Search Results (1,029)

Background: Post-traumatic growth (PTG) refers to positive psychological changes resulting from the struggle with highly challenging or traumatic life events. Psychosocial interventions have demonstrated efficacy in promoting psychological well-being in the aftermath of traumatic experiences. Cognitive Behavioral Therapy (CBT) is among the most extensively studied such interventions, aligning with the PTG model’s prerequisites for growth. Objective: The aim of this systematic review was to assess the efficacy of CBT and CBT-based interventions in promoting PTG. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Scopus, and Google Scholar databases from inception to December 2024. Eligibility criteria included: (a) the inclusion of a CBT or CBT-based intervention, (b) measurement of PTG using the Post-Traumatic Growth Inventory (PTGI), (c) study participants having experienced traumatic life events, and (d) articles written in English. Risk of bias was assessed independently by two reviewers. Due to the heterogeneity of included studies, a qualitative narrative synthesis approach was adopted. Risk of bias was assessed using the RoB-2 tool for RCTs, ROBINS-1 for quasi-experimental studies and Newcastle–Ottawa scale for cohort studies. Certainty of evidence, assessed using the GRADE framework, is considered low. Results: A total of 19 studies were included (13 randomized controlled trials, 3 quasi-experimental, and 3 longitudinal studies). While traditional CBT produced mixed results in fostering PTG, CBT-based therapeutic protocols—particularly those explicitly designed to target PTG or incorporating structured cognitive–emotional techniques—demonstrated more consistent benefits. Limitations of the included studies include measurement of PTG as a secondary outcome, small sample sizes, and the presence of confounding variables. Conclusions: Further high-quality, multicenter randomized controlled trials with standardized protocols are needed to clarify the role of CBT in promoting growth after trauma. Full article

Chronic pain is increasingly understood as a multidimensional condition in which, in a substantial subgroup of patients, a protective symptom can evolve into a persistent maladaptive disorder of the nervous system, while in others it may remain closely tied to ongoing mechanical or structural factors. Central sensitization (CS) represents a key mechanism underlying this transition, characterized by enhanced neural responsiveness and impaired endogenous pain inhibition, leading to a dissociation between pain and tissue pathology. The aim of this narrative review is to critically discuss current evidence on CS as a mechanism-based explanation for persistent pain, using lumbar disk herniation (LDH) as a clinical model of the radiological-clinical mismatch, and to discuss its direct implications for identifying sensitized phenotypes, multimodal assessment, and rehabilitation strategies. A total of 77 sources published between 2006 and 2026 were synthesized. These reviewed sources demonstrate that identification of the sensitized phenotype requires a multimodal assessment approach combining self-report measures, such as the Central Sensitization Inventory (CSI), with psychophysical methods including quantitative sensory testing (QST) and conditioned pain modulation (CPM). Cognitive-emotional factors are also critical, as postoperative kinesiophobia affects approximately 38.3% of LDH patients and is associated with increased pain intensity and reduced self-efficacy. Management strategies reported in these publications focus on mechanism-based interventions, particularly pain neuroscience education (PNE) and graded, time-contingent exercise, which aim to modify pain-related cognitions and restore endogenous inhibitory processes. These approaches may be supported by adjunctive therapies, including dry needling (DN), electro-dry needling (EDN), centrally acting pharmacological agents (e.g., serotonin–norepinephrine reuptake inhibitors [SNRIs] and gabapentinoids), and psychologically informed treatments such as cognitive behavioral therapy (CBT). While surgical decompression may reduce CS-related symptoms, preoperative sensitization does not necessarily predict poorer outcomes, highlighting the interaction between peripheral and central mechanisms. Adopting a sensitization-informed perspective may encourage a broader integration of contemporary pain models alongside traditional structural views in lumbar disc herniation clinical care. Full article

