Previous studies identified clusters of first-episode psychosis (FEP) patients based on cognition and premorbid adjustment. This study examined a range of socio-environmental risk factors associated with clusters of FEP, aiming a) to compare clusters of FEP and community controls using the Maudsley Environmental Risk Score for psychosis (ERS), a weighted sum of the following risks: paternal age, childhood adversities, cannabis use, and ethnic minority membership; b) to explore the putative differences in specific environmental risk factors in distinguishing within patient clusters and from controls.

A univariable general linear model (GLS) compared the ERS between 1,263 community controls and clusters derived from 802 FEP patients, namely, low (n = 223) and high-cognitive-functioning (n = 205), intermediate (n = 224) and deteriorating (n = 150), from the EU-GEI study. A multivariable GLS compared clusters and controls by different exposures included in the ERS.

The ERS was higher in all clusters compared to controls, mostly in the deteriorating (β=2.8, 95% CI 2.3 3.4, η2 = 0.049) and the low-cognitive-functioning cluster (β=2.4, 95% CI 1.9 2.8, η2 = 0.049) and distinguished them from the cluster with high-cognitive-functioning. The deteriorating cluster had higher cannabis exposure (meandifference = 0.48, 95% CI 0.49 0.91) than the intermediate having identical IQ, and more people from an ethnic minority (meandifference = 0.77, 95% CI 0.24 1.29) compared to the high-cognitive-functioning cluster.

High exposure to environmental risk factors might result in cognitive impairment and lower-than-expected functioning in individuals at the onset of psychosis. Some patients’ trajectories involved risk factors that could be modified by tailored interventions.

Brazil – one of the world's largest biocultural diversities – faces high rates of habitat loss, social inequality, and land conflicts impacting indigenous and local peoples. To challenge that, Brazilian sustainability science and education needs to be strengthened. We searched for elements in ongoing bottom-up sustainability social movements that can help serve that purpose. We found values, contents, and attitudes that, if incorporated into Brazilian sustainability science and education, can assist its transformative potential by reflecting local voices and critically engaging with (often-hegemonic) northern concepts.

In Brazil, a strong sustainability science and education is required to confront ‘glocal’ issues such as zoonotic pandemics and climate change, which are worsened by rampant ecosystem loss and social vulnerability. However, a largely disciplinary university system has been slow to meet these urgent needs. To address if and how dialogical processes with non-academics can prompt integration between distinct types of knowledge, we analyze four bottom-up sustainability initiatives that promote dialogues between science, the arts, religion, youth, and indigenous and local knowledge, and reflect on lessons learnt with movement organizers, scientists, and educators – the authors of this paper. Although sustainability science produced in dialogue with other forms of knowledge is still emerging in Brazil, we find that bottom-up initiatives outside academia can inspire science and education to approach sustainability as wholeness – a state of balance to be fulfilled when reached individually, collectively, and cosmically. We discuss how to approach a transdisciplinary and reflexive attitude in Brazilian sustainability science and education, and highlight its unique contribution to frontier topics in global sustainability debates.

Social movements’ values, contents, and attitudes can inspire transformative Brazilian sustainability science and education.

Children with prolonged hospital admissions for CHD often develop delirium. Antipsychotic medications (APMs) have been used to treat delirium but are known to prolong the QTc duration. There is concern for prolongation of the QTc interval in cardiac patients who may be more vulnerable to electrocardiogram (ECG) changes and may have postoperative QTc prolongation already. The goal of this study was to determine the effect of APM on QTc duration in postoperative paediatric cardiac patients and determine the effect of quetiapine and risperidone in treating delirium and QTc prolongation.

Retrospective study, July 1, 2017–May 31, 2022.

Tertiary children’s hospital.

Included were patients admitted to the paediatric cardiac ICU at Children’s Healthcare of Atlanta.

None.

ECGs, delirium scores, and drug information were collected. Delirium was defined as Cornell Assessment of Pediatric Delirium (CAPD) score >9. Mixed effect models were performed to evaluate the effect of surgery on QTc change and the effect of antipsychotics on QTc and CAPD changes. There were 139 children, 55% male and 67% surgical admissions. Median age was 5.9 months. Mean QTc increased after cardiac surgery by 18 ms (p = 0.014, 95% CI 3.65–32.4). There was no significant change in QTc after antipsychotic administration (p = 0.064). The mean CAPD score decreased (12.5–7.2; p < 0.001). Quetiapine had the most improvement in delirium, and risperidone had the least improvement (77.8%, n = 14; 37.8%, n = 34, respectively; p = 0.002).

