Evidence map›Paper›PMID 27567810›Full record

Trial reportJournal of Alzheimer's disease : JAD2016

A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease.

Andres M Lozano, Lisa Fosdick, M Mallar Chakravarty, Jeannie-Marie Leoutsakos, Cynthia Munro, Esther Oh, Kristen E Drake, Christopher H Lyman, Paul B Rosenberg, William S Anderson and 16 more

2 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of Alzheimer's disease : JAD, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 147 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 4 pooled it
23.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01608061 nacompletednot on this map

A Twelve Month Double-blind Randomized Controlled Feasibility Study to Evaluate the Safety, Efficacy and Tolerability of Deep Brain Stimulation of the Fornix (DBS-f) in Patients With Mild Probable Alzheimer's Disease

TypeinterventionalSponsorFunctional Neuromodulation LtdRan2012 to 2018Enrolled42ConditionsAlzheimer DiseaseArmsDBS-f on, DBS-f off
NCT04856072 nacompletednot on this map

Deep Brain Stimulation of the Fornix in Alzheimer's Disease: Investigations Into Clinical and Imaging Biomarkers and Dose Optimization

TypeinterventionalSponsorUniversity Health Network, TorontoRan2014 to 2023Enrolled11ConditionsAlzheimer DiseaseArmsDeep Brain Stimulation
3 · Its place in the literature

Who cites it

147 citing papers in PubMed, 4 syntheses or guidelines pooled it, 327 citations in OpenAlex.

  1. Pooled it
  2. An updated overview of recent and ongoing deep brain stimulation (DBS) trials in patients with dementia: a systematic review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023
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87 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 14 institutions in 2 countries.

Andres M LozanoDepartments of Medicine (Neurology), Surgery (Neurosurgery) Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.
Lisa FosdickFunctional Neuromodulation Ltd, Minneapolis, MN, USA.
M Mallar ChakravartyCerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, QC, Canada; Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, QC, Canada.
Jeannie-Marie LeoutsakosMemory 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.
Cynthia MunroMemory 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.
Esther OhMemory 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.
Kristen E DrakeFunctional Neuromodulation Ltd, Minneapolis, MN, USA.
Christopher H LymanMemory 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.
Paul B RosenbergMemory 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.
William S AndersonDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
David F Tang-WaiDepartments of Medicine (Neurology), Surgery (Neurosurgery) Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.
Jo Cara PendergrassClintara LLC, Boston, MA, USA.
Stephen SallowayDepartment of Neurology, Butler Hospital and the Alpert Medical School of Brown University, Providence, RI, USA.
Wael F AsaadDepartment of Neurosurgery, Rhode Island Hospital and the Alpert Medical School of Brown University, Providence, RI, USA.
Francisco A PonceDivision of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
Anna BurkeBanner Alzheimer's Institute, Phoenix, AZ, USA.
Marwan SabbaghDepartment of Neurology, University of Arizona College of Medicine, Phoenix, AZ, USA.
David A WolkPenn Memory Center, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Gordon BaltuchDepartment of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA.
Michael S OkunDepartments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.
Kelly D FooteDepartments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA.
Mary Pat McAndrewsDepartments of Medicine (Neurology), Surgery (Neurosurgery) Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.
Peter GiacobbeDepartments of Medicine (Neurology), Surgery (Neurosurgery) Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.
Steven D TargumFunctional Neuromodulation Ltd, Minneapolis, MN, USA.
Constantine G LyketsosMemory 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.
Gwenn S SmithMemory 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.
Johns Hopkins University · USInternational Neuromodulation Society · USUniversity of Toronto · CAUniversity of Florida · USBanner Alzheimer’s InstituteButler Hospital · USJohns Hopkins Medicine · USMcGill University · CANeurological Surgery · USPenn Center for AIDS Research · USRhode Island Hospital · USUniversity Health Network · CAUniversity of Arizona · USUniversity of Pennsylvania · US

Funding

'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI ALBERT, MARILYN S. · 1985 to 2019
$37.6M
UPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DETRE, JOHN A · 1991 to 2020
$35.1M
Exploring the relationship between cerebral glucose metabolism and change in cognition in the ADvance randomized control trial of Deep Brain StimulationR01AG042165 · NIA · JOHNS HOPKINS UNIVERSITY · PI LOZANO, ANDRES M., LYKETSOS, CONSTANTINE G · 2012 to 2016
$2.8M
NIA NIH HHS R01 AG042165
6 · The paper itself

Abstract

backgroundDeep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits. The safety and efficacy of DBS in dementia is unknown.

objectiveTo assess DBS of memory circuits as a treatment for patients with mild Alzheimer's disease (AD).

methodsWe 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.

resultsSurgery 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.

conclusionDBS 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.

Indexed as

AgedAlzheimer DiseaseDeep Brain StimulationDouble-Blind MethodFemaleFornix, BrainGlucoseHumansMaleMiddle AgedPilot ProjectsPositron-Emission TomographyGlucosedeep brain stimulationdementiafornixKeywords: Alzheimer’s disease

Identifiers

PMID27567810
PMCPMC5026133
OpenAlexW2503910289

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.