Abstract
BACKGROUND AND OBJECTIVES: ESRD is associated with substantial cognitive deficits but whether earlier kidney dysfunction predicts cognitive decline is less well defined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: A baseline urinary ACR ≥5 mg/g, a level not traditionally considered clinically significant, is independently associated with faster decline in cognitive function.