The QTc interval did not have a statistically significant change after the administration of antipsychotics, while there was improvement in the CAPD score. APMs may be administered safely without significant prolongation of the QTc and are an effective treatment for delirium.

Problematic drinking frequently co-occurs with depression among young adults, but often remains unaddressed in depression treatment. Evidence is insufficient on whether digital alcohol interventions can be effective in this young comorbid population. In a randomized controlled trial, we examined the effectiveness of Beating the Booze (BtB), an add-on digital alcohol intervention to complement depression treatment for young adults.

Participants were randomized to BtB + depression treatment as usual (BTB + TAU, n = 81) or TAU (n = 82). The primary outcome was treatment response, a combined measure for alcohol and depression after 6-month follow-up. Secondary outcomes were number of weekly drinks (Timeline Follow-back) and depressive symptoms (Center for Epidemiologic Studies Depression scale). Treatment response was analyzed using generalized linear modeling and secondary outcomes using robust linear mixed modeling.

Low treatment response was found due to lower than expected depression remission rates. No statistically significant between-group effect was found for treatment response after 6-month follow-up (odds ratio 2.86, p = 0.089, 95% confidence interval [CI] 0.85–9.63). For our secondary outcomes, statistically significant larger reductions in weekly drinks were found in the intervention group after 3-month (B = −4.00, p = 0.009, 95% CI −6.97 to −1.02, d = 0.27) and 6-month follow-up (B = −3.20, p = 0.032, 95% CI −6.13 to −0.27, d = 0.23). We found no statistically significant between-group differences on depressive symptoms after 3-month (B = −0.57, p = 0.732, 95% CI −3.83 to 2.69) nor after 6-month follow-up (B = −0.44, p = 0.793, 95% CI −3.69 to 2.82).

The add-on digital alcohol intervention was effective in reducing alcohol use, but not in reducing depressive symptoms and treatment response among young adults with co-occurring depressive disorders and problematic alcohol use.

Pre-registered on October 29, 2019 in the Overview of Medical Research in the Netherlands (OMON), formerly the Dutch Trial Register(https://onderzoekmetmensen.nl/en/trial/49219).

Patients with early Alzheimer Disease (AD) and Mild Cognitive Impairment of the Amnestic type (MCI-A) have been reported to show large variability of tapping scores. Factors that contribute to that variability remain undetermined. This preliminary study aimed to identify predictors of finger tapping variability in older adults evaluated for a neurodegenerative memory disorder. Based on earlier research with normally functioning adults, we predicted that the number of “invalid” tapping responses (i.e. failure of the index finger to adequately lift off the tapping key once it is depressed to produce the next number on a mechanical counter) and the female gender would predict finger tapping variability, but age and educational level would not predict variability.

This preliminary study included 4 groups of participants, comprised of 8 healthy controls (HC, 3 males; 73±7years); 12 persons with subjective memory complaints (SMC, 3 males; 69±5 years); 12 with MCI-A (7 males; 76±5 years) and 7 early AD (5 males; 75±6years). All participants were administered a modified version of the Halstead Finger Tapping Test (HFTT). Mean, range of tapping score (i.e. a measure of variability), and number of invalid taps across 7 trials in each hand were calculated. ANOVA was performed for the HFTT metrics with the main effect of group. Tukey HSD tests were used for post hoc comparisons between groups. Multiple regression analysis was performed to determine the degree to which the number of invalid tapping responses, sex, age, and educational level predicted finger tapping variability using all 4 groups.

