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PubMed2026

Effectiveness of Internet-Delivered Cognitive Behavioural Therapy (ICBT) in Improving Weight-Loss and Psychosocial Well-Being Among Adults With High BMI: A Systematic Review.

AIM: To examine the effectiveness of Internet-delivered Cognitive Behaviour Therapy (ICBT) in improving psychosocial well-being and promoting weight-loss in adults ≥ 18 years with BMI ≥ 25 kg/m2. BACKGROUND: Global obesity engenders significant physical and psychosocial health consequences. Second-wave ICBT focused on restructuring negative thoughts and behaviours has been explored as a potential intervention for elevated BMI and mental health concerns, but its effectiveness remains to be fully established, making further evaluation essential. METHODS AND DATA SOURCES: Eight databases were searched from inception to January 2025 for randomised controlled trials (RCTs), including participants ≥ 18 years with BMI ≥ 25 kg/m2 and second-wave ICBT evaluating BMI, weight, depression, eating behaviours, and self-esteem. This review followed PRISMA 2020. Study quality was assessed using the Cochrane Risk of Bias (ROB 2) and GRADE. Data were extracted using a modified Cochrane form. Random-effects meta-analysis calculated Standardised Mean Differences (SMD) with 95% confidence intervals, with subgroup analyses exploring heterogeneity. RESULTS: Nine trials with 2278 participants were included. Significant improvements were seen in BMI, weight, and depressive symptoms while self-esteem effects were small and non-significant. Compared with passive controls, ICBT showed greater improvements in BMI and weight, whereas differences versus active control were smaller and inconsistent. Face-to-face CBT demonstrated superior outcomes for depression and self-esteem. Male-tailored interventions showed greater improvements. Shorter programmes yielded larger short-term weight loss, while longer programmes supported more sustained effects. Narrative synthesis indicated improvements in emotional and external eating, with increased mindful and restrictive eating behaviours. CONCLUSION: ICBT improved weight, BMI, and depressive symptoms, with limited evidence for self-esteem. Male-tailored interventions and longer programmes may enhance sustainable outcomes. IMPACT: Future ICBT programs should integrate strategies targeting sustainable weight loss and psychosocial well-being to support long-term outcomes. NO PATIENT OR PUBLIC CONTRIBUTION: Patients or members of the public were not involved, as this study synthesised previously published data. TRIAL REGISTRATION: PROSPERO registration number: CRD42024497961.

Humans↗

PubMed2026

Playing with Fire, Losing the Drive: Bidirectional Links Between Problematic Smartphone Use and Grit Dimensions.

This study examined bidirectional longitudinal associations between grit dimensions (consistency of interest [CI] and perseverance of effort [PE]) and problematic smartphone use (PSU) and tested cognitive flexibility as a mediating mechanism. A sample of 1,641 Chinese university students (55.2 percent female; Mage = 20.1 years) completed measures at two time points 6 months apart. A four-variable cross-lagged panel model revealed that CI and PSU negatively predicted each other over time, whereas PSU unidirectionally predicted decreased PE. Cognitive flexibility partially mediated the PSU-to-PE pathway (indirect effect = -0.004, 95 percent bootstrap CI [-0.010, -0.0001]). Competing models analysis confirmed this directionality: the forward mediation (PSU → cognitive flexibility → PE) was significant, whereas the reverse was not. These findings demonstrate that grit dimensions exhibit distinct longitudinal patterns with PSU and identify cognitive flexibility as a cognitive mechanism through which PSU specifically undermines effort persistence. Implications for dimensional approaches to grit and targeted interventions are discussed.

Humans↗

PubMed2026

Effectiveness of transcranial direct current stimulation with and without positive mood induction on worry and transdiagnostic cognitive-emotional processes: A randomized controlled trial.

