Can a failure in the error-monitoring system explain unawareness of memory deficits in Alzheimer's disease?
Can a failure in the error-monitoring system explain unawareness of memory deficits in Alzheimer's disease?
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错误监控系统的故障能否解释阿尔茨海默病患者对记忆缺陷的无意识？
DOI：
10.1016/j.cortex.2023.05.014
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Andrade,Kati
中科院分区：
文献类型：
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作者：
Razafimahatratra,Solofo;Guieysse,Thomas;Lejeune,François-Xavier;Houot,Marion;Medani,Takfarinas;Dreyfus,Gérard;Klarsfeld,André;Villain,Nicolas;Pereira,FilipaRaposo;LaCorte,Valentina;George,Nathalie;Pantazis,Dimitrios;Andrade,Kati
记忆缺失是阿尔茨海默病（AD）患者的早期表现，往往会延误诊断。这种有趣的行为构成了病感失认症的一种形式，其神经机制在很大程度上仍然未知。我们假设病感失认症可能依赖于错误监测系统中的关键突触失效，这将阻止AD患者意识到自己的记忆障碍。为了进行研究，我们测量了两组在研究开始时只有主观记忆抱怨的淀粉样蛋白阳性个体在单词记忆识别任务中错误反应引起的事件相关电位（erp）：在五年研究期间进展为AD的人（PROG组）和认知正常的人（CTRL组）。基于所有受试者的最后一次EEG采集，在组内分析中观察到PROG组在AD诊断时（与研究开始时相比）以及在组间分析中与CTRL组相比，阳性误差（Pe）（与错误意识相关的ERP）的幅度显着降低。重要的是，在阿尔茨海默病诊断时，PROG组表现出病感失认的临床症状，高估了他们的认知能力，这一点可以从护理者/信息提供者与参与者在健康衰老脑护理监测的认知子量表上的差异得分中得到证明。据我们所知，这是第一个揭示阿尔茨海默病早期单词记忆识别任务中错误监测系统出现故障的研究。这一发现，以及PROG组观察到的认知障碍意识的下降，强烈表明错误监测系统中的突触功能障碍可能是AD患者对缺陷缺乏意识的关键神经机制。
Unawareness of memory deficits is an early manifestation in patients with Alzheimer’s disease (AD), which often delays diagnosis. This intriguing behavior constitutes a form of anosognosia, whose neural mechanisms remain largely unknown. We hypothesized that anosognosia may depend on a critical synaptic failure in the error-monitoring system, which would prevent AD patients from being aware of their own memory impairment. To investigate, we measured event-related potentials (ERPs) evoked by erroneous responses during a word memory recognition task in two groups of amyloid positive individuals with only subjective memory complaints at study entry: those who progressed to AD within the five-year study period (PROG group), and those who remained cognitively normal (CTRL group). A significant reduction in the amplitude of the positivity error (Pe), an ERP related to error awareness, was observed in the PROG group at the time of AD diagnosis (versus study entry) in intra-group analysis, as well as when compared with the CTRL group in inter-group analysis, based on the last EEG acquisition for all subjects. Importantly, at the time of AD diagnosis, the PROG group exhibited clinical signs of anosognosia, overestimating their cognitive abilities, as evidenced by the discrepancy scores obtained from caregiver/informant versus participant reports on the cognitive subscale of the Healthy Aging Brain Care Monitor. To our knowledge, this is the first study to reveal the emergence of a failure in the error-monitoring system during a word memory recognition task at the early stages of AD. This finding, along with the decline of awareness for cognitive impairment observed in the PROG group, strongly suggests that a synaptic dysfunction in the error-monitoring system may be the critical neural mechanism at the origin of unawareness of deficits in AD.