Frontotemporal dementia (FTD) remains challenging to diagnose owing to the marked clinical heterogeneity associated with the disease. This heterogeneity stems from the complex interplay of various clinical phenotypes, genetic mutations and underlying neuropathologies, such as TDP-43 and tau proteinopathies. Currently, there is no single confirmed biomarker that can reliably diagnose disease, specifically disease stage, disease subtype and underlying neuropathology. Recent research has indicated that neuroimaging techniques hold the most promise for the discovery of FTD biomarkers. We propose a protocol for a systematic review and meta-analysis to identify MRI and fluorodeoxyglucose positron emission tomography (FDG-PET) biomarkers associated with clinical, genetic and pathological subtypes of FTD. We aim to address the following research questions: can regional MRI volumetry and FDG-PET hypometabolism differentiate (1) FTD patients from healthy controls; (2) sporadic cases of FTD from healthy controls; (3) genetic cases of FTD (MAPT, GRN, and C9orf72 mutations); and (4) underlying neuropathology, specifically discriminating between tau- and TDP-43-based FTD?

Literature searches will be performed across three databases: Ovid Medline, Ovid Embase and Web of Science. Publications that have fewer than five participants, are non-human-based, not written in the English language or contain unpublished data will be excluded. Two independent investigators will screen and subsequently evaluate which publications to include. Should any disagreements arise, a third investigator will settle the discrepancy. After the random-effects meta-analysis has been used to extract and pool the data, I² analysis will be used to quantify heterogeneity.

Ethics approval will not be required for this research. On completion, the systematic review and meta-analysis will be published in a peer-reviewed journal.

CRD42024545302.

Encephalitis is brain parenchyma inflammation, frequently resulting in seizures which worsens outcomes. Early anti-seizure medication could improve outcomes but requires identifying patients at greatest risk of acute seizures. The SEIZURE (SEIZUre Risk in Encephalitis) score was developed in UK cohorts to stratify patients by acute seizure risk. A ‘basic score’ used Glasgow Coma Scale (GCS), fever and age; the ‘advanced score’ added aetiology. This study aimed to evaluate the score internationally to determine its global applicability.

Patients were retrospectively analysed regionally, and by country, in this international evaluation study. Univariate analysis was conducted between patients who did and did not have inpatient seizures, followed by multivariable logistic regression, hierarchical clustering and analysis of the area under the receiver operating curves (AUROC) with 95% CIs.

2032 patients across 13 countries were identified, among whom 1324 were included in SEIZURE score calculations and 970 were included in regression modelling. The involved countries comprised 19 organisations spanning all WHO regions.

The primary outcome was measuring inpatient seizure rates.

Autoantibody-associated encephalitis, low GCS and presenting with a seizure were frequently associated with inpatient seizures; fever showed no association. Globally, the score had limited discriminatory ability (basic AUROC 0.58 (95% CI 0.55 to 0.62), advanced AUROC 0.63 (95% CI 0.60 to 0.66)). The scoring system performed acceptably in western Europe, excluding Spain, with the best performance in Portugal (basic AUROC 0.82 (95% CI 0.69 to 0.94), advanced AUROC 0.83 (95% CI 0.72 to 0.95)).

The SEIZURE score performed best in several countries in Western Europe but performed poorly elsewhere, partly due to differing and unknown aetiologies. In most regions, the score did not reach a threshold to be clinically useful. The Western European results could aid in designing clinical trials assessing primary anti-seizure prophylaxis in encephalitis following further prospective trials. Beyond Western Europe, there is a need for tailored, localised scoring systems and future large-scale prospective studies with optimised aetiological testing to accurately identify high-risk patients.

Neurodegenerative disorders (NDDs) represent an unprecedented public health burden. These disorders are clinically heterogeneous and therapeutically challenging, but advances in discovery science and trial methodology offer hope for translation to new treatments. Against this background, there is an urgent unmet need for biomarkers to aid with early and accurate diagnosis, prognosis and monitoring throughout the care pathway and in clinical trials.

Investigations routinely used in clinical care and trials are often invasive, expensive, time-consuming, subjective and ordinal. Speech data represent a potentially scalable, non-invasive, objective and quantifiable digital biomarker that can be acquired remotely and cost-efficiently using mobile devices, and analysed using state-of-the-art speech signal processing and machine learning approaches. This prospective case–control observational study of multiple NDDs aims to deliver a deeply clinically phenotyped longitudinal speech dataset to facilitate development and evaluation of speech biomarkers.

