Causal relationship between multiparameter brain MRI phenotypes and age: evidence from Mendelian randomization
Wang X, Chen Q, Liu Y, Sun J, Li J, Zhao P, Cai L, Liu W, Yang Z, Wang Z, Lv H.
- DOI
- 10.1093/braincomms/fcae077
- Record issued
- 2026-08-05
- Engine
- 7.15.0
- Exported
- 2026-09-20
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/c02a7ede-8446-4f80-a3c3-61d70d615161 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×2−1★
- ReportingBiological variables not met−0.5★
- ReportingData & code availability not met−0.5★
- ReportingStudy design partially met−0.25★
- ReportingStatistical analysis partially met−0.25★
- References were not verified against Crossref/OpenAlex.
- Statistics were not checked: no recomputable values were found in this text — no test statistic reported with its degrees of freedom, no effect estimate printed with both a 95% CI and a p-value, and no percentage printed with both its count and its denominator.
- 01Biological variables not reported
The paper does not report key biological variables such as age, sex, and health status for the brain imaging GWAS sample, and only briefly mentions sex for the age GWAS.
“In the GWAS for age, the sample size was 11 856 individuals, including both males and females”
Methods - 02Data and code not shared
The data availability statement is vague, no data are deposited in a repository, no accession numbers are provided, and no custom code is shared.
“The datasets during and/or analysed during the current study are available from the corresponding author on reasonable request.”
Data availability
This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.
The paper is a Mendelian randomization study with a clear scientific premise and adequate reporting of methods and limitations. However, it lacks demographic details for the study populations, does not provide exact p-values or confidence intervals in the text, and has a vague data availability statement with no code sharing.
The evaluation was based on three independent AI reviewer runs and a copyedit pass. Ethical approvals were not applicable as the study uses public summary data. The reviewers diverged on study design (pass vs. warn) and statistical analysis (pass vs. warn); the synthesized statuses reflect the preponderance of evidence.
Numerical inconsistencies
1 finding · worst lowValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Internal contradictions in the reported numbersAssessed
- lowinternal contradictionThe abstract reports a beta of 0.151 for WMHs, but the forest plot in Figure 2 may show a different value; the paper does not provide CI for this beta in the text.
Abstract: 'β = 0.151'; Results: 'β = 0.151, P < 0.05' (consistent).
Abstractreviewer’s wording
Overstated conclusions
None foundConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
Checked — nothing surfaced.
11 major claims checked against the paper's own evidence: all adequately supported.
- supportedReviewers 1, 2, 3Age is causally related to increased volumes of white matter hyperintensities.The MR analysis with IVW shows a significant positive beta (β = 0.151, P < 0.05), supported by sensitivity analyses.Evidence: Results paragraph 1: 'a positive trend of increasing white matter hyperintensities (WMHs) with advancing age was found (IVW, β = 0.151, P < 0.05).'
“a positive trend of increasing white matter hyperintensities (WMHs) with advancing age was found (IVW, β = 0.151, P < 0.05).”
Results ¶1 - supportedReviewer 1Age causally deteriorates white matter integrity in specific tracts, including the inferior cerebellar peduncle and cerebral peduncle.The paper reports significant beta values for DTI and NODDI parameters in these tracts, with statistical significance.Evidence: Results paragraph 2: 'decreases in the average diffusion coefficient for the inferior cerebellar peduncle (β = −0.128), cerebral peduncle (β = −0.136) and bilateral cingulum hippocampus.'
decreases in the average diffusion coefficient for the inferior cerebellar peduncle (β = −0.128), cerebral peduncle (β = −0.136) and bilateral cingulum hippocampus.
Results ¶2reviewer’s wording - supportedReviewer 1Age causally decreases cortical thickness in multiple frontal and temporal regions.The paper lists specific regions with reduced cortical thickness, such as the planum temporale and frontal lobe regions, with statistical significance.Evidence: Results paragraph 1: 'For cortical thickness, except for the Planum temporary ... the areas where cortical thickness decreased are located in the frontal lobe.'
