Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients (n = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients (n = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets.

Further revisions to the checklists can include simplifying the words and sentences and providing relevant pictures to aid understanding. If the checklists are to be used for screening, standardization of how the checklists are to be completed and how children at risk of developmental delays can be identified on the checklists need to be provided. Parents' awareness of the importance of evaluating their child's development at 9 months, 18 months, and particularly at 2.5 years, needs to be raised. Developmental screening for children at these critical ages can be made mandatory. An electronic version of the health booklet is likely to facilitate implementation of developmental screening in the health care system.

Background Maternal prenatal infections have been linked to children’s neurodevelopment and cognitive outcomes. It remains unclear, however, whether infections occurring during specific vulnerable gestational periods can affect children’s cognitive outcomes. The study aimed to examine maternal infections in each trimester of pregnancy and associations with children’s developmental and intelligence quotients. The ALSPAC birth cohort was used to investigate associations between maternal infections in pregnancy and child cognitive outcomes. Methods Infection data from mothers and cognition data from children were included with the final study sample size comprising 7,410 mother-child participants. Regression analysis was used to examine links between maternal infections occurring at each trimester of pregnancy and children’s cognition at 18 months, 4 years, and 8 years. Results Infections in the third trimester were significantly associated with decreased verbal IQ at age 4 (p < .05, adjusted R2 = 0.004); decreased verbal IQ (p < .01, adjusted R2 = 0.001), performance IQ (p < .01, adjusted R2 = 0.0008), and total IQ at age 8 (p < .01, adjusted R2 = 0.001). Conclusion Results suggest that maternal infections in the third trimester could have a latent effect on cognitive development, only emerging when cognitive load increases over time, though magnitude of effect appears to be small. Performance IQ may be more vulnerable to trimester-specific exposure to maternal infection as compared to verbal IQ. Future research could include examining potential mediating mechanisms on childhood cognition, such as possible moderating effects of early childhood environmental factors, and if effects persist in future cognitive outcomes.

Culture is intrinsically linked with emotion expression, as culture provides rules regarding how to manage emotions when they occur. Thus far, existing literature has extensively compared norms for emotional expression and suppression, revealing significant differences among culturally distinct but also geographically distant groups (e.g., "collectivistic" Chinese versus "individualistic" U.S. Americans). The present study examines the impact of cultural diversity within Singapore, a heterogeneous Asian nation of 5.4 million residents. Using an expression suppression paradigm, eighty-three participants viewed emotion eliciting video clips and their expressions were analyzed according to the Emotion Facial Action Coding System (EmFACS, Ekman, Irwin, & Rosenberg, 1994) for signs of happiness and disgust. Participants tasked to manage their expression were successful; however cultural indicators such as ethnicity, collectivism, and concern for face affected expressivity under both suppression and natural expression conditions. These results emphasize the importance of exploring culture within national boundaries, as multiple cultural factors (e.g., ethnic groupings, values, and face) influenced expression.

Objective: Multimorbidity burden across disease cohorts and variations in clinico-radiographic presentations within normal pressure hydrocephalus (NPH) confound its diagnosis, and the assessment of its amenability to interventions. We hypothesized that novel imaging techniques such as 3-directional linear morphological indices could help in distinguishing between hydrocephalus vs. non-hydrocephalus and correlate with responsiveness to external lumbar drainage (CSF responsiveness) within NPH subtypes.Methodology: Twenty-one participants with NPH were recruited and age-matched to 21 patients with Alzheimer’s Disease (AD) and 21 healthy controls (HC) selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Patients with NPH underwent testing via the NPH programme with external lumbar drainage (ELD); pre- and post-ELD MRI scans were obtained. The modified Frailty Index (mFI-11) was used to stratify the NPH cohort, including Classic and Complex subtypes, by their comorbidity and frailty risks. The quantitative imaging network tool 3D Slicer was used to derive traditional 2-dimensional (2d) linear measures; Evans Index (EI), Bicaudate Index (BCI) and Callosal Angle (CA), along with novel 3-directional (3d) linear measures; z-Evans Index and Brain per Ventricle Ratio (BVR). 3-Dimensional (3D) ventricular volumetry was performed as an independent correlate of ventriculomegaly to CSF responsiveness.Results: Mean age for study participants was 71.14 ± 6.3 years (18, 85.7% males). The majority (15/21, 71.4%) of participants with NPH comprised the Complex subtype (overlay from vascular risk burden and AD); 12/21 (57.1%) were Non-Responders to ELD. Frailty alone was insufficient in distinguishing between NPH subtypes. By contrast, 3d linear measures distinguished NPH from both AD and HC cohorts, but also correlated to CSF responsiveness. The z-Evans Index was the most sensitive volumetric measure of CSF responsiveness (p = 0.012). Changes in 3d morphological indices across timepoints distinguished between Responders vs. Non-Responders to lumbar testing. There was a significant reduction of indices, only in Non-Responders and across multiple measures (z-Evans Index; p = 0.001, BVR at PC; p = 0.024). This was due to a significant decrease in ventricular measurement (p = 0.005) that correlated to independent 3D volumetry (p = 0.008).Conclusion. In the context of multimorbidity burden, frailty risks and overlay from neurodegenerative disease, 3d morphological indices demonstrated utility in distinguishing hydrocephalus vs. non-hydrocephalus and degree of CSF responsiveness. Further work may support the characterization of patients with Complex NPH who would best benefit from the risks of interventions.

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Background There is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children’s developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother–child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators. Methods Maternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age. Results In mediation models, significant total effects were found for MetS associations with children’s development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child’s COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models. Conclusions The results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children’s LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child’s cord blood markers (total indirect effects).

Objective: The effects of maternal exposure to adverse childhood experiences (ACEs) may be transmitted to subsequent generations through various biopsychosocial mechanisms. However, studies tend to focus on exploring one or two focal pathways with less attention paid to links between different pathways. Using a network approach, this paper explores a range of core prenatal risk factors that may link maternal ACEs to infant preterm birth (PTB) and low birthweight (LBW). Methods: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) ( n = 8379) to estimate two mixed graphical network models: Model 1 was constructed using adverse infant outcomes, biopsychosocial and environmental risk factors, forms of ACEs, and sociodemographic factors. In Model 2, ACEs were combined to represent a threshold ACEs score (≥4). Network indices (i.e., shortest path and bridge expected influence [1-step & 2-step]) were estimated to determine the shortest pathway from ACEs to infant outcomes, and to identify the risk factors that are vital in activating other risk factors and adverse outcomes. Results: Network analyses estimated a mutually reinforcing web of childhood and prenatal risk factors, with each risk connected to at least two other risks. Bridge influence indices suggested that childhood physical and sexual abuse and multiple ACEs were highly interconnected to others risks. Overall, risky health behaviours during pregnancy (i.e., smoking & illicit drug use) were identified as ‘active’ risk factors capable of affecting (directly and indirectly) other risk factors and contributing to the persistent activation of the global risk network. These risks may be considered priority candidate targets for interventions to disrupt intergenerational risk transmission. Our study demonstrates the promise of network analysis as an approach for illuminating the intergenerational transmission of adversity in its full complexity. HIGHLIGHTS We took a network approach to assessing links between ACEs and birth outcomes. ACEs, other prenatal risk factors, and birth outcomes had complex inter-connections Health behaviours in pregnancy were indicated as optimal intervention targets.