Evidence map›Paper›PMID 34151817›Full record

Trial reportJournal of Alzheimer's disease : JAD2021

Effect of Age on Clinical Trial Outcome in Participants with Probable Alzheimer's Disease.

Steven D Targum, Lisa Fosdick, Kristen E Drake, Paul B Rosenberg, Anna D Burke, David A Wolk, Kelly D Foote, Wael F Asaad, Marwan Sabbagh, Gwenn S Smith and 2 more

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 31% 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.

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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. 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
    Pooled it
  2. Article
  3. Review
  4. Review
  5. 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

12 authors at 8 institutions in 2 countries.

Steven D TargumFunctional Neuromodulation Ltd., Minneapolis MN, USA.
Lisa FosdickFunctional Neuromodulation Ltd., Minneapolis MN, USA.
Kristen E DrakeFunctional Neuromodulation Ltd., Minneapolis MN, 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.
Anna D BurkeDepartment of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.
David A WolkPenn Memory Center, Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
Kelly D FooteDepartments of and Neurosurgery and Neurology, University of Florida, Fixel Institute for Neurological Diseases, Gainesville, FL, USA.
Wael F AsaadDepartment of Neurosurgery, Rhode Island Hospital and the Alpert Medical School of Brown University, Providence, RI, USA.
Marwan SabbaghCleveland Clinic Lou Ruvo Center for Brain Health, Cleveland, OH, 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.
Andres M LozanoDepartment of Surgery (Neurosurgery), University of Toronto, Toronto, ON, Canada.
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.
International Neuromodulation Society · USJohns Hopkins University · USBarrow Neurological Institute · USBrown University · USCleveland Clinic · USPenn Center for AIDS Research · USUniversity of Florida · USUniversity of Toronto · CA

Funding

Research Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI MARILYN S. ALBERT · 2020 to 2026
$29.3M
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 P30 AG066507NIA NIH HHS R01 AG042165
6 · The paper itself

Abstract

backgroundAge may affect treatment outcome in trials of mild probable Alzheimer's disease (AD).

objectiveWe examined age as a moderator of outcome in an exploratory study of deep brain stimulation targeting the fornix (DBS-f) region in participants with AD.

methodsForty-two participants were implanted with DBS electrodes and randomized to double-blind DBS-f stimulation ("on") or sham DBS-f ("off") for 12 months.

resultsThe intervention was safe and well tolerated. However, the selected clinical measures did not differentiate between the "on" and "off" groups in the intent to treat (ITT) population. There was a significant age by time interaction with the Alzheimer's Disease Assessment Scale; ADAS-cog-13 (p = 0.028). Six of the 12 enrolled participants < 65 years old (50%) markedly declined on the ADAS-cog-13 versus only 6.7%of the 30 participants≥65 years old regardless of treatment assignment (p = 0.005). While not significant, post-hoc analyses favored DBS-f "off" versus "on" over 12 months in the < 65 age group but favored DBS-f "on" versus "off" in the≥65 age group on all clinical metrics. On the integrated Alzheimer's Disease rating scale (iADRS), the effect size contrasting DBS-f "on" versus "off" changed from +0.2 (favoring "off") in the < 65 group to -0.52 (favoring "on") in the≥65 age group.

conclusionThe findings highlight issues with subject selection in clinical trials for AD. Faster disease progression in younger AD participants with different AD sub-types may influence the results. Biomarker confirmation and genotyping to differentiate AD subtypes is important for future clinical trials.

Indexed as

AgedAged, 80 and overAgingAlzheimer DiseaseDeep Brain StimulationDouble-Blind MethodElectrodes, ImplantedFemaleHumansMaleMiddle AgedTreatment OutcomeAgeAlzheimer’s diseaseclinical trialsdeep brain stimulationsubject selection

Identifiers

PMID34151817
PMCPMC8461716
OpenAlexW3175262917

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.