Glymphatic system dysfunction has been increasingly implicated in Alzheimer’s disease (AD), yet its relationships with cerebral small vessel disease (CSVD), plasma biomarkers, and cognitive impairment across the AD remain incompletely understood.

We prospectively recruited 216 participants from Hainan General Hospital, including healthy controls (HC), individuals with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD dementia. All participants underwent brain magnetic resonance imaging, plasma biomarker testing, and neuropsychological assessments. White matter hyperintensity (WMH) volume from T2-weighted fluid-attenuated inversion recovery images served as a marker of CSVD. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index assessed glymphatic function. Plasma amyloid β-protein (Aβ) concentrations measured peripheral Aβ levels as a surrogate indicator of amyloid pathology.

The ALPS index was significantly lower in AD patients compared with HC, SCD, and MCI groups (all P < 0.01) and tended to be lower in the MCI group relative to SCD. After controlling for demographics and APOE4 status, ALPS positively correlated with the plasma Aβ42/Aβ40 ratio (r = 0.16, P = 0.038). ALPS index showed significant negative correlations with log-transformed juxtaventricular and juxtacortical WMH volumes (r = −0.32, P < 0.001; r = −0.19, P = 0.010), with marginal correlation for periventricular WMH (r = −0.13, P = 0.052).

Plasma Aβ levels and regional WMH burden are associated with glymphatic dysfunction as indicated by reduced ALPS. Impaired glymphatic clearance also correlates with cognitive impairment, providing theoretical support for novel pathophysiological hypotheses and potential therapeutic targets in AD pathogenesis.

Extreme hot weather poses increasing risks to mental health. Yet, factors affecting vulnerability are under-researched. This mixed-method study integrates a systematic review and qualitative investigation to identify risk and protective factors for heat-related mental health issues, leading to the co-development of a screening tool. This could inform future research and, pending validation in clinical settings, support mental health professionals in assessing vulnerability among service users.

We searched PubMed and Web of Science for publications on extreme heat, mental health, and risk/protective factors. In addition, we conducted six focus groups with 21 people with lived experience of heat and/or mental illness and 12 healthcare professionals. Transcripts were analyzed using thematic content analysis and informed the co-development of the screening tool.

Out of 764 articles identified by the systematic review, 47 were included. Evidence emerged for age, sex, existing mental illness, ethnicity, and socioeconomic status as risk factors. However, findings were inconsistent between studies, likely due to differences in study population and methodology. Protective effects included good physical health, social support, and exposure to green spaces. Our qualitative investigation identified additional risk and protective factors related to: (1) behavioral adaptability, (2) personal heat sensitivity, and (3) disparities in heat exposure. The resulting screening tool, HEAT-MH (Heat Exposure Assessment Tool for Mental Health), contains 15 questions on previous experiences of heat, general health, and lifestyle.

The mental health impacts of extreme heat depend on a range of risk and protective factors, including demographic, socioeconomic, health, and lifestyle characteristics.

While initial anhedonia predicts poor psychotherapy outcomes, little is known about its trajectory during treatment. This study aimed to: (1) identify distinct anhedonia trajectories during high-intensity depression treatment; (2) examine patient and treatment predictors; and (3) compare outcomes across treatment types.

Sessional anhedonia scores (PHQ-9 item-1) from 22,605 patients in NHS talking therapies (primarily receiving either cognitive-behavioral therapy [CBT] or counseling for depression [CfD]) were analyzed using latent growth curve (LGC) and growth mixture modeling. Multinomial logistic regression examined predictors of class membership.

A quadratic LGC model best fit the data, reflecting a decrease in symptoms before leveling out. Six latent classes emerged. Notably, three “non-responder” classes characterized by linear-stable or minimal-change patterns comprised over 50% of the sample (51.3%). In contrast, two “responder” classes (41.4%) exhibited improvement, typically shifting between sessions 4 and 6. This suggests an early “inflection point” where the trajectory of recovery is established. Poorer response was predicted by unemployment, chronic health conditions, psychotropic medication, and longer wait times. There was only a sufficient sample size to compare CBT and CfD treatment types. While CBT was associated with membership in specific classes, the probability of being a “responder” did not differ significantly between CBT and CfD.

Most patients followed non-responder trajectories, highlighting a major efficacy gap for anhedonia in standard depression protocols. The 4–6 session window suggests that if improvement is not observed early, the treatment strategy may require further evaluation. Further research into targeted anhedonia interventions is essential.

Cognitive difficulties, including problems with attention and executive processing, are common in major depressive disorder (MDD), and strongly predict psychosocial and occupational functioning. Impairment in sustained attention contributes to increased intra-individual variability (IIV) in reaction times observed during cognitive tasks. Understanding brain network changes associated with IIV could guide novel neuromodulation strategies targeting cognitive difficulties.

We analyzed baseline resting-state fMRI data from 209 patients with moderate-to-severe treatment-resistant MDD who participated in the BRIGhTMIND neuromodulation trial. Following a preregistered analytic protocol, we examined associations between: functional connectivity across three core brain networks (executive control, ECN; default mode, DMN; and salience network, SN); components of IIV derived from a choice reaction time task (using a three-parameter ex-Gaussian model); and functioning.

