De Meo Ermelinda, Portaccio Emilio, Cortese Rosa, Ruano Luis, Goretti Benedetta, Niccolai Claudia, Patti Francesco, Chisari Clara, Gallo Paolo, Grossi Paola, Ghezzi Angelo, Roscio Marco, Mattioli Flavia, Stampatori Chiara, Simone Marta, Viterbo Rosa Gemma, Bonacchi Raffaello, Rocca Assunta Maria, Leveraro Elisa, Giorgio Antonio, De Stefano Nicola, Filippi Massimo, Inglese Matilde, Amato Maria Pia
Department of Neuroinflammation, Institute of Neurology, Univeristy College of London, London, UK.
NEUROFARBA Department, Neurosciences Section, University of Florence, Florence, Italy.
Ann Clin Transl Neurol. 2025 Mar;12(3):512-522. doi: 10.1002/acn3.52291. Epub 2025 Jan 24.
We aim to investigate cognitive phenotype distribution and MRI correlates across pediatric-, elderly-, and adult-onset MS patients as a function of disease duration.
In this cross-sectional study, we enrolled 1262 MS patients and 238 healthy controls, with neurological and cognitive assessments. A subset of 222 MS patients and 92 controls underwent 3T-MRI scan for brain atrophy and lesion analysis. Multinomial probabilistic models identified likelihood of belonging to cognitive phenotypes ("preserved-cognition," "mild verbal memory/semantic fluency," "mild multi-domain," "severe attention/executive," and "severe multi-domain") and experiencing MRI abnormalities based on disease duration and age at onset.
In all groups, the likelihood of "preserved-cognition" phenotype decreased, whereas "mild multi-domain" increased with longer disease duration. In pediatric- and adult-onset patients, the likelihood of "mild verbal memory/semantic fluency" phenotypes decreased with longer disease duration, and that of "severe multi-domain" increased with longer disease duration. Only in adult-onset patients, the likelihood of "severe executive/attention" phenotype increased with longer disease duration. All groups displayed escalating probabilities of cortical, thalamic, hippocampal, and deep gray matter atrophy over disease course. Compared to adult, pediatric-onset patients showed lower probability of experiencing thalamic atrophy with longer disease duration, while elderly-onset showed higher probability of experiencing cortical and hippocampal atrophy.
Age at MS onset significantly influences the distribution of cognitive phenotypes and the patterns of regional gray matter atrophy throughout the disease course.
我们旨在研究儿童期、老年期和成年期发病的多发性硬化症（MS）患者的认知表型分布及其与MRI的相关性，并将其作为疾病持续时间的函数进行分析。
在这项横断面研究中，我们招募了1262例MS患者和238名健康对照者，对他们进行了神经学和认知评估。222例MS患者和92名对照者的子集接受了3T-MRI扫描，以进行脑萎缩和病变分析。多项概率模型根据疾病持续时间和发病年龄确定了属于认知表型（“认知保留”、“轻度言语记忆/语义流畅性”、“轻度多领域”、“重度注意力/执行功能”和“重度多领域”）以及出现MRI异常的可能性。
在所有组中，“认知保留”表型的可能性降低，而“轻度多领域”表型的可能性随疾病持续时间延长而增加。在儿童期和成年期发病的患者中，“轻度言语记忆/语义流畅性”表型的可能性随疾病持续时间延长而降低，“重度多领域”表型的可能性随疾病持续时间延长而增加。仅在成年期发病的患者中，“重度执行功能/注意力”表型的可能性随疾病持续时间延长而增加。在整个疾病过程中，所有组的皮质、丘脑、海马和深部灰质萎缩的概率都在不断增加。与成年期发病患者相比，儿童期发病患者丘脑萎缩的可能性随疾病持续时间延长而降低，而老年期发病患者皮质和海马萎缩的可能性更高。
MS发病年龄在整个疾病过程中显著影响认知表型的分布以及区域灰质萎缩的模式。
