Triglyceride-glucose index predicts cognitive decline and striatal dopamine deficiency in Parkinson disease in two cohorts

Abstract Heterogeneity is an important feature of cognitive impairment in patients with Parkinson’s disease (PD), with emerging evidence linking insulin resistance to accelerated cognitive decline. Our investigation examined the relationship between the triglyceride-glucose (TyG) index-a marker of i...

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Main Authors: Huimin Cao, Yuying Zhao, Ziyi Chen, Xiaoya Zou, Xinyi Du, Li Yi, Yu Ai, Hongzhou Zuo, Oumei Cheng, Parkinson’s Progression Markers Initiative
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-025-01100-1
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author Huimin Cao
Yuying Zhao
Ziyi Chen
Xiaoya Zou
Xinyi Du
Li Yi
Yu Ai
Hongzhou Zuo
Oumei Cheng
Parkinson’s Progression Markers Initiative
author_facet Huimin Cao
Yuying Zhao
Ziyi Chen
Xiaoya Zou
Xinyi Du
Li Yi
Yu Ai
Hongzhou Zuo
Oumei Cheng
Parkinson’s Progression Markers Initiative
author_sort Huimin Cao
collection DOAJ
description Abstract Heterogeneity is an important feature of cognitive impairment in patients with Parkinson’s disease (PD), with emerging evidence linking insulin resistance to accelerated cognitive decline. Our investigation examined the relationship between the triglyceride-glucose (TyG) index-a marker of insulin resistance-and cognition and striatal dopamine transporter (DAT) alterations in PD through cross-sectional and longitudinal analyses. In the primary cohort, higher TyG correlated with lower Mini-Mental State Examination (MMSE) scores (p < 0.001) and increased dementia risk (p = 0.014). Longitudinal analysis in the PPMI cohort showed higher baseline TyG predicted greater Montreal Cognitive Assessment (MoCA) decline (p = 0.019) and reduced DAT activity in caudate (p = 0.033) and putamen (p = 0.019) over 4 years.DAT activity in the caudate mediated 24.1% of the TyG index’s longitudinal effect on MoCA scores, while the TyG index mediated 16.9% of CSF GLP-1R’s effect. These results highlight the TyG index as a potential biomarker for identifying PD patients at higher risk of cognitive impairment.
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institution Kabale University
issn 2373-8057
language English
publishDate 2025-08-01
publisher Nature Portfolio
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series npj Parkinson's Disease
spelling doaj-art-118b78d12a4f4cc69632cd99833b3cbc2025-08-20T03:45:57ZengNature Portfolionpj Parkinson's Disease2373-80572025-08-011111910.1038/s41531-025-01100-1Triglyceride-glucose index predicts cognitive decline and striatal dopamine deficiency in Parkinson disease in two cohortsHuimin Cao0Yuying Zhao1Ziyi Chen2Xiaoya Zou3Xinyi Du4Li Yi5Yu Ai6Hongzhou Zuo7Oumei Cheng8Parkinson’s Progression Markers InitiativeDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Heterogeneity is an important feature of cognitive impairment in patients with Parkinson’s disease (PD), with emerging evidence linking insulin resistance to accelerated cognitive decline. Our investigation examined the relationship between the triglyceride-glucose (TyG) index-a marker of insulin resistance-and cognition and striatal dopamine transporter (DAT) alterations in PD through cross-sectional and longitudinal analyses. In the primary cohort, higher TyG correlated with lower Mini-Mental State Examination (MMSE) scores (p < 0.001) and increased dementia risk (p = 0.014). Longitudinal analysis in the PPMI cohort showed higher baseline TyG predicted greater Montreal Cognitive Assessment (MoCA) decline (p = 0.019) and reduced DAT activity in caudate (p = 0.033) and putamen (p = 0.019) over 4 years.DAT activity in the caudate mediated 24.1% of the TyG index’s longitudinal effect on MoCA scores, while the TyG index mediated 16.9% of CSF GLP-1R’s effect. These results highlight the TyG index as a potential biomarker for identifying PD patients at higher risk of cognitive impairment.https://doi.org/10.1038/s41531-025-01100-1
spellingShingle Huimin Cao
Yuying Zhao
Ziyi Chen
Xiaoya Zou
Xinyi Du
Li Yi
Yu Ai
Hongzhou Zuo
Oumei Cheng
Parkinson’s Progression Markers Initiative
Triglyceride-glucose index predicts cognitive decline and striatal dopamine deficiency in Parkinson disease in two cohorts
npj Parkinson's Disease
title Triglyceride-glucose index predicts cognitive decline and striatal dopamine deficiency in Parkinson disease in two cohorts
title_full Triglyceride-glucose index predicts cognitive decline and striatal dopamine deficiency in Parkinson disease in two cohorts
title_fullStr Triglyceride-glucose index predicts cognitive decline and striatal dopamine deficiency in Parkinson disease in two cohorts
title_full_unstemmed Triglyceride-glucose index predicts cognitive decline and striatal dopamine deficiency in Parkinson disease in two cohorts
title_short Triglyceride-glucose index predicts cognitive decline and striatal dopamine deficiency in Parkinson disease in two cohorts
title_sort triglyceride glucose index predicts cognitive decline and striatal dopamine deficiency in parkinson disease in two cohorts
url https://doi.org/10.1038/s41531-025-01100-1
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