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. 2025 Aug 13;11(1):240.
doi: 10.1038/s41531-025-01100-1.

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

Huimin Cao  1   2 , Yuying Zhao  1 , Ziyi Chen  1 , Xiaoya Zou  1 , Xinyi Du  1 , Li Yi  1 , Yu Ai  1 , Hongzhou Zuo  3 , Oumei Cheng  4   5 ; Parkinson’s Progression Markers Initiative
Collaborators, Affiliations

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

Huimin Cao et al. NPJ Parkinsons Dis. .

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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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. TyG levels of PD patients in different diagnostic groups.
A Comparison of the primary cohort; B Analysis of PPMI cohort. Abbreviations: TyG Triglyceride-glucose, PDNC Parkinson disease with normal cognitive, PDMCI Parkinson disease with mild cognitive impairment, PDD Parkinson disease dementia.
Fig. 2
Fig. 2. Curve fitting and subgroup analysis.
A Curve fitting of TyG and PDD; B Forest plot of TyG and MMSE scores. adjusting for Model3. Abbreviations: TyG Triglyceride-glucose, PDD Parkinson disease dementia, H&Y Hoehn and Yahr scale, HAMD Hamilton depression scale, BMI Body Mass Index.
Fig. 3
Fig. 3. Relationship between TyG and longitudinal cognitive decline and reduction of DAT activity in the caudate and putamen.
For visualization purposes, modeled longitudinal changes in MoCA scores (A) and reduction of DAT activity in the caudate (B) and putamen (C) are depicted in individuals with lower and higher levels of TyG index. Abbreviations: TyG Triglyceride-glucose, MoCA Montreal Cognitive Assessment, DAT dopamine transporter.
Fig. 4
Fig. 4. The relationships between CSF GLP-1R, TyG index and MoCA scores.
A Linear fitting graph of TyG index and CSF GLP-1R; B Mediation analysis about TyG index and CSF GLP-1R. Abbreviations: TyG Triglyceride-glucose; CSF GLP-1R cerebrospinal fluid glucagon-like peptide 1 receptor, MoCA Montreal Cognitive Assessment, DAT dopamine transporter.
See this image and copyright information in PMC

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