Compound hybridization has received attention due to its potential to address several diseases, including neurological disorders, cancer, infectious diseases, and others. Melatonin is a hormone with antioxidant, anti-inflammatory, and neuroprotective effects. Some drug design research has focused on synthesizing hybrid molecules in which melatonin is hybridized with other pharmacologically active compounds to increase therapeutic efficacy and reduce toxicity. These hybrids demonstrate improved binding affinity, selectivity, and pharmacokinetic characteristics compared to their separate components. This review shows the pharmacological assessment and therapeutic potential of diverse melatonin-based hybrids. These hybrids have exhibited significant efficacy in the treatment of complex diseases such as Alzheimer's disease, cancer, and inflammatory disorders. Hybridization leads to the synthesis of a new generation of structures that represent a promising therapeutic approach for disease treatment.

OBJECTIVES: A mixed-methods process evaluation was conducted alongside a randomised controlled trial of iACT4CARERS: an eight-session, online, self-help, Acceptance and Commitment Therapy (ACT) intervention with minimal therapist support for family carers of people with dementia. While the RCT evaluated its effects on anxiety, depression, and psychological flexibility, this study examined intervention implementation (fidelity and dose), contextual factors influencing engagement, and mechanisms of impact, focusing on how participants engaged with intervention content and therapist support to produce expected changes. METHODS: Data were collected from 249 intervention-group carers, including demographics, between-session ACT skill use, weekly values-based goal completion, and change in psychological flexibility (CompACT) from baseline to post-intervention. Platform analytics captured session completion and therapist interaction. Semi-structured interviews were conducted with a purposive sample of 28 carers (21% ethnic minority). RESULTS: iACT4CARERS was generally well received, with high completion, particularly among older, unemployed, and spousal carers. Engagement was shaped by carers' perceived need, reflecting subjective experience rather than dementia stage. Changes in psychological flexibility were influenced by carers' resonance with metaphors and case examples, and by their engagement with intervention content (e.g. note-taking) and therapists (e.g. therapeutic relationships). CONCLUSION: iACT4CARERS largely operated as intended; identified refinements could further enhance engagement and benefits.

Attention-deficit/hyperactivity disorder (ADHD) affects 2.5% of adults and is associated with cognitive decline and dementia. The neurobiological mechanisms contributing to adverse outcomes in ADHD are poorly understood. ADHD-related brain alterations may persist into later life and interact with ageing-related processes, potentially increasing susceptibility to neuropathology. This preregistered systematic review synthesised neuroimaging findings in adults aged 35 years and older with clinical, symptomatic, or genetic risk for ADHD, and summarised cognitive and clinical correlates. A search of five databases produced 13 included studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. Most studies (11/13) had low risk of bias. Compared to controls, ADHD groups exhibited alterations in fronto-striatal, fronto-parietal, and limbic systems implicated in executive control and attention. Middle-aged adults with clinical ADHD showed more widespread cortical structural differences, whereas older adults demonstrated abnormalities primarily in frontal regions, possibly reflecting attenuation of differences through ageing. Two functional studies in those with clinical ADHD reported frontal hypoactivation alongside parietal hyperactivation, consistent with compensatory recruitment. Among undiagnosed samples, there were interactions between genetic risk for ADHD and Alzheimer's disease-related pathology affecting brain and cognitive outcomes. Overall, ADHD-associated neurobiological alterations appear to persist into older age. Longitudinal investigations are needed to clarify these relationships.

