018

JAD

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Existing treatments for Alzheimer’s disease (AD) have questionable efficacy with a need for research into new and more effective therapies to both treat and possibly prevent the condition. This review examines a novel therapeutic modality that shows promise for treating AD based on modulating neuronal activity in the gamma frequency band through external brain stimulation. The gamma frequency band is roughly defined as being between 30 Hz-100 Hz, with the 40 Hz point being of particular significance. The epidemiology, diagnostics, existing pathological models, and related current treatment targets are initially briefly reviewed. Next, the concept of external simulation triggering brain activity in the gamma band with potential demonstration of benefit in AD is introduced with reference to a recent important study using a mouse model of the disease. The review then presents a selection of relevant studies that describe the neurophysiology involved in brain stimulation by external sources, followed by studies involving application of the modality to clinical scenarios. A table summarizing the results of clinical studies applied to AD patients is also reported and may aid future development of the modality. The use of a therapy based on modulation of gamma neuronal activity represents a novel non-invasive, non-pharmacological approach to AD. Although use in clinical scenarios is still a relatively recent area of research, the technique shows good signs of efficacy and may represent an important option for treating AD in the future.

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Section: Review Of Gamma Band Stimulatory and Related Studiesmentioning

confidence: 99%

Section: Review Of Gamma Band Stimulatory and Related Studiesmentioning

confidence: 99%

Section: Review Of Gamma Band Stimulatory and Related Studiesmentioning

confidence: 99%

Section: Review Of Gamma Band Stimulatory and Related Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Gamma Band Neural Stimulation in Humans and the Promise of a New Modality to Prevent and Treat Alzheimer’s Disease

McDermott

Porter

Hughes

et al. 2018

JAD

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“…Although a wide range of molecular targets have been identified for pharmaceutical interventions, it is also important to develop alternative nonpharmaceutical intervention strategies given the complexity of AD pathology. One of such strategies is a neuromodulation approach (Iaccarino et al, 2016;Mirzadeh et al, 2016;Senova et al, 2018;Adaikkan and Tsai, 2020).…”

Section: Introductionmentioning

confidence: 99%

Effects of optogenetic stimulation of basal forebrain parvalbumin neurons on Alzheimer’s disease pathology

Wilson

Fouda

Sakata

2020

Preprint

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Neuronal activity can modify Alzheimer's disease pathology. Although overexcitation of neurons can facilitate disease progression, the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. These beneficial effects of gamma oscillations can be caused by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or 40 Hz repetitive sensory stimuli. However, given the fact that cortical gamma oscillations can be induced by multiple mechanisms, it is still unclear whether other approaches to induce gamma oscillations can also be beneficial. Here we show that optogenetic activation of PV+ neurons in the basal forebrain (BF) increases amyloid burden, rather than reducing it. We applied 40 Hz optical stimulation in the BF of 5xFAD mice by expressing channelrhodopsin-2 (ChR2) in PV+ neurons. After one-hour induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-β42 in the frontal cortical region, but not amyloid-β40. The density of amyloid plaques also increased in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that effects of cortical gamma oscillations on Alzheimer's disease pathology can be bidirectional depending on their induction mechanisms. Significance StatementAlzheimer's disease (AD) is the most common cause of dementia. Although numerous molecular targets have been identified, the development of treatment is still a challenge. Accumulating evidence shows that artificial control of neuronal activity can modify AD pathology. In particular, the induction of cortical gamma (~40 Hz) oscillations can ameliorate AD pathology and improve cognitive functions. Here we show that optogenetic activation of parvalbumin-positive (PV+) neurons in the basal forebrain (BF) has opposite effects. By expressing channelrhodopsin-2 (ChR2) in PV+ neurons of an AD mouse model and optically stimulating BF PV+ neurons, we induced gamma oscillations Gamma oscillations and AD pathology 2 and found increased amyloid burden. These results imply that AD pathology can be modified bidirectionally depending on induction mechanisms of gamma oscillations.

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Alzheimer's disease: An evolving understanding of noradrenergic involvement and the promising future of electroceutical therapies

Slater

Wang

2021

Clinical & Translational Med

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In this review, we provide a brief overview of several of the most thoroughly researched pathogenic hypotheses for Alzheimer's disease (AD) and assess their clinical impact to-date. We focus specifically on recent research into the role of the locus coeruleus norepinephrine (LC-NE) system, in both AD pathogenesis and symptom exacerbation, as well as the potential to use advanced neural stimulation techniques as a novel therapeutic option in the earliest stages of neuropathology.

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The rationale for deep brain stimulation in Alzheimer’s disease

Cited by 30 publications

References 60 publications

Gamma Band Neural Stimulation in Humans and the Promise of a New Modality to Prevent and Treat Alzheimer’s Disease

Gamma Band Neural Stimulation in Humans and the Promise of a New Modality to Prevent and Treat Alzheimer’s Disease

Effects of optogenetic stimulation of basal forebrain parvalbumin neurons on Alzheimer’s disease pathology

Alzheimer's disease: An evolving understanding of noradrenergic involvement and the promising future of electroceutical therapies

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