Spinelli Edoardo Gioele, Orlandi Francesca, Basaia Silvia, Costa Francesco, Pisano Stefano, Ghirelli Alma, Canu Elisa, Castelnovo Veronica, Sibilla Elisa, Cecchetti Giordano, Caso Francesca, Magnani Giuseppe, Caroppo Paola, Prioni Sara, Villa Cristina, Tremolizzo Lucio, Appollonio Ildebrando, Verde Federico, Ticozzi Nicola, Silani Vincenzo, Filippi Massimo, Agosta Federica
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Eur J Neurol. 2025 Sep;32(9):e70275. doi: 10.1111/ene.70275.
Frontotemporal dementia (FTD) encompasses diverse clinical phenotypes, primarily characterized by behavioral and/or language dysfunction. A newly characterized variant, semantic behavioral variant FTD (sbvFTD), exhibits predominant right temporal atrophy with features bridging behavioral variant FTD (bvFTD) and semantic variant primary progressive aphasia (svPPA). This study investigates the longitudinal structural MRI correlates of these FTD variants, focusing on cortical and subcortical structural damage to aid differential diagnosis and prognosis.
Seventy-one FTD patients (bvFTD = 45, sbvFTD = 11, svPPA = 15) and 37 healthy controls participated in a prospective study involving up to 24 months of serial neurological, neuropsychological, and 3 T MRI assessments. Cortical thickness and subcortical/cerebellar volumes were analyzed with linear mixed-effect models. Support vector machine (SVM) models were used to classify subjects using baseline and longitudinal patterns of structural damage.
At baseline, sbvFTD showed right-predominant temporal pole involvement associated with significant right frontal atrophy. Longitudinally, bvFTD showed widespread bilateral cortical and basal ganglia damage, svPPA demonstrated steady temporal lobe progression, and sbvFTD progressed primarily in left temporal and frontal regions with limited right hemisphere involvement. Baseline cortical thickness of frontal regions predicted subsequent functional decline in bvFTD and sbvFTD. A multiclass SVM model provided a good diagnostic classification accuracy, with similar results when using baseline data only (82%) and adding longitudinal data (83%).
This study delineates the unique structural MRI features and progression of FTD variants, highlighting sbvFTD as a distinct entity with early extra-temporal involvement. These findings support the development of diagnostic and prognostic tools leveraging neuroimaging biomarkers.
额颞叶痴呆（FTD）包含多种临床表型，主要特征为行为和/或语言功能障碍。一种新发现的变异型，语义行为变异型FTD（sbvFTD），表现为以右侧颞叶萎缩为主，具有连接行为变异型FTD（bvFTD）和语义变异型原发性进行性失语（svPPA）的特征。本研究调查了这些FTD变异型的纵向结构MRI相关性，重点关注皮质和皮质下结构损伤，以辅助鉴别诊断和预后评估。
71例FTD患者（bvFTD = 45例，sbvFTD = 11例，svPPA = 15例）和37名健康对照者参与了一项前瞻性研究，该研究包括长达24个月的系列神经学、神经心理学和3T MRI评估。使用线性混合效应模型分析皮质厚度和皮质下/小脑体积。支持向量机（SVM）模型用于根据结构损伤的基线和纵向模式对受试者进行分类。
在基线时，sbvFTD表现为右侧颞极受累为主，伴有明显的右侧额叶萎缩。纵向来看，bvFTD表现为广泛的双侧皮质和基底节损伤，svPPA表现为颞叶稳定进展，而sbvFTD主要在左侧颞叶和额叶区域进展，右侧半球受累有限。额叶区域的基线皮质厚度可预测bvFTD和sbvFTD随后的功能衰退。多分类SVM模型提供了良好的诊断分类准确性，仅使用基线数据时（82%）和加入纵向数据时（83%）结果相似。
本研究描绘了FTD变异型独特的结构MRI特征和进展情况，突出了sbvFTD作为一种具有早期颞外受累的独特实体。这些发现支持利用神经影像学生物标志物开发诊断和预后工具。
