Evidence map›Paper›PMID 35599493›Full record

SynthesisJournal of Alzheimer's disease : JAD2022

Insulin-Like Growth Factor, Inflammation, and MRI Markers of Alzheimer's Disease in Predominantly Middle-Aged Adults.

Katharina Wittfeld, Mekala R Raman, Sarah C Conner, Asra Aslam, Alexander Teumer, Matthias Nauck, Norbert Hosten, Mohamad Habes, Charles DeCarli, Ramachandran S Vasan and 5 more

Open access · greenAbstract readMeta-Analysis
In one paragraph

Synthesis in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Longitudinal plasma proteomics: relation to incident Alzheimer's disease dementia and biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  3. Review
  4. Article
  5. Review
  6. Role of the Insulin-like Growth Factor System in Neurodegenerative Disease.International journal of molecular sciences · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. 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

15 authors at 7 institutions in 3 countries.

Katharina WittfeldGerman Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
Mekala R RamanDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
Sarah C ConnerDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Asra AslamLong School of Medicine, UT Health San Antonio, San Antonio, TX, USA.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Matthias NauckDZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany.
Norbert HostenInstitute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
Mohamad HabesGlenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX, USA.
Charles DeCarliDepartment of Neurology, University of California, Davis School of Medicine, Sacramento, CA, USA.
Ramachandran S VasanFramingham Heart Study, Framingham, MA, USA.
Alexa S BeiserDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
Jayandra J HimaliDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
Sudha SeshadriDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
Hans J GrabeGerman Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
Claudia L SatizabalDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
Boston University · USInstitute for Neurodegenerative Disorders · USGerman Center for Neurodegenerative Diseases · DEGerman Centre for Cardiovascular Research · DEThe University of Texas Health Science Center · USUniversitätsmedizin Greifswald · DEUniversity of California, Davis · US

Funding

FRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8M
UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI OLICHNEY, JOHN M · 1991 to 2020
$28.3M
South Texas Alzheimer's Disease Research CenterP30AG066546 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Mohamad Habes · 2021 to 2026
$24.0M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
Temporal Trends, Novel Imaging and Molecular Characterization of Preclinical and Clinical Alzheimer's Disease in the Framingham CohortsR01AG054076 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI DECARLI, CHARLES, SESHADRI, SUDHA · 2016 to 2020
$12.3M
Atrial fibrillation burden, vascular disease of the brain and cardiac MRI in MESAR01HL127659 · NHLBI · UNIVERSITY OF WASHINGTON · PI HECKBERT, SUSAN R · 2015 to 2018
$7.4M
Machine Learning and Large-scale Imaging analytics for dimensional representations of brain trajectories in aging and preclinical Alzheimer's Disease: The brain aging chart and the iSTAGING consortiumRF1AG054409 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVATZIKOS, CHRISTOS · 2017 to 2023
$6.3M
Multidisciplinary Training Program in Cardiovascular EpidemiologyT32HL125232 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Matthew G. Nayor, Vanessa Xanthakis · 2016 to 2026
$5.0M
THE UNIVERSITY OF TEXAS HOUSTON STROKE TRAINING PROGRAMT32NS007412 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI SAVITZ, SEAN I · 1998 to 2023
$4.6M
Collaborative GWAS of Dementia, AD and related MRI and Cognitive EndophenotypesR01AG033193 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SESHADRI, SUDHA · 2009 to 2016
$4.4M
Preclinical AD: Correlates of Amyloid, Tau PET and fcMRI in Framingham Gen 3 Young AdultsR01AG049607 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SESHADRI, SUDHA · 2015 to 2019
$3.1M
Microglial, Inflammatory and Omics Markers of Cerebral Small Vessel Disease in the CHARGE ConsortiumUH3NS100605 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI FORNAGE, MYRIAM, SESHADRI, SUDHA · 2018 to 2020
$3.0M
NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01 HC025195NHLBI NIH HHS R01 HL077477NHLBI NIH HHS R01 HL127659NHLBI NIH HHS T32 HL125232NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG066546NIA NIH HHS R01 AG031287NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054076NIA NIH HHS RF1 AG054409NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG052409NIGMS NIH HHS T32 GM074905NINDS NIH HHS R01 NS017950NINDS NIH HHS T32 NS007412NINDS NIH HHS UF1 NS125513NINDS NIH HHS UH2 NS100605NINDS NIH HHS UH3 NS100605
6 · The paper itself

Abstract

backgroundInsulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults.

objectiveTo investigate the association of serum IGF-1 and IGF binding protein 3 (IGFBP-3) concentrations with MRI markers of Alzheimer's disease in predominantly middle-aged adults, and further assess moderation by chronic inflammation.

methodsWe included participants from the Framingham Heart Study (n = 1,852, mean age 46±8, 46% men) and the Study of Health in Pomerania (n = 674, mean age 50±13, 42% men) with available serum IGF-1, IFGBP-3, as well as brain MRI. IGF-1 and IFGBP-3 were related to MRI outcomes (i.e., total brain, cortical gray matter, white matter, white matter hyperintensities (WMH), and hippocampal volumes) using multivariable regression models adjusting for potential confounders. Subgroup analyses by C-reactive protein (CRP) concentrations were also performed. Cohort-specific summary statistics were meta-analyzed using random-effects models and corrected for multiple comparisons.

resultsMeta-analysis results revealed that higher IGF-1 concentrations were associated with lower WMH (estimate [β] [95% CI], -0.05 [-0.09, -0.02], p = 0.006) and larger hippocampal volumes (0.07 [0.02, 0.12], p = 0.01), independent of vascular risk factors. These associations occurred predominantly in individuals with CRP concentrations < 75th percentile. We did not observe associations between IGFBP-3 and MRI outcomes.

conclusionOur findings suggest that IGF-1-related signaling may be implicated in brain health as early as midlife.

Indexed as

Alzheimer DiseaseInsulin-Like Growth Factor Binding Protein 3AdultBiomarkersC-Reactive ProteinFemaleHumansInflammationInsulin-Like Growth Factor IMagnetic Resonance ImagingMaleMiddle AgedBiomarkersC-Reactive ProteinInsulin-Like Growth Factor Binding Protein 3Insulin-Like Growth Factor IAlzheimer’s disease endophenotypecohort studyC-reactive proteinepidemiologyhippocampusinsulin-like growth factorneuroimagingwhite matter hyperintensity

Identifiers

PMID35599493
PMCPMC9472289
OpenAlexW4280562625

What OpenQuestion holds

Textmetadata
LicenceTDM
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.