A Phase I Trial of Deep Brain Stimulation of Memory Circuits in Alzheimer's Disease

被引：556

作者：

Laxton, Adrian W. ^{[1
]}

Tang-Wai, David F. ^{[2
,5
]}

McAndrews, Mary Pat ^{[3
]}

Zumsteg, Dominik ^{[4
]}

Wennberg, Richard ^{[5
]}

Keren, Ron ^{[2
]}

Wherrett, John ^{[2
,5
]}

Naglie, Gary ^{[2
]}

Hamani, Clement ^{[2
]}

Smith, Gwenn S. ^{[6
]}

Lozano, Andres M. ^{[1
]}

机构：

[1] Toronto Western Hosp, Div Neurosurg, Toronto, ON M5T 2S8, Canada

[2] Toronto Western Hosp, Univ Hlth Network Memory Clin, Toronto, ON M5T 2S8, Canada

[3] Toronto Western Hosp, Dept Psychol, Toronto, ON M5T 2S8, Canada

[4] Univ Zurich, Div Neurol, Zurich, Switzerland

[5] Univ Toronto, Toronto Western Hosp, Div Neurol, Toronto, ON M5T 2S8, Canada

[6] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA

来源：

ANNALS OF NEUROLOGY | 2010年 / 68卷 / 04期

关键词：

GLOBUS-PALLIDUS STIMULATION; LONGITUDINAL PET EVALUATION; AMYLOID DEPOSITION; DEFAULT NETWORK; FOLLOW-UP; IMPAIRMENT; SYSTEM; CORTEX; POPULATION; DEMENTIA;

D O I：

10.1002/ana.22089

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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;68:521-534

引用

页码：521 / 534

页数：14

共 63 条

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