A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease
Identifieur interne : 000836 ( Main/Exploration ); précédent : 000835; suivant : 000837A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease
Auteurs : Adrian W. Laxton [Canada] ; David F. Tang-Wai [Canada] ; Mary Pat Mcandrews [Canada] ; Dominik Zumsteg [Suisse] ; Richard Wennberg [Canada] ; Ron Keren [Canada] ; John Wherrett [Canada] ; Gary Naglie [Canada] ; Clement Hamani [Canada] ; Gwenn S. Smith [États-Unis] ; Andres M. Lozano [Canada]Source :
- Annals of Neurology [ 0364-5134 ] ; 2010-10.
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
Url:
DOI: 10.1002/ana.22089
Affiliations:
- Canada, Suisse, États-Unis
- Canton de Zurich, Maryland, Ontario
- Toronto, Zurich
- Université de Toronto, Université de Zurich
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Smith</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Psychiatry, John Hopkins University, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name><affiliation wicri:level="4"><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurosurgery, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-10">2010-10</date><biblScope unit="volume">68</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="521">521</biblScope><biblScope unit="page" to="534">534</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">D5AB9FE76587154004A039ACD27CF7D5098FB88D</idno><idno type="DOI">10.1002/ana.22089</idno><idno type="ArticleID">ANA22089</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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</div></front></TEI><affiliations><list><country><li>Canada</li><li>Suisse</li><li>États-Unis</li></country><region><li>Canton de Zurich</li><li>Maryland</li><li>Ontario</li></region><settlement><li>Toronto</li><li>Zurich</li></settlement><orgName><li>Université de Toronto</li><li>Université de Zurich</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Laxton, Adrian W" sort="Laxton, Adrian W" uniqKey="Laxton A" first="Adrian W." last="Laxton">Adrian W. Laxton</name></region><name sortKey="Hamani, Clement" sort="Hamani, Clement" uniqKey="Hamani C" first="Clement" last="Hamani">Clement Hamani</name><name sortKey="Keren, Ron" sort="Keren, Ron" uniqKey="Keren R" first="Ron" last="Keren">Ron Keren</name><name sortKey="Lozano, Andres M" sort="Lozano, Andres M" uniqKey="Lozano A" first="Andres M." last="Lozano">Andres M. Lozano</name><name sortKey="Mcandrews, Mary Pat" sort="Mcandrews, Mary Pat" uniqKey="Mcandrews M" first="Mary Pat" last="Mcandrews">Mary Pat Mcandrews</name><name sortKey="Naglie, Gary" sort="Naglie, Gary" uniqKey="Naglie G" first="Gary" last="Naglie">Gary Naglie</name><name sortKey="Tang Ai, David F" sort="Tang Ai, David F" uniqKey="Tang Ai D" first="David F." last="Tang-Wai">David F. Tang-Wai</name><name sortKey="Tang Ai, David F" sort="Tang Ai, David F" uniqKey="Tang Ai D" first="David F." last="Tang-Wai">David F. Tang-Wai</name><name sortKey="Wennberg, Richard" sort="Wennberg, Richard" uniqKey="Wennberg R" first="Richard" last="Wennberg">Richard Wennberg</name><name sortKey="Wherrett, John" sort="Wherrett, John" uniqKey="Wherrett J" first="John" last="Wherrett">John Wherrett</name><name sortKey="Wherrett, John" sort="Wherrett, John" uniqKey="Wherrett J" first="John" last="Wherrett">John Wherrett</name></country><country name="Suisse"><region name="Canton de Zurich"><name sortKey="Zumsteg, Dominik" sort="Zumsteg, Dominik" uniqKey="Zumsteg D" first="Dominik" last="Zumsteg">Dominik Zumsteg</name></region></country><country name="États-Unis"><region name="Maryland"><name sortKey="Smith, Gwenn S" sort="Smith, Gwenn S" uniqKey="Smith G" first="Gwenn S." last="Smith">Gwenn S. Smith</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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