{
  "abstract": "Background: Insulin resistance–related metabolic burden is associated with cognitive aging, but the relevant white matter microstructural features remain unclear. We examined statistical indirect associations between metabolic indices and cognition through tract-level white matter measures, including associations with subsequent cognitive change.\n\nMethods: Cross-sectional and longitudinal analyses used Health and Aging Brain Study–Health Disparities (HABS-HD) data. Exposures were the triglyceride–glucose (TyG) index and its composites with waist-to-height ratio (TyG-WHtR) and visceral adiposity index (TyG-VAI). Candidate mediators were axial and radial diffusivity (RD) in 32 white matter tracts; outcomes covered six cognitive domains. High-dimensional mediation analysis with within-model false discovery rate (FDR) correction selected candidate pathways, supplemented by model-level multiplicity analyses. Selection stability was assessed using 1,000 participant-level bootstrap samples. All candidates underwent longitudinal mixed-effects analysis, with indirect estimates calculated as baseline exposure–white matter coefficients multiplied by white matter-by-time coefficients. Intervals used 2,000 participant-level cluster bootstrap samples. Sensitivity analyses adjusted for white matter hyperintensity (WMH) volume and covariate-by-time interactions.\n\nResults: Of 2,606 participants, 788 had two cognitive assessments a median of 2.17 years apart. Fourteen candidate pathways were selected, all involving RD and TyG or TyG-WHtR; 11 had 95% conditional Monte Carlo uncertainty intervals excluding zero. Two of 36 models met the supplementary model-level FDR criterion. Five longitudinal pathways had negative indirect estimates with 95% bootstrap intervals excluding zero: four involved right cingulum RD and processing speed or executive function, and one involved right superior corona radiata RD and processing speed. Four also met the FDR criterion for RD-by-time interactions. The TyG-WHtR–right cingulum RD–executive function indirect estimate was -0.0054 per year (95% bootstrap interval, -0.0110 to -0.0009). Selection frequencies ranged from 6.7% to 42.0%. After WMH and WMH-by-time adjustment, intervals excluded zero for two of these five pathways, decreasing to one with additional core covariate-by-time interactions.\n\nConclusion: Triglyceride–glucose index and TyG-WHtR showed statistical indirect associations with cognition through white matter RD, with some pathways associated with subsequent cognitive change. Limited selection stability and sensitivity to WMH and covariate-by-time adjustment warrant evaluation in independent cohorts.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Radiology, The Second Affiliated Hospital of Xiamen Medical College , ,",
    "Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Hunan University of Medicine , ,",
    "Department of Cardiology, Xiamen Humanity Hospital, Fujian Medical University, Xiamen , ,",
    "Department of Neurology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University , ,",
    "Department of Radiology, The First Affiliated Hospital of Hunan University of Medicine , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Huaiyi Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhiliang Tian"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiaoqian Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Weiwei Gao"
    },
    {
      "affs": [
        4
      ],
      "name": "Jingjing She"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0dscvjqmkszn6.bib",
  "cited_by": 0,
  "doi": "10.3389/fnins.2026.1967890",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668860/?tool=EBI",
  "id": "0dscvjqmkszn6",
  "issns": [
    "1662-4548",
    "1662-453X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13668860",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7215125602",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668860/pdf/?tool=EBI",
  "pmcid": "PMC13668860",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/0dscvjqmkszn6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13668860",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13668860"
    },
    {
      "first_seen": "2026-10-30T12:19:23Z",
      "native_id": "10.3389/fnins.2026.1967890",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fnins.2026.1967890/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Dementia and Cognitive Impairment Research",
      "subfield": "psychiatry"
    }
  ],
  "title": "Insulin resistance–related metabolic burden, white matter microstructure, and cognitive change: the HABS-HD study",
  "title_text": "Insulin resistance–related metabolic burden, white matter microstructure, and cognitive change: the HABS-HD study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:23Z",
  "url": "https://research.draconitic.com/paper/0dscvjqmkszn6",
  "venue": "Frontiers in neuroscience",
  "versions": []
}