Repeatedly Measured Serum Creatinine and Cognitive Performance in Midlife: The Cardiovascular Risk in Young Finns Study

Neurology. 2022 Apr 11;10.1212/WNL.0000000000200268. doi: 10.1212/WNL.0000000000200268. Online ahead of print.

Abstract

Background and objectives: Serum creatinine is typically used to assess kidney function. Impaired kidney function and thereby high serum creatinine increases risk of poor cognitive performance. However, serum creatinine might have a non-linear association as low serum creatinine has been linked with 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 using latent class growth mixture modeling. Overall cognitive function and four specific domains such as 1) working memory, 2) episodic memory and associative learning, 3) reaction time, and 4) information processing were assessed using a computerized cognitive test.

Results: Four serum creatinine trajectory groups all 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 aged 34 to 49 years (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 the 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 associate with better memory and learning function in midlife.

Keywords: adulthood; cardiovascular risk; cognitive performance; kidney function; longitudinal; midlife; population-based; serum creatinine.