OBJECTIVES: This systematic review aims to synthesize evidence on the effectiveness of non-pharmacological interventions (e.g. behavioral interventions, psychoeducational interventions) for improving sleep among caregivers of people with mild cognitive impairment or dementia. METHODS: A literature search, conducted across eleven databases identified randomized controlled trials (RCTs), was conducted. The primary outcome was sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). Twenty-one RCTs involving 1,964 caregivers (mean age 64.06 years; 74.94% female) were included. RESULTS: Compared with control conditions (usual care, enhanced usual care, or attention control), non-pharmacological interventions significantly reduced PSQI score at end-of-intervention, based on five studies involving 334 caregivers (Mean Difference=-1.27 points, 95% confidence interval [-2.34, -0.19], =.021). All trials had a high overall risk of bias, and the certainty of evidence was very low. CONCLUSIONS: Non-pharmacological interventions may yield modest improvements in sleep quality among informal caregivers; however, confidence in this estimate is limited by high risk of bias of included studies and very low certainty of evidence.

is an uncommon cause of human infection and a rare cause of septic arthritis. We report an 81-year-old woman with diabetes mellitus, chronic kidney disease, gout, and dementia who developed septic arthritis of the distal interphalangeal joint of the right third finger during hospitalization for bacteremia. Computed tomography demonstrated erosive joint destruction with an adjacent abscess. Surgical incision, drainage, and arthrotomy revealed septic arthritis with associated abscess formation and degeneration of the terminal extensor tendon. Operative cultures grew together with multiple anaerobic organisms. The patient underwent surgical debridement, followed by prolonged oral doxycycline therapy and a short course of metronidazole for polymicrobial anaerobic coverage, resulting in complete clinical resolution. This case highlights an uncommon cause of native joint septic arthritis and emphasizes the importance of considering unusual pathogens in patients with pre-existing joint disease and atypical clinical presentations.

BACKGROUND: The glymphatic system facilitates cerebrospinal fluid-interstitial fluid exchange and contributes to the clearance of pathogenic proteins from the brain. Glymphatic dysfunction has been associated with Alzheimer's disease and related tauopathies; however, whether impaired glymphatic transport causally drives tau accumulation and neurodegeneration, and whether its enhancement confers therapeutic benefit, remains unclear. METHODS: Glymphatic water dynamics in PS19 tau transgenic mice were assessed using JJVCPE, a novel MRI-based approach for evaluating brain water exchange. The effect of pharmacological activation of aquaporin-4 (AQP4) with TGN-073 on glymphatic cerebrospinal fluid influx was examined in wild-type mice using dynamic contrast-enhanced MRI. Tau pathology, neurodegeneration, and cerebrospinal fluid tau levels were analyzed in PS19 mice following chronic TGN-073 treatment. AQP4-deficient PS19 mice were examined to determine target specificity. RESULTS: PS19 mice exhibited significant impairment of glymphatic water exchange at early disease stages, which progressively worsened with ageing. Pharmacological activation of AQP4 with TGN-073 robustly enhanced glymphatic-related tracer influx, reduced tau accumulation, neuronal loss, and gliosis, and was accompanied by increased cerebrospinal fluid tau levels. TGN-073 also restored perivascular AQP4 enrichment without significantly altering overall AQP4 abundance. Importantly, these beneficial effects were abolished in AQP4-deficient PS19 mice, demonstrating that both glymphatic enhancement and suppression of tau pathology and neurodegeneration are AQP4-dependent. CONCLUSIONS: Our findings support a mechanistic contribution of impaired glymphatic function to tau accumulation and neuronal vulnerability in tauopathy. Pharmacological activation of AQP4 enhances glymphatic function, restores perivascular AQP4 organization, and ameliorates tau pathology, neurodegeneration, and gliosis. These findings identify AQP4-mediated glymphatic modulation as a disease-relevant and therapeutically tractable pathway for tau-related neurodegenerative disorders.

