MRI and MRS Correlates of Cognitive Function in SLE

描述（由申请人提供）：系统性红斑狼疮（SLE）患者没有明显的神经或精神（NP）障碍，表现出认知功能障碍，提示相对微妙但临床上显著的中枢神经系统受累。在这些认知异常的患者中，困难的诊断和治疗决策往往是必要的，更好地了解其潜在的发病机制对于合理的治疗方法至关重要。我们建议通过定量脑结构（通过MRI；磁共振成像）和神经代谢物（通过MRS；质子磁共振波谱）检查无NP障碍（CI-SLE）的认知受损SLE患者的认知功能障碍的潜在机制。本研究的具体目的是首先比较CI-SLE与非认知障碍SLE （NCI-SLE）和健康对照者在选择定量MRI脑结构（全脑和海马）和质子MRS神经代谢物（海马结构和NAA/Cr；额部和顶枕区正常白质的NAA/Cr和Cho/Cr）上的差异。其次，我们旨在研究SLE患者的认知缺陷、脑结构和神经代谢物之间的关系。我们将从认知损伤指数和全脑测量之间的全局关系开始分析。然后，我们将评估与海马体大小和该区域NAA/Cr水平相关的学习和记忆测量。接下来我们将检查注意力/信息处理与白质高信号总量的关系。然后，我们将检查大脑额叶区NAA/Cr和Ch/Cr水平与注意力/信息处理和执行技能的关系。最后，我们将探讨SLE患者的主观认知主诉是否与特定的客观认知缺陷、定量脑结构和选择的神经代谢物有关。我们相信，了解与SLE患者认知功能障碍相关的生物学异常将指导进一步研究SLE患者中枢神经系统变化的潜在机制。这将更好地为临床医生提供明确的诊断途径和更好的治疗选择。

DESCRIPTION (provided by applicant): Systemic lupus erythematosus (SLE) patients without major overt neurological or psychiatric (NP) disorders have demonstrated cognitive dysfunction suggesting relatively subtle but clinically significant CNS involvement. Difficult diagnostic and treatment decisions are frequently necessary in these patients with cognitive abnormalities, and a better understanding of their underlying pathogenesis is critical to a rational approach to their management. We propose to identify potential mechanisms of cognitive dysfunction in SLE patients by examining quantitative brain structures (via MRI; magnetic resonance imaging), and neuronal metabolites (via MRS; proton magnetic resonance spectroscopy) in cognitively impaired SLE patients without NP disorders (CI-SLE). The specific aims of this proposal are first to compare CI-SLE to non-cognitively impaired SLE (NCI-SLE) and healthy control subjects on select quantitative MRI brain structures (whole brain and hippocampus) and proton MRS neurometabolites (NAA/Cr hippocampal structures and NAA/Cr; NAA/Cr and Cho/Cr in normal appearing white matter in frontal and parieto-occipital regions). Secondly, we aim to examine the relationship between cognitive deficits, brain structures and neurometabolites in the SLE patients. We will begin the analyses with a global relationship between a cognitive impairment index and whole brain measurement. We will then evaluate learning and memory measures in relation to the size of the hippocampus and NAA/Cr levels in that area. We will next examine attention/information processing in relation to total volume of white matter hyperintensities. Then we will examine NAA/Cr and Ch/Cr levels in frontal area of the brain in relation to attention/information processing and executive skills. Finally we will explore whether subjective cognitive complaints of SLE patients are associated with specific objective cognitive deficits, quantitative brain structures and select neurometabolites. We believe that understanding the biological abnormalities associated with cognitive dysfunction in SLE patients will guide further investigations directed at the underlying mechanisms of CNS changes in SLE. This will better prepare clinicians with clear diagnostic avenues and better treatment options in the future.