title: Deep Brain Stimulation Influences Brain Structure in Alzheimer's Disease.
abstract: BACKGROUND
  Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder.
  
  
  OBJECTIVE
  We hypothesized that DBS applied to the fornix in patients with Alzheimer's Disease (AD) could have an effect on brain structure.
  
  
  METHODS
  In six AD patients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism. We also compared volumetric changes to those in an age-, sex-, and severity-matched group of AD patients (n = 25) not receiving DBS.
  
  
  RESULTS
  We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophy was significantly slower in the DBS group compared to the matched AD group, and no matched AD patients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD.
  
  
  CONCLUSIONS
  We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease.
authors: Division of Neurosurgery, University of Alberta, Edmonton, Alberta, Canada.
authors: Tejas
authors: T
authors: Sankar
authors: Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec, Canada.
authors: M Mallar
authors: MM
authors: Chakravarty
authors: Joan XXIII University Hospital of Tarragona, Tarragona, Spain.
authors: Agustin
authors: A
authors: Bescos
authors: Son Espases University Hospital, Palma de Mallorca, Mallorca, Spain.
authors: Monica
authors: M
authors: Lara
authors: Department of Neurosurgery, Nihon University School of Medicine, Tokyo, Japan.
authors: Toshiki
authors: T
authors: Obuchi
authors: Department of Neurosurgery, Wake Forest University, Winston-Salem, NC, USA.
authors: Adrian W
authors: AW
authors: Laxton
authors: Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
authors: Mary Pat
authors: MP
authors: McAndrews
authors: University Health Network Memory Clinic, Toronto, Ontario, Canada; Division of Neurology, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
authors: David F
authors: DF
authors: Tang-Wai
authors: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Clifford I
authors: CI
authors: Workman
authors: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Gwenn S
authors: GS
authors: Smith
authors: Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada. Electronic address: lozano@uhnresearch.ca.
authors: Andres M
authors: AM
authors: Lozano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy*; D001284:Atrophy / Q000473:pathology / Q000628:therapy*; D046690:Deep Brain Stimulation; D005260:Female; D020712:Fornix, Brain / Q000378:metabolism / Q000473:pathology*; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size
chemical_list: D005947:Glucose
keywords: Alzheimer's disease; Deep brain stimulation; Fornix; Hippocampus; MRI; Volume