Evidence map›Paper›PMID 32919366›Full record

ArticleNeuroImage. Clinical2020

Multiple markers contribute to risk of progression from normal to mild cognitive impairment.

Jennifer S Rabin, Taylor E Neal, Hannah E Nierle, Sietske A M Sikkes, Rachel F Buckley, Rebecca E Amariglio, Kathryn V Papp, Dorene M Rentz, Aaron P Schultz, Keith A Johnson and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NeuroImage. Clinical, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
–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

7 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
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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.

Jennifer S RabinDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA; Harquail Centre for Neuromodulation and Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Medicine (Neurology), University of Toronto, Toronto, ON M5S 3H2, Canada.
Taylor E NealDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Hannah E NierleDepartment of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sietske A M SikkesAlzheimer Center and Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit, The Netherlands; Department of Epidemiology and Biostatistics, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, The Netherlands; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA.
Rachel F BuckleyDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA; Florey Institutes of Neuroscience and Mental Health, Melbourne and Melbourne School of Psychological Science, University of Melbourne, Melbourne, Australia; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Rebecca E AmariglioDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Kathryn V PappDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Dorene M RentzDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Aaron P SchultzDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Keith A JohnsonCenter for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, MA 02144, USA.
Reisa A SperlingDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Trey HeddenDepartment of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA. Electronic address: Trey.Hedden@mssm.edu.

Funding

Vascular factors, physical activity, and inflammation as modulators of neurodegenerative and cognitive trajectories (Project 2)P01AG036694 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Rachel Frances Buckley · 2010 to 2026
$50.2M
THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI FROSCH, MATTHEW P · 1985 to 2018
$42.1M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI STEVEN E ARNOLD · 2019 to 2026
$36.5M
Project 4P41EB015896 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI ROSEN, BRUCE R · 2012 to 2018
$9.8M
Role of age, dopamine, and tau related network disruption in setting a context for progression toward Alzheimer's DiseaseR01AG054110 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HEDDEN, JULIUS C · 2017 to 2021
$4.2M
Tau, amyloid, & white matter burden interact to impact brain networks in preclinical Alzheimer’s diseaseR01AG053509 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HEDDEN, JULIUS C · 2016 to 2020
$4.1M
A Storage Area Network for Structural and Functional Image AnalysisS10RR023401 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI FISCHL, BRUCE · 2009 to 2009
$2.0M
SILICON GRAPHICS PRISM EXTREME 128P/1TBS10RR023043 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI SORENSEN, ALMA GREGORY · 2006 to 2006
$1.5M
Mentoring Imaging Research in Early ADK24AG035007 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI SPERLING, REISA A. · 2010 to 2020
$1.4M
A 3.0 Tesla MRI System in a Neuroscience ICUS10RR019254 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI SORENSEN, ALMA GREGORY · 2004 to 2004
$500k
Computeserver Structural &Functional Image AnalysisS10RR019307 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI FISCHL, BRUCE · 2004 to 2004
$496k
Elucidating the mechanisms underlying sex differences in cognitive decline due to preclinical Alzheimer's diseaseK99AG061238 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI BUCKLEY, RACHEL FRANCES · 2019 to 2020
$273k
CIHRNCRR NIH HHS S10 RR019254NCRR NIH HHS S10 RR019307NCRR NIH HHS S10 RR023043NCRR NIH HHS S10 RR023401NIA NIH HHS K24 AG035007NIA NIH HHS K99 AG061238NIA NIH HHS P01 AG036694NIA NIH HHS P30 AG062421NIA NIH HHS P50 AG005134NIA NIH HHS R01 AG053509NIA NIH HHS R01 AG054110NIBIB NIH HHS P41 EB015896
6 · The paper itself

Abstract

objectiveTo identify a parsimonious set of markers that optimally predicts subsequent clinical progression from normal to mild cognitive impairment (MCI).

methods250 clinically normal adults (mean age = 73.6 years, SD = 6.0) from the Harvard Aging Brain Study were assessed at baseline on a wide set of markers, including magnetic resonance imaging markers of gray matter thickness and volume, white matter lesions, fractional anisotropy, resting state functional connectivity, positron emission tomography markers of glucose metabolism and β-amyloid (Aβ) burden, and a measure of vascular risk. Participants were also tested annually on a battery of clinical and cognitive tests (median follow-up = 5.0 years, SD = 1.66). We applied least absolute shrinkage and selection operator (LASSO) Cox models to determine the minimum set of non-redundant markers that predicts subsequent clinical progression from normal to MCI, adjusting for age, sex, and education.

results23 participants (9.2%) progressed to MCI over the study period (mean years of follow-up to diagnosis = 3.96, SD = 1.89). Progression was predicted by several brain markers, including reduced entorhinal thickness (hazard ratio, HR = 1.73), greater Aβ burden (HR = 1.58), lower default network connectivity (HR = 1.42), and smaller hippocampal volume (HR = 1.30). When cognitive test scores were added to the model, the aforementioned neuroimaging markers remained significant and lower striatum volume as well as lower scores on baseline memory and processing speed tests additionally contributed to progression.

conclusionAmong a large set of brain, vascular and cognitive markers, a subset of markers independently predicted progression from normal to MCI. These markers may enhance risk stratification by identifying clinically normal individuals who are most likely to develop clinical symptoms and would likely benefit most from therapeutic intervention.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAgedAmyloid beta-PeptidesBrainDisease ProgressionHumansMagnetic Resonance ImagingNeuropsychological TestsPositron-Emission TomographyTomography, X-Ray ComputedAmyloid beta-PeptidesAgingAlzheimer's diseaseAmyloidClinical Dementia RatingMemoryMild cognitive impairmentNeuroimagingSurvival

Identifiers

PMID32919366
PMCPMC7491146

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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.