People living with dementia, motor neuron disease, multiple sclerosis and Parkinson’s disease are eligible to participate. Healthy individuals (including relatives or carers of participants with neurological disease) are also eligible to participate as controls. Participants complete a study app with standardised speech recording tasks (including reading, free speech, picture description and verbal fluency tasks) and patient-reported outcome measures of quality of life and mood (EuroQol-5 Dimension-5 Level, Patient Health Questionnaire 2) every 2 months at home or in clinic. Participants also complete disease severity scales, cognitive screening tests and provide optional samples for blood-based biomarkers at baseline and then 6-monthly. Follow-up is scheduled for up to 24 months. Initially, 30 participants will be recruited to each group. Speech recordings and contemporaneous clinical data will be used to create a dataset for development and evaluation of novel speech-based diagnosis and monitoring algorithms.

Digital App for Speech and Health Monitoring Study was approved by the South Central—Hampshire B Ethics Committee (REC ref. 24/SC/0067), NHS Lothian (R&D ref. 2024/0034) and NHS Forth Valley (R&D ref. FV1494). Results of the study will be submitted for publication in peer-reviewed journals and conferences. Data from the study will be shared with other researchers and used to facilitate speech processing challenges for neurological disorders. Regular updates will be provided on the Anne Rowling Regenerative Neurology Clinic web page and social media platforms.

ClinicalTrials.gov NCT06450418 (pre-results).

Telerehabilitation (TR) programmes are increasingly recognised for their feasibility and potential benefits, such as eliminating travel time, reducing costs and providing a more comfortable rehabilitation experience at home. However, the comparative efficacy of remote physiotherapy compared with traditional in-person sessions for individuals with Parkinson’s disease (PD) remains uncertain. This study aims to evaluate the effects of TR compared with in-person physiotherapy in individuals with PD, focusing on both motor and non-motor outcomes.

This is a randomised, single-blind clinical trial with a mixed-methods approach. A total of 22 individuals diagnosed with PD will be randomly assigned to one of two groups. The experimental group will receive TR, consisting of remote physiotherapy sessions conducted once a week for 1 hour over a 4-month period. The control group will receive the same interventions in person. Interventions will include global muscle strengthening exercises, balance training, gait and motor coordination exercises, and cognitive training. The primary outcome will be motor function, measured using part III of the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale. Secondary outcomes will include cognition (Montreal Cognitive Assessment), gait (Functional Gait Assessment), mobility (Timed Up and Go Test) and quality of life (Parkinson’s Disease Questionnaire). Data will be analysed using repeated measures analysis of variance to compare outcomes between groups across four assessment points (baseline, midpoint, postintervention and 2 months follow-up). Additionally, a qualitative phase will explore participants’ perceptions and experiences regarding TR and in-person interventions, with assessments carried out 2 months after the completion of the 24-week interventions, through semistructured interviews that will be analysed using Bardin’s Content Analysis technique.

This protocol was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte (approval number: 5.553.701). All participants will provide written informed consent before inclusion. Results will be disseminated through peer-reviewed publications, scientific conferences and communication with participants and healthcare professionals.

RBR-6h5knrj.

People with epilepsy are at higher risk for hypertension, diabetes, hyperlipidaemia and obesity than the US general population. It is unknown whether these risk factors translate to increased cardiovascular mortality compared with the US general population.

To examine changes in the proportions of deaths due to cardiovascular causes among people with epilepsy in the USA.

Cardiovascular mortality among people with epilepsy is rising in the USA compared with the general population over the period from 2000 to 2019.

Retrospective, longitudinal US population study of all deaths among people with epilepsy due to cardiovascular causes compared with the US general population for the years 2000 through 2019. Source data were obtained from the Centers for Disease Control and Prevention (CDC) Multiple Cause of Death Database using all International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes for epilepsy (specifically all ICD-10 codes G40.0 through G40.919). The use of administrative datasets, like the CDC Multiple Cause Of Death Database, is a validated method that effectively captures US epilepsy mortality when using the ICD-10 codes G40.0–G40.9. Cardiovascular deaths were operationally defined as ischaemic heart disease, cerebrovascular disease, diabetes and hypertension. Data were stratified by age, race and gender. Relative proportions of each cause of death were expressed as a percentage of total deaths and evaluated on the log-odds scale using a logistic regression model. Standardised proportions were also used and reported.

