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Association of intraindividual differences in estimated glomerular filtration rates based on cystatin C and creatinine with dementia: A cohort study of the UK Biobank.

Overview

Authors: Zhiyi Mao1,2, Yuwei Peng1, Ruilang Lin1, Xinyue Guo2, Xiaorui Cui1, Yongfu Yu1, Xueying Zheng1,2
ORCID iDs: Zhiyi Mao
  1. Key Laboratory of Public Health Safety of Ministry of Education, NHC Key Laboratory for Health Technology Assessment, School of Public Health, Fudan University, Shanghai, China
  2. Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China
Institutions: Fudan University (China)
Journal: PloS one, volume 21, issue 3, article e0344566
Dates: received 9 November 2025; accepted 23 February 2026; published online 6 March 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1371/journal.pone.0344566 · PMID 41790841 · PMCID PMC12965570 · OpenAlex W7134134670
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), Alzheimer's / dementia (population), stroke (population), clinical / translational (subfield)
Methods: Statistics, Preprocessing
MeSH: Creatinine*, Cystatin C*, Dementia*, Glomerular Filtration Rate*, Aged, Alzheimer Disease, Biological Specimen Banks, Cohort Studies, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Neuroimaging, UK Biobank, United Kingdom (* major topic)
Journal subjects: Medicine and Health Sciences, Mental Health and Psychiatry, Dementia, Neurology, Alzheimer's Disease, Medical Conditions, Neurodegenerative Diseases, Research and Analysis Methods, Imaging Techniques, Neuroimaging, Biology and Life Sciences, Neuroscience, Cerebrovascular Diseases, Vascular Dementia, Epidemiology, Medical Risk Factors, Endocrinology, Endocrine Disorders, Diabetes Mellitus, Metabolic Disorders, Physiology, Renal Physiology, Glomerular Filtration Rate
Topic: Chronic Kidney Disease and Diabetes (Nephrology, Medicine), according to OpenAlex
Funding: National Natural Science Foundation of China (National Science Foundation of China) (82273730); Shanghai Municipal Natural Science Foundation (22ZR1414900); Three-Year Public Health Action Plan of Shanghai (GWVI-11.2-XD10, GWVI-11.1-01)
Citations: not cited yet (Europe PMC); 52 references in the paper

Abstract

Background: Dementia is a leading cause of cognitive decline, with Alzheimer’s disease (AD) and vascular dementia (VaD) being the most common subtypes. The intraindividual difference between the estimated glomerular filtration rate based on cystatin C and creatinine (eGFRdiff) may serve as an indicator of the overall health status of an individual. However, the relationships between the eGFRdiff and dementia risk, dementia subtypes, dementia-related neuroimaging changes, and cognitive functions remain unclear.

Methods: This study analysed data from over 450,000 participants in the UK Biobank who were followed for up to 15 years. The estimated glomerular filtration rate based on cystatin C (eGFRcys) and creatinine (eGFRcr) was calculated using the CKD-EPI equation, and eGFRdiff was defined as the difference between these values (eGFRdiff = eGFRcys − eGFRcr). Multivariate Cox regression models were used to evaluate the associations between the eGFRdiff and all-cause dementia (ACD), AD, and VaD, whereas cross-sectional analysis were used to examine the relationship among the eGFRdiff, dementia-related neuroimaging changes, and cognitive functions.

Results: Over a median follow-up of 13.5 years, 8,710 participants developed dementia, including 3,910 with AD and 1,893 with VaD. Each one standard deviation increase in eGFRdiff was associated with a reduced risk of dementia, with hazard ratios (95% confidence intervals) of 0.92 (0.90–0.94) for ACD, 0.94 (0.91–0.98) for AD, and 0.90 (0.85–0.94) for VaD. A negative eGFRdiff was associated with adverse neuroimaging changes, including lower total brain and gray matter volumes and higher white matter hyperintensities. Additionally, a negative eGFRdiff was associated with poorer performance across multiple cognitive domains.

Conclusion: A negative eGFRdiff was associated with an increased risk of dementia, adverse neuroimaging outcomes, and cognitive decline. These findings suggest that the eGFRdiff might be considered a potential associative indicator for dementia and cognitive impairment, suggesting potential clinical value in risk assessment and early intervention strategies.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data Availability

Data cannot be shared publicly because individual-level data deposition is explicitly prohibited by the UK Biobank Material Transfer Agreement and Research Ethics Committee approval (16/NW/0274). Data are available from the UK Biobank Access Team (contact via or https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access) for researchers who meet the criteria for access to confidential data. The data underlying the results presented in the study are available from UK Biobank (Application ID: 98410).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 16 MeSH terms, 3 funders, 49 references.

Cite

This paper

Mao, Z., Peng, Y., Lin, R., Guo, X., Cui, X., Yu, Y., & Zheng, X. (2026). Association of intraindividual differences in estimated glomerular filtration rates based on cystatin C and creatinine with dementia: A cohort study of the UK Biobank. PloS one, 21(3), e0344566. https://doi.org/10.1371/journal.pone.0344566

BibTeX

@article{mao2026association,
author = {Mao, Zhiyi and Peng, Yuwei and Lin, Ruilang and Guo, Xinyue and Cui, Xiaorui and Yu, Yongfu and Zheng, Xueying},
title = {{Association of intraindividual differences in estimated glomerular filtration rates based on cystatin C and creatinine with dementia: A cohort study of the UK Biobank}},
journal = {PloS one},
year = {2026},
month = mar,
volume = {21},
number = {3},
pages = {e0344566},
publisher = {PLOS},
issn = {1932-6203},
doi = {10.1371/journal.pone.0344566},
url = {https://doi.org/10.1371/journal.pone.0344566},
pmid = {41790841},
pmcid = {PMC12965570}
}

RIS

TY - JOUR
AU - Mao, Zhiyi
AU - Peng, Yuwei
AU - Lin, Ruilang
AU - Guo, Xinyue
AU - Cui, Xiaorui
AU - Yu, Yongfu
AU - Zheng, Xueying
TI - Association of intraindividual differences in estimated glomerular filtration rates based on cystatin C and creatinine with dementia: A cohort study of the UK Biobank
T2 - PloS one
J2 - PLoS One
PY - 2026
DA - 2026/03/06
VL - 21
IS - 3
SP - e0344566
SN - 1932-6203
PB - PLOS
DO - 10.1371/journal.pone.0344566
UR - https://doi.org/10.1371/journal.pone.0344566
LA - en
ER -

CSL-JSON

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