Greater IIV was linked to increased ECN-DMN functional connectivity. The ECN supports top-down control and externally directed cognition, while the DMN supports internal mentation and rumination. ECN-DMN connectivity was modulated by the SN, which prioritizes salient internal and external stimuli. Higher SN-ECN connectivity was associated with lower ECN-DMN connectivity and with faster mean reaction times. Both IIV and mean reaction time predicted functioning, with poorer functioning related to a slowed and inflexible response pattern.

Distinct components of reaction time variability are associated with specific patterns of brain network connectivity, largely independent of mood severity. Connectivity between the salience and executive control networks may represent a promising target for neuromodulation interventions focused on cognitive deficits in MDD.

Quality of social support is linked to mental health, but less is known about its long-term effects. We aimed to investigate the effects of the quality of social support on affective symptoms from midlife through later life.

Data were used from the MRC National Survey of Health and Development (NSHD), a prospective birth cohort originally consisting of 5,362 people born in 1946. Affective symptoms were measured at ages 53, 60–64, and 69 years using the General Health Questionnaire (GHQ-28), and longitudinal affective symptom trajectories were derived using growth mixture modeling. Quality of social support (positive and negative) was assessed at age 53 years with an adapted version of the Close Persons Questionnaire. Associations of positive and negative social support with affective symptoms at each age and with the longitudinal trajectories were tested using structural equation modeling and the R3 Step approach.

Four distinct affective symptom trajectories were identified: no/low symptoms (83%), low and increasing symptoms (8%), consistently moderate/high symptoms (5%), and moderate/high and decreasing symptoms (4%). In fully adjusted models, negative social support was associated with affective symptoms at all three ages (β: 0.09–0.16, all p-values < .001) and with the ‘consistently moderate/high symptoms’ trajectory (OR = 1.65, 95% CI: 1.36, 2.01, p < .001); no association was found for positive social support.

Results highlight the importance of negative social support as a potential modifiable factor in prevention and intervention initiatives for affective symptoms among adults from midlife to later life.

Inappropriate antibiotic allergy labeling often leads to the unnecessary avoidance of first-line therapies. The present study aimed to evaluate the current status of antibiotic allergy documentation and its assessment in patients undergoing surgery for which cefazolin was the recommended first-line prophylaxis in a Japanese hospital.

This retrospective observational study was conducted at a university hospital in Tokyo from 2021 to 2023; included patients with a history of antimicrobial allergy who underwent surgery for which cefazolin was recommended; and assessed patient demographics, details of the allergies in electronic health records (EHR), and perioperatively administered antimicrobial agents.

Of 2,402 eligible patients, 243 (10.1%) had a registered antimicrobial allergy. The drug classes most frequently recorded in the EHR were cephalosporins (25.0%) and penicillins (24.0%). Documentation of allergy assessments by a physician (9.0%) or specialist (7.0%) was rare. Although 51.9% of the labeled patients had received cefazolin, non-first-line agents had also been frequently administered. Notably, clindamycin had been administered to 30% of the cases and had been widely used even among patients with only a penicillin allergy label despite the low risk of cross-reactivity.

Antibiotic allergy labels in the EHR were often incomplete, infrequently assessed, and associated with substantial avoidance of first-line prophylaxis. Redesigning the EHR format to allow allergies to be distinguished from adverse events while retaining the standard evaluation pathways is essential to optimizing perioperative antimicrobial stewardship.

Although mental health and healthy lifestyle interventions are associated with functional outcomes in adolescence, the extent to which particular lifestyle factors explain relationships between mental health and outcome are unclear. Here we examined mediating effects of lifestyle factors on relationships between mental health and two functional outcomes measured 2–3 years later, as well as moderating effects of environmental risk factors on mediation strength in early adolescence.

We analyzed data from three waves of the Adolescent Brain Cognitive Development Study (ages 10–11, 11–12, and 12–13 years). Mediating effects of sleep quality, screen time, physical activity, and Mediterranean diet on the relationships between depression, anxiety, psychotic-like experience (PLE) distress, and total problems with two subsequent functional outcomes (academic functioning and social problems) were examined. Secondary analyses included environmental factors as moderators.

Sleep quality mediated 18.5%, 36.3%, and 8.3% of the relationships between depression, anxiety, and PLE distress with academic functioning, respectively (total problems mediation was nonsignificant). Screen time was the second strongest mediator. For social problems, only sleep quality showed >3% mediation (19.6–23.3%). Mediating effects of sleep and screen time on academic functioning decreased as financial adversity increased. Conversely, mediating effects of sleep quality on social problems increased with worsening family conflict, financial adversity, and school environment.

These results suggest that healthy lifestyle factors (particularly sleep quality) may partially explain associations between mental health and functioning in adolescents and suggest that these effects are modulated by environmental factors. These results may have implications for future intervention studies.