Within-group and between-group differences in the rate/proportions of deaths due to cerebrovascular disease, ischaemic heart disease, diabetes and hypertension among people with epilepsy and the general population over a 20-year period.

US epilepsy and general populations.

Age-adjusted mortality for cerebrovascular disease and diabetes increased significantly among people with epilepsy compared with the US general population over the 20-year period (p

Age-standardised proportions of deaths attributed to cerebrovascular disease and diabetes increased significantly among people with epilepsy from 2000 to 2019. Age-stratified proportions of deaths due to cerebrovascular disease and diabetes occurred primarily in the 35–64-year age range. The long decline in the proportions of deaths due to ischaemic heart disease among people with epilepsy ended after 2011, despite continuing to decline in the general population. The increase in proportions of cardiovascular deaths among people with epilepsy is likely due to higher cardiovascular risk factors compared with the general US population. Increased surveillance and treatment of cardiovascular risk factors among people with epilepsy are indicated, especially in the critical 35–64-year age group, where improved primary prevention may reduce cardiovascular risk and mortality.

To assess the comparative effectiveness of educational interventions in neurological disease for healthcare workers and students.

Systematic review.

Medline, Embase and Cochrane through to 1 June 2025.

Studies evaluating neurological disease educational interventions with a comparator group (observational cohort/randomised controlled trial (RCT)) were included.

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review was conducted (PROSPERO: CRD42023461838). Knowledge acquisition and educational methodologies were collected from each study. Study outcomes were classified using the Kirkpatrick and Kirkpatrick four-level model (learner reaction, knowledge acquisition, behavioural change, clinical outcome).¹ Risk of bias was assessed using the Newcastle-Ottawa scale for non-randomised studies and the Cochrane Risk of Bias tool for RCTs.^{2 3}

A total of 67 studies involving 4728 participants were included. Of these, 36 were RCTs, and 31 were observational studies. Virtual interventions were the most common (67.2%, n=45 studies), primarily targeting either medical students (46.3%, n=31 studies) or specialists (40.3%, n=27 studies). Overall, 70.1% (n=47) of studies demonstrated outcomes in favour of the intervention. However, few studies used K&K level 3/4 outcomes, with two studies evaluating behaviour change (level 3) and three assessing clinical outcomes (level 4 combined with other levels). No study exclusively assessed level 4 outcomes. Meta-analysis of 22 RCTs with calculable standardised mean differences (SMDs) (n=1748) showed a significant benefit of interventions (SMD 0.75, 95% CI 0.22 to 1.27, p=0.0056).

This review highlights a growing body of research particularly focusing on virtual techniques, specialist audiences and treatment-oriented content. Few studies assessed changes in practice or patient care. Non-specialists remain underrepresented. Future studies should prioritise assessing the clinical impact of educational interventions within non-specialist audiences.

This project explores the feasibility of setting up a neuropsychiatric de-identified database (DiD) and a Research Register (RR) to collect, analyse, monitor and systematically report clinical data for people with intellectual disabilities (PwIDs) and epilepsy.

A multicentre project designed to collect de-identified data from clinical records at three adult ID specialist services in England and Wales and to develop an RR of PwID and epilepsy. Patients added to the DiD will be identified from patient clinic lists, clinic letters, in-house databases and electronic systems. Patients to be added to the RR will also be identified through attendance for regular review at clinic appointments. The collected data will be entered into the Research Electronic Data Capture (REDCap) database. Personal details of PwID and their consultees will also be collected from participants who consent to be on the RR. Around 600 PwID and epilepsy (200 per site) will be added to the DiD at the three sites, while around 45–60 participants (15–20 per site) are anticipated to be added to the RR. Data analysis will involve using descriptive statistics to summarise feasibility outcomes, such as screening and recruitment rates, as well as the completeness of the collected data. The characteristics of the participants (demographic, ID classification, clinical, epilepsy history and antiseizure medication) will be summarised descriptively. Progression will be assessed using the Red/Amber/Green stop-go criteria to determine if a national register should be created.

Ethical approval (24/NW/0210) has been obtained from the Northwest-Haydock Research Ethics Committee and the University of Plymouth Faculty Research Ethics and Integrity Committee (reference no. 5284). The project is funded by Jazz Pharmaceuticals as an independent investigator-initiated support grant and, as such, has received independent peer review.

NCT06780501.

