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.

Mental disorders are intergenerationally associated, particularly affecting adolescent offspring. However, the extent of such intergenerational associations among adult women in China remains unclear. This study aimed to examine the intergenerational associations of depression and anxiety between two adult female generations.

This cross-sectional study included 2,130 grandmother-mother dyads from the Grandmothers, Mothers, and Their Children’s Health study. Depression and anxiety of the grandmaternal (G0) and maternal (G1) generations were assessed using the 10-item version of the Center for Epidemiologic Studies Depression Scale and the 7-item Generalized Anxiety Disorder Scale, respectively, with scores of 10 or higher defined as depression and anxiety. Statistical analyses included logistic regression, negative binomial regression, and restricted cubic spline analyses.

A total of 11.4% G0 and 11.5% G1 participants reported depression, and 4.1% G0 and 3.1% G1 participants reported anxiety. Depression in G0 was associated with 4.29-fold (95% CI: 3.09–5.94) and 3.50-fold (95% CI: 1.98–6.01) higher odds of depression and anxiety in G1, respectively, while anxiety in G0 was associated with 3.95-fold (95% CI: 2.41–6.35) and 5.47-fold (95% CI: 2.64–10.60) higher odds of depression and anxiety in G1, respectively; dose–response relationships were also observed. In addition, the intergenerational association of depression was stronger among G0 participants residing in rural areas, whereas G0 depression and anxiety were more strongly associated with anxiety in G1 among those with higher household income.

Mental disorders were intergenerationally associated between mothers and their adult daughters. These findings emphasize the importance of family-based interventions for mental health.

Methylphenidate is sometimes used to address residual symptoms of major depressive disorder (MDD), but concerns about psychiatric destabilization and limited long-term evidence have constrained its use. We examined the psychiatric safety of methylphenidate in adults with MDD in a large, real-world cohort.

Using the TriNetX Global Collaborative Network, we identified adults with MDD who initiated methylphenidate and matched them 1:1 with controls who did not receive methylphenidate. Patients with attention-deficit/hyperactivity disorder, bipolar disorder, mania, or recent psychiatric destabilization were excluded. The primary outcome was a composite of all-cause hospitalization or emergency room visits; secondary outcomes included hospitalization, emergency visits, suicidal behavior, manic episodes, and recurrence of MDD. Hazard ratios (HRs) were estimated with Cox proportional hazards models after propensity score matching.

Of 425,190 eligible patients, 3,211 matched pairs were included (mean age, 55.8 years; 58% female). Over 1 year, the composite outcome occurred less frequently in the methylphenidate group than in controls (574 vs. 694; HR, 0.85; 95% CI, 0.76–0.95). No significant differences were observed for hospitalization, emergency visits, suicidal behavior, manic episodes, or MDD recurrence. Results were consistent across subgroups defined by sex, age, and antidepressant class.

In adults with MDD, methylphenidate use was associated with a lower risk of hospitalization or emergency visits and was not linked to increased risk of suicidality, mania, or recurrence. These findings support the psychiatric safety of methylphenidate as an adjunctive treatment for selected patients, though longer follow-up is needed.

To examine the association between dietary patterns and metabolic syndrome (MetS) in western China, which has not been previously reported.

A population based cross-sectional study design. Dietary intake was assessed using a semi-quantitative FFQ. Principal component analysis identified dietary patterns and multivariate logistic regression evaluated their associations with MetS.

Population-based Cohort Study of Chronic Diseases in Xinjiang (PCCDX), conducted in 2022.

A total of 3208 individuals from PCCDX (mean age: 53·1 (sd 10·8) years; 49·1 % male).

MetS was diagnosed in 1762 participants (54·9 %). Four distinct dietary patterns were identified, with the refined grain–animal products dietary pattern being the dominant one. After adjusting for general demographic and lifestyle factors, a higher score in the refined grain–animal product pattern was associated with an increased risk of MetS. The OR for the second, third and fourth quartiles of the dietary score were 1·07 (95 % CI: 0·860, 1·322), 1·14 (0·923, 1·413) and 1·48 (1·189, 1·853), with a statistically significant trend (P = 0·003). Higher dietary scores in this pattern were also associated with increased risks of elevated waist circumference, high TAG and low HDL cholesterol (P < 0·05). Mediation analysis showed that visceral fat percentage partially mediated the association between the refined grain–animal product dietary pattern and low HDL-cholesterol, accounting for 17·2 % of the total effect (indirect effect = 0·005, P = 0·006). The other three dietary patterns showed no significant associations with MetS or its components.

This study highlights the high prevalence of MetS in western China and links a refined grains-animal products diet to poorer metabolic health, emphasising the need for region-specific dietary strategies.

Functional magnetic resonance imaging (fMRI) has revealed inconsistent neural activity patterns in major depressive disorder (MDD) across cognitive and affective domains, and this study used an activation likelihood estimation (ALE) meta-analysis to examine brain function abnormalities in working memory, reward processing, and emotion processing.

A systematic search was conducted in PubMed, Embase, Web of Science, ScienceDirect, and CNKI for fMRI studies comparing MDD patients with healthy controls (HCs), including data up to 3 December 2024. ALE meta-analysis was performed to examine activation patterns. Jackknife sensitivity analysis, risk of bias, and Newcastle–Ottawa scale were used to assess robustness and publication bias. Meta-regression analyses were conducted to explore the impact of covariates on the results.