Mean tapping score did not vary significantly across groups in the dominant [F (3, 35) = 0.633, p = 0.599] or non-dominant [F (3, 35) = 2.345, p = 0.090] hand. Range score approached a significant difference between groups in the dominant hand [F (3, 35) = 2.745, p = 0.058], with a clear significant effect of group on range score in the non-dominant hand [F (3, 35) = 4.078, p = 0.014]. Range score in the nondominant hand was significantly higher in the AD compared to SMC (p = 0.018) and HC (p = 0.024). Regression analysis revealed statistically significant findings for the dominant hand (R2 = 0.327, F (4, 34) = 4.130, p = 0.008) and for the non-dominant hand (R2 = 0.330, F (4, 34) = 4.180, p = 0.007). For both the dominant and non-dominant hands, number of invalid taps significantly predicted range score (ß = 0.453, p = 0.044, and ß = 0.498, p = 0.012, respectively). Sex, age, and education years did not predict range scores.

Variability of finger tapping in patients evaluated for neurodegenerative memory disorders and aged matched controls is predicted by the number of invalid tapping responses (comprising over 30% of the variance), but not by demographic variables in this clinical sample. Neurodegenerative disorders may eliminate a sex effect.

Aggregation of phosphorylated tau (pTau) is a hallmark feature of Alzheimer’s disease (AD). Novel assays now allow pTau to be measured in plasma. Elevated plasma pTau predicts subsequent development of AD, cortical atrophy and AD-related pathologies in the brain. We aimed to determine whether elevated pTau is associated with cognitive functioning in older adults prior to the development of dementia.

Independently living older adults (N = 48, mean age = 70.0 years; SD = 7.7; age range 55-88 years; 35.4% male) free of dementia or clinical stroke were recruited from the community and underwent blood draw and neuropsychological assessment. Plasma was assayed using the Quanterix Simoa® pTau-181 V2 Advantage Kit to quantify pTau-181 levels and APOE genotyping was conducted on the blood cell pellet fraction obtained from plasma separation. Global cognition was assessed using the Dementia Rating Scale-2 (DRS-2) and executive function was assessed using the Stroop, D-KEFS-2 Fluency, and Trails Making Test. Diagnosis of mild cognitive impairment (MCI) was determined based on overall neuropsychological performance. Participants were diagnosed as MCI if they scored >1 SD below norm-referenced values on 2 or more tests within a domain (language, executive, memory) or on 3 tests across domains.

Multiple linear regression analysis revealed a significant negative association between plasma pTau-181 levels and DRS-2 (B = -2.57, 95% CI (-3.68, -1.47), p <.001), Stroop Color-Word score (B = -2.64, 95% CI (-4.56, - 0.71), p = .009) and Fruits and Vegetables Fluency (B = -1.67, 95% CI (-2.84, -0.49), p = .007), adjusting for age, sex, education and APOE4 status. MCI diagnosis was determined for 43 participants, of which 8 (18.6%) met criteria. Logistic regression analysis revealed that pTau-181 levels are associated with increased odds of MCI diagnosis (OR = 2.18, 95% CI (1.01, 4.68), p = .046), after accounting for age, sex, education and APOE4 status.

Elevated plasma pTau-181 is associated with worse cognition, particularly executive function, and predicts MCI diagnosis in older adults. Higher plasma pTau-181 was associated with increased odds of MCI diagnosis. Detection of pTau-181 in plasma allows a novel, non-invasive method to detect burden of one form of AD pathology. These findings lend support to the use of plasma pTau-181 as a valuable marker in detecting even early cognitive changes prior to the development of AD. Additional longitudinal studies are warranted to explore the prognostic value of plasma pTau-181 over time.

The locus coeruleus (LC) innervates the cerebrovasculature and plays a crucial role in optimal regulation of cerebral blood flow. However, no human studies to date have examined links between these systems with widely available neuroimaging methods. We quantified associations between LC structural integrity and regional cortical perfusion and probed whether varying levels of plasma Alzheimer’s disease (AD) biomarkers (Aß42/40 ratio and ptau181) moderated these relationships.

64 dementia-free community-dwelling older adults (ages 55-87) recruited across two studies underwent structural and functional neuroimaging on the same MRI scanner. 3D-pCASL MRI measured regional cerebral blood flow in limbic and frontal cortical regions, while T1-FSE MRI quantified rostral LC-MRI contrast, a well-established proxy measure of LC structural integrity. A subset of participants underwent fasting blood draw to measure plasma AD biomarker concentrations (Aß42/40 ratio and ptau181). Multiple linear regression models examined associations between perfusion and LC integrity, with rostral LC-MRI contrast as predictor, regional CBF as outcome, and age and study as covariates. Moderation analyses included additional terms for plasma AD biomarker concentration and plasma x LC interaction.