The present study investigated the effectiveness of transcranial direct current stimulation (tDCS), with and without positive mood induction, on worry and key transdiagnostic cognitive-emotional processes, including attentional bias, working memory, problem solving, and emotion regulation, in individuals with high levels of worry. This single-blind randomized controlled trial included 45 individuals with high levels of worry. After a structured clinical interview, participants were randomly assigned, with gender balancing, to one of three groups: (1) tDCS alone, (2) tDCS combined with positive mood induction, or (3) a sham control group. Outcome measures were administered at three time points (pretest, posttest, and one-month follow-up) and assessed attentional bias (Dot Probe Task), working memory (1-back task), problem solving (Tower of London task), emotion regulation (Gross's Emotion Regulation Questionnaire), and worry severity (Penn State Worry Questionnaire; PSWQ). Repeated-measures ANOVA showed that both active groups (tDCS alone and tDCS + positive mood induction) significantly improved attentional bias, worry, working memory, problem solving, and emotion regulation compared to controls (p < 0.05). The combined intervention produced significantly greater gains than tDCS alone in working memory, problem solving, emotion regulation (p < 0.05), and reductions in attentional bias and worry (p < 0.001). All effects persisted at one-month follow-up (p < 0.05). tDCS reduces worry and attentional bias and enhances cognition and emotion regulation in individuals with high levels of worry. The combined intervention produced larger and more sustained improvements than tDCS alone across the assessed behavioral outcomes. These findings support further investigation of combining tDCS with structured positive mood induction while the mechanisms underlying the additional benefits remain to be established.

Humans↗

PubMed2026

Virtual Reality Mastoidectomy as Precadaver Training for Novices: A Randomized Crossover Study.

OBJECTIVES: To compare cognitive load during virtual reality (VR) simulation and cadaveric dissection (CD) mastoidectomy training in novice learners. To determine whether training order influences cognitive load, characterize cognitive load progression during the procedure, and assess whether VR training improves subsequent cadaveric performance. METHODS: In this randomized crossover study, 24 core surgical trainees with no prior mastoidectomy experience performed a cortical mastoidectomy in both VR and CD settings. Participants were randomized to either VR-first or CD-first training sequences. Cognitive load was measured using a bespoke auditory reaction-time device at baseline and 10, 30, and 50 min. Relative reaction time (RRT) served as an objective index of cognitive load. Cadaveric performance was assessed using the Modified Welling Scale by two blinded otologists. RESULTS: Cognitive load was significantly lower during VR than CD, with mean RRT rising 26% from baseline in VR versus 60% in CD (p < 0.001). Training order did not affect cognitive load in either modality, and RRT increased progressively throughout mastoidectomy in both VR and CD. Participants who began with VR achieved significantly higher cadaveric performance scores than those who began with CD (mean 9.50 vs. 4.96; p < 0.001), and inter-rater reliability for performance scoring was high. CONCLUSION: VR mastoidectomy reduces cognitive load and enhances subsequent cadaveric performance in novice trainees, supporting its role as a cognitively optimized precadaver training modality that complements, rather than replaces, cadaveric dissection. These findings suggest VR enhances early learning efficiency and resource utilization in novice otolaryngology training. LEVEL OF EVIDENCE: N/A.

Humans↗

PubMed2025

Social Responsiveness as a Mediator in Adapted Cognitive Behavioral Therapy for Autistic Youth with Maladaptive and Interfering Anxiety.

