de Boer Liset, Poos Jackie M, Van Den Berg Esther, De Houwer Julie F H, Swartenbroekx Tine, Dopper Elise G P, Boesjes Pam, Tahboun Najlae, Bouzigues Arabella, Foster Phoebe H, Ferry-Bolder Eve, Adams-Carr Kerala, Russell Lucy L, Convery Rhian S, Rohrer Jonathan D, Seelaar Harro, Jiskoot Lize C
Department of Neurology and Alzheimer Center Erasmus MC, Erasmus MC University Medical Centre, Rotterdam, the Netherlands; and.
Dementia Research Centre, University College London, United Kingdom.
Neurology. 2025 Mar 11;104(5):e213401. doi: 10.1212/WNL.0000000000213401. Epub 2025 Feb 14.
With upcoming clinical trials targeting preclinical stages of genetic frontotemporal dementia (FTD), early detection through cognitive screening is crucial. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) have potential as screening instruments for early-stage genetic FTD. However, no comparative evaluation has been performed. We aimed to compare MMSE and MoCA performance among presymptomatic, prodromal, and symptomatic pathogenic variant carriers to analyze which screening test has superior discriminative abilities.
We used cross-sectional and longitudinal data from 2 longitudinal genetic FTD cohort studies in the Netherlands and the United Kingdom, collected between 2021 and 2024. Participants were either presymptomatic, prodromal, or symptomatic pathogenic variant carriers or healthy controls (first-degree family members without pathogenic variants for FTD). Grouping was based on the global CDR-plus-NACC-FTLD score. Participants were assessed with both MoCA and MMSE. Statistical analyses compared total and subscores between groups and evaluated predictive and classification accuracy of both tests.
A total of 243 participants (mean age 49.9 ± 13.1 years, mean education 14.5 ± 3.0 years, 56% female), 157 of whom were pathogenic variant carriers (, , , , and ) and 86 controls, were included. Carriers were classified as presymptomatic (n = 119), prodromal (n = 18), or symptomatic (n = 20). Both MoCA [(3,239) = 16.565, < 0.001] and MMSE [(3,239) = 13.529, < 0.001] total scores differed significantly between groups, with controls (median MoCA 28.5, 95% CI 28.0-29.0; median MMSE 30, 95% CI 30.0-30.0) outperforming prodromal (median MoCA 26, 95% CI 23.0-27.0; median MMSE 29, 95% CI 27.5-29.5) and symptomatic (median MoCA 20.5, 95% CI 17.0-24.0; median MMSE 26, 95% CI 23.5-29.0) carriers. MoCA distinguished between presymptomatic carriers and controls (median MoCA 28, 95% CI 27.0-29.0), but MMSE did not. MoCA demonstrated superior discriminative ability compared with MMSE (MoCA area under the curve [AUC] = 0.87, 95% CI 0.81-0.94; MMSE AUC = 0.80, 95% CI 0.72-0.89).
Its higher sensitivity and better discriminative power make MoCA a more valuable tool for cognitive screening in upcoming clinical trials targeting preclinical FTD. Future studies should aim for larger sample sizes from additional study centers.
随着针对遗传性额颞叶痴呆（FTD）临床前期阶段的临床试验即将开展，通过认知筛查进行早期检测至关重要。简易精神状态检查表（MMSE）和蒙特利尔认知评估量表（MoCA）有潜力作为早期遗传性FTD的筛查工具。然而，尚未进行过比较评估。我们旨在比较MMSE和MoCA在症状前、前驱期和有症状的致病变异携带者中的表现，以分析哪种筛查测试具有更好的鉴别能力。
我们使用了来自荷兰和英国两项纵向遗传性FTD队列研究的横断面和纵向数据，这些数据于2021年至2024年期间收集。参与者为症状前、前驱期或有症状的致病变异携带者或健康对照（FTD无致病变异的一级家庭成员）。分组基于总体CDR加NACC - FTLD评分。对参与者进行MoCA和MMSE评估。统计分析比较了组间总分和子分数，并评估了两种测试的预测准确性和分类准确性。
共纳入243名参与者（平均年龄49.9±13.1岁，平均受教育年限14.5±3.0年，56%为女性），其中157名是致病变异携带者（ 、 、 、 、 ），86名是对照。携带者被分类为症状前（n = 119）、前驱期（n = 18）或有症状（n = 20）。MoCA[（3,239）= 16.565， < 0.001]和MMSE[（3,239）= 13.529， < 0.001]总分在组间差异显著，对照组（MoCA中位数28.5，95%置信区间28.0 - 29.0；MMSE中位数30，95%置信区间30.0 - 30.0）的表现优于前驱期（MoCA中位数26，95%置信区间23.0 - 27.0；MMSE中位数29，95%置信区间27.5 - 29.5）和有症状（MoCA中位数20.5，95%置信区间17.0 - 24.0；MMSE中位数26，95%置信区间23.5 - 29.0）携带者。MoCA能区分症状前携带者和对照组（MoCA中位数28，95%置信区间27.0 - 29.0），但MMSE不能。与MMSE相比，MoCA显示出更好的鉴别能力（MoCA曲线下面积[AUC] = 0.87，95%置信区间0.81 - 0.94；MMSE AUC = 0.80，95%置信区间0.72 - 0.89）。
MoCA更高的敏感性和更好的鉴别能力使其成为即将开展的针对临床前期FTD的临床试验中更有价值的认知筛查工具。未来研究应致力于从更多研究中心获取更大样本量。
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