Background/Objectives. Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by dopaminergic neuron loss, α-synuclein pathology, neuroinflammation, and cognitive decline. Synaptamide (N-Docosahexaenoylethanolamine (DHEA)) is an endogenous lipid mediator with documented anti-inflammatory and neurogenic properties, but its effects in PD models remain unexplored. This study aimed to evaluate the neuroprotective potential of synaptamide in a subchronic MPTP-induced mouse model of PD. Methods. Male C57BL/6 mice received MPTP (30 mg/kg/day, i.p., 5 days) with or without synaptamide (10 mg/kg/day, s.c., 13 days). Behavioral tests (open field, Y-maze, elevated plus maze, novel object recognition (NOR)) were performed, followed by immunohistochemical analysis of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra, and Western blotting for α-synuclein, p-α-synuclein, TH, and IL1β in brain homogenates and serum. In vitro Neuro-2a cells were co-treated with MPP⁺ (100 µM) and synaptamide (0.1–10 µM) for cytotoxicity assessment (MTS assay). Results. Synaptamide (10 µM) significantly attenuated MPP⁺-induced cytotoxicity in Neuro-2a cells. In vivo, MPTP caused a marked loss of TH⁺-neurons in the substantia nigra, which was prevented by synaptamide treatment. Importantly, this subchronic MPTP model recapitulates early biochemical alterations (e.g., α-synuclein phosphorylation at Ser129) rather than mature Lewy body pathology, a limitation that should be considered when interpreting these findings. Although no motor deficits or anxiety-like behavior were observed, the NOR test revealed MPTP-induced long-term memory impairment, which was fully restored by synaptamide. Conclusions. These findings suggest that synaptamide may exert effects on pathological processes associated with PD, warranting further investigation into its potential role in combination or supportive therapy for this disease. Full article

Background: Olfactory dysfunction is a pathology associated with viral infections, toxic damage, aging, and neurodegenerative diseases. Damage to the olfactory epithelium impairs olfactory function and related neurological behaviors. This study evaluated the restorative effects of Scutellaria baicalensis Georgi (SBG) extract and baicalein in a methimazole-induced olfactory dysfunction model. Methods: Olfactory epithelial damage was induced in mice with methimazole, followed by treatment with SBG extract or baicalein. Olfactory and neurobehavioral functions were assessed using odor-finding, novel object recognition (NOR), Morris water maze (MWM), open field (OFT), and elevated plus maze tests (EPM). Histological, immunohistochemical, and in vitro analyses were performed to evaluate epithelial regeneration, mature olfactory sensory neurons (OSNs) expressing olfactory marker protein (OMP), and proliferative activity. Results: Methimazole induced severe olfactory epithelial damage, impairing olfactory behavior and reducing learning and memory. Treatment with SBG extract and baicalein significantly improved olfactory and cognitive functions. Histological and immunohistochemical analyses confirmed restoration of epithelial structure and olfactory neurons. In vitro, SBG extract increased epithelial cell density and modulated proliferative activity. Conclusions: SBG extract and baicalein promote recovery of olfactory function and improve neurobehavioral outcomes, indicating their potential as therapies for olfactory dysfunction. Full article

Background/Objectives: Incorporating parent training into cognitive-behavioral therapy for anxious youth has not been shown to significantly improve outcomes perhaps because these interventions have not addressed potential interfering psychological barriers to implementing parenting changes and rarely offer between-session support. There is growing evidence that Acceptance and Commitment Therapy (ACT) can target these psychological barriers and generate more flexible and adaptive behavioral repertoires in parents of children with a variety of presenting challenges. Methods: Following a pilot trial of “Acceptance and Commitment Therapy for Parents of Anxious Children (ACT-PAC)” a six-week group-based intervention focused on targeting psychological barriers to parenting change using mindfulness and acceptance approaches, we collected qualitative feedback from participants in two post-treatment phases by conducting individual interviews and a focus group with participants that completed the intervention. Results: Analysis of interview responses revealed that parents found ACT principles and processes to be helpful, and many also appreciated the ACT-PAC group setting that allowed parents to recognize their experiences were shared by others and to self-disclose in a non-judgmental space. Feedback from the focus group further provides preliminary evidence that ACT-PAC is acceptable to and feasible for parent participants and suggests modifications such as involving additional caregivers, making resources more readily available, and creative structural changes that may facilitate between-session practice. Conclusions: Results suggest that the group-based intervention can be both maintained and improved for future participants. Limitations to generalizability in light of possible selection bias and the small focus group sample size are addressed. Full article