Numerous adaptations to interventions have been included in cognitive behavioral therapy (CBT) for autistic youth. This study examines the degree to which CBT adapted to the social needs of autistic youth confers significant benefit by promoting social responsiveness. A secondary analysis was conducted on a multisite randomized clinical trial (Wood et al. in JAMA Psychiatry 77:474-483, 2020) comparing adapted CBT with standard-of-practice CBT and treatment-as-usual (TA). Autistic youth (N = 167; aged 7-13) with maladaptive and interfering anxiety participated. The adapted CBT (BIACA) uses a modular format, with an emphasis on supplementing common CBT practice elements (reframing and graded exposure) with social skill supports. The primary outcome measure was the Pediatric Anxiety Rating Scale. Social responsiveness was assessed with the Social Responsiveness Scale, Second Edition. Participants' general mental health was assessed as a secondary outcome using the Brief Problem Checklist. Mediation was tested using the SPSS PROCESS macro. Analyses suggested that the effect of adapted CBT on anxiety was mediated by its effects on social responsiveness, with a statistically significant indirect effect. Youth randomly assigned to adapted CBT exhibited better overall mental health at posttreatment compared to those randomized to the other conditions, and this effect was also mediated by improved social responsiveness. CBT adapted to address some of the social needs of autistic youth may enhance mental health outcomes by supporting social responsiveness, perhaps increasing the ease and effectiveness with which some youth can navigate potentially stressful situations such as entering and participating in group activities.

Humans↗

PubMed2026

Cognitive-behavioral therapy for post COVID-19 condition: A pilot randomized controlled trial.

BACKGROUND: The post COVID-19 condition (PCC) is a disabling condition with urgent need for effective treatments. This pilot randomized controlled trial examined the feasibility and efficacy of a cognitive-behavioral therapy (CBT) for PCC in a parallel-group design. METHODS: N = 53 individuals with PCC were randomized to CBT (n = 27) or 16-week wait-list control (WLC) condition (n = 26). One participant allocated to WLC was excluded after randomization, resulting in an intention-to-treat (ITT) sample of N = 52 participants (CBT: n = 27, age: M = 48.59, SD = 11.52, 77.8% female; WLC: n = 25, Age: M = 48.44, SD = 9.81, 60% female). CBT comprised eight group and five individual sessions addressing cognitive and behavioral factors of symptom maintenance (treatment duration if completed: M = 14 weeks, SD = 1 week). Primary outcomes included fatigue (FSS), overall somatic symptom burden (PHQ-15), and respiratory and cardiovascular symptoms (SBQ™-LC "Breathing" and "Circulation"), assessed at pre-, post-assessment, and follow-up. RESULTS: Participants receiving CBT showed a significant medium-sized reduction in fatigue directly after treatment compared to the WLC condition (d = -0.58, p = .045), whereas the WLC group showed a significant increase in overall somatic symptoms (d = 0.60, p = .027). Results for respiratory symptoms were mixed, showing inconsistent patterns across analyses. Retrospectively assessed feasibility and treatment satisfaction were good, with few adverse effects reported. CONCLUSIONS: This pilot trial suggests the feasibility and preliminary efficacy of CBT for PCC. Larger RCTs with active control groups should confirm these findings.

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PubMed2026

Updated adjunctive minocycline for schizophrenia: A systematic review and meta-analysis of clinical and cognitive outcomes.

BACKGROUND: Minocycline has been proposed as an adjunctive treatment for schizophrenia due to its anti-inflammatory and neuroprotective properties. However, evidence regarding its efficacy across clinical and cognitive outcomes remains inconsistent. METHODS: A systematic review and meta-analysis of double-blind RCTs was conducted following PRISMA guidelines. PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Library were searched from January 2000 to August 2025. Eligible studies included patients with schizophrenia receiving adjunctive minocycline plus stable antipsychotics. Primary outcomes were PANSS total and subscale scores and overall cognitive performance. Secondary outcomes included SANS, CDS, CGI, GAF, and seven cognitive domains. Standardized mean differences (SMDs) with 95% CIs were calculated. RESULTS: Ten RCTs involving 895 participants were included. Adjunctive minocycline was associated with improvements in negative symptoms (PANSS negative: SMD = -0.55, 95% CI: -0.96 to -0.13; SANS: SMD = -0.75, 95% CI: -1.00 to -0.49) and overall psychopathology (PANSS total: SMD = -0.49, 95% CI: -0.80 to -0.18). Cognitive benefits were limited to a modest improvement in working memory (SMD = 0.24, 95% CI: 0.08 to 0.39), with no significant effects in other cognitive domains. Subgroup analyses suggested that illness stage, antipsychotic regimen, treatment duration, sample size, and geographic region may contribute to variability in treatment effects. Adverse event rates were comparable between groups. CONCLUSIONS: Adjunctive minocycline may improve negative symptoms and provide modest working memory benefits in schizophrenia. However, the evidence is limited by substantial heterogeneity, potential small-study effects, and inconsistent findings. Although short- to medium-term tolerability appeared comparable to placebo, larger, longer-term RCTs are needed to confirm its efficacy and safety.