Greater rostral LC-MRI contrast was linked to lower regional perfusion in limbic regions, such as the amygdala (ß = -0.25, p = 0.049) and entorhinal cortex (ß = -0.20, p = 0.042), but was linked to higher regional perfusion in frontal cortical regions, such as the lateral (ß = 0.28, p = 0.003) and medial (ß = 0.24, p = 0.05) orbitofrontal (OFC) cortices. Plasma amyloid levels moderated the relationship between rostral LC and amygdala CBF (Aß42/40 ratio x rostral LC interaction term ß = -0.31, p = 0.021), such that as plasma Aß42/40 ratio decreased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and amygdala perfusion decreased. Plasma ptau181levels moderated the relationship between rostral LC and entorhinal CBF (ptau181 x rostral LC interaction term ß = 0.64, p = 0.001), such that as ptau181 increased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and entorhinal perfusion decreased. For frontal cortical regions, ptau181 levels moderated the relationship between rostral LC and lateral OFC perfusion (ptau181 x rostral LC interaction term ß = -0.54, p = .004), as well as between rostral LC and medial OFC perfusion (ptau181 x rostral LC interaction term ß = -0.53, p = .005), such that as ptau181 increased (i.e., greater pathology), the strength of the positive relationship between rostral LC integrity and frontal perfusion decreased.

LC integrity is linked to regional cortical perfusion in non-demented older adults, and these relationships are moderated by plasma AD biomarker concentrations. Variable directionality of the associations between the LC and frontal versus limbic perfusion, as well as the differential moderating effects of plasma AD biomarkers, may signify a compensatory mechanism and a shifting pattern of hyperemia in the presence of aggregating AD pathology. Linking LC integrity and cerebrovascular regulation may represent an important understudied pathway of dementia risk and may help to bridge competing theories of dementia progression in preclinical AD studies.

The influence of prior knowledge on new learning is well established. However, there has been less research dedicated to teasing apart the key components of prior knowledge’s structure that contribute to memory enhancement. In the current study, we focused on event structures, which include various relations, such as associative, causal, and temporal. Given that events possess attributes relevant to numerous cognitive memory processes, we were most interested in exploring how event structures that possess causal relations enhance new memory formation. Specifically, we examined whether events that exhibit causal associative relations provide an additional boost to new learning compared to event structures with non-causal associative relations.

Forty-six undergraduate students took part in the study. Participants’ learning of the content of image pairs that exhibit everyday, real-world events were measured using a cued recall paradigm. The stimuli consisted of 60 image pairs that illustrated two events that were related causally and associatively (i.e., causal pairs); related only associatively (i.e., non-causal pairs); or not related at all (i.e., unrelated pairs). During an encoding phase, image pairs were presented one at a time, and after the presentation of each image pair, participants answered an encoding question that focused on the relationship between the two images. After the encoding phase and a short filler task, participants were shown a cue image (always the first picture from the pair) and were asked to provide a brief written description of the content of the second presented image from each pair. Also, as a manipulation check, we asked subjects to rate each image pair on causal direction and association strength after completion of the cued recall memory task.

We found that, relative to unrelated pairs, events that possess associative relations (i.e., both causal and non-causal items) benefit learning of new information. In addition, causal relations provided an additional boost to new learning. Specifically, cued recall performance is best for causal pairs, followed by non-causal pairs and unrelated pairs. Moreover, causal direction ratings significantly predict overall itemlevel accuracy above and beyond general associative relations that exist in events. We also examined recall accuracy for specific content information within each event (i.e., agent, action, object) and found that causal relations uniquely contribute to recall performance of objects and actions.

Overall, the present study’s findings suggest that prior event knowledge structures possessing causal and non-causal associative relations support new learning, especially compared to image pairs with no relations. Of interest, causality provides an additional boost to new learning above and beyond general associative relations. By focusing on the role of causality in event structures, our findings informed our understanding of how prior knowledge supports new learning. Considering that the effect of prior knowledge on new episodic learning is especially evident in older adults, since they more readily rely on their schematic knowledge, a future direction would entail investigating how causal links influence new memory formation in older adults.