Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer's Dementia: Potential Predictors of Cognitive Change and Results of a Long-Term Follow-Up in Eight Patients

Hardenacke, K.; Hashemiyoon, Rowshanak; Visser‐Vandewalle, Veerle; Zapf, Alexandra; Freund, H. J.; Sturm, Volker; Hellmich, Martin; Kuhn, Jens

doi:10.1016/j.brs.2016.05.013

Cited by 43 publications

(40 citation statements)

References 10 publications

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“…The youngest two patients with AD (P1: 63 years. ; P2: 61 years) from the former MEYND‐DBS (Kuhn et al ., ,b; Hardenacke et al ., ) cohort participated in the experiment after providing their written informed consent. Recordings took place at the University of Cologne and were approved by the local ethics committee (Otto von Guericke University Magdeburg).…”

Section: Methodsmentioning

confidence: 99%

“…At present, among pharmacological approaches to increase the cholinergic level in patients with AD, the deep brain stimulation of the NBM (NBM‐DBS) is considered to be a potential therapeutical option. The rationale of NBM‐DBS is to support residual cholinergic transmission by stabilizing oscillatory activity in memory‐relevant circuits and improves cognitive functions (Kuhn et al ., ,b; Hardenacke et al ., ). NBM‐DBS is an experimental, in selected cases therapeutically effective, non‐lesional treatment method delivering current rectangular pulses into dysfunctional brain structures via chronically implanted stimulation electrodes.…”

Section: Introductionmentioning

confidence: 97%

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Deep brain stimulation of the nucleus basalis of Meynert attenuates early EEG components associated with defective sensory gating in patients with Alzheimer disease – a two‐case study

Dürschmid

Reichert

Kuhn

et al. 2017

Eur J of Neuroscience

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Alzheimer's disease (AD) is associated with deterioration of memory and cognitive function and a degeneration of neurons of the nucleus basalis of Meynert (NBM). The NBM is the major input source of acetylcholine (ACh) to the cortex. The decreasing cholinergic innervation of the cortex due to degeneration of the NBM might be the cause of loss of memory function. NBM-Deep brain stimulation (NBM-DBS) is considered to serve as a potential therapeutic option for patients with AD by supporting residual cholinergic transmission to stabilize oscillatory activity in memory-relevant circuits. However, whether DBS could improve sensory memory functions in patients with AD is not clear. Here, in a passive auditory oddball paradigm, patients with AD (N = 2) listened to repetitive background tones (standard tones) randomly interrupted by frequency deviants in two blocks with NBM-DBS OFF and then NBM-DBS ON, while age-matched healthy controls (N = 6) repeated the experiment twice. The mismatch negativity in NBM-DBS OFF significantly differed from controls in both blocks, but not under NBM-DBS, which was likely due to a pronounced P50 increase overlapping with the N1 in NBM-DBS OFF. This early complex of EEG components recovered under stimulation to a normal level as defined by responses in controls. In this temporal interval, we found in patients with NBM-DBS ON (but not with NBM-DBS OFF) and in controls a strong repetition suppression effect to standard tones - with more attenuated responses to frequently repeated standard tones. This highlights the role of NBM-DBS for sensory gating of familiar auditory information into sensory memory.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Deep brain stimulation of the nucleus basalis of Meynert attenuates early EEG components associated with defective sensory gating in patients with Alzheimer disease – a two‐case study

Dürschmid

Reichert

Kuhn

et al. 2017

Eur J of Neuroscience

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“…One participant deteriorated after 26 months based on ADAS-Cog and MMSE scores, whereas the other participant had a stable ADAS-Cog and even improved MMSE score after 28 months. Hardenacke et al [33] then collated the results of the Phase I trial [4] and that of the two new patients [5] and suggested that NBM-DBS performed at a younger age and at an earlier disease stage may favorably impact cognitive functions and disease progression.…”