Cerebral amyloid angiopathy (CAA) commonly co-occurs with Alzheimer's disease (AD), yet the molecular changes that accompany vascular [Formula: see text]-amyloid deposition in human tissue remain incompletely defined. Herein, we use a novel imaging approach that combines matrix-assisted laser desorption/ionization imaging mass spectrometry (IMS) with immunofluorescence microscopy on the same sections of postmortem human frontal cortex to map the lipid microenvironment of leptomeningeal vasculature in cases with and without CAA. Autofluorescence-guided regions-of-interest were imaged by IMS in both negative and positive ion modes and registered to post-IMS-acquired microscopy images. Immunofluorescence microscopy using markers for collagen IV, [Formula: see text]-smooth muscle actin ([Formula: see text]SMA), and thiazine red enabled automated segmentation of total, amyloid-positive, and amyloid-negative vasculature regions. A CAA index, the ratio of amyloid-positive area to total vasculature area in a region imaged by IMS, was used to define vasculature and classify each case into having CAA, or CAA-present, and not having CAA, or CAA-absent. An interpretable machine learning approach (XGBoost models with Shapley additive explanations for interpretation) was trained on pixel-level spectra and identified lipid signatures of vascular identity shared across groups as well as class-specific marker candidates that distinguished CAA-present from CAA-absent vasculature. CAA-absent vessels were characterized by higher contributions from phosphatidylserines (e.g., long-chain polyunsaturated PS species). Univariate differences were inconsistent between the two groups, but multivariate models in negative mode yielded stable discriminatory features. These results define spatial lipid correlates of vascular amyloid pathology in the human brain and establish a multimodal framework for mechanistically linking lipid metabolism, vascular integrity, and CAA in AD.

BACKGROUND: Brain connectivity analysis based on magnetic resonance imaging is crucial for understanding neurological mechanisms. However, edge-based connectivity inference faces significant challenges, particularly the curse of dimensionality when estimating high-dimensional covariance matrices. Existing methods often struggle to account for the unknown latent topological structure among brain edges, leading to inaccurate parameter estimation and unstable inference. METHODS: To address these issues, this study proposes a Bayesian hierarchical model based on a finite-dimensional Dirichlet distribution. Unlike non-parametric approaches, our method utilizes a finite-dimensional Dirichlet distribution to model the latent topological structure of brain networks, ensuring constant parameter dimensionality and improving algorithmic stability. We reformulate the covariance matrix structure to guarantee positive definiteness and employ a Metropolis-Hastings algorithm to simultaneously infer network topology and correlation parameters. Furthermore, to alleviate the computational burden of parameter inference in large-scale networks, we optimized the calculation process of the likelihood function to reduce the algorithm's time complexity. Our implementation is available at https://github.com/mimi6501/BBeC. RESULTS: Simulations validated the recovery of both network topology and correlation parameters across various settings. Furthermore, we quantitatively compared the proposed framework with the Graphical Lasso and a Dirichlet process-based non-parametric Bayesian model. Experimental results show our model offers flexible parameter tuning while outperforming baselines in estimation accuracy and convergence stability. Sensitivity analysis reveals the diagonal adjustment parameter λ has minimal impact on model accuracy, and parameter sampling order has negligible impact on final inference. When applied to the Alzheimer's Disease Neuroimaging Initiative dataset, the model successfully identified structural subnetworks. The identified clusters were not only validated by composite anatomical metrics but also consistent with established findings in the literature, collectively demonstrating the model's reliability. The estimated covariance matrix also revealed that intragroup connection strength is stronger than intergroup connection strength. CONCLUSIONS: This study introduces a Bayesian framework for inferring brain network topology and high-dimensional covariance structures. The model configuration effectively reduces parameter dimensionality while ensuring the positive definiteness of covariance matrices. As a result, it offers an efficient and reliable tool for investigating intrinsic brain connectivity in large-scale neuroimaging studies.

Driving is a complex task that can be compromised by mood disorders and neurodegenerative conditions. Major depressive disorder (MDD) and Alzheimer's disease (AD) increase in prevalence with older age. Preclinical AD, identified through protein biomarkers, is strongly associated with an increased risk of developing AD. This study tracked the daily driving behaviors of older adults over an average period of 54 months and found participants with MDD and Positron Emission Tomography (PET) biomarker tau had a faster increase in risky driving behaviors, such as hard braking, and a slower decline in randomness of driving patterns, compared to healthy controls. Notably, participants with MDD were more likely to exhibit PET tau positivity than PET amyloid positivity, suggesting a potential interaction between MDD and tau pathology. These findings highlight the importance of monitoring older drivers for emerging functional vulnerability associated with mood disorders and neurodegeneration at an early stage.

