Department of Cognitive Neuroscience, Maastricht University, Maastricht, the Netherlands; Neuroscience Group, University of Antioquia, Medellin, Colombia; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Neuroscience Group, University of Antioquia, Medellin, Colombia.
Brain Res. 2019 Mar 15;1707:74-78. doi: 10.1016/j.brainres.2018.11.016. Epub 2018 Nov 13.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary stroke disorder and is caused by mutations of the NOTCH3 gene. Cognitive decline in CADASIL is characterized by early impairments of attention, memory, and executive functions. Studying asymptomatic individuals with CADASIL offers a unique genetic model to understand preclinical vascular cognitive impairment and dementia. This study aimed at examine whether early preclinical physiological changes could be observed in asymptomatic individuals with CADASIL, who will go on to develop vascular cognitive impairment and dementia later in life. Twenty-nine individuals (mean age: 54.1 years old) were included in the study; five CADASIL NOTCH3 mutation carriers and twenty-five age-matched non-carriers. Participants underwent a comprehensive clinical evaluation and neuropsychological testing. Event-related potentials (ERPs) were recorded during a picture recognition memory task. Analyses focused on the early frontal effect and parietal effect ERP components associated with familiarity and recollection memory. There were no differences between groups in behavioral performance during recognition memory discrimination or cognitive performance. Compared to non-carriers, CADASIL carriers had decreased amplitudes in both ERP components for hits and correct rejections. Among mutation carriers, lower amplitude at 500-600 ms in the left parietal region of interest for correct rejections was correlated with worse performance on measures of semantic fluency and inhibitory control. We conclude that cognitively unimpaired CADASIL carriers showed abnormalities in the neural correlates of recognition memory, years before clinical onset. Early disruptions of fronto-subcortical networks may explain preclinical changes in brain function during recognition memory. This work also demonstrates the potential usefulness of ERP brain correlates as preclinical markers of vascular dementia.
伴有皮质下梗死和白质脑病的常染色体显性脑动脉病（CADASIL）是遗传性中风疾病中最常见的形式，是由 NOTCH3 基因突变引起的。CADASIL 的认知能力下降的特征是注意力、记忆和执行功能的早期损害。对无症状的 CADASIL 患者进行研究提供了一个独特的遗传模型，可用于了解临床前血管性认知障碍和痴呆。本研究旨在观察无症状的 CADASIL 患者是否会出现早期临床前的生理变化，这些患者以后会发展为血管性认知障碍和痴呆。研究纳入了 29 名参与者（平均年龄：54.1 岁），包括 5 名 CADASIL NOTCH3 基因突变携带者和 25 名年龄匹配的非携带者。参与者接受了全面的临床评估和神经心理学测试。在图片识别记忆任务中记录事件相关电位（ERPs）。分析集中在与熟悉度和回忆记忆相关的早期额区效应和顶区效应 ERP 成分上。在识别记忆辨别或认知表现中，两组之间的行为表现没有差异。与非携带者相比，CADASIL 携带者在 hit 和正确拒绝的两个 ERP 成分的振幅都降低了。在突变携带者中，左顶叶感兴趣区正确拒绝的 500-600ms 时的振幅降低与语义流畅性和抑制控制测量的表现较差相关。我们得出结论，认知未受损的 CADASIL 携带者在临床发病前数年就表现出识别记忆的神经相关性异常。额皮质下网络的早期中断可能解释了识别记忆过程中脑功能的临床前变化。这项工作还证明了 ERP 脑相关性作为血管性痴呆的临床前标志物的潜在用途。
