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Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer’s dementia

Molecular Psychiatry volume 20, pages 353–360 (2015)Cite this article

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Abstract

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer’s disease. Here we report on six patients with mild to moderate Alzheimer’s disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer’s Disease Assessment Scale—cognitive subscale as the primary outcome measure. Electroencephalography and [18F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

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Acknowledgements

This study was supported by grants from the Marga and Walter Boll foundation and Medtronic Europe SARL.

Author information

Author notes

  1. J Kuhn and K Hardenacke: Shared first authorship.

  2. H-J Freund and V Sturm: Shared senior authorship.

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany

    J Kuhn, K Hardenacke, T Gruendler, C Bartsch & J Klosterkötter

  2. Department of Functional Neurosurgery and Stereotaxy, University of Cologne, Cologne, Germany

    D Lenartz, C P Bührle & V Sturm

  3. Faculty of Economics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

    T Gruendler

  4. Center for Behavioral Brain Sciences, Magdeburg, Germany

    T Gruendler & M Ullsperger

  5. Institute of Psychology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

    M Ullsperger

  6. Department of Neuroanatomy, University of Düsseldorf, Düsseldorf, Germany

    J K Mai & H-J Freund

  7. Institute of Neuroscience and Medicine, Research Centre Juelich, Juelich, Germany

    K Zilles, A Bauer & A Matusch

  8. University Hospital of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany

    K Zilles

  9. Department of Neurology, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany

    A Bauer

  10. Department of Geriatrics and St. Marien-Hospital, University of Cologne, Cologne, Germany

    R-J Schulz & M Noreik

  11. Department for Radiology, University of Cologne, Cologne, Germany

    D Maintz

  12. University of Cologne, Research Unit Ethics, Institute for the History of Medicine and Medical Ethics, Cologne, Germany

    C Woopen

  13. Department of Gerontopsychiatry, LVR Clinic Cologne, Cologne, Germany

    P Häussermann

  14. University of Cologne, Institute of Medical Statistics, Informatics and Epidemiology, Cologne, Germany

    M Hellmich

  15. Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Göttingen, Germany

    J Wiltfang

  16. Department of Stereotaxy and Functional Neurosurgery, Klinikum Merheim, Cologne, Germany

    M Maarouf

Authors
  1. J Kuhn
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  2. K Hardenacke
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  7. J K Mai
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  9. A Bauer
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  10. A Matusch
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  15. C Woopen
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  16. P Häussermann
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  17. M Hellmich
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  18. J Klosterkötter
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  19. J Wiltfang
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  20. M Maarouf
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  21. H-J Freund
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  22. V Sturm
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Corresponding author

Correspondence to J Kuhn.

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Competing interests

Jens Kuhn has occasionally received honoraria from AstraZeneca, Lilly, Lundbeck and Otsuka Pharma for lecturing at conferences and financial support to travel. He received financial support for studies from Medtronic Europe SARL (Meerbusch, Germany).

Doris Lenartz and Juergen K. Mai received financial assistance for travel to congresses from Medtronic Europe SARL. Mohammad Maarouf has occasionally received honoraria from Medtronic Europe SARL for lecturing at conferences and consulting. Volker Sturm disclosed financial support for studies and travel to congresses, and lecture fees from Medtronic Europe SARL and Advanced Neuromodulation Systems INC. He is also a co-holder of patents on desynchronized brain stimulation and shareholder of ANM-GmbH Juelich, a company that intends to develop new stimulators.

The remaining authors declare no conflict of interest.

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Kuhn, J., Hardenacke, K., Lenartz, D. et al. Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer’s dementia. Mol Psychiatry 20, 353–360 (2015). https://doi.org/10.1038/mp.2014.32

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