Search

IntroductionMultifactorial biological processes underpin dysregulation over several individual physiological systems. However, it is challenging to characterize and model this multisystemic dysregulation and its relationship with individual physiologic systems. We operationalized a theory-driven measure of multisystem dysregulation and empirically tested for measurement differences by key characteristics.MethodsWe used the Women's Health and Aging Studies (WHAS) I and II (N = 649), and the Health ABC study (N = 1515). Twelve biomarkers representing multiple systems including stress response (e.g., inflammation), endocrine system, and energy regulation were identified. A series of confirmatory factor analyses (CFA) were conducted to evaluate the interplay between physiological systems and underlying multisystem dysregulation. We evaluated convergent criterion validity of a score for multisystem dysregulation against the physical frailty phenotype, and predictive criterion validity with incidence of walking difficulty and mortality.ResultsA bifactor CFA, a model in which dysregulation of individual systems proceeds independently of generalized dysregulation, fit data well in WHAS (RMSEA: 0.019; CFI: 0.977; TLI: 0.961) and Health ABC (RMSEA: 0.047; CFI: 0.874; TLI: 0.787). The general dysregulation factor was associated with frailty (OR: 2.2, 95 % CI: 1.4, 3.5), and elevated risk of incident walking difficulty and mortality. Findings were replicated in Health ABC.DiscussionBiomarker data from two epidemiologic studies support the construct of multisystem physiological dysregulation. Results further suggest system-specific and system-wide processes have unique and non-overlapping contributions to dysregulation in biological markers.

Background Frailty is associated with poor outcomes in surgical patients including kidney transplant (KT) recipients. Transplant centers that measure frailty have better pre- and postoperative outcomes. However, clinical utility of existing tools is low due to time constraints. To address this major barrier to implementation in the preoperative evaluation of patients, we developed an abridged frailty phenotype. Methods The abridged frailty phenotype was developed by simplifying the 5 physical frailty phenotype (PFP) components in a two-center prospective cohort of 3 220 KT candidates and tested for efficiency (time to completion) in 20 candidates evaluation (January 2009 to March 2020). We examined area under curve (AUC) and Cohen's kappa agreement to compare the abridged assessment with the PFP. We compared waitlist mortality risk (competing risks models) by frailty using the PFP and abridged assessment, respectively. Model discrimination was assessed using Harrell's C-statistic. Results Of 3 220 candidates, the PFP and abridged assessment identified 23.8% and 27.4% candidates as frail, respectively. The abridged frailty phenotype had substantial agreement (kappa = 0.69, 95% CI: 0.66–0.71) and excellent discrimination (AUC = 0.861). Among 20 patients at evaluation, abridged assessment took 5–7 minutes to complete. The PFP and abridged assessment had similar associations with waitlist mortality (subdistribution hazard ratio [SHR] = 1.62, 95% CI: 1.26–2.08 vs SHR = 1.70, 95% CI: 1.33–2.16) and comparable mortality discrimination (p  = .51). Conclusions The abridged assessment is an efficient and valid way to identify frailty. It predicts waitlist mortality without sacrificing discrimination. Surgical departments should consider utilizing the abridged assessment to evaluate frailty in patients when time is limited. [ABSTRACT FROM AUTHOR]

Background Short and long sleep durations are associated with cognitive dysfunction. Given the increased prevalence of sleep abnormalities in the chronic kidney disease (CKD) population, we tested whether the association between sleep duration and cognitive function differed between older adults with and without CKD. Methods This was a study of 3215 older adults (age ≥60 years) enrolled in the National Health and Nutrition Examination Survey (2011–14) evaluating sleep duration, cognitive function (immediate recall, delayed recall, verbal fluency, executive function and processing speed and global cognition) and kidney function. We quantified the association between sleep duration and cognitive function using linear regression and tested whether the associations differed among those with CKD and without using a Wald test for interaction. Results Among 3215 participants, 13.3% reported 2–5 hours of sleep/day, 75.2% reported 6–8 hours, and 11.5% reported ≥9 hours. Persons with CKD were more likely to sleep ≥9 hours [odds ratio 1.73 (95% confidence interval 1.22–2.46)]. Among participants with CKD, those with a sleep duration ≥9 hours demonstrated worse global cognitive function (P for interaction = .01), immediate recall (P for interaction = .01) and verbal fluency (P for interaction = .004) than those with a sleep duration of 6–8 h; no differences were observed for participants with CKD who slept 2–5 hours. Among participants without CKD, sleep was not associated with any measures of cognitive function. Conclusions Longer sleep duration is associated with worse cognitive function only among persons with CKD, and global cognition, delayed recall and verbal fluency are particularly affected. Studies should identify interventions to improve sleep patterns and quality in this population. [ABSTRACT FROM AUTHOR]

Background Cognitive impairment is common among persons with chronic kidney disease (CKD), due in part to reduced kidney function. Given that physical activity (PA) is known to mitigate cognitive decline, we examined whether associations between CKD stage and global/domain-specific cognitive function differ by PA. Methods We leveraged 3223 participants (≥60 years of age) enrolled in National Health and Nutrition Examination Survey (NHANES, 2011–2014), with at least one measure of objective cognitive function [immediate recall (CERAD-WL), delayed recall (CERAD-DR), verbal fluency (AF), executive function/processing speed (DSST), global (average of four tests) or self-perceived memory decline (SCD)]. We quantified the association between CKD stage {no CKD: estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 and albuminuria [albumin:creatinine ratio (ACR)] <30 mg/g; stages G1–G3: eGFR ≥60 mL/min/1.73 m2 and ACR ≥30 mg/g or eGFR 30–59 mL/min/1.73 m2; stages G4 and G5: eGFR <30 mL/min/1.73 m2} and cognitive function using linear regression (objective measures) and logistic regression (SCD), accounting for sampling weights for nationally representative estimates. We tested whether associations differed by PA [Global Physical Activity Questionnaire, high PA ≥600 metabolic equivalent of task (MET) · min/week versus low PA <600 MET · min/week] using a Wald test. Results Among NHANES participants, 34.9% had CKD stages G1–G3, 2.6% had stages G4 and G5 and 50.7% had low PA. CKD stages G4 and G5 were associated with lower global cognitive function {difference = −0.38 standard deviation [SD] [95% confidence interval (CI) −0.62 to −0.15]}. This association differed by PA (Pinteraction = 0.01). Specifically, among participants with low PA, those with CKD stages G4 and G5 had lower global cognitive function [difference = −0.57 SD (95% CI −0.82 to −0.31)] compared with those without CKD. Among those with high PA, no difference was found [difference = 0.10 SD (95% CI −0.29–0.49)]. Similarly, the CKD stage was only associated with immediate recall, verbal fluency, executive function and processing speed among those with low PA; no associations were observed for delayed recall or self-perceived memory decline. Conclusions CKD is associated with lower objective cognitive function among those with low but not high PA. Clinicians should consider screening older patients with CKD who have low PA for cognitive impairment and encourage them to meet PA guidelines. [ABSTRACT FROM AUTHOR]