Evidence map›Paper›PMID 40338439›Full record

SynthesisGeroScience2026

Kynurenine pathway dysregulation in cognitive impairment and dementia: a systematic review and meta-analysis.

Kyonghwan Choe, Lieke Bakker, Daniel L A van den Hove, Simone J P M Eussen, Gunter Kenis, Inez H G B Ramakers, Frans R J Verhey, Bart P F Rutten, Sebastian Köhler

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Immune-proteo-metabolomic changes link to Aβ and tau pathology in Alzheimer disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. 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

9 authors.

Kyonghwan Choe *Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML), Mental Health and Neuroscience Research Institute (Mhens), Maastricht University, Maastricht, the Netherlands.
Lieke Bakker *Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML), Mental Health and Neuroscience Research Institute (Mhens), Maastricht University, Maastricht, the Netherlands.
Daniel L A van den HoveDepartment of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML), Mental Health and Neuroscience Research Institute (Mhens), Maastricht University, Maastricht, the Netherlands.
Simone J P M EussenDepartment of Epidemiology, Maastricht University, Maastricht, the Netherlands.
Gunter KenisDepartment of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML), Mental Health and Neuroscience Research Institute (Mhens), Maastricht University, Maastricht, the Netherlands.
Inez H G B RamakersDepartment of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML), Mental Health and Neuroscience Research Institute (Mhens), Maastricht University, Maastricht, the Netherlands.
Frans R J VerheyDepartment of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML), Mental Health and Neuroscience Research Institute (Mhens), Maastricht University, Maastricht, the Netherlands.
Bart P F RuttenDepartment of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML), Mental Health and Neuroscience Research Institute (Mhens), Maastricht University, Maastricht, the Netherlands.
Sebastian KöhlerDepartment of Psychiatry and Neuropsychology, European Graduate School of Neuroscience (EURON), Faculty of Health, Medicine and Life Sciences (FHML), Mental Health and Neuroscience Research Institute (Mhens), Maastricht University, Maastricht, the Netherlands. s.koehler@maastrichtuniversity.nl.ORCID http://orcid.org/0000-0002-2398-0609

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The kynurenine pathway (KP) might be involved in pathophysiological processes associated with dementia, but clinical studies reported contradictory results. This systematic review and meta-analysis summarized the available evidence for (i) differences in KP metabolites in patients with cognitive impairment compared to cognitively healthy individuals and (ii) associations between KP metabolites and cognitive functioning. English, full-length articles with prospective, cross-sectional, or case-control study designs, published in Pubmed, Embase, PsychINFO, or the Cochrane Database of Systematic Reviews up to October 2023, were included. Random-effects meta-analyses of standardized mean differences (SMD) were performed. Heterogeneity, meta-regression, small study bias, and study quality assessments were carried out. Of 8797 retrieved studies, 98 were eligible for the systematic review. Meta-analyses comparing Alzheimer's disease (AD) dementia patients to controls (n = 27 studies) indicated lower CSF levels of tryptophan (SMD = - 0.26 [95% CI - 0.41, - 0.12]), 3-hydroxykynurenine (- 0.21 [- 0.39, - 0.04]), anthranilic acid (- 0.28 [- 0.48, - 0.08]), and quinolinic acid (- 0.38 [- 0.56, - 0.21]) in AD dementia, while CSF levels of kynurenic acid were higher (0.18 [0.01, 0.35]). Blood levels of tryptophan (- 0.39 [- 0.51, - 0.28]), kynurenic acid (- 0.31 [- 0.47, - 0.15]), xanthurenic acid (- 0.34 [- 0.54, - 0.15]), and 3-hydroxyanthranilic acid (- 0.42 [- 0.61, - 0.22]) were lower in AD dementia. For some of these metabolites, similar directions were observed in meta-analyses comparing individuals with mild cognitive impairment with controls, although the number of included studies in these analyses was relatively small (n = 11). Associations with cognitive test scores were inconclusive and generally non-significant. These results suggest that AD dementia is associated with lower blood levels of several KP metabolites. Findings challenge current assumptions of neurotoxic quinolinic acid levels being associated with dementia.

Indexed as

Cognitive DysfunctionDementiaKynurenineHumansTryptophanKynurenineTryptophanAlzheimer’s diseaseCognitive functioningCognitive impairmentDementiaKynurenine pathwayKynurenines

Identifiers

PMID40338439
PMCPMC13356250

What Socratic holds

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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 Socratic graph.