Kidney Dysfunction and Cognitive Decline in Women

Renal Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
Clinical Journal of the American Society of Nephrology (Impact Factor: 4.61). 03/2012; 7(3):437-43. DOI: 10.2215/CJN.05330611
Source: PubMed


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.

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    • "In addition to a strong and independent association with stroke, albuminuria was also independently associated with cognitive decline [40,41]. UACR levels not traditionally considered significant might be used to identify cerebral arterial dysfunction even before evident diseases, such as stroke or dementia, are clinically manifested [42]. "
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    ABSTRACT: Background High normal values of urine albumin-to-creatinine ratio (UACR) have been reported to have predictive values for hypertension, incident stroke, and higher mortality in the general population. This study aimed to investigate the association between normal ranges of UACR and carotid intima-media thickness (CIMT) in adult population. Methods We performed a cross-sectional study in adults aged 45 to 74 years who were living in Namwon City, South Korea. Both common CIMTs were measured, and mean values were calculated. Normal values of UACR were defined as <30mg/g and categorized into quintiles; less than 6.50, 6.51-9.79, 9.80-13.49, 13.50-18.89, and more than 18.90 mg/g. The association between the quintiles of UACR and common CIMT was analyzed and stratified by sex. Results A total of 7555 participants (3084 men and 4471 women) with normal UACR were enrolled in the present study. Common CIMT was positively and independently associated with increasing quintiles of UACR in men and women, even after adjusting for potential confounders including age and cardiovascular risk factors. Compared to the first quintile, the fifth quintile showed odds ratios of 1.80 (95% confidence intervals, 1.26-2.55) and 1.97 (1.28-3.04) for increased CIMT (>0.9mm) in men and women, respectively. Conclusion Higher UACR values within normal ranges (<30 mg/g) were positively and independently associated with CIMT in a Korean general population, suggesting that higher normal values of UACR might be a risk marker of subclinical carotid atherosclerosis.
    Full-text · Article · Sep 2012 · Cardiovascular Diabetology
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    • "In a community-based cross-sectional study Elias et al. found that global performance and specific cognitive functions are negatively affected early in CKD [3]. Interestingly not only a decrease in GFR but also elevated urinary albumin/creatinine ratios is independently associated with faster decline in cognitive function [4]. Moreover, moderate renal impairment, has been shown to be associated with an excess risk of incident dementia among individuals in good to excellent health [5]. "
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    ABSTRACT: Background One hallmark of uremia is the impairment of neuro-cognitive function. Anecdotal clinical description from the early days of chronic dialysis therapy impressively illustrates the improvement of those functions by chronic hemodialysis treatment. Fortunately, today, uremia is only rarely observed in industrialized countries as many patients seek medical/nephrological attention prior to the occurrence of deadly complications of uremia. Case presentation We report a rare case of severe uremia and describe the day to day improvement in neuro-cognitive function by dialysis using state of the arte test battery – starting at a serum creatinine of 2443 μmol/l. Conclusions Especially executive functions, which are assumed to be localized in the frontal cerebral regions, are impaired in severe uremia and improve remarkably with the correction of severe uremia, i.e. initiation of dialysis.
    Full-text · Article · Aug 2012 · BMC Nephrology
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    Preview · Article · Mar 2012 · Clinical Journal of the American Society of Nephrology
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