Emerging evidence suggests that some of the earliest events contributing to neurodegeneration may occur upstream of classical proteinopathies, underscoring the urgency of identifying molecular pathways that link age-associated genomic instability to chronic neuroinflammation. Among these, DNA sensing through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis has emerged as an important mechanism by which nuclear and mitochondrial stress may promote innate immune activation. In aging and Alzheimer's disease (AD), oxidative stress, impaired DNA repair, and mitochondrial dysfunction can lead to the accumulation of cytosolic DNA and activation of cGAS-STING, contributing to sustained inflammatory signaling, cellular senescence, and synaptic dysfunction. In this review, we synthesize emerging mechanistic and translational insights linking cGAS-STING to genomic instability and neuroinflammation. We highlight the expanding roles of this pathway beyond classical immunity, including its influence on autophagy, cellular senescence, microglial activation, and neurovascular integrity as well as its interactions with key pathological features of age-related neurodegenerative disorders, particularly AD. Finally, we highlight recent advances in pharmacological and genetic modulation of cGAS-STING that support its potential as a therapeutic target for age-related neurodegenerative diseases. By reframing neurodegeneration through the lens of DNA sensing, this review provides an updated perspective on the potential role of cGAS-STING in age-related neurodegenerative diseases.

Unpartnered heterosexual women constitute a significant demographic within nursing home populations, yet their sexuality remains largely understudied. Although recent healthcare policies and research focus on improving residents' sexual wellbeing, they often reflect heteronormative assumptions, for instance by prioritizing life-long sex for heterosexual monogamous couples. While the heteronormativity of nursing home spaces has been highlighted in critical gerontological approaches that draw on LGBTQ+ lived experiences, its structuring of heterosexual women's lived experiences remains under-researched. This paper explores this gap through the stories of two heterosexual women living in dementia or psychiatric care units in a Belgian nursing home, both with a history of sex work. Embedded in a wider study using in-depth interviews, talking group sessions, and participant observation, it examines their experiences, desires, and imagination of sex and how these are entangled within the nursing home space. It reveals notions of later life sex and desire that extend beyond frameworks focused on activity or performance, to include imagination as a meaningful dimension. Moreover, the women's imageries of alternative relationships, spaces, and strategies for evading the discomforts of institutional life emerge as disruptors of heteronormative assumptions. Through this analysis, we expand understandings of women's heterosexuality in later life beyond heteronormativity and beyond binaries of desexualization and successful ageing. We underscore the value of intersectional and Critical New Materialist lenses that center on embodiment and practices within (imagined) space, rather than focusing primarily on heterosexual identity. These perspectives illuminate textured lived experiences that contribute to diversified understandings of sexual wellbeing in later life.

Neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal dementia (FTD) exhibit substantial biological and clinical heterogeneity, complicating diagnosis, subtype characterization, and prediction of disease progression. We introduce PatientSpace, a multimodal graph-based latent representation framework designed to model neurodegenerative disease heterogeneity using T1-weighted MRI and FDG-PET. PatientSpace is built upon a structured variational autoencoder that integrates multimodal neuroimaging features while organizing patients within a latent space constrained by age, diagnosis, and a consistency regularization term encouraging similarity between neuroimaging phenotypes. This design enables the construction of an interpretable patient graph in which neighborhood relationships reflect biological similarity. Applied to cohorts of cognitively normal individuals, AD, and FTD patients, PatientSpace revealed multiple disease clusters associated with distinct neuroimaging patterns and clinical severity. Diagnostic classification achieved performance comparable to state-of-the-art deep learning models, while graph-based neighborhood inference enabled prediction of structural volumes, metabolic activity, and cognitive severity. Projection of mild cognitive impairment (MCI) subjects from an independent cohort further showed that cluster membership was associated with differential risks of dementia conversion and distinct longitudinal trajectories. Together, these results demonstrate that PatientSpace provides an interpretable framework linking multimodal neuroimaging representations to disease subtypes, patient-level characterization, and progression modeling in neurodegenerative disorders.