For cortical thickness, except for the Planum temporary or temporary plane of the superior temporal gyrus (β = −0.125), the areas where cortical thickness decreased are located in the frontal lobe.
Results ¶1reviewer’s wording - supportedReviewer 1No causal association between age and cerebral microbleeds.The paper explicitly states that no positive results were found for microbleeds (IVW, P > 0.05).Evidence: Results paragraph 4: 'For cerebral microbleeds (SWI display), we did not find positive results (IVW, P > 0.05).'
“For cerebral microbleeds (SWI display), we did not find positive results (IVW, P > 0.05).”
Results ¶4 - supportedReviewer 2For white matter micro-integrity, fibres of the inferior cerebellar peduncle, cerebral peduncle, superior fronto-occipital fasciculus, and fibres within the limbic system were causally deteriorated.The paper reports specific β values and P-values for DTI and NODDI parameters in these regions, supporting the claim.Evidence: Results section: provides β values for specific regions (e.g., inferior cerebellar peduncle AD β = -0.128, ODI β = 0.173; cingulum hippocampus DTI and NODDI changes).
For the white matter integrity (DTI parameters)... decreases in the average diffusion coefficient for the inferior cerebellar peduncle ( β = −0.128), cerebral peduncle ( β = −0.136) and bilateral cingulum hippocampus (right: β = −0.227, left: β = −0.14) were found.
Results ¶2reviewer’s wording - supportedReviewer 2We also detected decreased cortical thickness of multiple frontal and temporal regions.The paper lists specific cortical regions with decreased thickness, e.g., planum temporale, and provides β values.Evidence: Results section: 'For cortical thickness, except for the Planum temporale... the areas where cortical thickness decreased are located in the frontal lobe.'
“We also detected decreased cortical thickness of multiple frontal and temporal regions ( P < 0.05).”
Results ¶1 - supportedReviewer 2Microbleeds were not related with aging.The paper explicitly states that no positive results were found for cerebral microbleeds, and this is consistent with the sensitivity analyses.Evidence: Results section: 'For cerebral microbleeds (SWI display), we did not find positive results (IVW, P > 0.05).'
“Microbleeds were not related with aging ( P > 0.05).”
Results ¶3 - supportedReviewers 2, 3Aging is a threat of brain health, leading to cortical atrophy mainly in the frontal lobes, as well as the white matter degeneration especially abnormal hyperintensity and deteriorated white matter integrity around the hippocampus.The paper's results support this summary: frontal/temporal cortical thinning, increased WMHs, and white matter changes in the limbic system.Evidence: Results and Discussion sections summarize these findings.
“Aging is a threat of brain health, leading to cortical atrophy mainly in the frontal lobes, as well as the white matter degeneration especially abnormal hyperintensity and deteriorated white matter integrity around the hippocampus.”
Conclusion - supportedReviewer 3Age causally deteriorates white matter micro-integrity in specific tracts (inferior cerebellar peduncle, cerebral peduncle, superior fronto-occipital fasciculus, limbic system).The MR results show significant beta values for these tracts in DTI and NODDI parameters, supporting the claim.Evidence: Abstract lists specific betas for these tracts. Results section provides details: 'axial diffusivity β = −0.128, orientation dispersion index β = 0.173' for inferior cerebellar peduncle, etc.
“For white matter micro-integrity, fibres of the inferior cerebellar peduncle (axial diffusivity β = −0.128, orientation dispersion index β = 0.173), cerebral peduncle (axial diffusivity β = −0.136), superior fronto-occipital fasciculus (isotropic volume fraction β = 0.163) and fibres within the limbic system were causally deteriorated.”
