Kidney-Metabolic Factors Associated with Cognitive Impairment in Chronic Kidney Disease: A Pilot Study.

INTRODUCTION: The associations of kidney-metabolic biomarkers with cognitive impairment (CI) beyond the estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) and albuminuria levels are not well understood. In exploratory analysis, our objective was to determine the extent that three kidney-metabolic factors, previously proposed as mechanisms of CI and commonly abnormal in chronic kidney disease (CKD), were associated with prevalent CI in CKD participants, adjusted for kidney function measures. METHODS: The study cohort included community-dwelling individuals aged ≥45 years with CKD (eGFR <60), not requiring dialysis, recruited from four health systems. We examined the serum biomarkers bicarbonate (CO2), TNFαR1, and cholesterol as primary exposures. A structured neuropsychological battery conducted by trained staff measured global and domain-specific cognitive performance. Logistic regression analyses estimated the cross-sectional associations between kidney-metabolic measures and global and cognitive domain-specific moderate/severe (Mod/Sev) CI, adjusted for the eGFR, urinary albumin-creatinine ratio (UACR, mg/g), demographics, comorbid conditions, and other kidney-metabolic biomarkers commonly abnormal in CKD. RESULTS: Among 436 CKD participants with mean age 70 years, 16% were Black, the mean eGFR was 34, and the median [IQR] UACR was 49 [0.0, 378] mg/g. In adjusted models, increased TNFαR1 was associated with global Mod/Sev CI (odds ratio [95% confidence interval] = 1.40 [1.02, 1.93]; p = 0.04); low bicarbonate (CO2 <20 mEq/L) with Mod/Sev memory impairment (3.04 [1.09, 8.47]; p = 0.03), and each 10-mg/dL lower cholesterol was associated with Mod/Sev executive function/processing speed impairment (1.12 [1.02, 1.23]; p = 0.02). However, after adjustment for multiple comparisons, these associations were no longer significant nor were any other kidney-metabolic factors significant for any CI classification. CONCLUSION: In exploratory analyses in a CKD population, three kidney-metabolic factors were associated with CI, but after adjustment for multiple comparisons, were no longer significant. Future studies in larger CKD populations are needed to assess these potential risk factors for CI.

Prevalence and Risk of Severe Cognitive Impairment in Advanced Chronic Kidney Disease.

Background: Our primary goal is to describe the prevalence, severity, and risk of cognitive impairment (CI) by estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) in a cohort enriched for advanced chronic kidney disease (CKD; eGFR < 45), adjusting for albuminuria, as measured by urine albumin-to-creatinine ratio (UACR, in mg/g). As both eGFR and albuminuria are associated with CI risk in CKD, we also seek to determine the extent that eGFR remains a useful biomarker for risk of CI in those with CKD and concomitant albuminuria. Methods: Chi-square tests measured the prevalence of severe CI and mild cognitive impairment (MCI) by eGFR level. Logistic regression models and generalized linear models measured risk of CI by eGFR, adjusted for UACR. Results: Participants were 574 adults with a mean age of 69; 433 with CKD (eGFR < 60, nondialysis) and 141 controls (eGFR ≥ 60). Forty-eight percent of participants with CKD had severe CI or MCI. The prevalence of severe CI was highest (25%) in those with eGFR < 30. eGFR < 30 was only associated with severe CI in those without albuminuria (UACR < 30; OR = 3.3; p = .02) and was not associated with MCI in similar models. Conclusions: One quarter of those with eGFR < 30 had severe CI. eGFR < 30 was associated with over threefold increased odds of severe CI in those with UACR < 30, but not with UACR > 30, suggesting that eGFR < 30 is a valid biomarker for increased risk of severe CI in those without concomitant albuminuria.

The Brain in Kidney Disease (BRINK) Cohort Study: Design and Baseline Cognitive Function.