This study aims to review case reports/series on West Nile virus (WNV) infection-associated cranial nerve (CN) neuropathy to explore the associated patterns and characteristics.

A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria.

We reviewed the literature in PubMed/Medline, Google Scholar and ScienceDirect databases to retrieve relevant case reports.

Case reports published in the past 25 years on CN neuropathy in WNV-infected patients, with no language or geographic restrictions.

Retrieved data included patient demographics, disease presentation and treatment outcomes. Descriptive statistical analyses were performed to describe frequency and characteristics of CN neuropathies. Cross tabulation was performed to calculate statistical significance of association between patient characteristics, disease factors and treatment outcomes. Risk of bias was assessed using the JBI Critical Appraisal Tool for case reports.

A total of 30 case reports satisfied inclusion criteria. These studies described 42 cases that developed CN neuropathies as an outcome of WNV infection. Patients were in the main males (54.8%) and had a mean age of 52.5±15.5 years. The most frequently affected CNs were, in descending order, optic (n=21, 50.0%), facial (n=14, 33.3%) and abducent nerves (n=8, 19.0%). Age was significantly associated with optic nerve neuropathy (≥51 years) and facial palsy (

CN neuropathy represents an important subset of neuroinvasive disease caused by WNV. There is a slight male preponderance among the patient population who are mostly middle aged. Optic and facial nerves are mostly affected. Most patients show complete recovery, particularly in the absence of chronic diseases. The role of systemic antivirals in improving disease outcomes should be further investigated. Early detection of CN neuropathies is recommended by routine CN screening and use of specific tools such as MRI and neurophysiological tests.

Stroke is a leading cause of death and disability in the Caribbean, yet there is limited published information on the availability and utilisation of diagnostic imaging and treatment methods. Inequities in healthcare infrastructure, access to neuroimaging and acute treatment options may contribute to poorer outcomes following stroke, particularly in the low-resource settings that characterise most of the Caribbean region. The objective of this review is to map the literature on access to diagnostic and therapeutic modalities for adult stroke care in the Caribbean to identify potential limitations in acute treatment and examine how restricted access may impact outcomes. The resulting data can help inform strategies for improving access to stroke care in resource-limited communities.

We will apply a three-step strategy based on the Joanna Briggs Institute methodological framework: first, a limited search to identify relevant articles; second, selection of key search terms; third, implementation into a comprehensive search strategy. The query will range from 1 January 1995 to 1 June 2025 (date of final search). Search results will be extracted and screened by two independent reviewers, and findings will be presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. We will consider studies focusing on ischaemic and haemorrhagic stroke in the Caribbean, emphasising access to diagnostic imaging, stroke centres, prehospital management and emergent treatment. Studies examining acute stroke management capacity within the region will be considered. Studies will be excluded if they: focus exclusively on primary stroke prevention, postacute care, longitudinal care pathways for stroke victims or paediatric populations; are unrelated to stroke diagnosis or treatment or are conducted outside the Caribbean.

This protocol aims to perform secondary analysis of previously published literature; therefore, ethical approval is not required. The results of this review will be disseminated through academic conferences and peer-reviewed publication.

Immune checkpoint inhibitors (ICIs) have become an important treatment option for selected cancer patients in recent years. In this overview of systematic reviews, we aim to present a comprehensive summary of the evidence on neurological immune-related adverse events (irAEs) in patients treated with ICIs.

The overview will follow the preferred reporting items for overview of reviews statement. All systematic reviews reporting on neurological irAEs in adult patients treated with ICIs will be included. We will search PubMed, EMBASE and Cochrane’s Database of Systematic Reviews. Two authors will independently screen studies and extract data, with disagreements resolved by discussion or a third reviewer. Methodological quality will be assessed using AMSTAR-2. We will assess overlap by identifying shared primary studies and summarising their frequency in a table. Data will be presented narratively and in tables; when possible, frequencies of neurological irAEs and weighted means, along with associated distributions, will be reported.

As this study involves secondary analysis of published literature and does not include primary data collection, ethical approval is not required. Findings will be disseminated through peer-reviewed publications.

CRD420251020892.

To evaluate the effects of singing interventions on well-being, mental health and communication, motor and respiratory functions through meta-analysis and to examine the practices used in the singing interventions.

Systematic review and meta-analysis.

Both randomised and non-randomised studies, involving participants living with Parkinson’s and receiving singing interventions.

