Evidence map›Paper›PMID 40566800›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Biomarker changes associated with fornix deep brain stimulation in Alzheimer's disease.

Jürgen Germann, Robert S C Amaral, Jennifer Tomaszczyk, Kazuaki Yamamoto, Gavin J B Elias, Flavia Venetucci Gouveia, Anna Vasilevskaya, Foad Taghdiri, Gabriel A Devenyi, Tejas Sankar and 28 more

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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Biomarker changes associated with fornix deep brain stimulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
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

38 authors.

Jürgen GermannDivision of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0003-0995-8226
Robert S C AmaralCerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
Jennifer TomaszczykDivision of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Kazuaki YamamotoDivision of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Gavin J B EliasDivision of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Flavia Venetucci GouveiaNeuroscience and Mental Health, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Anna VasilevskayaInstitute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Foad TaghdiriInstitute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Gabriel A DevenyiCerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
Tejas SankarDivision of Neurosurgery, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Jeannie-Marie LeoutsakosDivision of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview and Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Cynthia A MunroDivision of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview and Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Paul B RosenbergDivision of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview and Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Constantine G LyketsosDivision of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview and Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Esther S OhDivision of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
William S AndersonDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Zoltan MariDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Lisa FosdickFunctional Neuromodulation Ltd., Minneapolis, Minnesota, USA.
Kristen E DrakeFunctional Neuromodulation Ltd., Minneapolis, Minnesota, USA.
Steven D TargumFunctional Neuromodulation Ltd., Minneapolis, Minnesota, USA.
Jo Cara PendergrassAvanti Clinical Research, Plymouth, Massachusetts, USA.
Anna BurkeBarrow Neurological Institute, Phoenix, Arizona, USA.
Stephen SallowayDepartment of Neurology, Butler Hospital and the Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Wael F AsaadDepartment of Neurosurgery, Rhode Island Hospital and the Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Francisco A PonceDivision of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Marwan SabbaghDivision of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
David A WolkPenn Memory Center, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Gordon BaltuchDepartment of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Michael S OkunDepartments of Neurology and Neurosurgery, University of Florida, Fixel Institute for Neurological Diseases, Gainesville, Florida, USA.
Kelly D FooteDepartments of Neurology and Neurosurgery, University of Florida, Fixel Institute for Neurological Diseases, Gainesville, Florida, USA.
Peter GiacobbeDepartment of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Mary Pat McAndrewsKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
David F Tang-WaiKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Gwenn S SmithDivision of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview and Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
M Carmela TartagliaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
M Mallar ChakravartyKrembil Research Institute, University Health Network, Toronto, Ontario, Canada.
Andres M LozanoDivision of Neurosurgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Alzheimer's Disease Neuroimaging Initiative

Funding

Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI MARILYN S. ALBERT · 2020 to 2026
$29.3M
Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8M
Defining Targets for Tic Detection and Suppression in Tourette Syndrome Deep Brain StimulationUH3NS119844 · NINDS · UNIVERSITY OF FLORIDA · PI BUTSON, CHRISTOPHER R, GUNDUZ, AYSEGUL · 2021 to 2025
$5.0M
Web-based Automated Imaging Differentiation of ParkinsonismU01NS119562 · NINDS · UNIVERSITY OF FLORIDA · PI BARMPOUTIS, ANGELOS, OKUN, MICHAEL S · 2021 to 2025
$4.8M
Longitudinal Molecular Imaging of Neuropathology and Serotonin in Mild Cognitive ImpairmentR01AG059390 · NIA · JOHNS HOPKINS UNIVERSITY · PI SMITH, GWENN S · 2018 to 2022
$4.8M
Addressing Hearing Loss as a Common Unmet Contributor to Neuropsychiatric SymptomsR01AG076525 · NIA · JOHNS HOPKINS UNIVERSITY · PI CARRIE L NIEMAN, Esther Seunghee Oh · 2022 to 2026
$3.9M
Mobile Decision Support System for Nurse Management of Neuromodulation TherapyR01NR014852 · NINR · UNIVERSITY OF UTAH · PI BUTSON, CHRISTOPHER R, OKUN, MICHAEL S · 2015 to 2019
$2.9M
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
THE HUMAN THALAMOCORTICAL NETWORK IN TOURETTE SYNDROMER01NS096008 · NINDS · UNIVERSITY OF FLORIDA · PI GUNDUZ, AYSEGUL, OKUN, MICHAEL S · 2016 to 2020
$1.8M
ADVANCING THALAMIC NEUROSTIMULATION FOR SUPPRESING ESSENTIAL VOICE TREMORR01NS131342 · NINDS · UNIVERSITY OF FLORIDA · PI Evangelos A Christou, MICHAEL S OKUN · 2024 to 2026
$1.0M
University of Florida R25 Early Research Program for Neurology and Neurosurgery ResidentsR25NS108939 · NINDS · UNIVERSITY OF FLORIDA · PI HOH, BRIAN LIM, HOH, BRIAN LIM · 2019 to 2024
$537k
Canadian Institutes of Health Research Banting fellowship 202109BPF-471913-BPF-ADHD-184776Dr. Okun is a multi-PI of the NIH R25NS108939Dr. Okun's research R01NS096008Dr. Okun's research U01NS119562Dr. Okun's research UH3NS119844NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG072979NIA NIH HHS R01 AG042165NIA NIH HHS R01 AG059390NIA NIH HHS R01 AG076525NIH) R01AG042165NINDS NIH HHS R01 NS096008NINDS NIH HHS R01 NS131342NINDS NIH HHS R25 NS108939NINDS NIH HHS U01 NS119562NINDS NIH HHS UH3 NS119844NINR NIH HHS R01 NR014852
6 · The paper itself

Abstract

introductionDeep brain stimulation of the fornix (fx-DBS) is being investigated for treatment of Alzheimer's disease (AD). The therapy aims at alleviating memory and cognitive circuit dysfunction. In preclinical models of AD, electrical stimulation of the memory circuit has demonstrated a possible disease-modifying potential. Here we examined changes resulting from fx-DBS in hippocampal atrophy and amyloid accumulation in AD patients with fx-DBS.

methodsRepeated magnetic resonance imaging and positron emission tomography (PET) images acquired over the course of 12 months were used to assess changes in hippocampal volume in 36 ADvance trial patients compared to 40 matched untreated AD patients from the Alzheimer's Disease Neuroimaging Initiative, and in 10 separate patients with repeated flutemetamol PET and cerebrospinal fluid (CSF) markers.

resultsWe observed a reduction of hippocampal atrophy and amyloid beta (Aβ) PET binding, and an increase in the CSF Aβ/total-tau ratio in DBS patients. DISCUSSION: These findings highlight the potential of fornix deep brain stimulation to modify AD biomarkers and possibly progression in some patients. HIGHLIGHTS: Fornix deep brain stimulation (fx-DBS) is being investigated to treat Alzheimer's disease (AD). Results show that fx-DBS modifies imaging and cerebrospinal fluid (CSF) markers. It reduces hippocampal atrophy and increases the amyloid beta/total-tau CSF ratio. These findings highlight the potential of fx-DBS to modify AD.

Indexed as

Alzheimer DiseaseDeep Brain StimulationFornix, BrainHippocampusAgedAmyloid beta-PeptidesAtrophyBiomarkersFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedPositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesBiomarkerstau ProteinsAlzheimer's disease biomarkeramyloid clearancefornix DBShippocampal atrophyneuromodulation therapy

Identifiers

PMID40566800
PMCPMC12198481

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Registered trials

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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.