Deep brain stimulation influences brain structure in Alzheimer's disease

Tejas Sankar, M. Mallar Chakravarty, Agustin Bescos, Monica Lara, Toshiki Obuchi, Adrian W. Laxton, Mary Pat McAndrews, David F. Tang-Wai, Clifford I. Workman, Gwenn Smith, Andres M. Lozano

Research output: Contribution to journalArticle

Abstract

Background: Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder. Objective/Hypothesis: We hypothesized that DBS applied to the fornix in patients with Alzheimer's Disease (AD) could have an effect on brain structure. Methods: In six AD patients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism.We also compared volumetric changes to those in an age-, sex-, and severity-matched group of AD patients (n = 25) not receiving DBS. Results: We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophywas significantly slower in the DBS group compared to the matched AD group, and no matched AD patients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD. Conclusion:We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease.

Original languageEnglish (US)
Pages (from-to)645-654
Number of pages10
JournalBrain Stimulation
Volume8
Issue number3
DOIs
StatePublished - 2015

Fingerprint

Deep Brain Stimulation
Alzheimer Disease
Brain
Brain Fornix
Mammillary Bodies
Research Design
Nervous System Diseases
Neurodegenerative Diseases
Atrophy
Glucose

Keywords

  • Alzheimer's disease
  • Deep brain stimulation
  • Fornix
  • Hippocampus
  • MRI
  • Volume

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Biophysics
  • Medicine(all)

Cite this

Sankar, T., Chakravarty, M. M., Bescos, A., Lara, M., Obuchi, T., Laxton, A. W., ... Lozano, A. M. (2015). Deep brain stimulation influences brain structure in Alzheimer's disease. Brain Stimulation, 8(3), 645-654. https://doi.org/10.1016/j.brs.2014.11.020

Deep brain stimulation influences brain structure in Alzheimer's disease. / Sankar, Tejas; Chakravarty, M. Mallar; Bescos, Agustin; Lara, Monica; Obuchi, Toshiki; Laxton, Adrian W.; McAndrews, Mary Pat; Tang-Wai, David F.; Workman, Clifford I.; Smith, Gwenn; Lozano, Andres M.

In: Brain Stimulation, Vol. 8, No. 3, 2015, p. 645-654.

Research output: Contribution to journalArticle

Sankar, T, Chakravarty, MM, Bescos, A, Lara, M, Obuchi, T, Laxton, AW, McAndrews, MP, Tang-Wai, DF, Workman, CI, Smith, G & Lozano, AM 2015, 'Deep brain stimulation influences brain structure in Alzheimer's disease', Brain Stimulation, vol. 8, no. 3, pp. 645-654. https://doi.org/10.1016/j.brs.2014.11.020
Sankar T, Chakravarty MM, Bescos A, Lara M, Obuchi T, Laxton AW et al. Deep brain stimulation influences brain structure in Alzheimer's disease. Brain Stimulation. 2015;8(3):645-654. https://doi.org/10.1016/j.brs.2014.11.020
Sankar, Tejas ; Chakravarty, M. Mallar ; Bescos, Agustin ; Lara, Monica ; Obuchi, Toshiki ; Laxton, Adrian W. ; McAndrews, Mary Pat ; Tang-Wai, David F. ; Workman, Clifford I. ; Smith, Gwenn ; Lozano, Andres M. / Deep brain stimulation influences brain structure in Alzheimer's disease. In: Brain Stimulation. 2015 ; Vol. 8, No. 3. pp. 645-654.
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AU - Bescos, Agustin

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AU - Laxton, Adrian W.

AU - McAndrews, Mary Pat

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N2 - Background: Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder. Objective/Hypothesis: We hypothesized that DBS applied to the fornix in patients with Alzheimer's Disease (AD) could have an effect on brain structure. Methods: In six AD patients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism.We also compared volumetric changes to those in an age-, sex-, and severity-matched group of AD patients (n = 25) not receiving DBS. Results: We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophywas significantly slower in the DBS group compared to the matched AD group, and no matched AD patients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD. Conclusion:We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease.

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