Four databases (CINAHL, Medline, PsycINFO, Web of Science) and Google Scholar were searched. The last search was conducted on 3 April 2025.

Eligible studies reported on the following outcomes: quality of life, voice-related acoustic measures, respiratory function, mental health and motor function. The risk of bias was assessed using the Downs and Black Quality checklist for controlled studies and national heart, lung, blood institute study quality assessment tool for non-controlled studies.

Meta-analyses were conducted to pool effect sizes across included studies using random-effects models. All analyses were performed using Meta-Essentials. Additionally, key elements of singing practices were narratively synthesised.

23 studies (3 randomised controlled trials (RCTs), 20 non-RCTs) involving 540 participants were included in the analysis. Common elements of singing intervention practices included breathing exercises, vocal warm-ups and singing participants’ preferred songs, which are largely led by music therapists.Three meta-analyses based on RCTs were conducted on clinical outcome measures; results suggest that singing was favoured in only one outcome measure, vocal loudness during sustained vowel production (standard mean difference (SMD)=0.67, 95% CI 0.29 to 1.05, I²=0%). However, the certainty of this evidence is very low due to a high risk of bias, imprecision and indirectness. Further, when combining results from RCTs and non-RCTs, positive changes for three further outcome measures were observed: maximum phonation time (k=11, n=157, SMD=0.38, 95% CI 0.18 to 0.59, I²=23.48%), vocal loudness of sustained vowel (k=8, n=99, SMD=0.50, 95% CI 0.14 to 0.86, I²=50.96%) and a respiratory function measure of maximal inspiration pressure (k=4, n=65, SMD=0.46, 95% CI 0.07 to 0.85, I²=0%). However, these findings are largely based on non-controlled studies with very low quality of evidence.

Singing interventions may support people living with Parkinson’s, but due to insufficient high-quality evidence, we are unable to determine the effects of singing interventions. We discuss implications for future work and practice, emphasising that more robust RCTs are needed.

Growing evidence points towards the integral role of both central and peripheral inflammation across all neurodegenerative diseases, including dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). The immune alterations observed in these diseases may occur long before the onset of clinical and cognitive symptoms; however, the exact timing and role of inflammation in the pathogenesis of neurodegenerative disease remains unclear. Findings to date are conflicting, with most work focused on AD rather than other dementias and most studies from single sites and cross-sectional. Through longitudinally examining detailed phenotypes of the peripheral immune system using mass cytometry, the Immune Profiling in Early Cognitive Disorders study aims to uncover specific immune signatures in early AD and DLB, how these signatures change over time and how they relate to disease progression and cognitive changes.

Blood, cerebrospinal fluid, saliva and urine samples will be collected from a cohort of participants with either prodromal (mild cognitive impairment) or early dementia due to Lewy bodies or AD (MCI-LB and DLB; and MCI-AD and AD), alongside healthy controls. Through immunophenotyping with mass cytometry, detailed immune fingerprints will be identified for these groups. We will assess which key combinations of immune cell clusters are predictive of disease phenotype, cognitive decline and progression to dementia. Samples will also be evaluated with novel techniques to measure markers of degenerative pathology and inflammation.

This study was approved by the Preston North West Research Ethics committee (21/NW/0314) and is registered with the ISRCTN registry (ISRCTN62392656). The study is ongoing (since June 2022). Baseline visits are being undertaken, and follow-up visits have started for some participants. Full data analyses will be completed and submitted for publication upon conclusion of the study.

Intracerebral haemorrhage (ICH) is associated with high early mortality and morbidity. Early clinical deterioration is common and influenced by haematoma expansion, which can occur within the first hours after symptom onset. Transcranial duplex sonography (TCD) is a rapid, non-invasive tool that may aid in early ICH detection but is highly operator-dependent. Artificial intelligence (AI)-based analysis of ultrasound images has shown promise in other fields but has not yet been validated in acute ICH.

This is a single-centre, prospective feasibility study involving 500 patients with acute ischaemic and haemorrhagic stroke (

Ethical approval has been obtained. Informed consent will be collected. Data will be coded and stored securely. Results will be disseminated through peer-reviewed journals and conferences.

Not applicable at this stage (observational AI study).

