Data_Sheet_1_The nature of memory impairment in multiple sclerosis: understanding different patterns over the course of the disease.pdf

IntroductionMemory deficit is one of the most common and severe cognitive impairments in patients with multiple sclerosis and can greatly affect their quality of life. However, there is currently no agreement as to the nature of memory deficit in multiple sclerosis.
MethodsThis cross-sectional study, carried out at the Dr. Josep Trueta and Santa Caterina hospitals in Girona (Spain), was designed to determine the semiology of verbal memory deficit in the different stages of the disease. To this end, a modification of Rey’s verbal auditory test was created by introducing two recognition trials between the five learning trials, thus monitoring what happens in terms of acquisition versus the retrieval of information during the learning phase. Linear regression models were used to evaluate verbal episodic memory performance between-groups adjusting results by age, sex, educational level, and the presence of anxiety and/or depressive symptoms.
Results133 patients with multiple sclerosis, clinically isolated syndrome, and radiologically isolated syndrome and 55 healthy controls aged 18–65 years were assessed. It was observed that the memory processes of multiple sclerosis patients worsen with the progression of the disease. In this respect, patients in pre-diagnostic phases (radiologically isolated syndrome and clinically isolated syndrome) show no differences in verbal episodic memory compared to the healthy controls. Patients in the inflammatory stage (relapsing–remitting multiple sclerosis) show a previously learned information retrieval deficit, while patients in progressive stages (secondary progressive multiple sclerosis and primary progressive multiple sclerosis) do not even correctly acquire information.
DiscussionThese results provide significant information to assist in understanding the nature of memory deficits in multiple sclerosis over the course of the disease. These results are discussed in terms of possible cognitive rehabilitation strategies depending on the evolutive stage and are related to neuropathological mechanisms involved in the progression of the disease.

引言
记忆缺陷是多发性硬化（multiple sclerosis, MS）患者最常见且严重的认知障碍之一，可显著降低患者的生活质量。但目前学界对于多发性硬化患者记忆缺陷的本质尚未达成共识。

方法
本研究为横断面研究，在西班牙赫罗纳的何塞普·特鲁埃塔博士医院与圣卡特琳娜医院开展，旨在明确不同疾病分期下多发性硬化患者言语记忆缺陷的症状学特征。为此，本研究对雷伊听觉词语学习测验（Rey Auditory Verbal Learning Test）进行改良：在5次学习试次之间增设2次再认试次，以监测学习阶段中信息获取与提取的动态变化。本研究采用线性回归模型，以年龄、性别、受教育水平以及焦虑/抑郁症状存在情况作为混杂因素进行校正，比较组间的言语情景记忆表现。

结果
本研究共纳入133例多发性硬化、临床孤立综合征（clinically isolated syndrome, CIS）及放射学孤立综合征（radiologically isolated syndrome, RIS）患者，以及55名年龄在18~65岁之间的健康对照者。研究观察到，多发性硬化患者的记忆功能随疾病进展逐渐受损。在此方面，预诊断阶段患者（放射学孤立综合征与临床孤立综合征患者）的言语情景记忆表现与健康对照无显著差异。炎症阶段患者（复发缓解型多发性硬化（relapsing-remitting multiple sclerosis, RRMS）患者）仅表现为已学习信息的提取障碍，而进展阶段患者（继发进展型多发性硬化（secondary progressive multiple sclerosis, SPMS）与原发进展型多发性硬化（primary progressive multiple sclerosis, PPMS）患者）甚至无法正确获取信息。

讨论
本研究结果为阐明多发性硬化患者病程中记忆缺陷的本质提供了重要依据。本研究还结合不同疾病分期探讨了针对性认知康复策略的可行性，并将结果与疾病进展相关的神经病理机制进行了关联分析。