{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T06:27:52Z","timestamp":1786343272484,"version":"build-2736575974"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cerebral small vessel disease (CSVD) may worsen motor and cognitive impairment in Parkinson\u2019s disease (PD), yet whether peripheral metabolic inflammation mediates this link remains unclear. The triglyceride-glucose (TyG) index, a surrogate for insulin resistance, has been associated with CSVD and neurodegeneration. This study examined whether the TyG index statistically accounts for the association between CSVD burden and motor or cognitive deficits in PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cross-sectional study enrolled 362 PD patients. The 4-point scale assessed CSVD burden. Movement Disorder Society Unified Parkinson\u2019s Disease Rating Scale part III (MDS-UPDRS III) and Montreal Cognitive Assessment (MoCA) evaluated motor and cognitive function, separately. Spearman correlation and mediation analyses were performed, adjusting for age, sex, education, hypertension, diabetes, and daily dose equivalent of levodopa. Sensitivity analyses were conducted to assess the robustness and specificity of the findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CSVD burden was positively associated with MDS-UPDRS III (total effect\u202f=\u202f2.309, 95% CI [0.463, 4.155,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.014]) and negatively associated with TyG index (\n                      <jats:italic>a<\/jats:italic>\n                      \u202f=\u202f\u22120.067,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.025). TyG index was negatively associated with MDS-UPDRS III (\n                      <jats:italic>b<\/jats:italic>\n                      \u202f=\u202f\u22126.561,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). The indirect effect was 0.441 (95% CI [0.048, 0.958]), accounting for 19.1% of the total effect. This mediation was specific to TyG, as four alternative inflammatory indices showed no significant effects. Additional analyses adjusting for disease duration and Hoehn-Yahr staging confirmed robustness [indirect effect\u202f=\u202f0.288, 95% CI (0.019, 0.687)]. Neither fasting triglycerides nor glucose alone mediated the effect. No mediation was found for cognition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The TyG index statistically accounts for part of the association between CSVD and motor function in PD via a negative-to-negative pathway, suggesting a hypothesis-generating metabolic target that warrants prospective investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1902923","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T05:30:28Z","timestamp":1786339828000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Triglyceride-glucose index is associated with cerebral small vessel disease-related motor impairment in Parkinson\u2019s disease: a mediation analysis"],"prefix":"10.3389","volume":"18","author":[{"given":"Meimei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology II, Shaanxi Provincial People\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology II, Shaanxi Provincial People\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Zhang","sequence":"additional","affiliation":[{"name":"China National Clinical Research Center for Neurological Diseases (NCRC-ND)","place":["Beijing, China"]},{"name":"Department of Rehabilitation, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Feng","sequence":"additional","affiliation":[{"name":"China National Clinical Research Center for Neurological Diseases (NCRC-ND)","place":["Beijing, China"]},{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/s41531-025-01100-1","article-title":"Triglyceride-glucose index predicts cognitive decline and striatal dopamine deficiency in Parkinson disease in two cohorts","volume":"11","author":"Cao","year":"2025","journal-title":"NPJ Park. Dis."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.parkreldis.2020.12.025","article-title":"Cerebral small vessel disease may worsen motor function, cognition, and mood in Parkinson's disease","volume":"83","author":"Chen","year":"2021","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3617","DOI":"10.1007\/s10072-020-04452-z","article-title":"Effect of small vessel disease burden and lacunes on gait\/posture impairment in Parkinson's disease","volume":"41","author":"Chen","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1620118","DOI":"10.3389\/fnins.2025.1620118","article-title":"A high triglyceride-glucose index correlates with cognitive impairment in Parkinson's disease: a cross-sectional study","volume":"19","author":"Cheng","year":"2025","journal-title":"Front. Neurosci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"14574","DOI":"10.1038\/s41598-024-65396-4","article-title":"The association of regional cerebral blood flow and glucose metabolism in normative ageing and insulin resistance","volume":"14","author":"Deery","year":"2024","journal-title":"Sci. Rep."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e080952","DOI":"10.1136\/bmj-2024-080952","article-title":"Projections for prevalence of Parkinson's disease and its driving factors in 195 countries and territories to 2050: modelling study of global burden of disease study 2021","volume":"388","author":"Dongning","year":"2025","journal-title":"BMJ"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1161\/strokeaha.109.564914","article-title":"Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease","volume":"41","author":"Doubal","year":"2010","journal-title":"Stroke"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/s1474-4422(23)00131-x","article-title":"Neuroimaging standards for research into small vessel disease-advances since 2013","volume":"22","author":"Duering","year":"2023","journal-title":"Lancet Neurol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1212\/wnl.43.9.1683","article-title":"Pathologic correlates of incidental MRI white matter signal hyperintensities","volume":"43","author":"Fazekas","year":"1993","journal-title":"Neurology"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"8060259","DOI":"10.1155\/2020\/8060259","article-title":"Altered body composition and increased resting metabolic rate associated with the postural instability\/gait difficulty Parkinson's disease subtype","volume":"2020","author":"Femat-Rold\u00e1n","year":"2020","journal-title":"Parkinsons Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1686214","DOI":"10.3389\/fnagi.2025.1686214","article-title":"Correlation between cerebral small vessel disease and postural instability\/gait difficulty subtype in Parkinson's disease patients","volume":"17","author":"Ge","year":"2025","journal-title":"Front. Aging Neurosci."