We examined the use of pupillometry as an early risk marker of Alzheimer's disease (AD). Pupil dilation during a cognitive task has been shown to be an index of cognitive effort and may provide a marker of early change in cognition even before performance begins to decline. Individuals who require more effort to successfully perform a task may be closer to decline. We previously found greater compensatory effort to perform the digit span task in individuals with amnestic mild cognitive impairment (aMCI) who may be at greater risk for AD than individuals with non-amnestic MCI (naMCI). Task evoked pupil dilation is linked to increased norepinephrine output from the locus coeruleus (LC), a structure affected early in the AD pathological process. In this study, we measured pupil dilation during verbal fluency tasks in participants with aMCI or naMCI, and cognitively normal (CN) individuals. Based on our findings using the digit span task, we hypothesized that participants with aMCI would show greater compensatory cognitive effort than the other two groups.

This study included 101 older adults without dementia recruited from the UC San Diego Shiley-Marcos Alzheimer's Disease Research Center and San Diego community (mean [SD] age = 74.7 [5.8]; education = 16.6 [2.5]; N=58 female; N=92 White); 62 CN, 20 aMCI and 19 naMCI participants. Pupillary responses (change relative to baseline at the start of each trial) were recorded at 30 Hz using a Tobii X2-30 (Tobii, Stockholm, Sweden) during semantic (animals, fruits, vegetables) and phonemic (letters F, A, S) fluency tasks. Participants generated as many words as possible in a category (semantic) or starting with a given letter (phonemic) in 60 seconds.

Repeated measures ANOVA (3 groups X 2 fluency conditions) with age, education and sex as covariates showed a significant main effect of group (F(2,95)=3.64, p=.03), but no group X condition interaction (F<1). Pairwise comparisons showed significantly greater fluency task-evoked dilation for aMCI relative to CN (p=.015) and naMCI (p=.019) participants. When controlling for performance (total letter or category words produced), pupil dilation (cognitive effort) remained significantly greater in aMCI relative to the other two groups in both fluency conditions, suggesting pupil dilation informs risk beyond information provided by task performance.

In a previous sample of community-dwelling men who were an average of 13 years younger than the present sample, we found significantly greater pupil dilation during a digit span task in aMCI relative to naMCI and CN groups. In the present study, we replicated those findings in an older sample using a different cognitive task. Significantly greater pupil dilation was found in individuals with aMCI on verbal fluency tasks, indicating greater compensatory cognitive effort to maintain performance. Pupillometry provides a promising biomarker that might be used as an inexpensive and noninvasive additional screening tool for risk of AD.

We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.

The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.

We highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.

Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms.

In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006–2010, age = 55.0 ± 7.5 [40–70] years; second visit: 2014–2019; age = 62.7 ± 7.5 [44–80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and depressive symptoms on the second visit among 138 multimodal imaging phenotypes.

Longitudinal data were consistent with significant bidirectional causal relationship between SLEs and depressive symptoms. In cross-sectional analyses, SLEs were significantly associated with lower bilateral nucleus accumbal volume and lower fractional anisotropy of the forceps major. Depressive symptoms were significantly associated with extensive white matter hyperintensities, thinner cortex, lower subcortical volume, and white matter microstructural deficits, mainly in corticostriatal-limbic structures. Lower bilateral nucleus accumbal volume were the only imaging phenotypes with overlapping effects of depressive symptoms and SLEs (B = −0.032 to −0.023, p = 0.006–0.034). Depressive symptoms and SLEs significantly partially mediated the effects of each other on left and right nucleus accumbens volume (proportion of effects mediated = 12.7–14.3%, p < 0.001−p = 0.008). For the left nucleus accumbens, post-hoc seed-based analysis showed lower resting-state functional connectivity with the left orbitofrontal cortex (cluster size = 83 voxels, p = 5.4 × 10−5) in participants with high v. no SLEs.

The nucleus accumbens may play a key role in the reciprocity between stress and depressive symptoms.

The Neurological Predictor Scale (NPS) quantifies cumulative exposure to tumor- and treatment-related neurological risks. The Pediatric Neuro-Oncology Rating of Treatment Intensity (PNORTI) measures the intensity of different treatment modalities, but research is needed to establish whether it is associated with late effects. This study evaluated the predictive validity of the NPS and PNORTI for neuropsychological outcomes in pediatric brain tumor survivors.

