title: A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease.
abstract: Deep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits. The safety and efficacy of DBS in dementia is unknown.
  
  
  
  To assess DBS of memory circuits as a treatment for patients with mild Alzheimer's disease (AD).
  
  
  
  We evaluated active "on" versus sham "off" bilateral DBS directed at the fornix-a major fiber bundle in the brain's memory circuit-in a randomized, double-blind trial (ClinicalTrials.gov NCT01608061) in 42 patients with mild AD. We measured cognitive function and cerebral glucose metabolism up to 12 months post-implantation.
  
  
  
  Surgery and electrical stimulation were safe and well tolerated. There were no significant differences in the primary cognitive outcomes (ADAS-Cog 13, CDR-SB) in the "on" versus "off" stimulation group at 12 months for the whole cohort. Patients receiving stimulation showed increased metabolism at 6 months but this was not significant at 12 months. On post-hoc analysis, there was a significant interaction between age and treatment outcome: in contrast to patients <65 years old (n = 12) whose results trended toward being worse with DBS ON versus OFF, in patients≥65 (n = 30) DBS-f ON treatment was associated with a trend toward both benefit on clinical outcomes and a greater increase in cerebral glucose metabolism.
  
  
  
  DBS for AD was safe and associated with increased cerebral glucose metabolism. There were no differences in cognitive outcomes for participants as a whole, but participants aged≥65 years may have derived benefit while there was possible worsening in patients below age 65 years with stimulation.
authors: Departments of Medicine (Neurology), Surgery (Neurosurgery) Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.
authors: Andres M
authors: AM
authors: Lozano
authors: Functional Neuromodulation Ltd, Minneapolis, MN, USA.
authors: Lisa
authors: L
authors: Fosdick
authors: Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada; Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, QC, Canada.
authors: M Mallar
authors: MM
authors: Chakravarty
authors: Memory and Alzheimer's Treatment Center & Alzheimer's Disease Research Center, Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Jeannie-Marie
authors: JM
authors: Leoutsakos
authors: Memory and Alzheimer's Treatment Center & Alzheimer's Disease Research Center, Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Cynthia
authors: C
authors: Munro
authors: Memory and Alzheimer's Treatment Center & Alzheimer's Disease Research Center, Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Medicine, Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Esther
authors: E
authors: Oh
authors: Functional Neuromodulation Ltd, Minneapolis, MN, USA.
authors: Kristen E
authors: KE
authors: Drake
authors: Memory and Alzheimer's Treatment Center & Alzheimer's Disease Research Center, Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Christopher H
authors: CH
authors: Lyman
authors: Memory and Alzheimer's Treatment Center & Alzheimer's Disease Research Center, Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Paul B
authors: PB
authors: Rosenberg
authors: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: William S
authors: WS
authors: Anderson
authors: Departments of Medicine (Neurology), Surgery (Neurosurgery) Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.|University Health Network Memory Clinic, University of Toronto, Division of Neurology, Toronto, ON, Canada.
authors: David F
authors: DF
authors: Tang-Wai
authors: Clintara LLC, Boston, MA, USA.
authors: Jo Cara
authors: JC
authors: Pendergrass
authors: Department of Neurology, Butler Hospital and the Alpert Medical School of Brown University, Providence, RI, USA.
authors: Stephen
authors: S
authors: Salloway
authors: Department of Neurosurgery, Rhode Island Hospital and the Alpert Medical School of Brown University, Providence, RI, USA.
authors: Wael F
authors: WF
authors: Asaad
authors: Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
authors: Francisco A
authors: FA
authors: Ponce
authors: Banner Alzheimer's Institute, Phoenix, AZ, USA.
authors: Anna
authors: A
authors: Burke
authors: Department of Neurology, University of Arizona College of Medicine, Phoenix, AZ, USA.
authors: Marwan
authors: M
authors: Sabbagh
authors: Penn Memory Center, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
authors: David A
authors: DA
authors: Wolk
authors: Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
authors: Gordon
authors: G
authors: Baltuch
authors: Departments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.
authors: Michael S
authors: MS
authors: Okun
authors: Departments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.
authors: Kelly D
authors: KD
authors: Foote
authors: Departments of Medicine (Neurology), Surgery (Neurosurgery) Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.
authors: Mary Pat
authors: MP
authors: McAndrews
authors: Departments of Medicine (Neurology), Surgery (Neurosurgery) Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.
authors: Peter
authors: P
authors: Giacobbe
authors: Functional Neuromodulation Ltd, Minneapolis, MN, USA.
authors: Steven D
authors: SD
authors: Targum
authors: Memory and Alzheimer's Treatment Center & Alzheimer's Disease Research Center, Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Constantine G
authors: CG
authors: Lyketsos
authors: Memory and Alzheimer's Treatment Center & Alzheimer's Disease Research Center, Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Gwenn S
authors: GS
authors: Smith
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy*; D046690:Deep Brain Stimulation / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D020712:Fornix, Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D005947:Glucose
keywords: Keywords: Alzheimer’s disease; deep brain stimulation; dementia; fornix