Lombardo Flavia L, Lorenzini Patrizia, Mayer Flavia, Massari Marco, Piscopo Paola, Bacigalupo Ilaria, Ancidoni Antonio, Sciancalepore Francesco, Locuratolo Nicoletta, Remoli Giulia, Salemme Simone, Cappa Stefano, Perani Daniela, Spadin Patrizia, Tagliavini Fabrizio, Redolfi Alberto, Cotelli Maria, Marra Camillo, Caraglia Naike, Vecchio Fabrizio, Miraglia Francesca, Rossini Paolo Maria, Vanacore Nicola
National Centre for Disease Prevention and Health Promotion, Italian National Institute of Health, Rome, Italy.
National Center for Drug Research and Evaluation, Italian National Institute of Health, Rome, Italy.
Diagn Progn Res. 2024 Jul 25;8(1):11. doi: 10.1186/s41512-024-00172-6.
In recent years, significant efforts have been directed towards the research and development of disease-modifying therapies for dementia. These drugs focus on prodromal (mild cognitive impairment, MCI) and/or early stages of Alzheimer's disease (AD). Literature evidence indicates that a considerable proportion of individuals with MCI do not progress to dementia. Identifying individuals at higher risk of developing dementia is essential for appropriate management, including the prescription of new disease-modifying therapies expected to become available in clinical practice in the near future.
The ongoing INTERCEPTOR study is a multicenter, longitudinal, interventional, non-therapeutic cohort study designed to enroll 500 individuals with MCI aged 50-85 years. The primary aim is to identify a biomarker or a set of biomarkers able to accurately predict the conversion from MCI to AD dementia within 3 years of follow-up. The biomarkers investigated in this study are neuropsychological tests (mini-mental state examination (MMSE) and delayed free recall), brain glucose metabolism ([F]FDG-PET), MRI volumetry of the hippocampus, EEG brain connectivity, cerebrospinal fluid (CSF) markers (p-tau, t-tau, Aβ1-42, Aβ1-42/1-40 ratio, Aβ1-42/p-Tau ratio) and APOE genotype. The baseline visit includes a full cognitive and neuropsychological evaluation, as well as the collection of clinical and socio-demographic information. Prognostic models will be developed using Cox regression, incorporating individual characteristics and biomarkers through stepwise selection. Model performance will be evaluated in terms of discrimination and calibration and subjected to internal validation using the bootstrapping procedure. The final model will be visually represented as a nomogram.
This paper contains a detailed description of the statistical analysis plan to ensure the reproducibility and transparency of the analysis. The prognostic model developed in this study aims to identify the population with MCI at higher risk of developing AD dementia, potentially eligible for drug prescriptions. The nomogram could provide a valuable tool for clinicians for risk stratification and early treatment decisions.
ClinicalTrials.gov NCT03834402. Registered on February 8, 2019.
近年来，人们在痴呆症疾病修饰疗法的研发方面付出了巨大努力。这些药物主要针对前驱期（轻度认知障碍，MCI）和/或阿尔茨海默病（AD）的早期阶段。文献证据表明，相当一部分MCI患者不会发展为痴呆症。识别出患痴呆症风险较高的个体对于适当的管理至关重要，包括开具预期在不久的将来可用于临床实践的新型疾病修饰疗法的处方。
正在进行的INTERCEPTOR研究是一项多中心、纵向、干预性、非治疗性队列研究，旨在招募500名年龄在50 - 85岁的MCI患者。主要目的是识别一种或一组能够在随访3年内准确预测MCI向AD痴呆症转化的生物标志物。本研究中所研究的生物标志物包括神经心理学测试（简易精神状态检查表（MMSE）和延迟自由回忆）、脑葡萄糖代谢（[F]FDG - PET）、海马体的MRI容积测量、脑电图脑连接性、脑脊液（CSF）标志物（磷酸化tau蛋白（p - tau）、总tau蛋白（t - tau）、淀粉样β蛋白1 - 42（Aβ1 - 42）、Aβ1 - 42/1 - 40比值、Aβ1 - 42/p - Tau比值）以及载脂蛋白E（APOE）基因型。基线访视包括全面的认知和神经心理学评估，以及临床和社会人口统计学信息的收集。将使用Cox回归开发预后模型，通过逐步选择纳入个体特征和生物标志物。将根据区分度和校准来评估模型性能，并使用自助法进行内部验证。最终模型将以列线图的形式直观呈现。
本文详细描述了统计分析计划，以确保分析的可重复性和透明度。本研究中开发的预后模型旨在识别患AD痴呆症风险较高的MCI人群，这些人群可能符合药物处方条件。列线图可为临床医生进行风险分层和早期治疗决策提供有价值的工具。
ClinicalTrials.gov NCT03834402。于2019年2月8日注册。