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1212\/WNL.0b013e3181c34a7d","article-title":"The microbleed anatomical rating scale (MARS): reliability of a tool to map brain microbleeds","volume":"73","author":"Gregoire","year":"2009","journal-title":"Neurology"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"156272","DOI":"10.1016\/j.metabol.2025.156272","article-title":"Sarcopenia in Parkinson's disease: from pathogenesis to interventions","volume":"169","author":"Gui","year":"2025","journal-title":"Metabolism"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s10571-026-01708-8","article-title":"Peripheral inflammatory biomarkers in Parkinson's disease: clinical correlations and stratification","volume":"46","author":"Jiang","year":"2026","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"603","DOI":"10.2147\/ijgm.S346997","article-title":"Relationship of the triglyceride-glucose index with subclinical white matter hypersensitivities of presumed vascular origin among community-dwelling Koreans","volume":"15","author":"Jung","year":"2022","journal-title":"Int J Gen Med"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e13833","DOI":"10.1002\/jcsm.13833","article-title":"Associations of handgrip strength and testosterone with cerebral white matter hyperintensity and microstructural injury","volume":"16","author":"Li","year":"2025","journal-title":"J. Cachexia. Sarcopenia Muscle"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1736318","DOI":"10.3389\/fneur.2026.1736318","article-title":"Correlation of systemic immune inflammation index and systemic inflammatory response index with the severity of Parkinson's disease","volume":"17","author":"Li","year":"2026","journal-title":"Front. Neurol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"493","DOI":"10.3390\/biomedicines14030493","article-title":"Insulin resistance surrogates and cognitive impairment in Parkinson's disease: a cross-sectional study with interpretable machine learning","volume":"14","author":"Liang","year":"2026","journal-title":"Biomedicine"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1512109","DOI":"10.3389\/fneur.2025.1512109","article-title":"Association between cerebral small vessel disease and malnutrition risk: a retrospective cross-sectional study","volume":"16","author":"Liu","year":"2025","journal-title":"Front. Neurol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1177\/1877718x251316552","article-title":"Aging, cellular senescence and Parkinson's disease","volume":"15","author":"Ma","year":"","journal-title":"J. Parkinsons Dis."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"108070","DOI":"10.1016\/j.parkreldis.2025.108070","article-title":"The interplay between obesity and triglyceride-glucose index in modulating Parkinson's disease risk: a cross-sectional NHANES study of middle-aged and young adults","volume":"140","author":"Ma","year":"","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12933-020-01031-6","article-title":"High triglyceride-glucose index is associated with subclinical cerebral small vessel disease in a healthy population: a cross-sectional study","volume":"19","author":"Nam","year":"2020","journal-title":"Cardiovasc. Diabetol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"101979","DOI":"10.1016\/j.arr.2023.101979","article-title":"Antidiabetic agents as a novel treatment for Alzheimer's and Parkinson's disease","volume":"89","author":"Nowell","year":"2023","journal-title":"Ageing Res. Rev."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1476701","DOI":"10.3389\/fnagi.2024.1476701","article-title":"Total burden of cerebral small vessel disease predict subjective cognitive decline in patients with Parkinson's disease","volume":"16","author":"Qiu","year":"2024","journal-title":"Front. Aging Neurosci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1212\/wnl.0000000000000837","article-title":"Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden","volume":"83","author":"Staals","year":"2014","journal-title":"Neurology"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1760558","DOI":"10.3389\/fnins.2026.1760558","article-title":"Insulin resistance in cerebral small vessel disease: a mini review","volume":"20","author":"Su","year":"2026","journal-title":"Front. Neurosci."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s00455-015-9671-9","article-title":"Dysphagia in Parkinson's disease","volume":"31","author":"Suttrup","year":"2016","journal-title":"Dysphagia"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"970122","DOI":"10.3389\/fendo.2022.970122","article-title":"Triglyceride glucose index is associated with cerebral small vessel disease burden and cognitive impairment in elderly patients with type 2 diabetes mellitus","volume":"13","author":"Teng","year":"2022","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s10522-025-10250-x","article-title":"Circulating immune cells in cerebral small vessel disease: a systematic review","volume":"26","author":"Van der Taelen","year":"2025","journal-title":"Biogerontology"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/s1474-4422(13)70124-8","article-title":"Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration","volume":"12","author":"Wardlaw","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"S129","DOI":"10.3233\/jpd-223241","article-title":"Central and peripheral inflammation: connecting the immune responses of Parkinson's disease","volume":"12","author":"Williams","year":"2022","journal-title":"J. Parkinsons Dis."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.neurobiolaging.2024.02.007","article-title":"Association of peripheral immunity and cerebral small vessel disease in older adults without dementia: a longitudinal study","volume":"137","author":"Xiao","year":"2024","journal-title":"Neurobiol. Aging"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1538028","DOI":"10.3389\/fneur.2025.1538028","article-title":"Analysis of the correlation between peripheral blood inflammatory markers and imaging burden of cerebral small vessel disease","volume":"16","author":"Yang","year":"2025","journal-title":"Front. Neurol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"5343","DOI":"10.1007\/s10072-022-06113-9","article-title":"Lower serum triglyceride levels linked to more severe motor performance in Parkinson's disease","volume":"43","author":"Zhang","year":"2022","journal-title":"Neurol. Sci."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1902923\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T05:30:29Z","timestamp":1786339829000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1902923\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":34,"alternative-id":["10.3389\/fnagi.2026.1902923"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2026.1902923","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"article-number":"1902923"}}