• Archives of neurology · Sep 2012

    Clinical Trial

    Increased cerebral metabolism after 1 year of deep brain stimulation in Alzheimer disease.

    • Gwenn S Smith, Adrian W Laxton, David F Tang-Wai, Mary Pat McAndrews, Andreea Oliviana Diaconescu, Clifford I Workman, and Andres M Lozano.
    • Division of Geriatric Psychiatry and Neuropsychiatry, The Johns Hopkins University School of Medicine, The Johns Hopkins Bayview Medical Center, 5300 Alpha Commons Dr, 4th Floor, Baltimore, MD 21224, USA. gsmith95@jhmi.edu
    • Arch. Neurol. 2012 Sep 1;69(9):1141-8.

    BackgroundThe importance of developing unique, neural circuitry-based treatments for the cognitive and neuropsychiatric symptoms of Alzheimer disease (AD) was the impetus for a phase I study of deep brain stimulation (DBS) in patients with AD that targeted the fornix.ObjectiveTo test the hypotheses that DBS would increase cerebral glucose metabolism in cortical and hippocampal circuits and that increased metabolism would be correlated with better clinical outcomes.DesignOpen-label trial.SettingAcademic medical center.PatientsA total of 5 patients with mild, probable AD (1 woman and 4 men, with a mean [SD] age of 62.6 [4.2] years).InterventionDeep brain stimulation of the fornix.Main Outcome MeasuresAll patients underwent clinical follow-up and high-resolution positron emission tomography studies of cerebral glucose metabolism after 1 year of DBS.ResultsFunctional connectivity analyses revealed that 1 year of DBS increased cerebral glucose metabolism in 2 orthogonal networks: a frontal-temporal-parietal-striatal-thalamic network and a frontal-temporal-parietal-occipital-hippocampal network. In similar cortical regions, higher baseline metabolism prior to DBS and increased metabolism after 1 year of DBS were correlated with better outcomes in global cognition, memory, and quality of life.ConclusionsIncreased connectivity after 1 year of DBS is observed, which is in contrast to the decreased connectivity observed over the course of AD. The persistent cortical metabolic increases after 1 year of DBS were associated with better clinical outcomes in this patient sample and are greater in magnitude and more extensive in the effects on cortical circuitry compared with the effects reported for pharmacotherapy over 1 year in AD.

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