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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.


Annals Of Neurology, Volume: 68, No.: 4, Pages.: 521-534

Year of Publication



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.;

Bibtex Citation

@article{Laxton_2010, doi = {10.1002/ana.22089}, url = {}, year = 2010, month = {aug}, publisher = {Wiley-Blackwell}, volume = {68}, number = {4}, pages = {521--534}, author = {Adrian W. Laxton and David F. Tang-Wai and Mary Pat McAndrews and Dominik Zumsteg and Richard Wennberg and Ron Keren and John Wherrett and Gary Naglie and Clement Hamani and Gwenn S. Smith and Andres M. Lozano}, title = {A phase I trial of deep brain stimulation of memory circuits in Alzheimer{textquotesingle}s disease}, journal = {Annals of Neurology} }


adult, aged, aged, 80 and over, alzheimer disease, brain, brain mapping, cholinesterase inhibitors, complications, deep, deep brain stimulation, electroencephalography, etiology, female, frontal lobe, hippocampus, humans, hypothalamus, magnetic resonance imaging, male, memory disorders, methods, middle aged, neural pathways, neuropsychological tests, pathology, physiology, psychiatric status rating scales, radionuclide imaging, stimulation, therapeutic use, therapy, time factors

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Before and After Study

Type of Outcomes


Type of Interventions

Non-pharmacological Treatment

Non-Pharmaceutical Interventions