A.M.L. is a Tier 1 Canada Research Chair in Neuroscience and holds the R.R. Tasker Chair in Functional Neurosurgery at the University of Toronto. G.N. holds the Mary Trimmer Chair in Geriatric Medicine Research at the University of Toronto.
A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease†
Version of Record online: 4 AUG 2010
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 68, Issue 4, pages 521–534, October 2010
How to Cite
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. and Lozano, A. M. (2010), A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Ann Neurol., 68: 521–534. doi: 10.1002/ana.22089
- Issue online: 4 AUG 2010
- Version of Record online: 4 AUG 2010
- Manuscript Accepted: 19 MAY 2010
- Manuscript Revised: 14 MAY 2010
- Manuscript Received: 2 APR 2010
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.
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.
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.
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