Serena Low, Angela Moh, Bhuvaneswari Pandian, Huili Zheng, Sharon Pek, Jian-Jun Liu, Keven Ang, Tsz Kiu Kwan, Wern Ee Tang, Ziliang Lim, Tavintharan Subramaniam, Chee Fang Sum, Su Chi Lim
{"title":"交叉滞后面板分析和富含亮氨酸的α-2糖蛋白1介导的双重产物与2型糖尿病认知功能下降有纵向关联。","authors":"Serena Low, Angela Moh, Bhuvaneswari Pandian, Huili Zheng, Sharon Pek, Jian-Jun Liu, Keven Ang, Tsz Kiu Kwan, Wern Ee Tang, Ziliang Lim, Tavintharan Subramaniam, Chee Fang Sum, Su Chi Lim","doi":"10.1177/13872877251344881","DOIUrl":null,"url":null,"abstract":"<p><p>BackgroundElevated systolic blood pressure (SBP) and resting heart rate (RHR) contribute to pathogenesis of diabetic complications. They increase inflammation which can upregulate leucine-rich α-2-glycoprotein 1 (LRG1), an emerging biomarker of cognitive decline.ObjectiveTo examine association between double product (DP, derived from multiplying SBP and RHR) and cognitive function in type 2 diabetes (T2D), with possible mediation by plasma LRG1.MethodsIn this prospective cohort of 1319 patients (mean age 62.5 ± 7.3), plasma LRG1 was measured with enzyme-linked immunosorbent assay. Cognitive function was assessed using Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Cross-lagged panel analysis was done to examine temporal relationship between DP and cognitive function.ResultsBaseline DP was associated with lower baseline RBANS total score (adjusted coefficient = -2.43; 95%CI -4.76, -0.10; p = 0.041). 586 patients were followed up to 8.6 years. Baseline DP was associated with follow-up RBANS total score (adjusted coefficient = -3.80; 95%CI -6.51, -1.10; p = 0.006). It was also associated with lower follow-up RBANS scores in immediate memory and delayed memory with adjusted coefficients -4.38 (95%CI -8.49, -0.28; p = 0.036) and -5.12 (95%CI -9.88, -0.35; p = 0.035) respectively. In cross-lagged panel analysis, standardized effect size of baseline DP on follow-up RBANS total score (β = -0.08; p = 0.002) was larger than that of baseline RBANS total score on follow-up DP (β = -0.04; p = 0.266). LRG1 accounted for 14.7% of the association in mediation analysis (p = 0.035).ConclusionsDP was independently associated with cognitive function with possible mediation by LRG1. DP preceded decline in cognitive function. DP may be potential intervention and monitoring target for prevention of cognitive impairment and possibly Alzheimer's disease in T2D.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"668-677"},"PeriodicalIF":3.4000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Double product is longitudinally associated with reduced cognitive function in type 2 diabetes with insights from cross-lagged panel analysis and mediation by leucine-rich α-2-glycoprotein 1.\",\"authors\":\"Serena Low, Angela Moh, Bhuvaneswari Pandian, Huili Zheng, Sharon Pek, Jian-Jun Liu, Keven Ang, Tsz Kiu Kwan, Wern Ee Tang, Ziliang Lim, Tavintharan Subramaniam, Chee Fang Sum, Su Chi Lim\",\"doi\":\"10.1177/13872877251344881\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>BackgroundElevated systolic blood pressure (SBP) and resting heart rate (RHR) contribute to pathogenesis of diabetic complications. They increase inflammation which can upregulate leucine-rich α-2-glycoprotein 1 (LRG1), an emerging biomarker of cognitive decline.ObjectiveTo examine association between double product (DP, derived from multiplying SBP and RHR) and cognitive function in type 2 diabetes (T2D), with possible mediation by plasma LRG1.MethodsIn this prospective cohort of 1319 patients (mean age 62.5 ± 7.3), plasma LRG1 was measured with enzyme-linked immunosorbent assay. Cognitive function was assessed using Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Cross-lagged panel analysis was done to examine temporal relationship between DP and cognitive function.ResultsBaseline DP was associated with lower baseline RBANS total score (adjusted coefficient = -2.43; 95%CI -4.76, -0.10; p = 0.041). 586 patients were followed up to 8.6 years. Baseline DP was associated with follow-up RBANS total score (adjusted coefficient = -3.80; 95%CI -6.51, -1.10; p = 0.006). It was also associated with lower follow-up RBANS scores in immediate memory and delayed memory with adjusted coefficients -4.38 (95%CI -8.49, -0.28; p = 0.036) and -5.12 (95%CI -9.88, -0.35; p = 0.035) respectively. In cross-lagged panel analysis, standardized effect size of baseline DP on follow-up RBANS total score (β = -0.08; p = 0.002) was larger than that of baseline RBANS total score on follow-up DP (β = -0.04; p = 0.266). LRG1 accounted for 14.7% of the association in mediation analysis (p = 0.035).ConclusionsDP was independently associated with cognitive function with possible mediation by LRG1. DP preceded decline in cognitive function. DP may be potential intervention and monitoring target for prevention of cognitive impairment and possibly Alzheimer's disease in T2D.</p>\",\"PeriodicalId\":14929,\"journal\":{\"name\":\"Journal of Alzheimer's Disease\",\"volume\":\" \",\"pages\":\"668-677\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Alzheimer's Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/13872877251344881\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Alzheimer's Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/13872877251344881","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Double product is longitudinally associated with reduced cognitive function in type 2 diabetes with insights from cross-lagged panel analysis and mediation by leucine-rich α-2-glycoprotein 1.
BackgroundElevated systolic blood pressure (SBP) and resting heart rate (RHR) contribute to pathogenesis of diabetic complications. They increase inflammation which can upregulate leucine-rich α-2-glycoprotein 1 (LRG1), an emerging biomarker of cognitive decline.ObjectiveTo examine association between double product (DP, derived from multiplying SBP and RHR) and cognitive function in type 2 diabetes (T2D), with possible mediation by plasma LRG1.MethodsIn this prospective cohort of 1319 patients (mean age 62.5 ± 7.3), plasma LRG1 was measured with enzyme-linked immunosorbent assay. Cognitive function was assessed using Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Cross-lagged panel analysis was done to examine temporal relationship between DP and cognitive function.ResultsBaseline DP was associated with lower baseline RBANS total score (adjusted coefficient = -2.43; 95%CI -4.76, -0.10; p = 0.041). 586 patients were followed up to 8.6 years. Baseline DP was associated with follow-up RBANS total score (adjusted coefficient = -3.80; 95%CI -6.51, -1.10; p = 0.006). It was also associated with lower follow-up RBANS scores in immediate memory and delayed memory with adjusted coefficients -4.38 (95%CI -8.49, -0.28; p = 0.036) and -5.12 (95%CI -9.88, -0.35; p = 0.035) respectively. In cross-lagged panel analysis, standardized effect size of baseline DP on follow-up RBANS total score (β = -0.08; p = 0.002) was larger than that of baseline RBANS total score on follow-up DP (β = -0.04; p = 0.266). LRG1 accounted for 14.7% of the association in mediation analysis (p = 0.035).ConclusionsDP was independently associated with cognitive function with possible mediation by LRG1. DP preceded decline in cognitive function. DP may be potential intervention and monitoring target for prevention of cognitive impairment and possibly Alzheimer's disease in T2D.
期刊介绍：
The Journal of Alzheimer''s Disease (JAD) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer''s disease. The journal publishes research reports, reviews, short communications, hypotheses, ethics reviews, book reviews, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer''s disease.
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