University of Oulu

Hakala, J. O., Pahkala, K., Juonala, M., Salo, P., Kähönen, M., Hutri-Kähönen, N., Lehtimäki, T., Laitinen, T. P., Jokinen, E., Taittonen, L., Tossavainen, P., Viikari, J. S. A., Raitakari, O. T., & Rovio, S. P. (2022). Repeatedly measured serum creatinine and cognitive performance in midlife: The cardiovascular risk in young finns study. Neurology, 98(22), e2268–e2281.

Repeatedly measured serum creatinine and cognitive performance in midlife : the Cardiovascular Risk in Young Finns Study

Saved in:
Author: Hakala, Juuso O.1,2,3; Pahkala, Katja1,2,3; Juonala, Markus4;
Organizations: 1Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
2Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
3Paavo Nurmi Centre, Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku, Turku, Finland
4Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland
5Department of Clinical Physiology, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
6Department of Pediatrics, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
7Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
8Department of Clinical Physiology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
9Department of Paediatric Cardiology, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
10Department of Pediatrics, Tampere University Hospital, Tampere, Finland
11Department of Pediatrics, PEDEGO Research Unit and Medical Research Center, University of Oulu, and Oulu University Hospital Oulu, Finland
12Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.4 MB)
Persistent link:
Language: English
Published: Wolters Kluwer, 2022
Publish Date: 2023-04-11


Background and Objectives: Serum creatinine is typically used to assess kidney function. Impaired kidney function and thus high serum creatinine increase the risk of poor cognitive performance. However, serum creatinine might have a nonlinear association because low serum creatinine has been linked to cardiovascular risk and impaired cognitive performance. We studied the longitudinal association between serum creatinine and cognitive performance in midlife.

Methods: Since 2001, participants from the Cardiovascular Risk in Young Finns Study were followed up for 10 years. Serum creatinine was measured repeatedly in 2001, 2007, and 2011. Sex-specific longitudinal trajectories for serum creatinine among participants without kidney disease were identified with latent class growth mixture modeling. Overall cognitive function and 4 specific domains—working memory, episodic memory and associative learning, reaction time, and information processing—were assessed with a computerized cognitive test.

Results: Four serum creatinine trajectory groups with clinically normal serum creatinine were identified for both men (n = 973) and women (n = 1,204). After 10 years of follow-up, cognitive testing was performed for 2,026 participants 34 to 49 years of age (mean age 41.8 years). In men and women, consistently low serum creatinine was associated with poor childhood school performance, low adulthood education, low adulthood annual income, low physical activity, and smoking. Compared to the men in the low serum creatinine trajectory group, those in the high serum creatinine group had better overall cognitive performance (β = 0.353 SD, 95% CI 0.022–0.684) and working memory (β = 0.351 SD, 95% CI 0.034–0.668), while those in the moderate (β = 0.247 SD, 95% CI 0.026–0.468) or normal (β = 0.244 SD, 95% CI 0.008–0.481) serum creatinine groups had better episodic memory and associative learning. No associations were found for women.

Discussion: Our results indicate that in men, compared to low serum creatinine levels, consistently high levels may be associated with better memory and learning function in midlife.

see all

Series: Neurology
ISSN: 0028-3878
ISSN-E: 1526-632X
ISSN-L: 0028-3878
Volume: 98
Issue: 22
Pages: e2268 - e2281
DOI: 10.1212/wnl.0000000000200268
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by the Academy of Finland: grants 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), 41071 (Skidi) and 322098 (T.L); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; and EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for TO-AITION); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; and Finnish Society of Clinical Chemistry (T.L). K.P. is supported by Academy of Finland research fellowship (322112).
Copyright information: © 2022 American Academy of Neurology.