To date, there is not any cure or effective pharmacological therapy for dementia. Affordable and accessible serine supplementation exhibits a promising therapeutic potential for the prevention, delay or alleviation of dementia. Considering D-serine induces nephrotoxicity, neuronal excitotoxicity, and neuronal death in humans, serine-based therapy needs further investigation in the future.

Alzheimer's disease (AD) is a common age-related neurodegenerative disorder (NDD), with ageing as its primary risk factor. Cellular senescence, characterized by permanent cell-cycle arrest, apoptosis resistance and acquisition of the senescence-associated secretory phenotype (SASP), is the cellular hallmark of ageing. Recent evidence indicates that blood-brain barrier (BBB) dysfunction precedes cognitive decline and pathological protein deposition, representing an early event in AD, with the neurovascular unit (NVU) providing the structural and functional basis of the BBB. Mounting evidence shows that the core NVU cells-brain microvascular endothelial cells (BMECs), pericytes and astrocytes-enter senescence under AD-related conditions. SASP factors released by these cells disrupt BBB junction proteins and trans-BBB transport systems, and propagate senescence within the NVU via paracrine signaling. Peripheral inflammatory mediators and immune cells then traverse the compromised BBB, aggravating AD pathology, while accumulating Aβ, tau and reactive oxygen species (ROS) reciprocally accelerate NVU senescence, constituting a proposed vicious cycle. At the molecular level, the cGAS-STING pathway concurrently drives senescence maintenance, SASP induction and type I interferon (IFN-I)-mediated downregulation of BBB junction proteins, serving as a key convergence point linking NVU senescence to BBB injury. From the NVU perspective, this review systematically examines how cellular senescence drives BBB dysfunction and AD progression, clarifies the role of cGAS-STING as a molecular node, and discusses therapeutic strategies targeting NVU senescence to preserve BBB integrity, aiming to offer new insights into AD mechanisms and treatment.

Alzheimer's disease (AD) is a neurodegenerative disorder that significantly impacts millions globally, with rising prevalence among the aging population, emphasizing the need for effective interventions. Isoleucine, a branched-chain amino acid, crosses the blood-brain barrier and plays a role in various neurological disorders. In this study, we investigated the association of isoleucine with AD traits using the BXD mouse reference population, revealing significant correlations with Y-maze performance, anxiety assays, contextual fear conditioning, and the age of onset for working memory deficits. In vitro, exogenous isoleucine supplementation in HT22 and PC12 cells increased amyloid precursor protein (APP) and phosphorylated tau (p-tau) levels. Subsequent analysis identified 2,000 probes correlated with isoleucine and revealed STAT3 as a candidate downstream regulator. Overexpression of STAT3 increased APP and p-tau levels, and STAT3 inhibition abolished this effect, suggesting that isoleucine modulates AD progression via STAT3 activation. Mendelian randomization analysis further supported a causal relationship between elevated isoleucine levels and AD risk. This work provides insights into isoleucine as a potential risk factor for AD and identifies STAT3 as a mediator of isoleucine-related AD susceptibility.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. has been widely utilized in traditional Chinese medicine for its potential to enhance memory-related functions. In traditional medical practices, it is also commonly prescribed for conditions associated with cognitive decline and age-related disorders. These ethnopharmacological uses are closely linked to neurodegenerative disorders, in which neuroinflammation plays a central role. Ginkgo biloba has shown anti-inflammatory and neuroprotective properties, yet its underlying mechanisms in modulating neuroinflammation are still not fully understood. AIM OF THE STUDY: Neuroinflammation is critically involved in cognitive impairment and neurodegenerative diseases, while therapeutic options remain limited. Ginkgo biloba extract 50 (GBE50) is a standardized formulation with potential neuroprotective properties. This study aimed to assess its effects on neuroinflammation-associated cognitive dysfunction and to clarify the mechanisms involved. METHODS: Presenilin 1/2 conditional double knockout mice served as a cognitive impairment model, with behavioral tests used to evaluate cognitive function. The constituents of GBE50 were identified by UPLC-Q-TOF-MS, and ATP content was quantified using biochemical assays. The expression of P2X7 receptor, NLRP3 inflammasome-related proteins, inflammatory cytokines, and synaptic markers was determined at both mRNA and protein levels using qRT-PCR and Western blotting. Microglial activation and P2X7R distribution were assessed via immunofluorescence, and hippocampal synaptic plasticity was examined using LTP recordings. RESULTS: Using UPLC-Q-TOF-MS, 51 compounds were characterized in GBE50, mainly flavonoids and terpene lactones, which are likely responsible for its biological activities. Treatment with GBE50 markedly alleviated cognitive impairment in PS cDKO mice. It downregulated P2X7R and key components of the NLRP3 inflammasome (NLRP3, NEK7, Caspase-1, and ASC), while also reducing the transcription of pro-inflammatory cytokines including Il-1β, Il-18, and Tnf-α. In parallel, GBE50 restored synaptic protein levels and improved long-term potentiation deficits. CONCLUSION: Collectively, our findings suggest that modulation of the ATP-P2X7R-NLRP3 axis contributes to the neuroprotective effects of GBE50 in AD, highlighting this pathway as a promising therapeutic target for preventing AD-related neurodegeneration.