Abstract - supportedReviewer 3Aging leads to decreased cortical thickness of multiple frontal and temporal regions.The paper reports significant decreases in cortical thickness in frontal and temporal regions (P<0.05), supporting the claim.Evidence: Results: 'For cortical thickness, except for the Planum temporale... the areas where cortical thickness decreased are located in the frontal lobe.' Abstract states 'decreased cortical thickness of multiple frontal and temporal regions (P < 0.05).'
We also detected decreased cortical thickness of multiple frontal and temporal regions (P < 0.05).
Abstractreviewer’s wording - supportedReviewer 3Microbleeds are not causally related to aging.The MR analysis found no significant association (P>0.05), supporting the claim.Evidence: Results: 'For cerebral microbleeds (SWI display), we did not find positive results (IVW, P > 0.05).' Abstract: 'Microbleeds were not related with aging (P > 0.05).'
Microbleeds were not related with aging (P > 0.05).
Abstractreviewer’s wording
Data authenticity concerns
1 finding · worst lowAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
- Other integrity concernAssessed
2 integrity concerns flagged (0 high).
- lowotherThe paper does not adjust for multiple testing across many outcomes, increasing the risk of false positives.
Results with a bilateral P-value of <0.05 were assessed to determine statistical significance.
Resultsreviewer’s wording
Reporting gaps
4 findings · worst highRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Biological variables not reportedAssessed
- Data and code not sharedAssessed
- Statistical reporting gaps (tests, assumptions, effect sizes)Assessed
- Study-design details incomplete (controls, blinding, power)Assessed
The introduction reviews the literature on brain aging, highlighting the heterogeneity and limitations of cross-sectional studies. It clearly states the rationale for using MR to overcome confounding and reverse causation. The paper also discusses how MR addresses the limitations of prior research.
“MR is a method that utilizes genome-wide association study (GWAS) data to analyse and mitigate discrepancies in epidemiological research.”
“A large number of imaging-related studies are dedicated to revealing age-related changes, such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) or the Rotterdam study”
“Therefore, Mendelian randomization (MR) was used to explore the causal relationship between age (aging) and brain morphometric changes on neuroimaging.”
“In addition, observational studies have various confounding factors and biases, which are almost inevitable.”
“A large number of imaging-related studies are dedicated to revealing age-related changes, such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) or the Rotterdam study”
“If we base our understanding of age-related brain changes on neurodegenerative diseases alone, the regional changes in brain atrophy caused by these diseases will be more extensive, which cannot explain why these changes are completely caused by aging. There are many risk factors related to aging and brain health status, so it is difficult to eliminate the influence of confounding factors and explore the causal link between aging and brain alterations.”
“Although more and more studies are using MR analysis, this method itself is imperfect. The use of test hypotheses cannot avoid the generation of false positive results, which can lead to phenomena that do not match the facts”
The paper uses two-sample MR with IVW as primary analysis, MR-PRESSO for outlier removal, and sensitivity analyses. However, no a priori power calculation is reported, and the inclusion/exclusion criteria for the GWAS datasets are not explicitly stated. Outlier handling via MR-PRESSO is described. Randomization, blinding, and other experimental design elements are not applicable to this MR study.
“heterogeneity was evaluated, and multiple effects were tested using three distinct techniques: IVW, MR-Egger and weighted median regression.”
“SNPs and outliers associated with brain imaging, as identified by MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), were excluded.”
“SNPs and outliers associated with brain imaging, as identified by MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), were excluded.”
The paper states that the age GWAS includes both males and females, but no demographics are provided for the brain imaging GWAS from UK Biobank. Age, weight, health status, and race/ethnicity are not reported. Since the study relies on publicly available summary statistics, the original cohort characteristics are not described, which limits assessment of generalizability and potential confounding.
“In the GWAS for age, the sample size was 11 856 individuals, including both males and females”
“In the GWAS for age, the sample size was 11 856 individuals, including both males and females”
The paper uses only publicly available summary statistics from the UK Biobank and MRC-IEU. No individual-level data were accessed. The UK Biobank has its own ethics approval, but the current study does not generate new subject data, making ethics sub-criteria not applicable.
