Background: Monoclonal antibodies (mAbs) are currently among the most investigated targets for potential disease-modifying therapies in Alzheimer’s disease (AD). Objective: Our objectives were to identify all registered trials investigating mAbs in MCI due to AD or AD at any stage, retrieve available published and unpublished data from all registered trials, and analyze data on safety and efficacy outcomes. Methods: A systematic search of all registered trials on ClinicalTrials.gov and EUCT was performed. Available results were searched on both platforms and on PubMed, ISI Web of Knowledge, and The Cochrane Library. Results: Overall, 101 studies were identified on 27 mAbs. Results were available for 50 trials investigating 12 mAbs. For 18 trials, data were available from both published and unpublished sources, for 21 trials only from published sources, and for 11 trials only from unpublished sources. Meta-analyses of amyloid-related imaging abnormalities (ARIA) events showed overall risk ratios of 10.65 for ARIA-E and of 1.75 for ARIA-H. The meta-analysis of PET-SUVR showed an overall significant effect of mAbs in reducing amyloid (SMD –0.88), but when considering clinical efficacy, data on CDR-SB showed that treated patients had a statistically significant but clinically non-relevant lower worsening (MD –0.15). Conclusion: Our results suggest that the risk-benefit profile of mAbs remains unclear. Research should focus on clarifying the effect of amyloid on cognitive decline, providing data on treatment response rate, and accounting for minimal clinically important difference. Research on mAbs should also investigate the possible long-term impact of ARIA events, including potential factors predicting their onset.

Introduction: No systematic reviews were published in the last years investigating epidemiological data, involving myasthenia gravis (MG) and related myasthenic syndromes. This systematic review aimed to estimate the prevalence, incidence, and mortality of all MG types and myasthenic syndromes worldwide. Methods: All literature published up to February 2024 was retrieved by searching the databases “Medline,” “Embase,” “ISI Web of Science” and “CINAHL” using the following search terms: (epidemiolog* OR frequency OR prevalence OR incidence OR mortality) AND (myasth* OR “anti-acetylcholine receptor antibody” OR “AChR” OR “MuSK” OR “anti-muscle specific kinase antibody” OR “LRP4” OR “seronegative MG”). Results: A total of 94 studies, performed between 1952 and 2022, were included. Prevalence of MG ranged from 20 to 475 cases per million, with a mean prevalence of 173.3 (95% confidence interval [CI]: 129.7–215.5) cases per million and a median prevalence of 129.6 cases per million. Incidence rates ranged from 2.3 to 61.3 cases per million person-years, with a mean incidence of 15.7 (95% CI: 11.5–19.9) and a median of 13.3 cases. Mortality rates showed a mean of 1.4 (95% CI: 0.8–2.1) cases per million person-years. Acetylcholine receptor (AChR)-MG was the clinical subtype more frequent in terms of prevalence and incidence. Discussion: The prevalence and incidence of MG have significantly increased over the last years worldwide, probably due to the improvement of epidemiological methodologies and current advances in diagnosis. However, we observed a significant variation in frequencies of MG between and within countries because of methodological biases and complex heterogeneity of the disease characterized by several phenotypes and different clinical responses.

Introduction: Approximately 2 million people in Italy are currently living with dementia or mild cognitive impairment (MCI), and 4 million are involved as family members or caregivers. Considering the significant impact of dementia, the Italian Ministry of Health entrusted the Italian National Institute of Health (Istituto Superiore di Sanità) with the development of a guideline within the Italian National Guideline System (Sistema Nazionale Linee Guida, SNLG) on the diagnosis and treatment of dementia and MCI. The main objective was to provide evidence-based recommendations aimed at reducing the variability and ensuring the appropriateness of clinical practices throughout the whole care process from identification and diagnosis to the end of life for people with dementia (PwD) or MCI and their families/caregivers. Methods: The GRADE-ADOLOPMENT approach was used to adopt, adapt and update the guideline developed by the National Institute for Health and Care Excellence in 2018 (NG97). The methodology was based on the Methodological Handbook produced by the SNLG. A multidisciplinary panel of 29 experts and four representatives of family members/caregivers discussed and approved 47 review questions. Of these, 34 questions were adopted from the NG97, and 13 were new questions, including 10 questions referring to MCI. Systematic literature reviews were performed for each question, and a team of methodological and clinical experts qualitatively assessed and summarised results from included studies based on the GRADE approach. To facilitate the implementation and dissemination of the contents of this guideline, a care pathway and a leaflet dedicated to PwD or MCI and their families/caregivers were also developed. Results: The literature review for this guideline included studies published up to November 2023. More than 1000 peer-reviewed publications were included, covering the following areas: (i) identification, diagnosis and post-diagnostic support; (ii) care models and care coordination; (iii) pharmacological interventions for cognitive symptoms; (iv) non-pharmacological interventions for cognitive symptoms; (v) non-cognitive symptoms, intercurrent illnesses and palliative care. The multidisciplinary panel discussed and approved 167 clinical practice recommendations and 39 research recommendations. Commentary: Italy’s first National Guideline on dementia and MCI addresses diagnosis, treatment and care within the National Healthcare System. It includes recommendations on pharmacological and non-pharmacological approaches, and emphasises tailored interventions, comprehensive cognitive assessment, staff training and palliative care. The guideline also underlines the need to involve PwD in decision-making and supporting caregivers throughout the entire course of the disease. Conclusions: Structured strategies for the dissemination and implementation of the guideline will be defined within the Italian Fund for Alzheimer and other Dementias 2024–2026. An interactive care pathway and a leaflet dedicated to PwD and their carers are already available. The guideline will be updated starting January 2027, but early updates may be planned in case of breakthrough advancements.