Evidence map›Paper›PMID 26725994›Full record

Observational studyEuropean journal of neurology2016

Interleukin-6, interleukin-6 receptor gene variant, small-vessel disease and incident dementia.

K Miwa, S Okazaki, M Sakaguchi, H Mochizuki, K Kitagawa

Abstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in European journal of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
3.1field-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

27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Observational
  5. Article
  6. Novel inflammatory markers in intracerebral hemorrhage: Results from Olink proteomics analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Circulating Cytokines PredictFrontiers in aging neuroscience · 2021
    Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. 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

5 authors at 2 institutions in 1 country.

K MiwaDepartment of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.
S OkazakiDepartment of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.
M SakaguchiDepartment of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.
H MochizukiDepartment of Neurology and Stroke Center, Osaka University Graduate School of Medicine, Osaka, Japan.
K KitagawaDepartment of Neurology, Tokyo Women's Medical University, Tokyo, Japan.
Osaka University · JPTokyo Women's Medical University · JP

Funding

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
Multidisciplinary Training Program in Cardiovascular EpidemiologyT32HL125232 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Matthew G. Nayor, Vanessa Xanthakis · 2016 to 2026
$5.0M
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
CHARGE: Identifying Risk & Protective SNV for AD in ADSP Case-control SampleU01AG049505 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI SESHADRI, SUDHA · 2014 to 2017
$3.0M
Microglial, Inflammatory and Omics Markers of Cerebral Small Vessel Disease in the CHARGE ConsortiumUH2NS100605 · NINDS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FORNAGE, MYRIAM, SESHADRI, SUDHA · 2016 to 2017
$2.0M
ADSP Follow-up in Multi-Ethnic Cohorts via Endophenotypes, Omics & Model SystemsU01AG052409 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI FORNAGE, MYRIAM, SESHADRI, SUDHA · 2016 to 2020
$1.6M
Neurotrophic Factors: Genetic Variation and Serum Levels in Brain AgingR01AG031287 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SESHADRI, SUDHA · 2009 to 2010
$1.2M
THE FRAMINGHAM HEART STUDY-N01HC25195-268025195-268025195N01HC025195 · HC · TRUSTEES OF BOSTON UNIVERSITY · PI WOLF, PHILIP A · 2002 to 2006
–
NHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01 HC025195NIA NIH HHS R01 AG031287NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054076NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG052409NINDS NIH HHS R01 NS017950NINDS NIH HHS UH2 NS100605
6 · The paper itself

Abstract

background and purposeMixed neurogenerative and vascular dementia has emerged as the leading cause of dementia in the elderly. Inflammation is implicated in atherosclerosis, cerebral small-vessel disease (SVD) as well as cognitive impairment. However, longitudinal data on the predictive value of circulating inflammatory markers including gene variants and magnetic resonance imaging (MRI) findings in incident dementia are scarce. It was investigated whether circulating interleukin-6 (IL-6), C-reactive protein (CRP) and gene variants increase dementia risk.

methodsIn a cohort of Japanese participants with vascular risk factors in an observational study from 2001, the association between baseline IL-6, CRP levels, gene variants [interleukin-6 receptor (IL-6R), rs2228145; IL-6, rs2097677; CRP, rs3093059] and incident all-cause dementia was evaluated. Baseline MRI was used to determine SVD (lacuna, white matter hyperintensities) and atrophy (medial-temporal lobe atrophy, bicaudate ratio). Cox proportional hazards analyses were performed for predictors of dementia, adjusting for age, sex, apolipoprotein Eε4, education, cerebrovascular events, vascular risk factors and MRI findings.

resultsOf 803 subjects (mean 67.0 ± 8.5 years, males 59%), during a mean of 7.5 ± 3.2 years follow-up, 60 incident dementia patients (Alzheimer's disease 31; vascular dementia 17; mixed-type six; other six) were diagnosed. In multivariable analyses adjusted for age, sex, cerebrovascular events, MRI findings and IL-6R variant (rs2228145), IL-6 levels (relative risk 1.68, P = 0.048) or highest tertile (relative risk 2.38, P = 0.031) for all-cause dementia remained significant. Although subjects with rs2228145 carrier had significantly higher IL-6 levels, a significant association between rs2228145 and dementia was not observed. Conversely, CRP and remaining gene variants were not associated with dementia.

conclusionsThe deleterious effect of higher IL-6 on dementia remains consistent irrespective of conventional risk factors, MRI findings and IL-6R variant.

Indexed as

AgedAged, 80 and overCerebral Small Vessel DiseasesDementiaFemaleFollow-Up StudiesHumansInterleukin-6MaleMiddle AgedReceptors, Interleukin-6IL6 protein, humanIL6R protein, humanInterleukin-6Receptors, Interleukin-6C-reactive proteindementiagenetic variantsIL-6IL-6Rprospective studysingle nucleotide polymorphismsmall-vessel disease

Identifiers

PMID26725994
OpenAlexW2257784511

What OpenQuestion holds

Textmetadata
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.