Risk of cognitive decline following epilepsy surgery can be a significant barrier for patients pursuing surgery, and post-surgical cognitive changes can impact quality of life (QOL), surgical satisfaction and functional independence. Readiness Brain Operation Optimization Training (ReBOOT) is a virtual cognitive prehabilitation intervention that provides patients with psychoeducation and cognitive strategies prior to surgery to increase pre-surgical preparedness and post-surgical functional independence in the circumstance that a patient experiences cognitive decline after surgery. The primary aim of this feasibility trial is to evaluate the acceptability, adherence and procedural feasibility of implementing ReBOOT in patients being evaluated for epilepsy surgery. Secondary, explorative objectives include examining preliminary trends in QOL, compensatory strategy use, cognitive function and psychosocial outcomes to inform a future definitive trial.

This is a single-centre, parallel-group, feasibility randomised controlled trial of a standardised cognitive prehabilitation programme for patients who are considering epilepsy surgery. Participants are randomly assigned to intervention (n=32) or control groups (n=32). The intervention group is enrolled in ReBOOT, a virtual programme that includes two 1-hour individual sessions and four 1-hour group sessions. Feasibility outcomes include attendance, homework adherence, attrition and participant satisfaction for participants randomised to the intervention group. Exploratory analyses will use longitudinal linear mixed-effects models to describe trends in exploratory outcomes over time. Data will be used to refine procedures and estimate parameters (eg, effect sizes and variance) for a future fully powered trial.

Cleveland Clinic Institutional Review Board approved the study protocol, which is publicly available and registered on the National Institutes of Health ClinicalTrials.gov (NCT05992402) site. Results will be disseminated through conference presentations and academic publications, as well as shared with outside study sponsors (Society for Clinical Neuropsychology—Division 40 of the American Psychological Association; American Epilepsy Society).

NCT05992402.

This systematic review aims to examine the association between maternal psychological distress (specifically perceived stress, clinical anxiety and depressive symptoms), measured exclusively during pregnancy, and child neurodevelopmental outcomes assessed within the first 3 years of life (0–36 months), including cognitive, language, socioemotional and behavioural development.

The review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered on PROSPERO (CRD42024599742). It focused exclusively on studies assessing maternal distress during the prenatal period and its impact on cognitive, language, socioemotional and behavioural outcomes in infancy and toddlerhood.

A comprehensive search of six databases, PubMed, Web of Science, Cochrane Library, Embase, EBSCOhost and PsycINFO, was conducted up to 10 April 2025, using structured combinations of keywords related to maternal stress and child development.

: Studies were included if they assessed psychological distress during pregnancy with validated tools and evaluated neurodevelopmental outcomes in children aged 0–36 months using standardised measures. Excluded were studies measuring distress only postnatally, animal models, non-original articles and studies without neurodevelopmental endpoints.

Data were extracted and reviewed independently by two authors using predefined criteria, with a third reviewer resolving disagreements. Methodological quality was assessed using the Cochrane Risk of Bias in Non-randomised Studies of Exposures tool for non-randomised studies and Cohort Studies. Given study heterogeneity, a structured narrative synthesis with standardised effect summaries was used.

44 studies met the inclusion criteria. Across these, small, correlational associations linked higher maternal distress during pregnancy with modest differences in cognitive and language scores and with elevated risks of behavioural and socioemotional difficulties. Children exposed to higher distress more often showed attention problems, greater negative emotionality, lower verbal ability and weaker emotion regulation, with effects frequently attenuated after adjustment and selective attrition.

Maternal psychological distress during pregnancy is a context-sensitive correlate, not a proven cause, of early neurodevelopmental differences across cognitive, emotional and behavioural domains.

Research in people with relapsing remitting multiple sclerosis (PwRRMS) is increasingly focusing on non-motor symptoms like cognitive impairment, fatigue and depression. Due to the high negative impact on quality of life and high socioeconomic costs based on these symptoms, more specific research to improve non-motor symptoms is needed. Transcutaneous auricular vagus nerve stimulation (taVNS) has been found to be a cognitive enhancer in preclinical research and was successfully used for the treatment of psychiatric and neurological disorders to combat dysfunctional cognitive and affective processes. However, the capacity of taVNS to improve cognitive and other non-motor symptoms in PwRRMS has not been tested yet. The aim of this study is to evaluate the therapeutic potential of taVNS on cognitive processing speed. Based on ample evidence demonstrating that taVNS promotes adaptive cognitive and affective processes, we hypothesised that taVNS would alleviate cognitive processing speed in PwRRMS.

