Remote Digital Cognitive Assessment Reveals Cognitive Deficits Related to Hippocampal Atrophy in Autoimmune Limbic Encephalitis
Remote Digital Cognitive Assessment Reveals Cognitive Deficits Related to Hippocampal Atrophy in Autoimmune Limbic Encephalitis
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远程数字认知评估揭示了与自身免疫性边缘脑炎海马萎缩相关的认知缺陷
DOI：
10.1101/2023.07.25.23292765
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发表时间：
2023
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通讯作者：
Shibata K
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作者：
Shibata K
研究背景自身免疫性边缘系统脑炎（autoimmune limbic encephalitis，ALE）是一种由致病性自身抗体介导的以脑边缘系统炎症为特征的神经系统疾病。由于认知功能障碍在ALE急性治疗后持续存在，因此准确评估长期认知结局对于临床评估和试验非常重要。然而，评估认知是昂贵的和未满足的需要存在有效的digital methods.MethodsIn这个横断面验证研究中，我们调查了远程数字平台是否可以识别以前的特征认知障碍慢性ALE患者和数字指标是否与标准的神经心理学评估和海马体积。本研究招募了具有慢性和稳定表现并接受ALE临床诊断的ALE患者。通过牛津大学（英国）认知神经学实验室测试计划招募的21名ALE患者和54名年龄匹配的健康对照的认知表现，使用Cognitron在线平台的12项认知任务进行了评估。该平台在国家健康与护理研究所（NIHR）的支持下进行了优化，可远程交付给老年人和患者群体。主要结局指标是行为表现以及相应的神经影像学和神经心理学评估指标。结果2021年2月15日至2022年4月21日期间，21名ALE患者（平均年龄63.01岁，14名男性）和54名健康对照（平均年龄65.56岁，23名男性）完成了数字认知评估。ALE患者在记忆、视觉空间能力、执行功能和语言方面表现明显较差。在数字和空间跨度，目标检测（注意力）和情绪辨别方面没有观察到障碍。在线认知任务的整体得分与已建立的Addenbrooke认知考试III（ACE）纸笔测试显着相关。与使用远程数字测试但不使用ACE的对照组相比，在ALE中确定了视觉空间处理和语言的缺陷，突出了计算机化测试对残余认知障碍的更高敏感性。最后，ALE患者和健康对照组的海马体积与在线认知scores.InterpretationThese研究结果表明，慢性ALE患者的微妙认知缺陷，他们经常表现出完全恢复的残疾和对日常活动的依赖措施，使用远程在线平台是可检测的，这也与海马萎缩有关。这种方法可以促进复杂神经系统疾病的认知特征的表征。未来的纵向研究，旨在评估这种数字化方法的进一步临床characterization.FundingThe惠康信托基金，医学研究理事会，国家卫生研究所，罗兹奖学金，和贝罗基金会奖学金的效用是必要的。
BackgroundAutoimmune limbic encephalitis (ALE) is a neurological disease characterised by inflammation of the limbic regions of the brain, mediated by pathogenic autoantibodies. Because cognitive deficits persist following acute treatment of ALE, the accurate assessment of long-term cognitive outcomes is important for clinical assessments and trials. However, evaluating cognition is costly and an unmet need exists for validated digital methods.MethodsIn this cross-sectional validation study, we investigated whether a remote digital platform could identify previously characterised cognitive impairments in patients with chronic ALE and whether digital metrics would correlate with standard neuropsychological assessment and hippocampal volume. Patients with ALE who had a chronic and stable presentation and received a clinical diagnosis of ALE were recruited for this study. The cognitive performance of 21 patients with ALE and 54 age-matched healthy controls — enrolled via the University of Oxford (UK) Cognitive Neurology Lab testing programme — was assessed with a battery of 12 cognitive tasks from the Cognitron online platform. The platform was optimised with National Institute for Health and Care Research (NIHR) support to be deliverable remotely to elderly and patient groups. The primary outcome measure was behavioural performance and corresponding neuroimaging and neuropsychological assessment metrics.FindingsBetween February 15, 2021, and April 21, 2022, 21 patients with ALE (mean age 63.01 years, 14 males) and 54 healthy controls (mean age 65.56 years, 23 males) completed the digital cognitive assessment. Patients with ALE performed significantly worse in memory, visuospatial abilities, executive function, and language. No impairments in digit & spatial span, target detection (attention) and emotion discrimination were observed. The global score on the online cognitive tasks correlated significantly with the established Addenbrooke's Cognitive Examination III (ACE) pen-and-paper test. Deficits in visuospatial processing and language were identified in ALE compared to controls using remote digital testing but not using the ACE, highlighting higher sensitivity of computerised testing to residual cognitive impairment. Finally, the hippocampal volumes of patients with ALE and healthy controls correlated with online cognitive scores.InterpretationThese findings demonstrate that subtle cognitive deficits in patients with chronic ALE, who often show full recovery in measures of disability and dependence on daily activities, are detectable using a remote online platform, which also relates to hippocampal atrophy. Such methods may facilitate the characterisation of cognitive profiles in complex neurological diseases. Future longitudinal studies designed to assess the utility of such digital methods for further clinical characterisation are needed.FundingThe Wellcome Trust, Medical Research Council, National Institute for Health Research, Rhodes Scholarship, and the Berrow Foundation Scholarship.