Humans↗

PubMed2026

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n = 15,765) consisted of UK Biobank participants (MDD only n = 1230; T2DM only n = 3644; comorbid T2DM + MDD n = 721). Individuals with T2DM + MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR = 4.44, 95% CI = [3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM + MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM + MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM + MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

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PubMed2026

Glymphatic dysfunction mediates inflammation-driven vascular burden and cognitive decline in cerebral small vessel disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is increasingly recognized as a disorder involving microvascular dysfunction, impaired perivascular clearance, and inflammatory processes. However, how systemic inflammatory burden, neurovascular coupling (NVC), glymphatic MRI markers, vascular lesion burden, and cognition are interrelated remains unclear. MATERIALS AND METHODS: In this prospective study, 155 patients with CSVD and 70 healthy controls (HCs) underwent multimodal MRI. NVC was quantified using the cerebral blood flow/fractional amplitude of low-frequency fluctuations ratio. Glymphatic function was assessed via the diffusion tensor image analysis along the perivascular space (ALPS) index, choroid plexus volume (CPV), and perivascular space (PVS) fractions. Structural equation modeling (SEM) was employed to evaluate the direct and indirect effects of inflammatory markers on vascular burden and cognitive performance. RESULTS: Patients with CSVD exhibited significantly diminished NVC (specifically in the right median cingulate and left frontal gyri) and impaired glymphatic function (lower ALPS-index; higher CPV and PVS fractions) compared to HCs. SEM revealed that inflammatory biomarkers exerted both a direct effect on vascular burden and a substantial indirect effect (accounting for 66.3% of the total effect) mediated through two pathways: a single-mediation path via glymphatic function (42.8%) and a serial-mediation path via NVC and glymphatic function (23.5%). Increased vascular burden was significantly associated with poorer cognitive performance. CONCLUSION: Inflammation drives CSVD progression and cognitive decline primarily through the disruption of NVC and glymphatic clearance mechanisms. These findings highlight glymphatic dysfunction as a critical mediator of inflammation-related structural brain damage.

Humans↗

PubMed2026

The effects of mindfulness-based cognitive therapy in the psychological and physical health of cancer patients: A systematic review and meta-analysis.

PURPOSE: No prior systematic review has specifically evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) in improving both psychological and physical outcomes among cancer populations. This study aims to assess MBCT's effects on cancer patients' mental and physical health. METHOD: Following PRISMA guidelines and with PROSPERO registration (CRD42023453581), we systematically searched PubMed, Cochrane CENTRAL, Embase, and Web of Science for randomized controlled trials (RCTs) were searched up to June 2026. Eligible trials enrolled adults (≥ 18 years) with any cancer type/stage, compared MBCT delivered per standard manual against non-MBCT controls, and reported at least one validated measure of distress, depression, or anxiety; secondary outcomes included fatigue, quality of life, and mindfulness skills. Two reviewers independently selected studies, extracted data, and assessed risk of bias using the Cochrane tool; random-effects meta-analyses were performed in Stata 16. RESULTS: 11 RCTs comprising 1122 participants (mean age 54.8 years; 91% female) were included. MBCT produced large, significant reductions in psychological distress (SMD = -0.81, 95% CI-1.27 to-0.40), depression (SMD = -0.95, 95% CI -1.40 to-0.49), and anxiety (SMD = -0.86, 95% CI -1.22 to-0.51). It also markedly decreased fatigue (SMD = -0.83, 95% CI-1.10 to-0.56), improved quality of life (SMD = 0.56, 95% CI 0.22-0.88), and enhanced mindfulness skills (SMD = 0.76, 95% CI 0.59-0.92). CONCLUSIONS: This meta-analysis is the first to exclusively synthesize RCT evidence of standardized MBCT in cancer care, demonstrating significant dual benefits for emotional and physical well-being while providing strong support for integrating MBCT into comprehensive oncology rehabilitation.