This study protocol describes the prospective, single-centre, SHAM-controlled, single-blinded trial with a planned sample size of 60 participants (30 PwRRMS, with a diagnosis of multiple sclerosis according to McDonald criteria and 30 healthy controls; age: 18–50 years). The Symbol Digit Modalities Test (SDMT) will be used to determine cognitive processing speed, Beck Depression Inventory-II to determine depression and Fatigue Scale for Motor and Cognitive Functions to determine fatigue. The severity of multiple sclerosis will be assessed using the Expanded Disability Status Scale. After baseline assessment, a taVNS protocol (duration: 30 min, tolerance threshold, pulse width: 250 μs, stimulation frequency: 25 Hz, 30 s on/30 s off) will be applied, followed by post-intervention assessment.

The study was reviewed and approved by the local ethics committee of the University Medical Centre Greifswald (study reference number: BB137/24). Clinical trial registration: www.drks.de, number: DRKS00034912. Study results will be disseminated through academic conferences as well as peer-reviewed publications.

DRKS00034912.

Dementia is a chronic and progressive neurological condition characterised by cognitive and functional impairment. It is often associated with multimorbidity and imposes a significant economic burden on healthcare systems and families, especially in low-income and middle-income countries. In Peru, where dementia cases are increasing rapidly, timely detection and referral for diagnosis is crucial. This protocol is part of the IMPACT Salud project in Peru. Here, we focus on a specific component aimed at validating an mHealth tool for the detection of cognitive and functional impairment and assessing its cost-effectiveness. We will also assess changes in cognitive and functional impairment as well as health economic outcomes over 1 year.

This observational study will be conducted in four geographically diverse regions of Peru. Community health workers are expected to contact approximately 32 000 participants (≥60 years) to apply an mHealth-enabled tool that includes cognitive and functional instruments: Ascertain Dementia 8, Peruvian version of Rowland Universal Dementia Assessment Scale and Pfeffer Functional Activities Questionnaire. From this large sample, we aim to find 3600 participants and their study partners to enrol and interview at baseline regarding sociodemographic characteristics, lifestyles, comorbidities and health economic data including resource use, costs and health-related quality of life (HR-QoL). Psychologists, blind to previous results, will assess dementia stage of the participants using an abbreviated Clinical Dementia Rating (CDR) scale. At 6-month follow-up, participants will complete a brief health economics questionnaire on resource use, costs and HR-QoL. To validate the accuracy of the detection tool, a subsample of 600 participants who completed the baseline will undergo a gold-standard clinical neuropsychological assessment. This subsample will participate in a 12-month follow-up, including health economics, cognitive and functional impairment tests and the CDR scale. Results will be analysed and presented by cognitive status, site, sex and multimorbidity profile. Finally, data from all stages and external sources will inform a decision model to implement a cost-effectiveness analysis of the detection tool at the national level.

The study received ethics approval in Peru (Universidad Peruana Cayetano Heredia: CONSTANCIA-CIEI-378-33-23) and in the UK (Imperial College London: ICREC/SETREC reference number 6647445). Informed consent will be obtained from participants and their study partners, considering the participant’s capacity to consent. For illiterate participants, consent will be obtained through a witnessed procedure involving study partners, with a fingerprint obtained instead of a signature. The results will be disseminated through conferences, published articles, public presentations (particularly to those involved in dementia care) and presentations or meetings with local health authorities.

With the global ageing population accelerating, the prevalence of Alzheimer’s disease (AD) continues to rise annually. However, the underlying mechanisms of AD remain unclear, and effective treatments are still lacking. Apolipoprotein E (ApoE) gene polymorphism and dietary habits are critical risk factors for AD. Time-restricted feeding (TRF), an intermittent fasting strategy that limits the daily window of food intake while maintaining nutritional balance, has garnered significant attention in recent years for its potential to improve cognitive dysfunction. This study aims to investigate the effect of TRF on cognitive improvement in AD patients within the context of genetic background and to explore the role of ApoE polymorphism in these mechanisms.

This single-centre, prospective, randomised, open-label, blinded-endpoint trial will recruit 160 patients with mild to moderate cognitive impairment due to AD from Peking University Shenzhen Hospital. Participants will be stratified based on ApoE genotype into ApoE4 non-carriers and ApoE4 carriers, then randomly assigned to either a TRF intervention group or a normal control group for a 24-month intervention period. The primary outcomes are changes in the Minimum Mental State Examination scale score, Montreal Cognitive Assessment scale score and Clinical Dementia Rating-Sum of Boxes scale score. Key secondary outcomes include the Activities of Daily Living scale score, blood AD biomarkers, lipid levels, ketone body levels and cerebral glutamate levels. Follow-up assessments will be conducted at baseline, 6, 12, 18 and 24 months.

