Evidence map›Paper›PMID 38111006›Full record

ArticleMolecular neurodegeneration2023

Advanced structural brain aging in preclinical autosomal dominant Alzheimer disease.

Peter R Millar, Brian A Gordon, Julie K Wisch, Stephanie A Schultz, Tammie Ls Benzinger, Carlos Cruchaga, Jason J Hassenstab, Laura Ibanez, Celeste Karch, Jorge J Llibre-Guerra and 24 more

Open access · goldAbstract read
In one paragraph

Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Observational
  3. Review
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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

34 authors at 12 institutions in 7 countries.

Peter R MillarDepartment of Neurology, Washington University in St. Louis, St. Louis, MO, USA. pmillar@wustl.edu.ORCID 0000-0003-4588-739X
Brian A GordonMallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA.
Julie K WischDepartment of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
Stephanie A SchultzDepartment of Neurology, Harvard Medical School, Boston, MA, USA.
Tammie Ls BenzingerMallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
Jason J HassenstabDepartment of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
Laura IbanezDepartment of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
Celeste KarchDepartment of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
Jorge J Llibre-GuerraDepartment of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
John C MorrisDepartment of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
Richard J PerrinDepartment of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
Charlene Supnet-BellDepartment of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
Chengjie XiongDepartment of Biostatistics, Washington University in St. Louis, St. Louis, MO, USA.
Ricardo F AllegriInstituto Neurológico Fleni, Buenos Aires, Argentina.
Sarah B BermanDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
Jasmeer P ChhatwalDepartment of Neurology, Harvard Medical School, Boston, MA, USA.
Patricio A Chrem MendezInstituto Neurológico Fleni, Buenos Aires, Argentina.
Gregory S DayDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Anna HofmannGerman Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany.
Takeshi IkeuchiDepartment of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
Mathias JuckerGerman Center for Neurodegenerative Diseases (DZNE), 72076, Tübingen, Germany.
Jae-Hong LeeDepartment of Neurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Johannes LevinDepartment of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany.
Francisco LoperaUniversidad de Antioquia, Medellín, Colombia.
Yoshiki NiimiUnit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Bunkyo-Ku, Tokyo, Japan.
Victor J Sánchez-GonzálezDepartamento de Clínicas, CUALTOS, Universidad de Guadalajara, Tepatitlán de Morelos, Jalisco, México.
Peter R SchofieldNeuroscience Research Australia, Sydney, NSW, Australia.
Ana Luisa Sosa-OrtizInstituto Nacional de Neurologia y Neurocirugía MVS, CDMX, Ciudad de México, Mexico.
Jonathan VögleinDepartment of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany.
Dominantly Inherited Alzheimer Network
Randall J BatemanDepartment of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
Beau M Ances *Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
Eric M McDade *Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
Washington University in St. Louis · USGerman Center for Neurodegenerative Diseases · DEHarvard University · USInstituto Nacional de Neurología y Neurocirugía · MXNiigata University · JPUlsan College · KRUniversidad de Antioquia · COUniversidad de Guadalajara · MXUniversity of Pittsburgh · USUniversity of Tokyo Hospital · JPUNSW Sydney · AUWinnMed · US

