Cardiovascular disease and depression as mediators between red blood cell distribution width to albumin ratio and cognitive impairment in older adults

BackgroundCognitive impairment is a major public health concern in aging populations, and early identification of risk factors is critical. The red blood cell distribution width to albumin ratio (RAR) has emerged as a potential biomarker reflecting inflammatory and nutritional status, but its associ...

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Main Authors: Hui Wang, Xinyu Bai, Cong Wang, Sensen Wu, Dikang Pan, Lianrui Guo, Peng Yu, Jianming Guo, Yongquan Gu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Physiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2025.1587635/full
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author Hui Wang
Xinyu Bai
Cong Wang
Sensen Wu
Dikang Pan
Lianrui Guo
Peng Yu
Jianming Guo
Yongquan Gu
author_facet Hui Wang
Xinyu Bai
Cong Wang
Sensen Wu
Dikang Pan
Lianrui Guo
Peng Yu
Jianming Guo
Yongquan Gu
author_sort Hui Wang
collection DOAJ
description BackgroundCognitive impairment is a major public health concern in aging populations, and early identification of risk factors is critical. The red blood cell distribution width to albumin ratio (RAR) has emerged as a potential biomarker reflecting inflammatory and nutritional status, but its association with cognitive impairment remains unclear.ObjectiveThis study investigates the relationship between RAR and cognitive impairment in older adults, and explores potential mediating variables that may influence this association.MethodsA total of 2,913 participants aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 cycles were analyzed, including 1,291 with cognitive impairment. Logistic regression assessed the association between RAR and cognitive impairment, adjusting for potential confounders such as age, gender, race, education, marital status, weight, height, and comorbidities. Restricted cubic spline (RCS) analysis evaluated the dose-response relationship and identified nonlinear thresholds. Subgroup analyses explored interactions between RAR and demographic/clinical factors. Causal mediation analysis, using a generalized linear model with a probit link and adjusting for age, sex, race, and education, was performed to estimate total, direct, and indirect effects via bootstrap resampling.ResultsRAR was positively associated with cognitive impairment (P < 0.05). RCS analysis revealed a nonlinear threshold, with RAR ≥3.2 significantly increasing the risk of cognitive impairment (OR = 1.24, 95% CI: 1.11–1.38, P < 0.001). Subgroup analysis showed significant interactions between RAR and cardiovascular disease (CVD), hypertension, and depression (P for interaction <0.05). Stratified analysis found a stronger association between RAR and cognitive impairment in individuals without hypertension, CVD, or depression. Mediation analysis indicated that CVD (P = 0.036) and depression (P = 0.032) partially mediated the relationship, with CVD explaining 4.49% of the total effect. Hypertension had no significant mediating effect.ConclusionRAR is significantly associated with cognitive impairment, with a stronger association when RAR ≥3.2. CVD and depression partially mediate this relationship, suggesting RAR as a potential biomarker for cognitive impairment in older adults.
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spelling doaj-art-209c41618c444b828c95c4e7d935c71f2025-08-20T02:09:23ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-06-011610.3389/fphys.2025.15876351587635Cardiovascular disease and depression as mediators between red blood cell distribution width to albumin ratio and cognitive impairment in older adultsHui Wang0Xinyu Bai1Cong Wang2Sensen Wu3Dikang Pan4Lianrui Guo5Peng Yu6Jianming Guo7Yongquan Gu8Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, ChinaBackgroundCognitive impairment is a major public health concern in aging populations, and early identification of risk factors is critical. The red blood cell distribution width to albumin ratio (RAR) has emerged as a potential biomarker reflecting inflammatory and nutritional status, but its association with cognitive impairment remains unclear.ObjectiveThis study investigates the relationship between RAR and cognitive impairment in older adults, and explores potential mediating variables that may influence this association.MethodsA total of 2,913 participants aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 cycles were analyzed, including 1,291 with cognitive impairment. Logistic regression assessed the association between RAR and cognitive impairment, adjusting for potential confounders such as age, gender, race, education, marital status, weight, height, and comorbidities. Restricted cubic spline (RCS) analysis evaluated the dose-response relationship and identified nonlinear thresholds. Subgroup analyses explored interactions between RAR and demographic/clinical factors. Causal mediation analysis, using a generalized linear model with a probit link and adjusting for age, sex, race, and education, was performed to estimate total, direct, and indirect effects via bootstrap resampling.ResultsRAR was positively associated with cognitive impairment (P < 0.05). RCS analysis revealed a nonlinear threshold, with RAR ≥3.2 significantly increasing the risk of cognitive impairment (OR = 1.24, 95% CI: 1.11–1.38, P < 0.001). Subgroup analysis showed significant interactions between RAR and cardiovascular disease (CVD), hypertension, and depression (P for interaction <0.05). Stratified analysis found a stronger association between RAR and cognitive impairment in individuals without hypertension, CVD, or depression. Mediation analysis indicated that CVD (P = 0.036) and depression (P = 0.032) partially mediated the relationship, with CVD explaining 4.49% of the total effect. Hypertension had no significant mediating effect.ConclusionRAR is significantly associated with cognitive impairment, with a stronger association when RAR ≥3.2. CVD and depression partially mediate this relationship, suggesting RAR as a potential biomarker for cognitive impairment in older adults.https://www.frontiersin.org/articles/10.3389/fphys.2025.1587635/fullred blood cell distribution width/albumin ratiocognitive impairmentNHANESolder adultscardiovascular diseasedepression
spellingShingle Hui Wang
Xinyu Bai
Cong Wang
Sensen Wu
Dikang Pan
Lianrui Guo
Peng Yu
Jianming Guo
Yongquan Gu
Cardiovascular disease and depression as mediators between red blood cell distribution width to albumin ratio and cognitive impairment in older adults
Frontiers in Physiology
red blood cell distribution width/albumin ratio
cognitive impairment
NHANES
older adults
cardiovascular disease
depression
title Cardiovascular disease and depression as mediators between red blood cell distribution width to albumin ratio and cognitive impairment in older adults
title_full Cardiovascular disease and depression as mediators between red blood cell distribution width to albumin ratio and cognitive impairment in older adults
title_fullStr Cardiovascular disease and depression as mediators between red blood cell distribution width to albumin ratio and cognitive impairment in older adults
title_full_unstemmed Cardiovascular disease and depression as mediators between red blood cell distribution width to albumin ratio and cognitive impairment in older adults
title_short Cardiovascular disease and depression as mediators between red blood cell distribution width to albumin ratio and cognitive impairment in older adults
title_sort cardiovascular disease and depression as mediators between red blood cell distribution width to albumin ratio and cognitive impairment in older adults
topic red blood cell distribution width/albumin ratio
cognitive impairment
NHANES
older adults
cardiovascular disease
depression
url https://www.frontiersin.org/articles/10.3389/fphys.2025.1587635/full
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