Evidence map›Paper›PMID 37867465›Full record

Observational studyHuman brain mapping2023

T1 and FLAIR signal intensities are related to tau pathology in dominantly inherited Alzheimer disease.

Farzaneh Rahmani, Matthew R Brier, Brian A Gordon, Nicole McKay, Shaney Flores, Sarah Keefe, Russ Hornbeck, Beau Ances, Nelly Joseph-Mathurin, Chengjie Xiong and 25 more

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in Human brain mapping, 2023. 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
0.7field-weighted citation impact, top 27% 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

4 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Observational
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

35 authors at 11 institutions in 5 countries.

Farzaneh RahmaniWashington University School of Medicine, St. Louis, Missouri, USA.ORCID 0000-0002-0530-2054
Matthew R BrierWashington University School of Medicine, St. Louis, Missouri, USA.
Brian A GordonWashington University School of Medicine, St. Louis, Missouri, USA.
Nicole McKayWashington University School of Medicine, St. Louis, Missouri, USA.
Shaney FloresWashington University School of Medicine, St. Louis, Missouri, USA.
Sarah KeefeWashington University School of Medicine, St. Louis, Missouri, USA.
Russ HornbeckWashington University School of Medicine, St. Louis, Missouri, USA.
Beau AncesWashington University School of Medicine, St. Louis, Missouri, USA.
Nelly Joseph-MathurinWashington University School of Medicine, St. Louis, Missouri, USA.
Chengjie XiongWashington University School of Medicine, St. Louis, Missouri, USA.
Guoqiao WangWashington University School of Medicine, St. Louis, Missouri, USA.
Cyrus A RajiWashington University School of Medicine, St. Louis, Missouri, USA.
Jorge J Libre-GuerraWashington University School of Medicine, St. Louis, Missouri, USA.
Richard J PerrinWashington University School of Medicine, St. Louis, Missouri, USA.
Eric McDadeWashington University School of Medicine, St. Louis, Missouri, USA.
Alisha DanielsWashington University School of Medicine, St. Louis, Missouri, USA.
Celeste KarchWashington University School of Medicine, St. Louis, Missouri, USA.
Gregory S DayMayo Clinic, Department of Neurology, Jacksonville, Florida, USA.
Adam M BrickmanTaub Institute for Research on Alzheimer's Disease & the Aging Brain, and Department of Neurology College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Michael FulhamRoyal Prince Alfred Hospital (RPA), Sydney, Australia.
Clifford R JackMayo Clinic, Rochester, Minnesota, USA.
Christian la La FougèreDepartment of Nuclear Medicine and Clinical Molecular Imaging, University Hospital Tuebingen, Tübingen, Germany.
Gerald ReischlDepartment of Nuclear Medicine and Clinical Molecular Imaging, University Hospital Tuebingen, Tübingen, Germany.
Peter R SchofieldNeuroscience Research Australia, Sydney, New South Wales, Australia.
Hwamee OhBrown University, Providence, Rhode Island, USA.
Johannes LevinDepartment of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany.
Jonathan VögleinDepartment of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany.
David M CashUK Dementia Research Institute at University College London, London, UK.ORCID 0000-0001-7833-616X
Igor YakushevDepartment of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany.
Takeshi IkeuchiNiigata University, Brain Research Institute, Niigata, Japan.
William E KlunkUniversity of Pittsburgh, Pittsburgh, Pennsylvania, USA.
John C MorrisWashington University School of Medicine, St. Louis, Missouri, USA.
Randall J BatemanWashington University School of Medicine, St. Louis, Missouri, USA.
Tammie L S BenzingerWashington University School of Medicine, St. Louis, Missouri, USA.
Dominantly Inherited Alzheimer Network (DIAN)
Washington University in St. Louis · USGerman Center for Neurodegenerative Diseases · DEBrown University · USColumbia University · USJacksonville College · USMayo Clinic · USNiigata University · JPRoyal Prince Alfred Hospital · AUUK Dementia Research Institute · GBUniversity of Pittsburgh · USUNSW Sydney · AU