Background: Falls and fall-related injuries are common in older adults and are frequently accompanied by fear of falling (FoF), which may lead to activity avoidance and functional decline. Because many interventions target falls or FoF in isolation, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to identify, describe, and evaluate interventions reporting both falls and FoF outcomes in older adults. Methods: This systematic review and meta-analysis were registered in PROSPERO (CRD420251113137) and conducted in accordance with PRISMA guidelines. PubMed, Embase, and Web of Science were searched from inception to 4 November 2025. Eligible studies were English-language RCTs that included adults aged ≥60 years, evaluated nonpharmacological interventions, and reported both FoF and falls. Methodological quality was assessed using the PEDro scale. Random-effects meta-analyses were performed for FoF (Hedges g), and Bayesian random-effects binomial meta-analyses were conducted for falls. Results: Ten RCTs published between 1998 and 2018 (sample sizes per trial: n = 27–540) were included. Interventions included cognitive–behavioral therapy-based programs, Tai Chi, physiotherapist-led strength and balance training, computerized visual feedback, and video-guided home exercise. PEDro scores ranged from 6 to 9 (mean, 7.7). Pooled analyses showed no significant effect on FoF at the end of intervention (g = −0.20, 95% CI −1.45 to 1.05; p = 0.68; high heterogeneity) or at follow-up (g = −0.14, 95% CI −0.60 to 0.33; p = 0.50). For falls, postintervention evidence favored the null (BF₁₀ = 0.16; pooled estimate −0.01, 95% credible interval [CrI] −0.30 to 0.14). Follow-up results were inconclusive (BF₁₀ = 2.07; pooled CrI −0.56 to 0.00), with substantial uncertainty. Conclusions: Across RCTs that measured both outcomes, interventions did not consistently improve both FoF and falls outcomes. These findings may suggest a partial dissociation between psychological and physical fall-related outcomes, highlighting the need for integrated, adequately powered trials that utilize standardized measures and longer follow-up periods. Full article

Background/Objectives: Insomnia is one of the most prevalent and persistent symptoms among patients with breast cancer, yet it remains under-recognized and undertreated in routine clinical practice. Beyond its impact on sleep quality, insomnia is increasingly understood as a multidimensional condition involving neurobiological, psychological, and behavioral mechanisms, closely intertwined with cancer-related stress and psychiatric comorbidities. This narrative review aims to provide a comprehensive and integrative overview of insomnia in breast cancer, focusing on its epidemiology, pathophysiological underpinnings, neuropsychiatric correlates, and clinical implications, while highlighting gaps in current research and management. Methods: A narrative review of the literature was conducted, including studies published in major medical databases (PubMed, Scopus, and Web of Science) up to 2025. Relevant articles addressing insomnia, sleep disturbances, psychiatric symptoms, and neurobiological mechanisms in breast cancer populations were selected and synthesized. Results: Insomnia affects a substantial proportion of breast cancer patients across the disease trajectory, from diagnosis to survivorship. Its etiology is multifactorial, involving dysregulation of the hypothalamic–pituitary–adrenal axis, inflammatory processes, and circadian rhythm, as well as treatment-related factors such as chemotherapy, endocrine therapy, and menopausal symptoms. Insomnia frequently co-occurs with depression, anxiety, fatigue, and pain, forming symptom clusters that significantly impair quality of life and may influence clinical outcomes. Emerging evidence supports a bidirectional relationship between insomnia and psychiatric vulnerability, suggesting a shared neurobiological substrate within the brain–body stress axis. Conclusions: Insomnia in breast cancer should be conceptualized as a neuropsychiatric condition embedded within a broader stress-related symptom network rather than as an isolated sleep disturbance. Improved screening, interdisciplinary management, and the integration of evidence-based interventions such as cognitive behavioral therapy for insomnia are essential. Research should focus on personalized and mechanistically informed approaches to better address this highly prevalent yet insufficiently managed condition. Full article

Mental health disorders among adolescents have risen significantly in recent years, particularly following the COVID-19 pandemic, highlighting the need for effective preventive and supportive interventions. Nurses play a key role in the promotion, early detection, and management of mental health issues in adolescents, both in school and community settings. This study aimed to synthesize quantitative and qualitative evidence on the role, effectiveness, and implementation of nursing interventions for adolescent mental health. A systematic mixed-methods review was conducted in accordance with the PRISMA 2020 guidelines. It was registered in PROSPERO (CRD42024502076). Databases including PubMed, Scopus, SciELO, Dialnet, BVS, and Cuiden were searched for studies published between 2014 and 2024. Twelve studies met the inclusion criteria, comprising randomized and non-randomized quantitative studies, qualitative studies, and previous reviews. The interventions identified included cognitive-behavioral therapy programs, resilience and life skills training, physical activity initiatives, digital interventions, and mental health literacy strategies. Overall, the findings suggest improvements in symptoms of anxiety and depression, coping skills, resilience, and knowledge about mental health, particularly in structured school-based programs. Qualitative evidence highlighted the importance of accessibility, multidisciplinary collaboration, cultural sensitivity, and sustained commitment for successful implementation. However, considerable heterogeneity was observed in study designs, interventions, and outcome measures. In conclusion, nursing interventions can make a positive contribution to adolescents’ mental health, particularly in school and community settings. However, further rigorous, long-term studies are needed to strengthen the evidence base. Full article

