Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
J Neurol. 2024 Apr;271(4):1571-1583. doi: 10.1007/s00415-023-12102-5. Epub 2023 Nov 26.
Available criteria for cognitive phenotypes in multiple sclerosis (MS) do not consider the severity of impairment.
To identify cognitive phenotypes with varying degrees of impairment in MS patients and describe their demographic, clinical and MRI characteristics.
Two hundred and forty-three MS patients and 158 healthy controls underwent neuropsychological tests to assess memory, attention, and executive function. For each domain, mild impairment was defined as performing 1.5 standard deviations below the normative mean on two tests, while the threshold for significant impairment was 2 standard deviations. Patients were classified into cognitive phenotypes based on severity of the impairment (mild/significant) and number of domains affected (one/more).
Five cognitive phenotypes emerged: Preserved cognition (PC; 56%), Mild Single-Domain Impairment (MSD; 15%), Mild Multi-Domain Impairment (MMD; 9%), Significant Single-Domain Impairment (SSD; 12%), Significant Multi-Domain Impairment (SMD; 8%). Compared with PC, MSD patients were older, had longer disease duration (DD) and higher T2-hyperintense lesion volume (LV; all p ≤ 0.02); MMD patients were older, had longer DD, higher disability, higher T2 LV and lower thalamic volume (all p ≤ 0.01); SSD patients had longer DD and lower gray matter cortical volume, thalamic, caudate, putamen and accumbens volumes (all p ≤ 0.04); and SMD patients were older, had longer DD, higher disability and more extensive structural damage in all brain regions explored (all p ≤ 0.03), except white matter and amygdala volumes.
We identified five cognitive phenotypes with graded levels of impairment. These phenotypes were characterized by distinct demographic, clinical and MRI features, indicating potential variations in the neural substrates of dysfunction throughout disease stages.
多发性硬化症（MS）的认知表型标准并未考虑损害程度。
在 MS 患者中确定具有不同损害程度的认知表型，并描述其人口统计学、临床和 MRI 特征。
243 名 MS 患者和 158 名健康对照者接受神经心理学测试，以评估记忆、注意力和执行功能。对于每个领域，轻度损害定义为在两项测试中低于正常平均值 1.5 个标准差，而显著损害的阈值为 2 个标准差。根据损害程度（轻度/显著）和受影响的领域数量（一个/多个）将患者分为认知表型。
出现了五种认知表型：认知正常（PC；56%）、轻度单域损害（MSD；15%）、轻度多域损害（MMD；9%）、显著单域损害（SSD；12%）、显著多域损害（SMD；8%）。与 PC 相比，MSD 患者年龄更大，疾病持续时间（DD）更长（均 p≤0.02），T2 高信号病变体积（LV）更高；MMD 患者年龄更大，DD 更长，残疾程度更高，T2 LV 更高，丘脑体积更小（均 p≤0.01）；SSD 患者 DD 更长，灰质皮质体积、丘脑、尾状核、壳核和伏隔核体积更小（均 p≤0.04）；SMD 患者年龄更大，DD 更长，残疾程度更高，所有脑区的结构损伤更广泛（均 p≤0.03），除了白质和杏仁核体积。
我们确定了五种具有不同损害程度的认知表型。这些表型具有不同的人口统计学、临床和 MRI 特征，表明在疾病的不同阶段，功能障碍的神经基础可能存在差异。
