Background: The prevalence of end-stage renal disease (ESRD) is increasing worldwide, with the majority of new ESRD cases diagnosed in patients >60 years of age. These older patients are at... Show moreBackground: The prevalence of end-stage renal disease (ESRD) is increasing worldwide, with the majority of new ESRD cases diagnosed in patients >60 years of age. These older patients are at increased risk for impaired cognitive functioning, potentially through cerebral small vessel disease (SVD). Novel markers of vascular integrity may be of clinical value for identifying patients at high risk for cognitive impairment. Methods: We aimed to associate the levels of angiopoietin-2 (Ang-2), asymmetric dimethylarginine and a selection of eight circulating angiogenic microRNAs (miRNAs) with SVD and cognitive impairment in older patients reaching ESRD that did not yet initiate renal replacement therapy (n = 129; mean age 75.3 years, mean eGFR 16.4 mL/min). We assessed brain magnetic resonance imaging changes of SVD (white matter hyperintensity volume, microbleeds and the presence of lacunes) and measures of cognition in domains of memory, psychomotor speed and executive function in a neuropsychological test battery. Results: Older patients reaching ESRD showed an unfavourable angiogenic profile, as indicated by aberrant levels of Ang-2 and five angiogenic miRNAs (miR-27a, miR-126, miR-132, miR-223 and miR-326), compared with healthy persons and patients with diabetic nephropathy. Moreover, Ang-2 was associated with SVD and with the domains of psychomotor speed and executive function, while miR-223 and miR-29a were associated with memory function. Conclusions: Taken together, these novel angiogenic markers might serve to identify older patients with ESRD at risk of cognitive decline, as well as provide insights into the underlying (vascular) pathophysiology. Show less
Spoel, E. van der; Roelfsema, F.; Heemst, D. van 2021
Objective: To investigate the relationship between LH and testosterone (T), which characteristics associate with the strength of this relationship, and their interrelationships with GH, TSH,... Show moreObjective: To investigate the relationship between LH and testosterone (T), which characteristics associate with the strength of this relationship, and their interrelationships with GH, TSH, cortisol, and ACTH.Design: Hormones were measured in serum samples collected every 10 minutes during 24 hours from 20 healthy men, comprising 10 offspring of long-lived families and 10 control subjects, with a mean (SD) age of 65.6 (5.3) years. We performed cross-correlation analyses to assess the relative strength between 2 timeseries for all possible time shifts.Results: Mean (95% CI) maximal correlation was 0.21 (0.10-0.31) at lag time of 60 minutes between LH and total T concentrations. Results were comparable for calculated free, bioavailable, or secretion rates of T. Men with strong LH-T cross-correlations had, compared with men with no cross-correlation, lower fat mass (18.5 [14.9-19.7] vs. 22.3 [18.4-29.4] kg), waist circumference (93.6 [5.7] vs. 103.1 [12.0] cm), high-sensitivity C-reactive protein (0.7 [0.4-1.3] vs. 1.8 [0.8-12.3] mg/L), IL-6 (0.8 [0.6-1.0] vs. 1.2 [0.9-3.0] pg/mL), and 24-hour mean LH (4.3 [2.0] vs. 6.1 [1.5] U/L), and stronger LH-T feedforward synchrony (1.5 [0.3] vs. 1.9 [0.2]). Furthermore,T was positively cross-correlated withTSH (0.32 [0.21-0.43]), cortisol (0.26 [0.19-0.33]), and ACTH (0.26 [0.19-0.32]).Conclusions: LH is followed by T with a delay of 60 minutes in healthy older men. Men with a strong LH-T relationship had more favorable body composition, inflammatory markers, LH levels, and LH-T feedforward synchrony. We observed positive correlations between T and TSH, cortisol, and ACTH. Show less
Koopman, J.J.E.; Bodegom, D. van; Heemst, D. van; Westendorp, R.G.J. 2015
