Cognitive Indicators of Preclinical Behavioral Variant Frontotemporal Dementia in MAPT Carriers
Cognitive Indicators of Preclinical Behavioral Variant Frontotemporal Dementia in MAPT Carriers
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DOI：
10.1017/s1355617718001005
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发表时间：
2019-02-01
影响因子：
2.6
通讯作者：
Cosentino, Stephanie
中科院分区：
文献类型：
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作者：
Cheran, Gayathri;Wu, Liwen;Cosentino, Stephanie
目的：尚未确定临床前行为变异型额颞叶痴呆（bvFTD）的认知指标。为了研究这些指标，我们比较了12名不符合bvFTD诊断标准的致病性MAPT突变携带者在一系列认知测量方面的横截面表现（即，临床前）与32个人口统计学匹配的家族性非携带者（n = 44）。研究临床前携带者提供了一个罕见的一瞥紧急疾病，环境和遗传背景下，通过比较家族控制。研究方法：对携带者状态不知情的评估人员进行标准化神经心理电池评估，评估注意力、速度、执行功能、语言、记忆力、空间能力和社会认知。通过错误发现率方法校正混合效应模型的结果以进行多重比较，结果在p <0.05时被认为是显著的。为了控制潜在的家族间变异所产生的六个家庭的登记，家庭被视为随机效应，而载体状态，年龄，性别和教育被视为固定效应。结果：31个认知得分中有17个得分存在组间差异，除空间能力外，其余得分均存在组间差异。正如假设的那样，携带者在执行功能和社会认知的具体指标上表现较差，但在注意力、速度、语义处理以及记忆储存和提取方面也表现较差。结论：最值得注意的是，组间差异出现在记忆储存的措施，挑战长期存在的想法，缺乏遗忘功能的神经心理测试在早期bvFTD。目前的研究结果提供了关于可能对早期bvFTD敏感的特定指标的重要临床相关信息，并促进了对疾病早期发生的神经认知变化的理解。(JINS，2019，25，184-194）
Objectives: The cognitive indicators of preclinical behavioral variant Frontotemporal Dementia (bvFTD) have not been identified. To investigate these indicators, we compared cross-sectional performance on a range of cognitive measures in 12 carriers of pathogenic MAPT mutations not meeting diagnostic criteria for bvFTD (i.e., preclinical) versus 32 demographically-matched familial non-carriers (n = 44). Studying preclinical carriers offers a rare glimpse into emergent disease, environmentally and genetically contextualized through comparison to familial controls. Methods: Evaluating personnel blinded to carrier status administered a standardized neuropsychological battery assessing attention, speed, executive function, language, memory, spatial ability, and social cognition. Results from mixed effect modeling were corrected for multiplicity of comparison by the false discovery rate method, and results were considered significant at p < .05. To control for potential interfamilial variation arising from enrollment of six families, family was treated as a random effect, while carrier status, age, gender, and education were treated as fixed effects. Results: Group differences were detected in 17 of 31 cognitive scores and spanned all domains except spatial ability. As hypothesized, carriers performed worse on specific measures of executive function, and social cognition, but also on measures of attention, speed, semantic processing, and memory storage and retrieval. Conclusions: Most notably, group differences arose on measures of memory storage, challenging long-standing ideas about the absence of amnestic features on neuropsychological testing in early bvFTD. Current findings provide important and clinically relevant information about specific measures that may be sensitive to early bvFTD, and advance understanding of neurocognitive changes that occur early in the disease. (JINS, 2019, 25, 184-194)