BACKGROUND: The Brain in Kidney Disease (BRINK) Study aims to identify mechanisms that contribute to increased risk for cognitive impairment in patients with chronic kidney disease (CKD). We describe the rationale, design, and methods of the study and report baseline recruitment and cognitive function results. STUDY DESIGN: Longitudinal observational cohort study of the epidemiology of cognitive impairment in CKD. The primary aim is to characterize the association between (1) baseline and incident stroke, white matter disease, estimated glomerular filtration rate (eGFR), inflammation, microalbuminuria, and dialysis initiation and (2) cognitive decline over 3 years in a CKD cohort with a mean eGFR<45 mL/min/1.73 m(2). SETTING & PARTICIPANTS: Community-dwelling participants 45 years or older recruited from 4 health systems into 2 groups: reduced eGFR, defined as eGFR<60 mL/min/1.73 m(2) (non-dialysis dependent), and control, defined as eGFR≥60 mL/min/1.73 m(2). PREDICTOR: eGFR group. OUTCOMES: Performance on cognitive function tests and structural brain magnetic resonance imaging. MEASUREMENTS: Sequential cognitive and physical function testing, serum and urine biomarker measurement, and brain magnetic resonance images over 3 years. RESULTS: Of 554 participants, mean age was 69.3 years; 333, 88, and 133 had eGFRs<45 (non-dialysis dependent, nontransplantation), 45 to <60, and ≥60 (controls) mL/min/1.73 m(2), respectively. Mean eGFR in reduced-eGFR participants was 34.3 mL/min/1.73 m(2). Baseline cognitive performance was significantly associated with eGFR in all domains except language. Participants with eGFRs<30 mL/min/1.73 m(2) performed significantly worse than those with eGFRs≥30 mL/min/1.73 m(2) on tests of memory, processing speed, and executive function. Participants with reduced eGFRs overall scored worst on the Immediate Brief Visual-Spatial Memory Test-Revised. LIMITATIONS: Healthy cohort bias, competing risk for death versus cognitive decline. CONCLUSIONS: Cognitive function was significantly worse in participants with eGFRs<30 mL/min/1.73 m(2). Future BRINK analyses will measure risk factors for cognitive decline using the longitudinal data.

Expecting innovation: psychoactive drug primes and the generation of creative solutions.

Many individuals expect that alcohol and drug consumption will enhance creativity. The present studies tested whether substance related primes would influence creative performance for individuals who possessed creativity-related substance expectancies. Participants (n = 566) were briefly exposed to stimuli related to psychoactive substances (alcohol, for Study 1, Sample 1, and Study 2; and marijuana, for Study 1, Sample 2) or neutral stimuli. Participants in Study 1 then completed a creative problem-solving task, while participants in Study 2 completed a divergent thinking task or a task unrelated to creative problem solving. The results of Study 1 revealed that exposure to the experimental stimuli enhanced performance on the creative problem-solving task for those who expected the corresponding substance would trigger creative functioning. In a conceptual replication, Study 2 showed that participants exposed to alcohol cues performed better on a divergent thinking task if they expected alcohol to enhance creativity. It is important to note that this same interaction did not influence performance on measures unrelated to creative problem solving, suggesting that the activation of creativity-related expectancies influenced creative performance, specifically. These findings highlight the importance of assessing expectancies when examining pharmacological effects of alcohol and marijuana. Future directions and implications for substance-related interventions are discussed.

Driving after use of alcohol and marijuana in college students.

Driving after use of marijuana is almost as common as driving after use of alcohol in youth (P. M. O'Malley & L. D. Johnston, 2003). The authors compared college students' attitudes, normative beliefs and perceived negative consequences of driving after use of either alcohol or marijuana and tested these cognitive factors as risk factors for substance-related driving. Results indicated that youth perceived driving after marijuana use as more acceptable to peers and the negative consequences as less likely than driving after alcohol use, even after controlling for substance use. Results of zero-inflated Poisson regression analyses indicated that lower perceived dangerousness and greater perceived peer acceptance were associated with increased engagement in, and frequency of, driving after use of either substance. Lower perceived likelihood of negative consequences was associated with increased frequency for those who engage in substance-related driving. These results provide a basis for comparing how youth perceive driving after use of alcohol and marijuana, as well as similarities in the risk factors for driving after use of these substances.

Acute variation in cognitive function in hemodialysis patients: a cohort study with repeated measures.

BACKGROUND: Although cognitive function in hemodialysis patients is believed to be best 24 hours after the dialysis session, the extent of variation during the dialysis cycle is unknown. STUDY DESIGN: Cohort study with repeated measures. SETTING & PARTICIPANTS: Hemodialysis centers; patients aged 55 years or older. PREDICTOR: Time of assessment related to the dialysis session. Time 1 (T1) occurred approximately 1 hour before the dialysis session; T2, 1 hour into the session; T3, 1 hour after; and T4, the next day. OUTCOMES: Measures of cognitive function using a 45-minute cognitive battery. An average composite score was calculated to measure global cognitive function, equal to the average of subjects' standardized scores on all tests given at each test time. Times were classified as best and worst according to composite scores. MEASUREMENTS: Testing was conducted on average over 2 dialysis sessions to avoid test fatigue. The cognitive battery included tests of verbal fluency, immediate and delayed verbal and visual memory, and executive function, administered at 4 times. RESULTS: In the 28 subjects who completed testing at 3 or 4 testing times, mean age was 66.7 +/- 9.5 years and mean dialysis vintage was 44.7 +/- 33.3 months. Using a general linear model for correlated data, the composite score was significantly lower (poorer) during dialysis (T2) than shortly before the session (T1) or on the next day (T4; P < 0.001 for both). LIMITATIONS: Relatively small sample size, testing delays, results may not be generalizable. CONCLUSION: Global cognitive function varies significantly during the dialysis cycle, being worst during dialysis and best shortly before the session or on the day after. Clinician visits may be most effective at these times.