Humans↗

PubMed2026

Epigenetic Clocks of Biological Aging and Cognitively Healthy Longevity: The Women's Health Initiative Memory Study.

BACKGROUND: Little is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODS: We examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n = 1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n = 956, 16.4%); vs. 3) death before age 90 (n = 2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. RESULTS: Each standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR = 0.66; 95% CI 0.61-0.71), PCGrimAge (OR = 0.64; 95% CI 0.59-0.69), PCPhenoAge (OR = 0.73; 95% CI 0.68-0.78) and DunedinPACE (OR = 0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. CONCLUSION: All epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.

Healthspan↗

PubMed2026

Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.

BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a ≥ 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.

Humans↗

PubMed2026

Association between Kidney Tubular Secretory Clearance with Cognitive Function among Adults with CKD in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Persons with CKD are disproportionally affected with cognitive impairment, yet the pathophysiology linking the two conditions is unclear. Because kidney tubule secretion is essential for clearance of medications, uremic toxins, and metabolites, we hypothesized that worse tubular secretion would be associated with reduced cognitive function in CKD. METHODS: The Systolic Blood Pressure Intervention Trial tested a systolic blood pressure target <120 mmHg vs. <140 mmHg in hypertensive individuals at high cardiovascular risk. In paired blood and urine specimens from 1,937 participants with eGFR <60 ml/min/1.73m2, we measured 10 endogenous tubule-secreted metabolites and calculated a urine/plasma ratio for each, then averaged these to generate a summary secretion score. We used unadjusted and multivariable-adjusted linear regression and mixed models to evaluate cross-sectional and longitudinal associations of the secretion score with the Montreal Cognitive Assessment, Digit Symbol Coding, and Logical Memory immediate and delayed tests-measured at baseline and months 24 and 48 of follow-up. Multivariable Cox regression evaluated associations with incident probable dementia and mild cognitive impairment, adjudicated by prespecified criteria. RESULTS: Mean age was 73 ± 9 years, 41% were women, mean eGFR was 48.2 ± 11.4 ml/min/1.73m2, median albuminuria was 14.8 [7.1-48.6] mg/g. Lower secretion score was associated with a 0.06 higher adjusted logical memory delayed score (95% CI: 0.02, 0.11) but not with other cognitive tests at baseline or longitudinal cognitive decline. After a median 4.1 years of follow-up, 118 developed probable dementia and 187 developed mild cognitive impairment. Each 1-SD lower secretion score was associated with lower risk of probable dementia (HR 0.78, 95% CI: 0.63, 0.98) but not mild cognitive impairment. CONCLUSIONS: Among Systolic Blood Pressure Intervention Trial participants with CKD, lower estimated tubular secretion was not associated with worse cognition at baseline or during longitudinal follow-up.

Journal Article↗

PubMed2026

CNNM2 in schizophrenia: multilevel evidence of genetic susceptibility, magnesium homeostasis, neurodevelopment and cognitive dysfunction.

