Sex Differences in the Risk of Cognitive Impairment: The Chronic Renal Insufficiency Cohort (CRIC) Study

Background: Women in the general population face a greater risk of cognitive decline compared to men. However, whether this sex-specific risk pattern of cognitive decline translates to individuals with chronic kidney disease (CKD) remains largely unknown. Accordingly, this study examined sex differences in the risk of cognitive impairment in patients with CKD who participated in the Chronic Renal Insufficiency Cohort (CRIC) study. Methods: Incident cognitive impairment was defined as a decline in Modified Mini-Mental State Examination (3MS) score greater than 1 standard deviation (SD) below the cohort mean. In the entire cohort, Cox proportional hazard models were used to compare sex differences in the risk of incident cognitive impairment. In a sub-group of postmenopausal women, Cox proportional hazard models were used to determine the association of 1) the age of menopause and 2) reproductive lifespan, calculated by subtracting the age of menarche from the age of menopause, with the risk of incident cognitive impairment. Results: Patients with CKD (n=2,460; 45% F; mean±SD age 58±11 y; eGFR 46±15 ml/min/1.73m2) were included. Men had a higher risk of cognitive impairment than women (Figure 1A). In the sub-group analysis, postmenopausal women with CKD (n=636; age 61±7 y; eGFR 44±14 ml/min/1.73m2) were included. An earlier age of menopause (Figure 1B) and a shorter reproductive lifespan (Figure 1C) were associated with a greater risk of cognitive impairment. Conclusion: Unlike in the general population, men with CKD had a greater risk of cognitive impairment than women. However, among women with CKD, female-specific factors, such as earlier age of menopause and shorter reproductive lifespan, were associated with a higher risk of cognitive decline, suggesting the influence of sex-specific mechanisms in this population. Funding: Private Foundation SupportFigure 1. Sex differences in the risk of cognitive impairment in patients with CKD (A). The association of the age of menopause (B) and reproductive lifespan (C) with the risk of cognitive impairment in postmenopausal women with CKD. Asterisk indicates significant hazard ratio.