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A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease

Laxton, Adrian W., Tang‐Wai, David F., McAndrews, Mary Pat, Zumsteg, Dominik, Wennberg, Richard, Keren, Ron, Wherrett, John, Naglie, Gary, Hamani, Clement, Smith, Gwenn S., Lozano, Andres M.·2010·Annals of Neurology

Abstract

Objective: Alzheimer disease (AD) is characterized by functional impairment in the neural elements and circuits underlying cognitive and memory functions. We hypothesized that fornix/hypothalamus deep brain stimulation (DBS) could modulate neurophysiological activity in these pathological circuits and possibly produce clinical benefits. Methods: We conducted a phase I trial in 6 patients with mild AD receiving ongoing medication treatment. Patients received continuous stimulation for 12 months. Three main lines of investigation were pursued including: (1) mapping the brain areas whose physiological function was modulated by stimulation using standardized low‐resolution electromagnetic tomography, (2) assessing whether DBS could correct the regional alterations in cerebral glucose metabolism in AD using positron emission tomography (PET), and 3) measuring the effects of DBS on cognitive function over time using clinical scales and instruments. Results: DBS drove neural activity in the memory circuit, including the entorhinal, and hippocampal areas and activated the brain's default mode network. PET scans showed an early and striking reversal of the impaired glucose utilization in the temporal and parietal lobes that was maintained after 12 months of continuous stimulation. Evaluation of the Alzheimer's Disease Assessment Scale cognitive subscale and the Mini Mental State Examination suggested possible improvements and/or slowing in the rate of cognitive decline at 6 and 12 months in some patients. There were no serious adverse events. Interpretation: There is an urgent need for novel therapeutic approaches for AD. Modulating pathological brain activity in this illness with DBS merits further investigation. Ann Neurol 2010

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Metadata

Authors
Laxton, A. W., Tang‐Wai, D. F., McAndrews, M. P., Zumsteg, D., Wennberg, R., Keren, R., Wherrett, J., Naglie, G., Hamani, C., Smith, G. S., & Lozano, A. M.
Venue
Annals of Neurology
Publisher
Wiley
Published
2010-08-04
Volume
68
Issue
4
Pages
521-534
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
OpenAlex
W2096577216
Cited by
812
References
25
FWCI
30.74
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. https://app.cochat.ai/papers/10.1002/ana.22089
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Laxton, A. W., Tang‐Wai, D. F., McAndrews, M. P., Zumsteg, D., Wennberg, R., Keren, R., Wherrett, J., Naglie, G., Hamani, C., Smith, G. S., & Lozano, A. M. (2010). A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Annals of Neurology. https://doi.org/10.1002/ana.22089

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