Funding

Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MICHAEL W WEINER · 2016 to 2026
$226.7M
Early Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
Imaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI SCHINDLER, SUZANNE ELIZABETH · 2005 to 2025
$49.5M
Project 4 (Genetic modifiers for APOE-associated Alzheimer's disease pathogenesis)U19AG069701 · NIA · MAYO CLINIC JACKSONVILLE · PI Na Zhao · 2021 to 2026
$42.0M
DIAN-TU Next Generation Prevention Trial - Data Request Management SupplementR01AG053267 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2017 to 2023
$34.9M
Research Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI DAVID M. HOLTZMAN · 2020 to 2026
$28.7M
A Phase-2b, Double-Blind, Randomized Controlled Trial to Evaluate the Activity and Safety of Inebilizumab in Anti-N-methyl-D-aspartate receptor (NMDAR) Encephalitis and Assess Markers of DiseaseU01NS120901 · NINDS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Stacey Lynn Clardy · 2021 to 2026
$19.6M
Democratising Machine Learning for researchers working in Alzheimer's spaceR01AG058676 · NIA · UNIVERSITY OF MELBOURNE · PI MASTERS, COLIN · 2018 to 2022
$10.9M
INVESTIGATIONS OF DEMENTIA IN PARKINSON DISEASER01NS075321 · NINDS · WASHINGTON UNIVERSITY · PI CAMPBELL, MEGHAN C, PERLMUTTER, JOEL SYNES · 2011 to 2021
$8.2M
Protein Aggregation and Neurotransmitter Deficits in Parkinson DiseaseR01NS097799 · NINDS · WASHINGTON UNIVERSITY · PI PAUL T KOTZBAUER · 2016 to 2026
$5.8M
Alzheimer's Association SG-20-690363-DIANNIA NIH HHS 5-R01-AG052550NIA NIH HHS K01 AG073526NIA NIH HHS K23 AG064029NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P01-AG026276NIA NIH HHS P01-AG03991NIA NIH HHS P30 AG066444NIA NIH HHS P30-AG066444NIA NIH HHS R01 AG052550NIA NIH HHS R01 AG053267NIA NIH HHS R01 AG054567NIA NIH HHS R01 AG057777NIA NIH HHS R01 AG058676NIA NIH HHS R01 AG074909NIA NIH HHS U01 AG057195NIA NIH HHS U19 AG024904NIA NIH HHS U19 AG032438NIA NIH HHS U19-AG032438NIA NIH HHS U19 AG069701NIH HHS S10 OD025214NINDS NIH HHS R01 NS075321NINDS NIH HHS R01 NS097799NINDS NIH HHS U01 NS120901
6 · The paper itself

Abstract

background"Brain-predicted age" estimates biological age from complex, nonlinear features in neuroimaging scans. The brain age gap (BAG) between predicted and chronological age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD), in which AD progression is highly predictable with minimal confounding age-related co-pathology.

methodsWe modeled BAG in 257 deeply-phenotyped ADAD mutation-carriers and 179 non-carriers from the Dominantly Inherited Alzheimer Network using minimally-processed structural MRI scans. We then tested whether BAG differed as a function of mutation and cognitive status, or estimated years until symptom onset, and whether it was associated with established markers of amyloid (PiB PET, CSF amyloid-β-42/40), phosphorylated tau (CSF and plasma pTau-181), neurodegeneration (CSF and plasma neurofilament-light-chain [NfL]), and cognition (global neuropsychological composite and CDR-sum of boxes). We compared BAG to other MRI measures, and examined heterogeneity in BAG as a function of ADAD mutation variants, APOE ε4 carrier status, sex, and education.

resultsAdvanced brain aging was observed in mutation-carriers approximately 7 years before expected symptom onset, in line with other established structural indicators of atrophy. BAG was moderately associated with amyloid PET and strongly associated with pTau-181, NfL, and cognition in mutation-carriers. Mutation variants, sex, and years of education contributed to variability in BAG.

conclusionsWe extend prior work using BAG from sporadic AD to ADAD, noting consistent results. BAG associates well with markers of pTau, neurodegeneration, and cognition, but to a lesser extent, amyloid, in ADAD. BAG may capture similar signal to established MRI measures. However, BAG offers unique benefits in simplicity of data processing and interpretation. Thus, results in this unique ADAD cohort with few age-related confounds suggest that brain aging attributable to AD neuropathology can be accurately quantified from minimally-processed MRI.

Indexed as

Alzheimer DiseaseAgingAmyloidAmyloid beta-PeptidesBiomarkersBrainHumansPositron-Emission Tomographytau ProteinsAmyloidAmyloid beta-PeptidesBiomarkerstau ProteinsAlzheimer diseaseBrain agingMachine learningStructural MRI

Identifiers

PMID38111006
PMCPMC10729487
OpenAlexW4389903073

What OpenQuestion holds

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LicenceCC BY
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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.