“The UK Biobank is a major prospective epidemiological study that includes multimodal brain imaging, genetics and sustained health outcomes, which is approved by the Northwest Multi-Centre Research Ethics Committee.”
“The UK Biobank is a major prospective epidemiological study that includes multimodal brain imaging, genetics and sustained health outcomes, which is approved by the Northwest Multi-Centre Research Ethics Committee.”
“The UK Biobank is a major prospective epidemiological study that includes multimodal brain imaging, genetics and sustained health outcomes, which is approved by the Northwest Multi-Centre Research Ethics Committee.”
The paper reports the use of R version 4.2.1 and the 'TwoSampleMR' package for statistical analysis. It also references the Oxford Brain Imaging Genetics web server. No antibodies, cell lines, or other wet-lab reagents were used, so those criteria are not applicable.
“All statistical analyses including MR and data visualization were performed using the ‘TwoSampleMR’ ( https://github.com/MRCIEU/TwoSampleMR ) in R (version 4.2.1).”
The paper names the IVW, MR-Egger, and weighted median methods. It reports p-values only as thresholds (P < 0.05) rather than exact values. Effect sizes (β) are reported but not always with confidence intervals; the forest plots show CIs, but the text does not. The software is identified. The paper does not report sample sizes for each outcome in the imaging GWAS, and the assumptions of the instrumental variable methods are not explicitly discussed, though pleiotropy and heterogeneity are tested. No individual data points are presented.
“a positive trend of increasing white matter hyperintensities (WMHs) with advancing age was found (IVW, β = 0.151, P < 0.05).”
“In MR analysis, heterogeneity was evaluated, and multiple effects were tested using three distinct techniques: IVW, MR-Egger and weighted median regression.”
“Results with a bilateral P -value of <0.05 were assessed to determine statistical significance.”
“a positive trend of increasing white matter hyperintensities (WMHs) with advancing age was found (IVW, β = 0.151, P < 0.05).”
“In MR analysis, heterogeneity was evaluated, and multiple effects were tested using three distinct techniques: IVW, MR-Egger and weighted median regression.”
“To comprehensively evaluate pleiotropy in the MR test, the MR Egger intercept test and retention analysis were applied. Cochran’s Q test was used in each MR analysis to detect heterogeneity between exposure and outcome”
The paper states that data are available from the corresponding author on reasonable request, which is considered inadequate. No repository deposit or accession numbers are provided for the GWAS summary statistics used. The code is limited to referencing the TwoSampleMR package; no custom scripts are shared. The paper also references the UK Biobank brain imaging website but does not provide a direct link to the specific data used.
“The datasets during and/or analysed during the current study are available from the corresponding author on reasonable request.”
“The datasets during and/or analysed during the current study are available from the corresponding author on reasonable request.”
“The datasets during and/or analysed during the current study are available from the corresponding author on reasonable request.”
The paper includes a STROBE-MR statement, comprehensive methods, results, and a dedicated limitations section. All pre-specified outcomes are reported, including negative results for microbleeds. Funding sources and conflicts of interest are stated.
“In this study, we followed the principles of the STROBE-MR (strengthening the reporting of observational studies in epidemiology using mendelian randomization) statement”
“However, there are inevitably some limitations: (i) although more and more studies are using MR analysis, this method itself is imperfect.”
“For cerebral microbleeds (SWI display), we did not find positive results (IVW, P > 0.05).”
“In this study, we followed the principles of the STROBE-MR (strengthening the reporting of observational studies in epidemiology using mendelian randomization) statement”
“However, there are inevitably some limitations: (i) although more and more studies are using MR analysis, this method itself is imperfect.”
“In this study, we followed the principles of the STROBE-MR (strengthening the reporting of observational studies in epidemiology using mendelian randomization) statement”
No trial/study registration detected. Reporting guideline cited: STROBE.
Broken references and links
None foundReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
Checked — nothing surfaced.
