Evidence map›Paper›PMID 30054439›Full record

ArticleNeurology2018

CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease.

Shorena Janelidze, Niklas Mattsson, Erik Stomrud, Olof Lindberg, Sebastian Palmqvist, Henrik Zetterberg, Kaj Blennow, Oskar Hansson

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07284316 (Effect of a Multidomain Intervention Plus Turmeric on the Prevention of Cognitive Decline in People Over 55 Years of Age With Insulin Resistance), which is not on this map. Cited by 217 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
217citing papers in PubMed, 5 pooled it
14.4field-weighted citation impact, top 1% 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.

NCT07284316 phase2 / phase3active not recruitingnot on this mapstarted 2025, after this paper: background citation

Effect of a Multidomain Intervention Plus Turmeric on the Prevention of Cognitive Decline in People Over 55 Years of Age With Insulin Resistance: A Randomized Clinical Trial

TypeinterventionalSponsorInstituto Mexicano del Seguro SocialRan2025 to 2027Enrolled100ConditionsCognitive Decline, Subjective Cognitive Impairment, Insulin ResistanceArmsTurmeric extract, Control: Placebo. 500mg gelatin in capsules 2 times a day
3 · Its place in the literature

Who cites it

217 citing papers in PubMed, 5 syntheses or guidelines pooled it, 356 citations in OpenAlex.

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  7. A phase 2A/B randomized trial of metabolic modulators intranasal insulin and empagliflozin for MCI and early AD.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  8. Article
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  11. New perspectives on VEGF signalling in Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026
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  12. CSF fibrinogen predicts longitudinal Tau accumulation in cognitively unimpaired older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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157 more citing papers are in PubMed but not listed here.

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

8 authors at 3 institutions in 2 countries.

Shorena JanelidzeFrom the Clinical Memory Research Unit (S.J., N.M., E.S., O.L., S.P., O.H.), Department of Clinical Sciences, Lund University; Department of Neurology (N.M., S.P.) and Memory Clinic (E.S., O.H.), Skåne University Hospital; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London.
Niklas MattssonFrom the Clinical Memory Research Unit (S.J., N.M., E.S., O.L., S.P., O.H.), Department of Clinical Sciences, Lund University; Department of Neurology (N.M., S.P.) and Memory Clinic (E.S., O.H.), Skåne University Hospital; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London.
Erik StomrudFrom the Clinical Memory Research Unit (S.J., N.M., E.S., O.L., S.P., O.H.), Department of Clinical Sciences, Lund University; Department of Neurology (N.M., S.P.) and Memory Clinic (E.S., O.H.), Skåne University Hospital; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London.
Olof LindbergFrom the Clinical Memory Research Unit (S.J., N.M., E.S., O.L., S.P., O.H.), Department of Clinical Sciences, Lund University; Department of Neurology (N.M., S.P.) and Memory Clinic (E.S., O.H.), Skåne University Hospital; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London.
Sebastian PalmqvistFrom the Clinical Memory Research Unit (S.J., N.M., E.S., O.L., S.P., O.H.), Department of Clinical Sciences, Lund University; Department of Neurology (N.M., S.P.) and Memory Clinic (E.S., O.H.), Skåne University Hospital; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London.
Henrik ZetterbergFrom the Clinical Memory Research Unit (S.J., N.M., E.S., O.L., S.P., O.H.), Department of Clinical Sciences, Lund University; Department of Neurology (N.M., S.P.) and Memory Clinic (E.S., O.H.), Skåne University Hospital; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London.
Kaj BlennowFrom the Clinical Memory Research Unit (S.J., N.M., E.S., O.L., S.P., O.H.), Department of Clinical Sciences, Lund University; Department of Neurology (N.M., S.P.) and Memory Clinic (E.S., O.H.), Skåne University Hospital; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London.
Oskar HanssonFrom the Clinical Memory Research Unit (S.J., N.M., E.S., O.L., S.P., O.H.), Department of Clinical Sciences, Lund University; Department of Neurology (N.M., S.P.) and Memory Clinic (E.S., O.H.), Skåne University Hospital; Institute of Neuroscience and Physiology (H.Z., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London. Oskar.Hansson@med.lu.se.
University of Gothenburg · SESahlgrenska University Hospital · SEUniversity College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo measure CSF levels of biomarkers reflecting microglia and astrocytes activation, neuroinflammation, and cerebrovascular changes and study their associations with the core biomarkers of Alzheimer disease (AD) pathology (β-amyloid [Aβ] and tau), structural imaging correlates, and clinical disease progression over time.

methodsThe study included cognitively unimpaired elderly (n = 508), patients with mild cognitive impairment (MCI, n = 256), and patients with AD dementia (n = 57) from the longitudinal Swedish BioFINDER cohort. CSF samples were analyzed for YKL-40, interleukin (IL)-6, IL-7, IL-8, IL-15, IP-10, monocyte chemoattractant protein 1, intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), placental growth factor, and fms-related tyrosine kinase 1 (Flt-1). MRI data were available from 677 study participants. Longitudinal clinical assessments were conducted in control individuals and patients with MCI (mean follow-up 3 years, range 1-6 years).

resultsCSF levels of YKL-40, ICAM-1, VCAM-1, IL-15, and Flt-1 were increased during the preclinical, prodromal, and dementia stages of AD. High levels of these biomarkers were associated with increased CSF levels of total tau, with the associations, especially for YKL-40, being stronger in Aβ-positive individuals. The results were similar for associations between phosphorylated tau and YKL-40, ICAM-1, and VCAM-1. High levels of the biomarkers were also associated with cortical thinning (primarily in the precuneus and superior parietal regions) and with subsequent cognitive deterioration in patients without dementia as measured with Mini-Mental State Examination (YKL-40) and Clinical Dementia Rating Sum of Boxes (YKL-40, ICAM-1, VCAM-1 and IL-15). Finally, higher levels of CSF YKL-40, ICAM-1, and Flt-1 increased risk of development of AD dementia in patients without dementia.

conclusionsNeuroinflammation and cerebrovascular dysfunction are early events occurring already at presymptomatic stages of AD and contribute to disease progression.

Indexed as

AgedAged, 80 and overAmyloid beta-PeptidesApolipoprotein E4BiomarkersCerebrovascular DisordersChitinase-3-Like Protein 1Cognitive DysfunctionCytokinesEncephalitisFemaleHumansIntercellular Adhesion Molecule-1Magnetic Resonance ImagingMaleMiddle AgedAmyloid beta-PeptidesApolipoprotein E4BiomarkersCHI3L1 protein, humanChitinase-3-Like Protein 1CytokinesFLT1 protein, humanIntercellular Adhesion Molecule-1MAPT protein, humanPlacenta Growth Factortau ProteinsVascular Cell Adhesion Molecule-1Vascular Endothelial Growth Factor Receptor-1

Identifiers

PMID30054439
PMCPMC6133624
OpenAlexW2883326166

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LicenceCC BY
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Registered trials

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.