A retrospective chart review was completed of pediatric brain tumor survivors (PBTS) (n = 161, Mage = 13.47, SD = 2.80) who were at least 2 years from the end of tumor-directed treatment. Attention, intellectual functioning, perceptual reasoning, processing speed, verbal reasoning, and working memory were analyzed in relation to the NPS and PNORTI.

NPS scores ranged from 1 to 11 (M = 5.57, SD = 2.27) and PNORTI scores ranged from 1 (n = 101; 62.7%) to 3 (n = 18; 11.2%). When controlling for age, sex, SES factors, and time since treatment, NPS scores significantly predicted intellectual functioning [F(7,149) = 12.86, p < .001, R2 = .38] and processing speed [F(7,84) = 5.28, p < .001, R2 = .31]. PNORTI scores did not significantly predict neuropsychological outcomes.

The findings suggest that the NPS has value in predicting IF and processing speed above-and-beyond demographic variables. The PNORTI was not associated with neuropsychological outcomes. Future research should consider establishing clinical cutoff scores for the NPS to help determine which survivors are most at risk for neuropsychological late effects and warrant additional assessment.

Suicidal behaviors are prevalent among college students; however, students remain reluctant to seek support. We developed a predictive algorithm to identify students at risk of suicidal behavior and used telehealth to reduce subsequent risk.

Data come from several waves of a prospective cohort study (2016–2022) of college students (n = 5454). All first-year students were invited to participate as volunteers. (Response rates range: 16.00–19.93%). A stepped-care approach was implemented: (i) all students received a comprehensive list of services; (ii) those reporting past 12-month suicidal ideation were directed to a safety planning application; (iii) those identified as high risk of suicidal behavior by the algorithm or reporting 12-month suicide attempt were contacted via telephone within 24-h of survey completion. Intervention focused on support/safety-planning, and referral to services for this high-risk group.

5454 students ranging in age from 17–36 (s.d. = 5.346) participated; 65% female. The algorithm identified 77% of students reporting subsequent suicidal behavior in the top 15% of predicted probabilities (Sensitivity = 26.26 [95% CI 17.93–36.07]; Specificity = 97.46 [95% CI 96.21–98.38], PPV = 53.06 [95% CI 40.16–65.56]; AUC range: 0.895 [95% CIs 0.872–0.917] to 0.966 [95% CIs 0.939–0.994]). High-risk students in the Intervention Cohort showed a 41.7% reduction in probability of suicidal behavior at 12-month follow-up compared to high-risk students in the Control Cohort.

Predictive risk algorithms embedded into universal screening, coupled with telehealth intervention, offer significant potential as a suicide prevention approach for students.

Postpartum depression (PPD) affects up to one in five mothers and birthing parents, yet as few as 10% access evidence-based treatment. One-day cognitive behavioral therapy (CBT)-based workshops for PPD have the potential to reach large numbers of sufferers and be integrated into stepped models of care.

This randomized controlled trial of 461 mothers and birthing parents in Ontario, Canada with Edinburgh Postnatal Depression Scale (EPDS) scores ⩾10, age ⩾18 years, and an infant <12 months of age compared the effects of a 1-day CBT-based workshop plus treatment as usual (TAU; i.e. care from any provider(s) they wished) to TAU alone at 12-weeks post-intervention on PPD, anxiety, the mother–infant relationship, offspring behavior, health-related quality of life, and cost-effectiveness. Data were collected via REDCap.

Workshops led to meaningful reductions in EPDS scores (m = 15.77 to 11.22; b = −4.6, p < 0.01) and were associated with three times higher odds of a clinically significant decrease in PPD [odds ratio (OR) 3.00, 95% confidence interval (CI) 1.93–4.67]. Anxiety also decreased and participants had three times the odds of clinically significant improvement (OR 3.20, 95% CI 2.03–5.04). Participants reported improvements in mother–infant bonding, infant-focused rejection and anger, and effortful control in their toddlers. The workshop plus TAU achieved similar quality-adjusted life-years at lower costs than TAU alone.

One-day CBT-based workshops for PPD can lead to improvements in depression, anxiety, and the mother–infant relationship and are cost-saving. This intervention could represent a perinatal-specific option that can treat larger numbers of individuals and be integrated into stepped care approaches at reasonable cost.