Chronic kidney disease and cognitive decline in patients with type 2 diabetes at elevated cardiovascular risk

Chloë Verhagen; Jolien Janssen; Crista A. Minderhoud; Esther van den Berg; Christoph Wanner; Anna Passera; Odd Erik Johansen; Geert Jan Biessels

doi:10.1016/j.jdiacomp.2022.108303

Chronic kidney disease and cognitive decline in patients with type 2 diabetes at elevated cardiovascular risk

Chloë Verhagen, Jolien Janssen, Crista A. Minderhoud, Esther van den Berg, Christoph Wanner, Anna Passera, Odd Erik Johansen, Geert Jan Biessels^*

^*Corresponding author for this work

Neurology

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Abstract

Aims: We addressed the question whether chronic kidney disease (CKD) may contribute to cognitive decline in type 2 diabetes. Methods: Participants with type 2 diabetes with elevated cardiovascular risk or CKD from cognition substudies of two large trials were studied prospectively (CARMELINA: n = 2666, mean ± SD age 68.1 ± 8.7 years, CAROLINA: n = 4296; 64.7 ± 9.4 years). Estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) at baseline were related to cognitive performance (Mini-Mental State Examination (MMSE) and attention and executive functioning score (A&E)) in linear regression analyses, adjusted for demographics, cardiovascular risk factors and treatment, at baseline and follow-up. Results: CKD at baseline was more common in CARMELINA than CAROLINA (eGFR<60 in 72.6 % and 19.6 %, macroalbuminuria in 35.0 % and 4.1 %, respectively). Baseline eGFR was related to A&E in CARMELINA (b = 0.02 per 10 ml/min/1.73m², 95%CI [0.01,0.03]). Baseline UACR was related to A&E in CAROLINA (b = −0.01 per doubling of UACR mg/g, 95%CI [−0.02,−0.002]). Baseline UACR predicted decline in A&E in CAROLINA (median 6.1 years follow-up; b = −0.01, 95%CI [−0.03,−0.0001] per doubling of UACR mg/g). Conclusions: eGFR and UACR were associated with A&E in two cohorts with type 2 diabetes, enriched for CKD and cardiovascular disease. The small effect size estimates indicate limited impact of kidney dysfunction on cognition in this setting. ClinicalTrials.gov

Original language	English
Article number	108303
Journal	Journal of Diabetes and its Complications
Volume	36
Issue number	10
DOIs	https://doi.org/10.1016/j.jdiacomp.2022.108303
Publication status	Published - Oct 2022

Bibliographical note

Funding Information:
This manuscript is based on data collected from studies sponsored by Boehringer Ingelheim. The manuscript and data analyses have been prepared independently from Boehringer IngelheimThe authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. OEJ was previously employed by Boehringer Ingelheim. The UMC Utrecht has received research support from Boehringer Ingelheim for GJBs projects. CW has received grant support, fees for advisory services and lecturing from Boehringer Ingelheim.

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© 2022 The Authors

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@article{8ccb4fcd2ed248e38fd0ca9ccea357f4,

title = "Chronic kidney disease and cognitive decline in patients with type 2 diabetes at elevated cardiovascular risk",

abstract = "Aims: We addressed the question whether chronic kidney disease (CKD) may contribute to cognitive decline in type 2 diabetes. Methods: Participants with type 2 diabetes with elevated cardiovascular risk or CKD from cognition substudies of two large trials were studied prospectively (CARMELINA: n = 2666, mean ± SD age 68.1 ± 8.7 years, CAROLINA: n = 4296; 64.7 ± 9.4 years). Estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) at baseline were related to cognitive performance (Mini-Mental State Examination (MMSE) and attention and executive functioning score (A&E)) in linear regression analyses, adjusted for demographics, cardiovascular risk factors and treatment, at baseline and follow-up. Results: CKD at baseline was more common in CARMELINA than CAROLINA (eGFR<60 in 72.6 % and 19.6 %, macroalbuminuria in 35.0 % and 4.1 %, respectively). Baseline eGFR was related to A&E in CARMELINA (b = 0.02 per 10 ml/min/1.73m2, 95%CI [0.01,0.03]). Baseline UACR was related to A&E in CAROLINA (b = −0.01 per doubling of UACR mg/g, 95%CI [−0.02,−0.002]). Baseline UACR predicted decline in A&E in CAROLINA (median 6.1 years follow-up; b = −0.01, 95%CI [−0.03,−0.0001] per doubling of UACR mg/g). Conclusions: eGFR and UACR were associated with A&E in two cohorts with type 2 diabetes, enriched for CKD and cardiovascular disease. The small effect size estimates indicate limited impact of kidney dysfunction on cognition in this setting. ClinicalTrials.gov",

author = "Chlo{\"e} Verhagen and Jolien Janssen and Minderhoud, {Crista A.} and {van den Berg}, Esther and Christoph Wanner and Anna Passera and Johansen, {Odd Erik} and Biessels, {Geert Jan}",