Ethical approval for this study was obtained from the Research Ethics Committee of Peking University Shenzhen Hospital (Ethics No. 2024–151). Written informed consent will be obtained from all participants before the commencement of the trial. The findings will be disseminated through peer-reviewed publications.

ChiCTR2400092653

Duchenne and Becker muscular dystrophies (DMD and BMD) are devastating conditions characterised by progressive muscle degeneration and weakness. Despite advances in understanding their pathogenetic processes, there is a critical need for reliable biomarkers to aid in patient stratification and inform clinical decision-making, predict disease progression and evaluate therapeutic responses. Several promising protein biomarkers have been investigated as potential diagnostic/prognostic tools, but, to date, this evidence has not been systematically synthesised. We aim to comprehensively and critically review and summarise published studies reporting the use of protein signatures of muscular damage in DMD and BMD.

We will systematically search Ovid MEDLINE (PubMed), OVID Embase, OVID Evidence-Based Medicine Reviews and Cochrane Library to retrieve all relevant articles. For ongoing trials, we will search WHO International clinical trials registry and ClinicalTrials.gov registry. We will include studies that measure circulating and urine levels of established and/or promising protein biomarkers associated with skeletal muscular damage and disease progression, such as creatine kinase, myoglobin, skeletal troponin I fast-twitch (type II), myostatin, creatine/creatinine ratio, creatinine and titin. We will consider randomised controlled trials, observational studies and longitudinal cohort studies with serial sampling, without restrictions on sample size, geographic location or language, while excluding animal and in vitro studies. Two independent reviewers will screen articles for inclusion using predefined eligibility criteria and extract data of retained articles. A third author will be consulted in case of disagreement. The approach recommended by the Agency for Healthcare Research and Quality’s Methods Guide for Effectiveness and Comparative Effectiveness Reviews will be used. The risk of bias and reporting quality will be assessed with standardised scales. The analysis will involve a structured narrative synthesis and evidentiary tables. If a meta-analysis is possible, biomarker data for each outcome will be pooled using random effects models. Subgroup analyses have been planned as a function of age, genetic mutation, disease severity, imaging and clinical assessment, length of the observation and risk of bias.

Ethics approval is not required for this study as no original data will be collected. The findings will be shared through peer-reviewed publications and conference presentations. Additionally, this systematic review will guide the recommendations of the Duchenne Regulatory Science Consortium. This work will provide a rigorous, exhaustive and accessible evidence synthesis to identify candidate biomarkers of potential clinical value. Furthermore, it is expected that these results could be used to facilitate the development of future research strategies and guidelines, inform resource allocation decisions and accelerate the route towards clinical implementation of biomarkers for DMD and BMD.

CRD42024549471. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024549471

Neurodevelopmental disabilities (NDs) affect early communication, social engagement and parent-child interactions. Children with NDs often struggle with prelinguistic skills, such as maintaining eye contact and using gestures, which are essential for language development. Parenting behaviour plays a key role in fostering these abilities, and early interventions involving parents can enhance socio-communicative and linguistic outcomes. The present multicentred randomised controlled trial evaluates the effectiveness of a parent-involved speech therapy intervention in improving early socio-communicative skills in children with NDs.

Sixty children with NDs aged 6 months to 5 years will be randomly assigned to either the intervention group (IG, n=30), receiving a parent-involved speech therapy intervention focused on socio-communicative skills, or the control group (CG, n=30), receiving care-as-usual speech therapy. Participants will be recruited from eight rehabilitation centres in Lombardy, Italy. Both interventions will last 8 weeks, with weekly 45 min sessions led by trained speech therapists. Primary outcomes include early communication and intersubjective skills and parenting behaviour, assessed at baseline (T0) and post-intervention (T2—2 months from enrolment). Socio-cognitive skills and socio-emotional development will be considered as secondary outcomes. Feasibility and potential confounders (eg, parental stress) will be measured and controlled between groups.

The study has received formal approval by the deputed ethical committee for all eight participant centres (Comitato Etico Lombardia 2 – Protocol n. R1916/24 – L2-109). Results of the main trial and of the exploratory aims will be submitted for publication in peer-reviewed journals and international conferences.

NCT06666777.