Kidney Dysfunction and Cognitive Decline in Women

Abstract

ESRD is associated with substantial cognitive deficits but whether earlier kidney dysfunction predicts cognitive decline is less well defined. More than 1700 women aged ≥70 years in the Nurses' Health Study had plasma creatinine and urinary albumin/creatinine ratios (ACRs) measured in 2000, within 12 months of their initial cognitive testing. These participants had repeated assessments of cognition administered by phone every 2 years, including tests for general cognition, verbal memory, verbal fluency, and working memory for up to 6 years of follow-up. Mixed-effects regression analysis was applied to calculate mean differences in the rate of cognitive decline between women with an estimated GFR <60 ml/min per 1.73 m(2) or an ACR ≥5 mg/g versus referent levels. The median age was 74 years at initial cognitive testing, 99% of women were Caucasian, median plasma creatinine was 0.8 mg/dl, and 25% had an ACR ≥5 mg/g. The difference in cognitive decline with a baseline ACR ≥5 mg/g versus an ACR <5 mg/g was equivalent to the difference observed with 2-7 years of aging; that is, a higher ACR was associated with 2-7 times faster decline in all four cognitive domains assessed (all P values <0.05) than that attributed to each 1 year of aging alone. No associations were observed between an eGFR <60 ml/min per 1.73 m(2) and cognitive decline. A baseline urinary ACR ≥5 mg/g, a level not traditionally considered clinically significant, is independently associated with faster decline in cognitive function.