note = "Funding Information: This manuscript is based on data collected from studies sponsored by Boehringer Ingelheim. The manuscript and data analyses have been prepared independently from Boehringer IngelheimThe authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. OEJ was previously employed by Boehringer Ingelheim. The UMC Utrecht has received research support from Boehringer Ingelheim for GJBs projects. CW has received grant support, fees for advisory services and lecturing from Boehringer Ingelheim. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = oct,

doi = "10.1016/j.jdiacomp.2022.108303",

language = "English",

volume = "36",

journal = "Journal of Diabetes and its Complications",

issn = "1056-8727",

publisher = "Elsevier Inc.",

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T1 - Chronic kidney disease and cognitive decline in patients with type 2 diabetes at elevated cardiovascular risk

AU - Verhagen, Chloë

AU - Janssen, Jolien

AU - Minderhoud, Crista A.

AU - van den Berg, Esther

AU - Wanner, Christoph

AU - Passera, Anna

AU - Johansen, Odd Erik

AU - Biessels, Geert Jan

N1 - Funding Information: This manuscript is based on data collected from studies sponsored by Boehringer Ingelheim. The manuscript and data analyses have been prepared independently from Boehringer IngelheimThe authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. OEJ was previously employed by Boehringer Ingelheim. The UMC Utrecht has received research support from Boehringer Ingelheim for GJBs projects. CW has received grant support, fees for advisory services and lecturing from Boehringer Ingelheim. Publisher Copyright: © 2022 The Authors

PY - 2022/10

Y1 - 2022/10

N2 - Aims: We addressed the question whether chronic kidney disease (CKD) may contribute to cognitive decline in type 2 diabetes. Methods: Participants with type 2 diabetes with elevated cardiovascular risk or CKD from cognition substudies of two large trials were studied prospectively (CARMELINA: n = 2666, mean ± SD age 68.1 ± 8.7 years, CAROLINA: n = 4296; 64.7 ± 9.4 years). Estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) at baseline were related to cognitive performance (Mini-Mental State Examination (MMSE) and attention and executive functioning score (A&E)) in linear regression analyses, adjusted for demographics, cardiovascular risk factors and treatment, at baseline and follow-up. Results: CKD at baseline was more common in CARMELINA than CAROLINA (eGFR<60 in 72.6 % and 19.6 %, macroalbuminuria in 35.0 % and 4.1 %, respectively). Baseline eGFR was related to A&E in CARMELINA (b = 0.02 per 10 ml/min/1.73m2, 95%CI [0.01,0.03]). Baseline UACR was related to A&E in CAROLINA (b = −0.01 per doubling of UACR mg/g, 95%CI [−0.02,−0.002]). Baseline UACR predicted decline in A&E in CAROLINA (median 6.1 years follow-up; b = −0.01, 95%CI [−0.03,−0.0001] per doubling of UACR mg/g). Conclusions: eGFR and UACR were associated with A&E in two cohorts with type 2 diabetes, enriched for CKD and cardiovascular disease. The small effect size estimates indicate limited impact of kidney dysfunction on cognition in this setting. ClinicalTrials.gov

AB - Aims: We addressed the question whether chronic kidney disease (CKD) may contribute to cognitive decline in type 2 diabetes. Methods: Participants with type 2 diabetes with elevated cardiovascular risk or CKD from cognition substudies of two large trials were studied prospectively (CARMELINA: n = 2666, mean ± SD age 68.1 ± 8.7 years, CAROLINA: n = 4296; 64.7 ± 9.4 years). Estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) at baseline were related to cognitive performance (Mini-Mental State Examination (MMSE) and attention and executive functioning score (A&E)) in linear regression analyses, adjusted for demographics, cardiovascular risk factors and treatment, at baseline and follow-up. Results: CKD at baseline was more common in CARMELINA than CAROLINA (eGFR<60 in 72.6 % and 19.6 %, macroalbuminuria in 35.0 % and 4.1 %, respectively). Baseline eGFR was related to A&E in CARMELINA (b = 0.02 per 10 ml/min/1.73m2, 95%CI [0.01,0.03]). Baseline UACR was related to A&E in CAROLINA (b = −0.01 per doubling of UACR mg/g, 95%CI [−0.02,−0.002]). Baseline UACR predicted decline in A&E in CAROLINA (median 6.1 years follow-up; b = −0.01, 95%CI [−0.03,−0.0001] per doubling of UACR mg/g). Conclusions: eGFR and UACR were associated with A&E in two cohorts with type 2 diabetes, enriched for CKD and cardiovascular disease. The small effect size estimates indicate limited impact of kidney dysfunction on cognition in this setting. ClinicalTrials.gov

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Chronic kidney disease and cognitive decline in patients with type 2 diabetes at elevated cardiovascular risk

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