Section: Clinical Studies On Deep Brain Stimulation For Admentioning

confidence: 99%

“…The inclusion of patients with CDR, MMSE, and ADS-Cog 11 scores that already signify cognitive decline beyond the mild cognitive impairment stage [44] and at the start of the dementia phase warrants serious consideration when patients with EOAD are included in a study, given EOAD's more aggressive disease course [16]. Considering the initial results of Laxton et al [1] and Hardenacke et al [33] showing that patients in an earlier disease stage are more likely to benefit from DBS, there is a need to modify the cognitive status cut-offs for participants <65 participating in DBS for EOAD studies. EOAD patients that have a CDR score >0.5, MMSE score <23, and ADAS-Cog 11 score >18 [45], and possess mutations predisposing them to more aggressive cognitive deterioration [22,23] should not be included in DBS studies unless more evidence has been gathered regarding the efficacy of DBS in later AD stages.…”

Section: Considerations For Patient Selectionmentioning

confidence: 99%

Ethical Considerations for Deep Brain Stimulation Trials in Patients with Early-Onset Alzheimer’s Disease

Viaña

Bittlinger

Gilbert

2017

JAD

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Several studies of deep brain stimulation (DBS) of the fornix or the nucleus basalis of Meynert have been recently conducted in people with Alzheimer's disease, with several recruiting participants <65 and thus have early-onset Alzheimer's disease (EOAD). Although EOAD accounts for less than 5.5% of AD cases, ethical considerations must still be made when performing DBS trials including these participants since a portion of people with EOAD, especially those possessing autosomal-dominant mutations, have an atypical and more aggressive disease progression. These considerations include appropriate patient selection and signing of an informed consent for genetic testing; appropriate study design; potential outcomes that people with EOAD could expect; and accurate interpretation and balanced discussion of trial results. Finally, recommendations for future DBS for AD trials will be made to ensure that EOAD patients will not experience avoidable harms should they be enrolled in these experimental studies.

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“…Stimulation of each special region is efficient in the treatment of special diseases. For example, stimulation of internal capsules [7], nucleus accumbens [8], [9], nucleus basalis of Meynert [10], caudate nucleus [11] and Cingulum [12] is efficient in treatment of obsessive-compulsive disorder (OCD), disorder-major depression, Alzheimer, and chronic neuropathic pain. The need of surgery and difficulty of exerting E-field in this method, are two major deficiencies that cause to effort of using TMS method for non-invasive stimulation of the deep regions too [13].…”

Section: ) Introductionmentioning

confidence: 99%

A Novel Approach on dTMS Coil Design Based on Tractography and Neural Cable Theory

Am¹,

Abdolali²

2019

Preprint

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Deep transcranial magnetic stimulation (dTMS) plays a useful role in the treatment of many diseases. In previous designs, it is only desired to maximize the absolute value of the electric field in the target zone. Whereas due to the nerve cable equation (NCE), the membrane potential of a nerve cell is changed due to the rate of change in the tangential electric field ( ̅ l/ ). In this paper, the criterion of the design is to maximize ̅ l/ along the nerve cell fiber and simultaneously minimize the absolute value of the electric field. The direction of the nerve fibers is obtained using Tractography. Then, the specifications of source and coils such as position and spatial angles are determined in such a way that every two coils cancel the absolute value of the electric field of each other by using reciprocity theorem. This happened whereas the ̅ l/ is maximized. For better comparison, a 20-coil array is designed for stimulation of cingulum region of the brain. Results of this array are compared with results of the FO8-Halo coil and it is shown that with the same value for ̅ l/ , an absolute value of the induced field in the brain for the 20-coil array is much smaller than the FO8-Halo coil. Also, designed coil array requires smaller sources. So, the array can stimulate the target zone more accurately and with higher efficiency. This new technique can solve the problem of stimulation of the large areas of the brain and stimulate the desired target zone with more accuracy.

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Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer's Dementia: Potential Predictors of Cognitive Change and Results of a Long-Term Follow-Up in Eight Patients

Cited by 43 publications

References 10 publications

Deep brain stimulation of the nucleus basalis of Meynert attenuates early EEG components associated with defective sensory gating in patients with Alzheimer disease – a two‐case study

Deep brain stimulation of the nucleus basalis of Meynert attenuates early EEG components associated with defective sensory gating in patients with Alzheimer disease – a two‐case study

Ethical Considerations for Deep Brain Stimulation Trials in Patients with Early-Onset Alzheimer’s Disease

A Novel Approach on dTMS Coil Design Based on Tractography and Neural Cable Theory

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