Motorist’s disorientation syndrome (MDS) is seen in 1 to 5% of patients in a tertiary neurotology clinic and remains an underdiagnosed pathology. It was first described in 1985 by Page & Gresty, using the term “visual vertigo”. Patients described sensations of veering or turning over while driving an automobile when visual input was restricted. This was exacerbated at high speeds, on winding roads, going down hills, or when overtaken by a vehicle. All patients in this initial study had peripheral or central neurotological abnormalities and showed exaggerated responses during optokinetic stimulation. Some sufferers considered giving up driving. The first aims of this narrative review were to delineate the symptoms of MDS as detailed in the literature, to outline precipitating situations and to discuss associated pathologies such as anxiety. The second aim was to differentiate MDS from similar syndromes, such as persistent postural-perceptual dizziness (PPPD) and motion sickness (MS). In addition, we looked at the role of vestibular assessments and discussed the involvement of the otolith organs and semicircular canals. In this review, eight publications were analyzed. MDS is related to a visual-vestibular or a visio-visual conflict and occurs in drivers (both males and females). It is associated with anxiety in 17–39% of cases. Mild vestibular-test abnormalities or exaggerated response to opto-kinetic stimulations are seen in 60–100% of cases. Between 50 and 62% of patients have a migraine history. Convergence and strabismic problems are also often seen. Symptoms usually settle after 6 ± 4 years but can persist for longer in females. MDS is multifactorial, and similar to certain forms of PPPD but different than MS. Its pathophysiology is still in question, and we support the role of the velocity storage integrator as a recent hypothesis. Treatment includes vestibular rehabilitation, virtual reality, cognitive behavioral therapies and orthoptic sessions, and the results are promising. The authors also strongly feel that future research on clarifying MDS pathology should study a wider scope of vestibular assessments to evaluate semicircular canal/otolithic function, as well as the vestibulo-ocular reflex, analyze optokinetic nystagmus time constant, and perform a systematic orthoptic examination. Full article

Background: Multimodal rehabilitation represents standard practice in musculoskeletal care, where exercise therapy is routinely combined with manual therapy, electrotherapy, education, and cognitive–behavioral strategies. However, research has largely evaluated these modalities in isolation, and no bibliometric synthesis has characterized multimodal rehabilitation despite its predominance in routine practice. Objective: To characterize global research activity, thematic clusters, and diagnostic patterns underpinning multimodal musculoskeletal rehabilitation and to examine their alignment with contemporary rehabilitation guidelines and practice models. Methods: A bibliometric and altmetric analysis was performed using Web of Science Core Collection (1989–2026). Studies indexed under exercise therapy, manual therapy, electrotherapy, education, and cognitive–behavioral approaches were included. Network analyses (co-occurrence, co-authorship, thematic evolution, and bibliographic coupling) were conducted using Bibliometrix and VOSviewer. Diagnostic subgroups included osteoarthritis, low back pain, chronic musculoskeletal pain, tendinopathy, and shoulder disorders. Results: A total of 409 publications were identified. Five multimodal combinations were recurrent: exercise + education, exercise + cognitive–behavioral therapy, exercise + manual therapy, exercise + electrotherapy, and mixed multimodal programs. Diagnostic subgrouping showed distinct patterns, with osteoarthritis and low back pain clustering around exercise + education, chronic musculoskeletal pain around exercise + CBT/self-management, and tendinopathy/shoulder disorders around exercise + manual therapy. Temporal analyses demonstrated a shift from unimodal electrophysical agents toward guideline-aligned biopsychosocial models. Altmetric signals suggested relevant dissemination and policy attention. Conclusions: Multimodal musculoskeletal rehabilitation is research-intensive, diagnosis-specific, and aligned with guideline recommendations prioritizing exercise, education, self-management, and behavioral strategies. These findings support multimodal rehabilitation as a maturing evidence-based practice model with implications for pragmatic trials, guideline implementation, and clinical service delivery. Beyond research implications, these patterns are relevant for musculoskeletal care pathways, training of rehabilitation professionals and health system planning. Full article

