Mild cognitive impairment (MCI) is an intermediate stage between normal and pathological brain aging, with 30% to 50% progressing to dementia within 3 to 5 years. Early identification of individuals a Show more
Mild cognitive impairment (MCI) is an intermediate stage between normal and pathological brain aging, with 30% to 50% progressing to dementia within 3 to 5 years. Early identification of individuals at high risk of progression is crucial for public health strategies. The INTERCEPTOR project included 398 MCI individuals. Baseline assessment included harmonized procedures for sociodemographic, clinical, neuropsychological, genetic (apolipoprotein E), cerebrospinal fluid (amyloid beta tau), electroencephalogram (brain connectivity), magnetic resonance imaging (hippocampal volumetry), and fluorodeoxyglucose positron emission tomography. The baseline and follow-up were completed by 351 individuals with MCI with neuropsychological tests every 6 months for 3 years. Dementia developed in 104 individuals (29.6%), including 85 (22.4%) who met core clinical criteria for probable and possible Alzheimer's disease dementia. A Cox model combining clinical and sociodemographic data achieved a concordance index of 72%, which increased to 82% when neuropsychology and biomarkers were added. The INTERCEPTOR nomogram represents a tool for predicting dementia progression risk, supporting public health strategies, including screening for risk assessment and risk/benefit ratio in innovative treatments. Show less
Congenital myasthenic syndromes (CMS) are often underdiagnosed due to phenotypic overlap with other neuromuscular disorders. Limited epidemiological data and low awareness hinder early diagnosis, whic Show more
Congenital myasthenic syndromes (CMS) are often underdiagnosed due to phenotypic overlap with other neuromuscular disorders. Limited epidemiological data and low awareness hinder early diagnosis, which is key for effective treatment. Early recognition of CMS is important as symptomatic treatments often specific for genetic subtypes exist and emerging therapies are in the pipeline. This study aims to estimate the prevalence of genetically confirmed CMS in the United Kingdom and explore geographical variations. Prevalence was calculated as of 31 December 2023, including genetically confirmed CMS patients residing in the United Kingdom and known to be alive. Patients with missing geographic or living status data were excluded. Prevalence was estimated overall and compared between UK regions served by a highly specialized neuromuscular service (hsNMS) and those without such services (non-hsNMS). A cohort of 442 genetically confirmed CMS patients was identified. CHRNE deficiency, DOK7, RAPSN were the most common subtypes. The UK prevalence was 6.5 cases per million overall and 8.5 cases per million in the pediatric population. The overall prevalence was statistically higher in hsNMS (8.8 cases per million) compared to non-hsNMS regions (5.9 cases per million). Homozygous patients had a more clustered distribution particularly around urban area. Our results suggest there is likely underdiagnosis of CMS in many areas of the United Kingdom and hsNMS may play an important diagnostic role. Variations may also be related to other cultural clustering and founder effects. Further research should explore how healthcare access, ethnicity, and consanguinity contribute to regional variation and diagnostic rates. Show less