Association between antenatal glucocorticoid exposure and the activity of the stress system, cognition, and behavior in 8‐ to 9‐year‐old children: A prospective observational study

Introduction Glucocorticoid (GC) ‐induced fetal programming of the activity of the hypothalamus–pituitary–adrenal axis (HPAA) and its associated cognitive and behavioral consequences in later life have been well characterized in several animal species. However, information on humans is scarce. In this study, we examined HPAA activity markers and associated outcomes at 8 to 9 years of age among children prenatally exposed to GC for suspected preterm birth. Our hypothesis was that antenatal exposure to the betamethasone (BM) is associated with exacerbation of HPAA activity in childhood. Material and methods Prospective observational study in 31 children whose mothers received single ( n = 19) or multiple ( n = 12) courses of BM for threatened preterm birth but born with normal weight appropriate for the gestational age (median 37+ 6 weeks of gestation) compared with 38 non‐exposed, age‐matched children. Primary end point was the activity of the HPAA in response to the Trier Social Stress Test. Secondary end points were changes in autonomic nervous system (ANS) activity, cognitive performance (IQ), attention‐deficit/hyperactivity disorder (ADHD) symptoms, and electrocortical activity (EEG). Results There was no statistically significant difference in HPAA activity markers between antenatal BM exposed and unexposed groups. ANS activity in BM‐exposed children shifted towards a higher parasympathetic tone reflected by a higher overall high‐frequency band power of heart rate variability. IQ scores were within normal limits for both groups; however, BM‐exposed children had lower IQ scores than the unexposed group. BM‐exposed group had marginally more ADHD core symptoms and increased electrocortical activity in the occipital brain region compared with controls. A monotonic dose–response relation between BM exposure and activity of the ANS and IQ was estimated in post‐hoc analyses. Conclusions Antenatal exposure to BM in the context of threatened preterm birth was not associated with changes in HPAA activity in childhood. However, BM exposure may be associated with changes in ANS activity. Antenatal GC prophylaxis is a valuable and often life‐saving therapy, but its prescription may warrant a well‐balanced risk–benefit assessment

Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study

Background COVID-19 survivors may experience a wide range of chronic cognitive symptoms for months or years as part of post-COVID-19 conditions (PCC). To date, there is no definitive objective cognitive marker for PCC. We hypothesised that a key common deficit in people with PCC might be generalised cognitive slowing. Methods To examine cognitive slowing, patients with PCC completed two short web-based cognitive tasks, Simple Reaction Time (SRT) and Number Vigilance Test (NVT). 270 patients diagnosed with PCC at two different clinics in UK and Germany were compared to two control groups: individuals who contracted COVID-19 before but did not experience PCC after recovery (No-PCC group) and uninfected individuals (No-COVID group). All patients with PCC completed the study between May 18, 2021 and July 4, 2023 in Jena University Hospital, Jena, Germany and Long COVID clinic, Oxford, UK. Findings We identified pronounced cognitive slowing in patients with PCC, which distinguished them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. Cognitive slowing was evident even on a 30-s task measuring simple reaction time (SRT), with patients with PCC responding to stimuli ∼3 standard deviations slower than healthy controls. 53.5% of patients with PCC's response speed was slower than 2 standard deviations from the control mean, indicating a high prevalence of cognitive slowing in PCC. This finding was replicated across two clinic samples in Germany and the UK. Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in patients with PCC. Furthermore, cognitive slowing on the SRT was highly correlated with the poor performance of patients with PCC on the NVT measure of sustained attention. Interpretation Together, these results robustly demonstrate pronounced cognitive slowing in people with PCC, which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. This might be an important factor contributing to some of the cognitive impairments reported in patients with PCC. Funding Wellcome Trust (206330/Z/17/Z), NIHR Oxford Health Biomedical Research Centre, the Thüringer Aufbaubank (2021 FGI 0060), German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890)

Validation of an Automated Scoring Program for a digital Complex Figure Copy Task within healthy ageing and stroke

Objective Complex Figure Copy Tasks are one of the most commonly employed neuropsychological tests. However, manual scoring of this test is time-consuming, requires training, and can then still be inconsistent between different examiners. We aimed to develop and evaluate a novel, automated method for scoring a tablet-based Figure Copy Task. Method A cohort of 261 healthy adults and 203 stroke survivors completed the computerised Oxford Cognitive Screen – Plus Figure Copy Task. Responses were independently scored by two trained human raters and by a novel automated scoring program. Results Overall, the Automated Scoring Program was able to reliably extract and identify the separate figure elements (average sensitivity and specificity of 92.10% and 90.20% respectively) and assigned total scores which agreed well with manual scores (ICC = .83). Receiver Operating Curve analysis demonstrated that, compared to overall impairment categorisations based on manual scores, the Automated Scoring Program had an overall sensitivity and specificity of 80% and 93.40% respectively (AUC = 86.70%). Automated total scores also reliably distinguished between different clinical impairment groups with acute stroke survivors scoring significantly worse than longer term survivors, which in turn scored worse than neurologically healthy adults. Conclusions These results demonstrate that the novel automated scoring algorithm was able to reliably extract and accurately score Figure Copy Task data, even in cases where drawings were highly distorted due to comorbid fine-motor deficits. This represents a significant advancement as this novel technology can be employed to produce immediate, unbiased, and reproducible scores for Figure Copy Task responses in clinical and research environments