This study examines how multiple dimensions of socio-emotional well-being relate to cognitive functioning in older adults, and whether the associations vary by cognitive status, depression, and socio-demographic factors.

Data from the Harmonized Cognitive Assessment Protocol of the Survey of Health, Ageing and Retirement in Europe (n = 2,650; mean age = 76; 54.5% females) were used to test associations between life satisfaction, meaning in life, social connectedness, and loneliness with global, domain-specific cognitive performance, and informant-rated cognitive decline.

Linear mixed models, with individuals nested within five countries, found that higher life satisfaction, meaning in life, and social connectedness were associated with better cognitive outcomes, whereas greater loneliness was associated with worse performance and greater informant-rated decline. The largest effect sizes were observed for meaning in life (median β = .10) and loneliness (median β = −.09) across cognitive measures. The associations generally remained significant adjusting for well-known clinical (e.g., diabetes), behavioral (e.g., physical inactivity), and psychological (depressive symptomatology) risk factors for dementia. Moderation and sensitivity analyses suggested that associations with global cognition hinged on the inclusion of participants classified with cognitive impairment, while some domain-specific associations (e.g., loneliness and episodic memory) were observed only in individuals without cognitive impairment. Overall, evidence for moderation by cognitive status, depression and age was limited, and no moderation was observed for sex or education.

The results underscore the importance of socio-emotional well-being in cognitive aging and highlight the need for longitudinal research to clarify mechanistic pathways and inform targeted interventions.

Cardiopulmonary bypass-induced inflammation is associated with poor postoperative outcomes. Bypass exposure has been associated with shifts in lymphocyte populations. This study aimed to describe two cytokine profiles associated with T and NK cells and their effects on clinical markers of postoperative cardiovascular dysfunction in children undergoing cardiac surgery with cardiopulmonary bypass.

Children from two major children’s hospitals undergoing corrective cardiac surgery with cardiopulmonary bypass were included. Plasma was collected pre-, 0 to 4 hours post- and 24 hours (when available) postoperatively. Plasma concentrations of cytokines were quantified using enzyme-linked immunosorbent assays. Delta cytokine concentrations were compared to vasoactive infusion score and percent fluid balance on postoperative day one. Vascular reactivity was assessed in a subset of the cohort. Confirmation of endothelial-specific effects of interferon-γ and interleukin-17A was performed in microvascular endothelial cells, assessing cytokine levels by enzyme-linked immunosorbent assays or trans-endothelial electrical resistance.

A total of 26 children were included in the analysis. Interferon-γ was inversely associated with vasoactive infusion score (p < 0.05), whereas interleukin-17A and interleukin-23 were associated with greater cumulative postoperative fluid balance (p < 0.01 and 0.03, respectively). Peak vascular reactivity is strongly associated with interferon-γ (p = 0.001), but not with circulating interleukin-17A. Human microvascular endothelial cell exposure to interferon-γ increased endothelial permeability and cytokine production.

Interferon-γ and interleukin-17A may be associated with cardiovascular dysfunction in children after exposure to cardiopulmonary bypass, albeit with differential clinical features. Interferon-γ may directly impact vascular measures, while the impact of interleukin-17A may relate to fluid accumulation.

Social anxiety disorder (SAD) is one of the most common anxiety disorders and is associated with significant impairment and societal costs. The association between SAD and mortality remains poorly understood, partly because in epidemiological research it is rarely studied independently from other anxiety disorders. In this population-based matched cohort and sibling control study, we estimated the risk of all-cause and cause-specific mortality in individuals with SAD.

From a population of individuals born from 1932 and living in Sweden between 1997 and 2020, we identified all cases of SAD (Swedish ICD-10 code F40.1) in the National Patient Register. Each of these individuals was matched on sex, birth year and county of residence with 10 individuals who had never received a diagnosis. Mortality data were extracted from the Cause of Death Register. Risks were estimated using Cox proportional hazards regression models. Models adjusted for sociodemographic covariates and other lifetime psychiatric disorders. We also identified all clusters of full siblings and conducted within-sibling comparisons to account for unmeasured familial confounding.

The matched cohort included 57,360 individuals with SAD and 573,600 unexposed individuals. During the follow-up, 2355 deaths were registered within the exposed cohort vs. 7800 deaths in the matched cohort (crude mortality rates, 5.25 and 1.73 per 1000 person-years, respectively). The full cohort was followed up for a mean of 7.87 years (standard deviation 5.23). In models adjusting for sociodemographic variables, individuals with SAD had a 2.24-fold increased hazard of all-cause mortality (95% confidence interval [CI], 2.13–2.35). The increased risk was observed for both natural (adjusted hazard ratio [HR], 1.62; 95% CI 1.52–1.72) and unnatural causes of death (HR, 4.18; 95% CI 3.82–4.58). The results were robust to additional adjustment for psychiatric comorbidities, but the magnitude of the associations was attenuated, particularly when adjusting for substance use disorders. In the sibling cohort, 39,993 individuals with SAD were compared with their 64,640 unaffected siblings. While the estimates were also attenuated, they remained statistically significant (HR for all-cause mortality, 1.40; 95% CI 1.36–1.45).

Individuals with SAD face an increased risk of mortality, attributable primarily to unnatural causes of death, such as suicide, but also to natural causes, even after adjusting for socioeconomic variables. Psychiatric comorbidities, particularly substance use disorders, and shared familial factors may also contribute to this excess death. Further study of underlying mechanisms may inform prevention and early intervention strategies to reduce mortality in this vulnerable population.

Drug use disorder (DUD) clusters in families due partly to shared environment, including sibling influences. Low academic achievement (AA) in adolescence increases DUD risk. This study examined whether low AA in an older sibling causally increases DUD risk in younger siblings.

We studied all Swedish full sibling pairs (n = 309,666) born 1972–1985 and ≤ 5 years apart. Older sibling AA was assessed at age 16. Using Month-of-Birth (MoB) as an instrument, we conducted instrumental variable (IV) analyses and propensity score (PS) models to evaluate the causal impact of older sibling AA on younger sibling DUD risk, assessed by DUD registration in national medical, criminal, or pharmacy registries.

Older sibling AA significantly predicted younger sibling DUD risk across models. Beta coefficients (±95% CI) were 2.04 (1.97–2.12) in raw analysis, 1.88 (0.74–3.02) in IV, and 1.26 (1.17–1.34) in PS models. Together with the strong first-stage association, the IV estimates remain positive under small departures from the ideal identifying assumptions. Effect sizes declined with increasing sibling age differences (p = 0.036 for IV; p < 0.0001 for PS) and were strongest in male–male pairs (IV: 4.01 [1.42–6.61]; PS: 1.74 [1.55–1.93]). Mediation by older sibling DUD was modest.

Findings from two causal inference approaches support a largely causal link between low AA in an older sibling and increased DUD risk in younger siblings. Stronger effects in close-aged and male–male pairs further support this conclusion. Interventions to improve AA in older siblings may yield indirect preventive benefits for younger siblings.