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PubMed · 41006106

Association Between Ratio of Triglycerides to HDL-C and Cognitive Impairment: A Longitudinal Population-Based Analysis and Mendelian Randomization Study.

Yucheng Huang·Lijia Zheng·Meng-Meng Lyu
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Abstract

OBJECTIVES: This study aimed to explore the longitudinal association between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and cognitive impairment in older adults and further assess potential causality using Mendelian randomization (MR). DESIGN: Longitudinal population-based analysis combined with two-sample MR. Data from Waves 6-8 (2015-2019) of the Survey of Health, Ageing, and Retirement in Europe (SHARE) were analyzed using hierarchical regression models and mixed linear effects models. MR utilized genome-wide association studies (GWAS) summary data. PARTICIPANTS: 11,444 adults aged &#x2265;60 years from SHARE Wave 6, with longitudinal follow-up in Waves 7 (N = 2,775) and 8 (N = 5,469). MEASUREMENTS: TG/HDL-C ratio, cognitive function (orientation, immediate/delayed recall, verbal fluency, numeracy), and cognitive impairment (defined as scores >1.5 SD below age-group mean). Covariates included socio-demographics, health behaviors, comorbidities, and national-level factors. MR employed genetic variants associated with TG/HDL-C as instrumental variables. RESULTS: Higher TG/HDL-C ratios were negatively associated with total cognitive scores (&#x3b2; = -0.115, &#x3c7;&#xb2; = 15.44, df = 1, p < 0.001), immediate recall (&#x3b2; = -0.029, &#x3c7;&#xb2; = 12.34, df = 1, p < 0.001), delayed recall (&#x3b2; = -0.028, &#x3c7;&#xb2; = 7.33, df = 1, p < 0.001), verbal fluency (&#x3b2; = -0.038, &#x3c7;&#xb2; = 11.53, df = 1, p < 0.001), and numeracy (&#x3b2; = -0.019, &#x3c7;&#xb2; = 4.55, df = 1, p < 0.05) in fully adjusted models. Longitudinal analysis revealed increased cognitive impairment risk in the highest TG/HDL-C quartile (OR=1.43, 95% CI:1.01-2.03, &#x3c7;&#xb2; = 9.24, df = 1) over 4 years. MR supported a causal link between elevated TG/HDL-C and cognitive decline. CONCLUSIONS: Elevated TG/HDL-C ratios are longitudinally associated with cognitive decline in older adults. Managing lipid metabolism may mitigate cognitive impairment, highlighting the importance of TG/HDL-C as a modifiable risk factor in aging populations.

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HumansMendelian Randomization AnalysisCognitive DysfunctionTriglyceridesLongitudinal StudiesMaleAgedFemaleCholesterol, HDLMiddle AgedGenome-Wide Association StudyEuropeSHARETG/HDL-C ratioscognitive impairmentmendelian randomizationmultilevel analysisJournal Article

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Yucheng Huang, Lijia Zheng, Meng-Meng Lyu. 2025-09-02. Association Between Ratio of Triglycerides to HDL-C and Cognitive Impairment: A Longitudinal Population-Based Analysis and Mendelian Randomization Study.. https://doi.org/10.1016/j.jagp.2025.08.007

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