Perioperative anxiety is a common psychophysiological stress response experienced by patients before and after surgery, with a global prevalence of approximately 48%. Its occurrence is influenced by multiple factors including age, sex, type of surgery, and psychosocial determinants. The underlying pathophysiological mechanisms are complex, involving multi-system interactions such as autonomic nervous system imbalance, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, dysfunction of limbic system neural circuits, and neuroinflammation. Current assessment strategies are evolving from sole reliance on psychological scales toward multimodal approaches incorporating objective biomarkers including heart rate variability, cortisol, and electroencephalography. Management paradigms have shifted from traditional pharmacological premedication to integrated systems encompassing structured patient education, digital health tools, neuromodulation techniques, and cognitive behavioral therapy. However, significant gaps persist regarding standardized screening protocols, biomarker validation, and targeted intervention pathways for high-risk populations. Future management is likely to require more individualized risk assessment and intervention selection. Biomarker-based risk prediction, artificial intelligence-assisted intervention decision-making, and the deep integration of digital therapeutics such as virtual reality with existing enhanced recovery pathways will be key directions for improving patient outcomes and recovery quality. This structured narrative review summarizes current evidence on perioperative anxiety in adults, focusing on epidemiology, pathophysiological mechanisms, assessment tools, biomarkers, and multimodal management strategies. Full article

This study conceptualizes the theological principle declared by the Apostle Paul in 2 Corinthians 12:9–10—“My power is made perfect in weakness” (ἡ γὰρ δύναμίς μου ἐν ἀσθενείᾳ τελεῖται)—as the Perfection in Weakness Paradox (PIW) and examines it through an integrative lens with contemporary third-wave psychotherapies. A Reformed theological exegesis of 2 Corinthians 12:9–10 identifies two foundational axes: sola gratia (grace alone) and the acknowledgment of weakness. The core mechanisms of Self-Compassion (Neff), Acceptance and Commitment Therapy (ACT; Hayes), Post-Traumatic Growth (PTG; Tedeschi and Calhoun), and Rumination-Focused Cognitive Behavioral Therapy (RFCBT; Watkins) are then analyzed for their systematic parallels with PIW’s theological structure—acceptance of weakness, dissolution of self-criticism, meaning-making through suffering, and transformation of rumination. The evidence-based framework of Spiritual Psychiatry is applied to examine the relationship between spiritual practices and mental health from neuroscientific and clinical perspectives. The central thesis is bidirectional: (1) the revelatory principle of 2 Corinthians provides theological foundations for the healing mechanisms of third-wave psychotherapies, and (2) the empirical evidence of these psychotherapeutic theories offers convergent support for and strengthens the theological interpretation of 2 Corinthians in a contemporary clinical context. This integrative framework proposes a new model for interdisciplinary dialogue between theology and psychiatry and discusses implications for clinical practice. Full article

Background: Preoperative anxiety and postoperative pain are prevalent and are frequently associated with poor postoperative functional outcomes. Comprehensive postoperative management, including both pharmacological and psychological components, is essential for proper postoperative care and better recovery. While the analgesic effect of traditional non-pharmacological intervention, such as cognitive behavior therapy, has been investigated by other trial studies, the newer innovative methods for delivering psychological interventions for reducing anxiety and pain are extensively being investigated. Virtual reality (VR) has emerged as a novel and promising technology that offers opportunities to mitigate patient perception and cognitive responses, and has been shown to be associated with lower levels of anxiety and pain. The aim of this randomized clinical trial (RCT) is to determine whether delivering the psychological content through virtual reality (VR) along with the standard preoperative and postoperative care results in better anxiety and pain relief outcomes than standard care in patients undergoing spinal surgery. Methods: This study protocol outlines a parallel-group RCT to be conducted in the Department of Neurosurgery at the University Clinical Hospital of Medical University of Lodz. The objective is to assess the efficacy of immersive VR environments in reducing preoperative anxiety and postoperative pain intensity in the following day after surgery. Adult patients (18–70) will be randomly assigned to either (1) standard care before surgery (control group), (2) VR exposure simulating the hospital environment alongside standard care, or (3) VR-based exposure to calming natural landscapes accompanied by soothing background sound along with standard care. In each group, a minimum of 50 patients will be recruited. The primary outcome is the change in preoperative anxiety measured using the State-Trait Anxiety Inventory-State (STAI-S) scale from baseline to immediately after intervention. Secondary outcomes include postoperative pain measured using the Visual Analogue Scale (VAS), postoperative analgesic consumption, patient satisfaction, and VR-related adverse effects. To facilitate a comprehensive understanding of the VR intervention’s impact, the primary outcome will be complemented with measures of the adverse effects, level of immersion, and level of presence in the VR environment. Secondary outcomes of self-reported satisfaction scores and postoperative analgesics from patients’ medical charts will be assessed. Conclusions: This trial will evaluate whether VR-based interventions may reduce preoperative anxiety and postoperative pain in patients undergoing spine surgery. This study may provide evidence supporting the future implementation of VR as a non-pharmacological adjunct in perioperative care. This intervention may hold significant clinical relevance clinically, particularly in patients with high level of preoperative anxiety, by offering an alternative method to pharmacological anxiolytics in the future. Full article