Neurodegenerative and neuroinflammatory diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, are increasingly associated with disruption of the microbiota-gut-brain axis. Common alterations include reduced beneficial microbial taxa, impaired short-chain fatty acid production, intestinal and blood-brain barrier dysfunction, and sustained inflammatory responses. These findings support the development of microbiota-targeted dietary interventions. This review summarizes current evidence on polyphenols, bioactive peptides, and pectin-derived oligosaccharides (POS) as prebiotic or prebiotic-like compounds with potential activity through the microbiota-gut-brain axis. Particular attention is given to structure-function relationships, host-microbe interactions, and the sustainable recovery of these compounds from food by-products. Preclinical studies suggest that these bioactives may reduce microglial activation, improve mitochondrial function, strengthen intestinal and blood-brain barrier integrity, and enhance cognitive or motor performance. Early clinical studies also indicate possible benefits on mood, selected cognitive outcomes, metabolic regulation, and inflammatory biomarkers, although evidence remains limited. Microbiota-derived metabolites from polyphenols, such as urolithins, together with glycomacropeptide and POS, appear to be key mediators. However, clinical validation in major neurodegenerative diseases remains fragmented. Standardized formulations, mechanistic trials, harmonized endpoints, and precision-nutrition strategies are required to confirm their therapeutic potential.

Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and impaired cognitive functions; its prevalence is increasing with the growth of the global elderly population. Unfortunately, early diagnostic and treatment methods developed by modern medicine have limited effectiveness for this disease. This situation has increased interest in natural ingredients, such as curcumin, which have beneficial effects on health. Some preclinical studies evaluating the efficacy of curcumin in Alzheimer's disease suggest that it may have preventive, protective, and therapeutic effects through various mechanisms, including anti-amyloidogenic effects, improvement of tau pathology, cholinesterase inhibition, anti-inflammatory and antioxidant effects, metal chelation, microbiota modulation, and epigenetic regulation. Similarly, some preclinical studies indicate that curcumin-based probes may offer a promising approach to the diagnosis of Alzheimer's disease. However, inconsistencies exist between preclinical and clinical studies. Curcumin's low bioavailability and high systemic elimination may be among the most significant causes of these inconsistencies. It is also thought that this situation may be related to differences and limitations in preclinical and clinical study designs. There is a need for preclinical studies that follow comprehensive, standardized protocols and for larger-scale, long-term, well-designed clinical trials to evaluate the effectiveness of curcumin in the early diagnosis, prevention, and treatment of Alzheimer's disease. In addition, potential risks, such as the toxicological effects of curcumin with increased bioavailability and curcumin-drug interactions in Alzheimer's patients, should be evaluated.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I. = 50-66%) and Alzheimer's dementias(28.0% = 95%C.I. = 17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I. = 17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I. = 36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I. = 38.3-45.6%), anxiety(32.0%;95%C.I. = 26.5-37.6%), MDD + anxiety(24.7%;95%C.I. = 17.9-34.3%), and dementia(19.8%;95%C.I. = 12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I. = 21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I. = 12.0-46.0%), MDD in PVI patients (20.0%;95%C.I. = 13.0-29.0%); in coronary artery disease: MDD + anxiety(19.8%;95%C.I. = 16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I. = 0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I. = 0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I. = 0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Impaired insulin sensitivity has been implicated in neurodegeneration, but whether clinically accessible indices of insulin sensitivity predict dementia risk in the general population remains unclear. We examined associations of the estimated glucose disposal rate (eGDR), a validated marker of insulin sensitivity, with incident all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD), and assessed whether eGDR modifies genetic susceptibility to AD. We included 290,898 dementia-free participants from the UK Biobank. eGDR was calculated using waist circumference, hypertension, and glycated hemoglobin. AD polygenic risk score (AD-PRS) was categorized into tertiles. Longitudinal associations were assessed using Kaplan-Meier (KM) survival analysis and Cox proportional hazards models, with restricted cubic splines employed to examine potential non-linear relationships. Joint effects and interactions between eGDR and AD-PRS were evaluated. The robustness of findings was tested through extensive subgroup and sensitivity analyses. Over a mean follow-up of 13.23 years, 4794 participants developed ACD, 2138 developed AD, and 1070 developed VaD. KM curve revealed that dementia incidence differed significantly across eGDR quartiles (all log-rank P < 0.001). RCS showed significant non-linear inverse associations between eGDR and dementia risk (all P for non-linearity < 0.001). In fully adjusted Cox models, each 1-unit higher eGDR was associated with lower risk of ACD (HR 0.92, 95% CI 0.90-0.94), AD (0.94, 0.92-0.97), and VaD (0.82, 0.78-0.85). Compared with eGDR-Q1, Q4 had lower risks of ACD (HR 0.67), AD (HR 0.70), and VaD (HR 0.42) (all P < 0.001). eGDR modified AD genetic risk (P for interaction < 0.001); participants with low AD-PRS and high eGDR had the lowest AD risk (HR 0.17, 95% CI 0.12-0.23 vs. high AD-PRS and low eGDR group). Findings were consistent across subgroup and sensitivity analyses. Higher eGDR, indicative of greater insulin sensitivity, was associated with reduced risk of incident all-cause and cause-specific dementia, with a significant non-linear inverse dose-response relationship observed. Individuals with both high eGDR low high AD-PRS exhibited the lowest risk of developing AD. These findings suggest that insulin sensitivity may represent a modifiable target for dementia prevention, particularly among individuals with elevated genetic susceptibility.