Schizophrenia (SCZ) is a common psychiatric disorder with a complex, genetically and environmentally influenced etiology, but the specific pathogenesis remains unclear. In recent years, the SCZ susceptibility gene CNNM2 (encoding cyclin M2) located at the 10q24.32-33 locus has received widespread attention. The well-validated SCZ risk interval 10q24.32-33 harbors two independent risk variants: rs11191580 in NT5C2 (significantly associated with CNNM2 mRNA and protein levels) and rs7914558 in CNNM2. Results from functional genomic analyses indicate that lower CNNM2 expression is significantly associated with SCZ. Imaging genetics studies have demonstrated that carriers of risk alleles of CNNM2 SNPs exhibit alterations in brain structure. Animal model studies have revealed that Cnnm2 downregulation in mice leads to impairments in sensorimotor gating and cognitive function. As an Mg2+ transporter, CNNM2 primarily maintains systemic Mg2+ homeostasis. According to clinical studies, a proportion of patients with SCZ exhibit reduced Mg2+ concentrations in plasma and cerebrospinal fluid. CNNM2 dysfunction may contribute to the pathology of SCZ by disrupting Mg2+ homeostasis, thereby affecting neurodevelopment and synaptic plasticity. A systematic consolidation of current evidence supporting the involvement of CNNM2 in SCZ pathogenesis provides a direction for further investigation of the pathological mechanisms underlying this disease, and for identification of novel targets for clinical intervention..

Schizophrenia↗

PubMed2026

Efficacy and safety of cannabinoid-based interventions for behavioral and cognitive symptoms in dementia: systematic review and meta-analysis.

BACKGROUND: Behavioral and cognitive symptoms are frequent in Alzheimer's disease and dementia, and available pharmacological options offer limited benefit. Cannabinoid-based therapies have been proposed as alternatives, but evidence remains inconclusive. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library through November 2025 for randomized controlled trials evaluating cannabinoids in Alzheimer's disease or dementia. Primary outcomes were agitation measured by the Cohen-Mansfield Agitation Inventory (CMAI) and neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). Secondary outcomes included cognition using the Mini-Mental State Examination (MMSE) and adverse events. Standardized Mean Differences (SMDs) and Risk Ratios (RRs) were synthesized using random-effects (REML) and Bayesian random-effects models. Risk of bias was evaluated with RoB 2, and certainty of evidence with GRADE. RESULTS: Nine trials (334 participants) met inclusion criteria. Cannabinoids did not improve CMAI (SMD -0.58, 95% CI -1.71 to 0.55; I2 = 84%), NPI-NH total (SMD -0.02, 95% CI -1.00 to 0.96; I2 = 67%), NPI-NH agitation (SMD -0.44, 95% CI -1.45 to 0.57; I2 = 48%), or MMSE (SMD 0.86, 95% CI -16.33 to 18.06; I2 = 96%). Bayesian posterior estimates were close to zero, supporting the absence of effect. Leave-one-out analyses reduced heterogeneity only after excluding influential trials but did not alter results. Certainty of evidence was moderate for behavioral outcomes and low for cognition. Overall adverse events were similar to placebo, while somnolence was more frequent with cannabinoids (RR 2.03, 95% CI 1.29-3.20). CONCLUSIONS: Cannabinoid-based therapies do not improve agitation, neuropsychiatric symptoms, or cognition in Alzheimer's disease and increase somnolence.

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PubMed2025

Mediators of Change in Cognitive Behavioral and Mindfulness-Based Online-Interventions for Hypoactive Sexual Desire Dysfunction in Women.

Low sexual desire is a common sexual problem among women. When it is accompanied by significant personal distress, it may be diagnosed as hypoactive sexual desire dysfunction (HSDD). Both cognitive behavioral therapy (CBT) and mindfulness-based therapy (MBT) are effective treatments for HSDD when delivered in person or online. In this randomized controlled treatment study, CBT and MBT consisted of eight guided self-help modules delivered online, and participants completed measures at pretreatment and after 3, 6, and 12 months. Nine variables were examined as potential mediators of treatment outcomes (i.e., sexual desire and sexual distress), namely mindfulness, self-compassion, rumination, body connection, self-consciousness, relationship satisfaction, sexual communication, depression, and anxiety. In total, 212 women diagnosed with HSDD were randomized to either CBT or MBT (Mage = 36.3, SD = 10.2). Improvements in self-compassion, rumination, body connection, and self-consciousness partially mediated treatment outcomes in at least one of the treatment groups. Mediation effects were mostly small, explaining up to 15% of the total effects. No systematic differences in mediation pathways between CBT and MBT were found. These findings emphasize the importance of emotion regulation, metacognitive processes, and embodiment for the effective treatment of HSDD. Future research should refine treatment components to enhance efficacy and ensure that psychological interventions adequately address common concerns among women with HSDD.