Anxiety disorders are disabling and treated with cognitive-behavioral or exposure-based psychotherapy. However, many patients remain symptomatic, fail to remit, relapse, or discontinue treatment. This narrative review examined whether psychotherapy non-response, defined here as persistent clinically significant anxiety symptoms, avoidance, or functional impairment after an apparently adequate psychotherapy trial, may reflect mismatch between therapeutic mechanisms and the dominant processes maintaining anxiety, and aimed to develop a usable taxonomy of mechanistic non-response. This structured narrative review followed SANRA principles. PubMed/MEDLINE, Scopus, PsycINFO, Web of Science, and the Cochrane Library were searched for peer-reviewed literature published from 1 January 2000 to 30 April 2026, including selected earlier landmark studies. Clinical, experimental, neurobiological, psychophysiological, process, and theoretical evidence were synthesized narratively. Psychotherapy mechanisms were organized around inhibitory learning, cognitive reappraisal, attentional modulation, emotion regulation, avoidance reversal, and interpersonal learning. Anxiety maintenance was multilevel, involving threat neurocircuitry, stress-related learning conditions, intolerance of uncertainty, attentional threat capture, safety behaviors, avoidance reinforcement, developmental adversity, and attachment insecurity. Non-response was framed as mismatch between the dominant maintaining process and the therapeutic mechanism expected to modify it. Six failure modes were identified: impaired inhibitory learning, cognitive rigidity/intolerance of uncertainty, stress-related learning impairment, attentional dysregulation, attachment-related barriers, and chronic avoidance dominance. Psychotherapy non-response in adult anxiety disorders should prompt mechanistic reformulation rather than repetition of the same intervention or labeling as treatment resistance. The taxonomy links recognizable failure signatures to mechanism-matched adaptations: redesigned exposure, uncertainty-focused work, attentional interventions, sequencing when arousal or sleep impairs learning, relational repair, and reduction in avoidance contingencies. The narrative review provides a concise clinical taxonomy and practical mechanism-matched adaptations to guide reformulation and treatment redesign after psychotherapy non-response in routine care. The taxonomy supports mechanism-matched reformulation after psychotherapy non-response and requires prospective validation. Full article

Alzheimer’s disease (AD) lacks effective disease-modifying therapies, and extracellular vesicles (EVs) derived from adipose-derived mesenchymal stromal cells (ADMSCs) have emerged as promising therapeutic candidates. In this study, we investigated the brain biodistribution and dose-dependent effects of intranasally administered ADMSC-EVs in female APP/PS1 mice, with age-matched wild-type mice and vehicle-treated transgenic mice serving as controls. EV biodistribution was assessed using PKH26 labeling, cognitive performance was evaluated using the Morris water maze, Y-maze, and novel object recognition tests, and hippocampal amyloid pathology and plasma AD-related biomarkers were analyzed. Intranasally delivered ADMSC-EVs rapidly reached multiple brain regions, including the hippocampus, improved learning and memory performance, and reduced hippocampal amyloid-β 1-42 (Aβ42) deposition and plaque burden. These effects followed a nonlinear dose–response pattern, with reduced efficacy at low doses and no additional benefits at high doses. Notably, partial behavioral and pathological benefits persisted after treatment cessation. Together, these findings show that intranasal ADMSC-EVs exert therapeutic effects in APP/PS1 mice and support the importance of dose optimization and post-treatment durability in the development of EV-based interventions for AD. Full article