Funding

Imaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9M
Dominantly Inherited Alzheimer NetworkUF1AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2014 to 2017
$21.6M
DOMINANTLY INHERITED ALZHEIMER NETWORK TRIAL: AN OPPORTUNITY TO PREVENT DEMENTIAU01AG042791 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2013 to 2018
$8.9M
PET Imaging of Neuroinflammation in Genetic Alzheimer's DiseaseR01AG052550 · NIA · WASHINGTON UNIVERSITY · PI Beau M Ances, Tammie Lee Smith Benzinger · 2018 to 2026
$4.2M
PURCHASE OF A SIEMENS NEXT GENERATION PET/CTS10OD025214 · OD · WASHINGTON UNIVERSITY · PI WOODARD, PAMELA K · 2018 to 2018
$2.0M
PET and MRI Evaluation of Cerebral Inflammation and Metabolic Stress in Relapsing Multiple SclerosisK23NS128325 · NINDS · WASHINGTON UNIVERSITY · PI Matthew Ryan Brier · 2023 to 2026
$931k
Evaluation of the neurovascular unit in the setting of pathogenesis and treatment of autosomal dominant Alzheimer diseaseK01AG080123 · NIA · WASHINGTON UNIVERSITY · PI Nelly Cecile Joseph-Mathurin · 2023 to 2026
$376k
NIA NIH HHS K01 AG080123NIA NIH HHS R01 AG052550NIA NIH HHS R01AG052550-01A1NIA NIH HHS U01 AG042791NIA NIH HHS U01AG042791-02NIA NIH HHS U19 AG032438NIA NIH HHS U19AG032438NIA NIH HHS U19AG03243808NIA NIH HHS UF1 AG032438NIA NIH HHS UF1AG032438NIH HHS S10 OD025214NINDS NIH HHS K23 NS128325
6 · The paper itself

Abstract

Carriers of mutations responsible for dominantly inherited Alzheimer disease provide a unique opportunity to study potential imaging biomarkers. Biomarkers based on routinely acquired clinical MR images, could supplement the extant invasive or logistically challenging) biomarker studies. We used 1104 longitudinal MR, 324 amyloid beta, and 87 tau positron emission tomography imaging sessions from 525 participants enrolled in the Dominantly Inherited Alzheimer Network Observational Study to extract novel imaging metrics representing the mean (μ) and standard deviation (σ) of standardized image intensities of T1-weighted and Fluid attenuated inversion recovery (FLAIR) MR scans. There was an exponential decrease in FLAIR-μ in mutation carriers and an increase in FLAIR and T1 signal heterogeneity (T1-σ and FLAIR-σ) as participants approached the symptom onset in both supramarginal, the right postcentral and right superior temporal gyri as well as both caudate nuclei, putamina, thalami, and amygdalae. After controlling for the effect of regional atrophy, FLAIR-μ decreased and T1-σ and FLAIR-σ increased with increasing amyloid beta and tau deposition in numerous cortical regions. In symptomatic mutation carriers and independent of the effect of regional atrophy, tau pathology demonstrated a stronger relationship with image intensity metrics, compared with amyloid pathology. We propose novel MR imaging intensity-based metrics using standard clinical T1 and FLAIR images which strongly associates with the progression of pathology in dominantly inherited Alzheimer disease. We suggest that tau pathology may be a key driver of the observed changes in this cohort of patients.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAtrophyBiomarkersHumansMagnetic Resonance ImagingPositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesBiomarkerstau Proteinsamyloid PETdominantly inherited Alzheimer diseasequantitative MR imagingT1 and FLAIR signal intensitytau PET

Identifiers

PMID37867465
PMCPMC10681640
OpenAlexW4387866065

What OpenQuestion holds

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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.