3 data/code links checked; 3 live.
- datahttps://open.win.ox.ac.uk/ukbiobank/big40/LIVEHTTP 200Resolved page looks like data.
- datahttps://www.fmrib.ox.ac.uk/ukbiobank/index.htmlLIVEHTTP 200Resolves, but the content could not be matched to the paper.
- codeGitHubLIVEHTTP 200https://github.com/MRCIEU/TwoSampleMRResolves to GitHub (code repository).
Copyediting
13 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 13 minor suggestions below.
13 copyedit issues flagged: mostly clarity, grammar, consistency.
- MINORconsistencyAbstract, line 1“To explore the causal relationship between age and brain health (cortical atrophy, white matter integrity, white matter hyperintensities and cerebral microbleeds in various brain regions) related multiparameter imaging features”→ Consider rephrasing for clarity: 'To explore the causal relationship between age and multiparameter brain imaging features related to brain health, including cortical atrophy, white matter integrity, white matter hyperintensities, and cerebral microbleeds in various brain regions.'The original sentence is a bit tangled.
- MINORgrammarResults, paragraph 1“we found that the volumes of the right lateral occidental cortex and left intragalarine cortex were significantly decreased”→ Correct 'intragalarine' to 'intracalcarine' (standard terminology).Typo: 'intragalarine' should be 'intracalcarine'.
- MINORclarityDiscussion, paragraph 2“The anterior cingulate cortex (ACC) is considered the neuroanatomical interface between emotion and cognition, and we found a causal relationship between aging and a decrease of the cortical area in ACC.”→ Specify that the decrease is in surface area, as earlier in the results it is reported as 'surface area'.This clarifies the metric.
- MINORgrammarIntroduction, paragraph 1“the number, diameter and length of dendrites per neuron decreases”→ the number, diameter and length of dendrites per neuron decreaseSubject-verb agreement: 'number' is singular but the list is plural, use 'decrease'.
- MINORclarityAbstract“Age is causally related to increased volumes of white matter hyperintensities ( β = 0.151).”→ Consider adding a confidence interval to the beta estimate.Repetition of 'causally' in abstract and discussion.
- MINORgrammarResults, paragraph 1“the volumes of the right lateral occidental cortex and left intragalarine cortex were significantly decreased”→ the volumes of the right lateral occipital cortex and left intracalcarine cortex were significantly decreasedTypographical errors: 'occidental' should be 'occipital', 'intragalarine' should be 'intracalcarine'.
- MINORconsistencyThroughout“WHMs”→ WMHsInconsistent abbreviation: sometimes 'WHMs', sometimes 'WMHs'. Standardize to 'WMHs'.
- MINORclarityDiscussion, paragraph 1“between the brain (including the cerebellum) and the spinal cord”→ between the brain (including the cerebellum) and the spinal cordAwkward phrasing; consider rephrasing.
- MINORclarityMaterials and methods, GWAS statistics of brain imaging derived phenotypes“neural orientation dispersion and density imaging (NODDI)”→ Change to 'neurite orientation dispersion and density imaging (NODDI)' for standard terminology.Term is slightly non-standard.
- MINORclarityIntroduction, paragraph 2“The collection of longitudinal imaging data necessitates the registration of consecutive brain scans and the use of physics-based models to interpret the resulting data.”→ Consider rewording for clarity: 'Collecting longitudinal imaging data requires registering consecutive brain scans and using physics-based models to interpret the results.'Run-on sentence.
- MINORclarityIntroduction, paragraph 3“There are many risk factors related to aging and brain health status, so it is difficult to eliminate the influence of confounding factors and explore the causal link between aging and brain alterations.”→ Simplify: 'Many risk factors are related to aging and brain health, making it difficult to eliminate confounding and explore causal links.'Awkward phrasing.
- MINORclarityStrength and limitations“The method selected in this paper is two-sample MR, which may adversely affect the data overlap”→ Clarify: 'The two-sample MR design may be affected by sample overlap between the exposure and outcome GWAS.'Unclear meaning.