Humans↗

PubMed2026

Effectiveness and implementation of task-sharing cognitive-behavioral interventions for perinatal mental health: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of cognitive-behavioral interventions (CBIs) delivered by nonspecialist providers (NSPs) on perinatal depressive (PND) and anxiety symptoms, and to narratively synthesize their implementation processes and reported implementation outcomes, including acceptability, feasibility, fidelity, cost, and sustainability. METHODS: We systematically searched eight databases from inception to April 8, 2025. Eligible studies were randomised controlled trials (RCTs) assessing CBIs delivered by NSPs for PND and/or anxiety. Two reviewers independently screened, extracted, and assessed trials. Meta-analyses employed random-effects models, with subgroup, sensitivity, meta-regression, and publication bias analyses conducted in Stata 18.0. Implementation processes and outcomes were reported as frequencies or percentages across trials. RESULTS: A total of 47 trials (11, 357 participants) were included in the systematic review, of which 37 trials (8,709 participants) were included for meta-analyses. CBIs were conducted in 12 countries. Nurses and midwives delivered 45% of CBIs. CBIs were associated with reduced PND post-intervention compared with control conditions (standardized mean difference [SMD] -0.49, 95% CI -0.63 to -0.35; I² = 86.8%). Limited evidence from four trials suggested a small sustained effect at 12 months (SMD -0.14, 95% CI -0.27 to -0.02; I² = 26.4%). Reductions in anxiety symptoms were observed immediately post-intervention (SMD, -0.45, 95% CI -0.65 to -0.25; I²=81%), but evidence for longer-term effects was limited. Subgroup analyses confirmed consistent effects across diverse settings, populations, and intervention characteristics. Reporting of implementation processes (e.g., training, supervision, fidelity) was limited, with only 23.4% of trials assessing fidelity and 10.6% evaluating costs. CONCLUSIONS: NSP-delivered CBIs showed beneficial effects on PND and anxiety, with generally encouraging evidence for acceptability and feasibility. However, evidence for sustained effects beyond the immediate post-intervention period remains limited. Future studies should strengthen long-term follow-up and improve reporting of implementation processes and outcomes, particularly in rural and adolescent perinatal populations, to inform scalable and equitable task-sharing models.

Humans↗

PubMed2026

Breaking the Debilitating Cycle: Pathophysiology, Assessment, and Multimodal Intervention of Secondary Debilitation After Hip Fracture in Older Adults-A Narrative Review.

Hip fractures pose a serious threat to the quality of life among older adults and impose a heavy burden on both society and families. Although current surgical techniques for hip fractures have become increasingly refined, postoperative quality of life and overall function in older adult populations often steeply decline. This decline is marked by "secondary debilitation," characterized by exacerbated sarcopenia, functional impairment, and physiological reserve depletion-a process that becomes a risk factor for recurrent fractures, creating a "vicious cycle" with hip fractures. This article provides a comprehensive overview of the pathophysiological mechanisms underlying "secondary debilitation," discusses the clinical application of risk assessment tools, and presents a phased, stepwise intervention strategy aimed at interrupting the "vicious cycle." The strategy includes early rapid rehabilitation, nutritional support, and prevention of complications; a mid-phase multimodal approach involving multidisciplinary management, comanaged wards, fracture liaison services, and systematic rehabilitation; and, finally, late-phase exploration of emerging pharmacotherapies and treatment methods. This review seeks to offer an evidence-based foundation for optimizing clinical risk assessment and developing precise interventional strategies.

Humans↗