PURPOSE: To examine global research trends in delirium prevention through a bibliometric analysis and provide a structured overview of its development and emerging directions. DESIGN: A bibliometric analysis. METHODS: Data were retrieved from the Web of Science Core Collection, focusing on publications between January 1, 2015, and December 31, 2024. The analysis utilized VOSviewer, CiteSpace, and the Bibliometrix R package to evaluate publication trends, contributing countries, institutions, authors, and research focus areas. FINDINGS: Annual publication output increased steadily from 2015 to 2024, indicating a growing research interest in postoperative delirium. The United States contributed the largest share of publications (26.8%), followed by China (12.1%), Japan (8.5%), and Australia (6.7%). Harvard University and Harvard Medical School were the most productive institutions. Inouye SK and Ely EW were the most prolific authors. International collaboration was centered on a network involving the United States, China, and Germany. The most-cited article was by Su X et al in The Lancet (2016; 512 citations), and the most locally cited reference was Inouye SK's Confusion Assessment Method (1990; 268 citations). Keyword analysis identified 11 major research themes, including postoperative delirium, cognitive impairment, dexmedetomidine, nursing-led nonpharmacological interventions, dementia, advanced age, machine learning, electroencephalogram monitoring, neuroinflammation, intensive care unit, cardiac surgery, and hip fracture. CONCLUSIONS: Research on postoperative delirium prevention has increased steadily over the past decade, with the United States and leading academic institutions contributing substantially to the field. Current research has focused on major risk factors and preventive interventions, while emerging topics such as machine learning, electroencephalogram monitoring, and neuroinflammation suggest new directions for future studies. Further research should address nonsurgical populations, integrated intervention strategies, long-term outcomes, and mechanistic pathways to support more precise and multidisciplinary prevention approaches.

BACKGROUND: Most patients with cardiogenic shock (CS) survive to hospital discharge, yet data are lacking regarding patient-centered outcomes beyond discharge, including functional status and health-related quality of life (HRQoL). OBJECTIVES: This study aims to evaluate patient-centered outcomes experienced by CS survivors. METHODS: A prospective cohort study enrolled survivors of Society of Coronary Angiography and Intervention Stage C or greater CS at 2 hospitals from December 2023 to August 2024. The primary outcome was functional disability at 3-month follow-up, defined as a modified Rankin Scale ≥2. Patient-reported HRQoL was measured at 3 months using the EQ-5D, which encompasses 5 health domains to generate a composite index score. RESULTS: A total of 141 patients enrolled, with 118 completing 3-month follow-up (87% of eligible patients). Median age was 60; 22% were women, 28% of Black race, and 20% of Hispanic ethnicity. More than one-third (36%) received temporary mechanical circulatory support. Functional disability was common at discharge (66%) and 3 months (46%). Most commonly reported problems on the EQ-5D were pain (67%), mobility limitations (48%), and anxiety/depression (35%), and 18% reported problems with self-care. Median EQ-5D Index Score was 0.84 (Q1-Q3: 0.69-0.94), relative to a U.S. population median of 0.94 for 55-64 years of age. Functional status was inversely correlated with HRQoL at 3 months (r = -0.68; P < 0.001). CONCLUSIONS: Survivors of CS experienced high rates of functional limitations through 3 months, with pain and impaired mobility particularly prevalent. Patient-reported HRQoL was below population norms and significantly associated with functional status. These findings indicate that functional impairments occur frequently after CS, and further work will be necessary to define optimal strategies to improve multidomain recovery for this population.

BACKGROUND: Periodontitis is a prevalent chronic inflammatory condition that frequently co-occurs with systemic chronic diseases. Although older adults experience a high burden of both periodontitis and chronic conditions, the extent to which age-specific evidence has been synthesised remains unclear. OBJECTIVES: To map and synthesise existing systematic reviews and meta-analyses examining associations between periodontitis and chronic conditions relevant to older adults and to identify evidence gaps related to age-specific analyses. METHOD: A scoping review and evidence gap map were conducted in accordance with Joanna Briggs Institute guidance and the PRISMA-ScR checklist. Seven electronic databases were searched, published between 2010 and 2024. Reviews examining associations between periodontitis and chronic conditions prevalent in older adults were included. Age focus and age-stratified analyses were extracted and mapped. RESULTS: Twenty-four studies were included. Across the studies included, periodontitis was generally reported to be associated with chronic conditions. Evidence specific to older adults was limited and mainly concentrated on cognitive impairment and dementia. Most systematic reviews included pooled general adult data without age stratification. Age-specific synthesis was largely absent for several chronic conditions and heterogeneity in disease definitions and sensitivity to confounding was common. CONCLUSION: Despite evidence suggesting associations between periodontitis and chronic conditions, age-specific evidence particularly for older adults remains limited.