- MINORclarityStrength and limitations“Although we conducted a sensitivity analysis, neuroimaging data needs to avoid biased estimation of effects in order to reveal complex relationships between features and phenotypes, clinical biomarkers, genetic variations and brain related health indicators”→ Break into shorter sentences: 'Although we conducted a sensitivity analysis, neuroimaging data require careful handling to avoid biased estimation. This is necessary to reveal complex relationships among features, phenotypes, clinical biomarkers, genetic variations, and brain health indicators.'Run-on sentence.
In a post-publication audit, the paper is moderately robust but has notable reporting gaps. An informed reader should weigh the missing participant demographics and the lack of exact p-values and confidence intervals in the text. The authors should consider issuing a correction or supplement to address the data and code availability statement, and to provide demographic details for the GWAS samples.
- 1.HIGHdata codeReplace the vague data availability statement ('available on reasonable request') with a concrete repository link (e.g., Zenodo, Figshare) or managed-access platform with conditions, and deposit the GWAS summary statistics used.The current statement is insufficient for reproducibility and would not meet the standards of most journals; a correction or supplement is warranted.
- 2.HIGHdata codeDeposit the custom analysis scripts (e.g., R code for SNP selection, MR-PRESSO, and visualization) in a public repository (e.g., GitHub, Zenodo) with a persistent identifier.Without code, the analysis cannot be fully reproduced, undermining the study's robustness.
- 3.HIGHrigorReport the demographic characteristics (age, sex distribution, health status, race/ethnicity) of the participants in the UK Biobank brain imaging GWAS sample in the Methods section.Missing demographics limit assessment of generalizability and potential confounding, and are essential for interpreting the study's applicability.
- 4.HIGHstatisticsProvide exact p-values (e.g., p = 0.023) instead of thresholds (P < 0.05) for all reported results in the text and tables.Threshold-only p-values obscure the strength of evidence and are considered imprecise reporting; exact values allow readers to assess significance appropriately.
- 5.HIGHstatisticsInclude 95% confidence intervals for all causal effect estimates (β) in the Results text, not just in forest plots.Confidence intervals convey precision and are standard for reporting effect sizes; their absence in the text is a notable gap.
- 6.HIGHreportingAdd a formal conflicts-of-interest statement (e.g., 'The authors declare no competing interests') in the Declarations section.A missing COI statement is a standard reporting requirement and its absence may raise concerns about undisclosed conflicts.
- 7.MEDIUMrigorReport a power analysis or sample size justification for the MR analysis, including expected effect sizes and number of SNPs, in the Methods section.A power analysis helps assess whether the study was adequately powered to detect the hypothesized effects.
- 8.MEDIUMrigorState the inclusion/exclusion criteria for the GWAS datasets used (e.g., UK Biobank, MRC-IEU) in the Methods section.Explicit dataset selection criteria are needed to understand the study population and potential biases.
- 9.MEDIUMstatisticsAddress multiple testing across the many outcomes and brain regions tested, e.g., by applying a Bonferroni or FDR correction, or by clearly stating that the results are exploratory.Without correction, the risk of false positives is elevated, and readers should be informed of this limitation.
- 10.MEDIUMcopyeditCorrect typographical errors: change 'intragalarine' to 'intracalcarine' and 'occidental' to 'occipital' in the Results section.Typographical errors in anatomical terms could mislead readers and undermine precision.
- 11.MEDIUMcopyeditStandardize the abbreviation for white matter hyperintensities to 'WMHs' throughout the manuscript (currently sometimes 'WHMs').Inconsistent abbreviations cause confusion and should be harmonized.
- 12.LOWreportingClarify the potential impact of sample overlap between the exposure and outcome GWAS in the limitations section.The two-sample MR design assumes no sample overlap; the paper should discuss whether this assumption is violated and the potential consequences.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.