Sixty-nine studies (2,073 MDD individuals and 2,009 HCs) were included. MDD individuals showed hyperactivation in the bilateral parahippocampal gyrus, subcallosal gyrus, lentiform nucleus, left claustrum, insula, and anterior cingulate cortex, alongside hypoactivation in the right lentiform nucleus, parahippocampal gyrus, fusiform gyrus, and other regions. Domain-specific analyses revealed working memory-related hyperactivation in the right middle and superior frontal gyrus, reward-related hyperactivation in the bilateral lentiform nucleus, right claustrum, and left caudate, and emotion-related hyperactivation in the bilateral parahippocampal gyrus, bilateral lentiform nucleus, right subcallosal gyrus, right anterior cingulate cortex, and left claustrum. Jackknife sensitivity analysis confirmed robustness, with no significant publication bias or covariate impact.

Aberrant activation in the lentiform and caudate nuclei across reward and emotion tasks suggests striatal dysfunction plays a key role in emotion-motivation interplay, highlighting the striatum as a potential target for future therapies.

In the cultural context of China, it holds profound significance for nursing students to engage in discussions about hospice and palliative care with their families. This study aimed to explore nursing students’ willingness to discuss hospice and palliative care with their families and the factors associated with it.

Nursing students from three schools in three Chinese provinces (n = 1,234) completed questionnaires on general information, hospice and palliative care awareness, attitude toward death, and willingness to discuss hospice and palliative care with their families. This cross-sectional analysis utilized logistic regression to investigate the predictors of participants’ willingness to discuss hospice and palliative care with their families.

The mean hospice and palliative care knowledge score was 6.68, and 19.1% were willing to discuss the topic with their families. Factors associated with nursing students’ willingness to discuss hospice and palliative care with their families included region, whether their family members considered talking about death a taboo, whether a family member was severely ill and at risk of death, their knowledge of World Hospice and Palliative Care Day, hospice and palliative care knowledge score, and death avoidance attitude. Participants with higher hospice and palliative care knowledge scores were more willing to discuss the topic with their families, while a higher death avoidance score was associated with unwillingness.

Nursing students significantly lack hospice and palliative care awareness, and their willingness to discuss the topic with their families needs improvement. Nursing schools should provide systematic and standardized hospice and palliative care education and communication skills training.

Depression and anxiety are prevalent mental health disorders. While sleep duration has been extensively studied, sleep regularity may play a critical role. We aimed to examine associations between objectively measured sleep regularity and incident depression and anxiety and to investigate whether meeting recommended sleep duration modifies these associations.

In 79,666 UK Biobank participants without baseline depression or anxiety, wrist accelerometers worn for 7 days yielded a sleep regularity index (SRI) and average sleep duration. SRI was categorized as irregular (≤51), moderately irregular (52–70), or regular (≥71). Sleep duration was classified by age-specific recommendations (7–9 hours for ages 18–64 years; 7–8 hours for over 65 years). Cox regression models assessed associations between sleep parameters and mental health outcomes.

During a median follow-up of 7.5 years, 1,646 participants developed depression, and 2,097 developed anxiety. Compared to irregular sleepers, regular sleepers had a 38% lower depression risk (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.52–0.73) and a 33% lower anxiety risk (HR, 0.67; 95%CI, 0.58–0.77). Participants with both irregular sleep and nonrecommended duration exhibited the highest risks (depression HR, 1.91; 95%CI, 1.55–2.35; anxiety HR, 1.61; 95%CI, 1.35–1.93). Notably, irregular sleepers who met duration guidelines still faced elevated risks (depression HR, 1.48; 95%CI, 1.18–1.86; anxiety HR, 1.35; 95%CI, 1.11–1.64).

Greater sleep regularity is independently associated with lower depression and anxiety risk regardless of sleep duration, suggesting that sleep–wake consistency should be considered in mental health promotion strategies alongside traditional sleep duration recommendations.

Compelling evidence claims that gut microbial dysbiosis may be causally associated with major depressive disorder (MDD), with a particular focus on Alistipes. However, little is known about the potential microbiota–gut–brain axis mechanisms by which Alistipes exerts its pathogenic effects in MDD.

We collected data from 16S rDNA amplicon sequencing, untargeted metabolomics, and multimodal brain magnetic resonance imaging from 111 MDD patients and 102 healthy controls. We used multistage linked analyses, including group comparisons, correlation analyses, and mediation analyses, to explore the relationships between the gut microbiome (Alistipes), fecal metabolome, brain imaging, and behaviors in MDD.

Gut microbiome analysis demonstrated that MDD patients had a higher abundance of Alistipes relative to controls. Partial least squares regression revealed that the increased Alistipes was significantly associated with fecal metabolome in MDD, involving a range of metabolites mainly enriched for amino acid, vitamin B, and bile acid metabolism pathways. Correlation analyses showed that the Alistipes-related metabolites were associated with a wide array of brain imaging measures involving gray matter morphology, spontaneous brain function, and white matter integrity, among which the brain functional measures were, in turn, associated with affective symptoms (anxiety and anhedonia) and cognition (sustained attention) in MDD. Of more importance, further mediation analyses identified multiple significant mediation pathways where the brain functional measures in the visual cortex mediated the associations of metabolites with behavioral deficits.

Our findings provide a proof of concept that Alistipes and its related metabolites play a critical role in the pathophysiology of MDD through the microbiota–gut–brain axis.