轻度认知损伤的语义记忆研究述评

轻度认知损伤（Mild cognitive impairment,MCI）是介于正常老化与痴呆之间的过渡阶段,表现为与年龄和教育程度不相称的认知功能减退。本文回顾了近期有关MCI语义记忆的研究,分析比较了各研究的实验任务及结果,得出MCI患者存在一定程度的由多种原因造成的语义记忆损伤,语义记忆测验对MCI的早期筛查和转归预测有重要作用。最后指出将来的研究需要将包括语义记忆成分在内的多种认知测验相结合,以便及早发现有可能发展为痴呆的危险个体并开展相应干预。     

Differential Memory Test Sensitivity for Diagnosing Amnestic Mild Cognitive Impairment and Predicting Conversion to Alzheimer's Disease

ABSTRACT

Episodic memory is the first and most severely affected cognitive domain in Alzheimer's disease (AD), and it is also the key early marker in prodromal stages including amnestic mild cognitive impairment (MCI). The relative ability of memory tests to discriminate between MCI and normal aging has not been well characterized. We compared the classification value of widely used verbal memory tests in distinguishing healthy older adults (n = 51) from those with MCI (n = 38). Univariate logistic regression indicated that the total learning score from the California Verbal Learning Test-II (CVLT-II) ranked highest in terms of distinguishing MCI from normal aging (sensitivity = 90.2; specificity = 84.2). Inclusion of the delayed recall condition of a story memory task (i.e., WMS-III Logical Memory, Story A) enhanced the overall accuracy of classification (sensitivity = 92.2; specificity = 94.7). Combining Logical Memory recognition and CVLT-II long delay best predicted progression from MCI to AD over a 4-year period (accurate classification = 87.5%). Learning across multiple trials may provide the most sensitive index for initial diagnosis of MCI, but inclusion of additional variables may enhance overall accuracy and may represent the optimal strategy for identifying individuals most likely to progress to dementia.     

进行中任务变化对轻度认知功能障碍者基于事件前瞻记忆的影响

本实验采用2被试组别(MCI组、正常老年组) × 3进行中任务变化(无变化、顺序变化、随机变化)被试间设计探究进行中任务变化对轻度认知功能障碍者基于事件前瞻记忆的影响。结果表明：(1)轻度认知功能障碍者的前瞻记忆成绩显著低于正常老年人的前瞻记忆成绩; (2)进行中任务变化对两组被试前瞻记忆和进行中任务的反应时影响存在显著差异。进行中任务变化越大, 轻度认知功能障碍者完成前瞻记忆和进行中任务的反应速度越慢; 而正常老年被试则不受影响。研究支持前瞻记忆策略加工的理论观点, 认为执行功能损伤可能是导致轻度认知功能障碍者前瞻记忆失败的主要原因。     

轻度认知功能障碍患者工作记忆中 脑电能量及皮质联络功能的变化特征

探讨轻度认知功能障碍患者（MCI）工作记忆状态下脑电能量及皮质联络功能的变化特征。被试为从社区选取的35名轻度认知功能障碍患者和34名健康志愿者。采用简单计算回忆方法,结果发现工作记忆加工过程中会引起4.0~18.0Hz范围内功率值的改变,且MCI组高于正常对照组;MCI患者在中央、顶、颞叶的半球间相干系数均显著高于正常对照组。研究结果提示MCI患者可能存在中央、顶、颞叶皮层的功能减退,工作记忆状态下通过代偿机制仍能维持加工的有效性     

Performance of an Adapted Version of the Timed Up-and-Go Test in People with Cognitive Impairments

In clinical practice, older people with cognitive impairment may have difficulties to understand the instructions of the Timed Up-and-Go (TUGT) test and present a bad performance. The purpose of this study was to identify differences in the TUGT performance, in an adapted version, between older adults with preserved cognition (PC), mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to identify the association between the adapted TUGT performance and cognition among groups. A cross-sectional study was conducted with 118 community-dwelling older adults divided in three groups: PC (n?=?40), MCI (n?=?40) and AD (n?=?38). The evaluation was composed by the adapted TUGT and cognitive assessment (Addenbrooke's Cognitive Examination and Frontal Assessment Battery). Only the cadence of TUGT presented significant difference between groups, specifically between AD versus MCI and PC groups. The main correlations were found between time of TUGT with fluency domain and global cognitive function, especially in the AD Group. The findings contribute to the understanding of how cognition interferes on functional mobility in older people with MCI and AD. The adapted TUGT is easy to perform in clinical practice and can be useful when assessing mobility in people with cognitive impairment.     

Neuropsychological predictors of conversion to probable Alzheimer disease in elderly with mild cognitive impairment

In the field of neuropsychology, it is essential to determine which neuropsychological tests predict Alzheimer's disease (AD) in people with mild cognitive impairment (MCI) and which cut‐off points should be used to identify people at greater risk for converting to dementia. The aim of the present study was to analyse the predictive value of the cognitive tests included in a neuropsychological battery for conversion to AD among MCI participants and to analyse the influence of some sociodemographic variables – sex, age, schooling – and others, such as follow‐up time and emotional state. A total of 105 participants were assessed with a neuropsychological battery at baseline and during a 3‐year follow‐up period. For the present study, the data were analysed at baseline. During the follow‐up period, 24 participants (22.85%) converted to dementia (2.79 ± 1.14 years) and 81 (77.14%) remained as MCI. The logistic regression analysis determined that the long delay cued recall and the performance time of the Rey figure test were the best predictive tests of conversion to dementia after an MCI diagnosis. Concerning the sociodemographic factors, sex had the highest predictive power. The results reveal the relevance of the neuropsychological data obtained in the first assessment. Specifically, the data obtained in the episodic verbal memory tests and tests that assess visuospatial and executive components may help to identify people with MCI who may develop AD in an interval not longer than 4 years, with the masculine gender being an added risk factor.     

认知和情绪冲突的监控与解决：来自轻度认知损伤的证据

轻度认知损伤(mild cognitive impairment, MCI)是介于正常老化和痴呆之间的过渡阶段。近年来, 执行控制的损伤被认为是MCI的核心特征之一。当前, 在MCI执行控制的领域内, 对冲突监控与解决的特征及其神经机制的研究较少。本研究拟通过认知及情绪冲突实验范式, 结合脑成像技术, 探讨遗忘型MCI (amnestic MCI, aMCI)认知和情绪冲突的监控与解决的特征及相应的脑激活模式; 通过对比aMCI和正常老年人在认知和情绪冲突任务中激活的神经环路, 考察aMCI是否在执行加工的神经网络上存在激活异常。在上述研究基础上, 研究者拟探讨aMCI在执行控制的冲突监控与解决上是否存在一般性的损伤机制, 同时试图寻找aMCI在执行控制的冲突监控与解决方面的认知及神经生物学标记。这对深入理解痴呆的发病进程并有针对性的开展痴呆的早期识别与干预具有重要的理论意义和实践意义。     

Repetition-lag training to improve recollection memory in older people with amnestic mild cognitive impairment. A randomized controlled trial

The results of a randomized controlled trial of repetition-lag training in older adults with amnestic mild cognitive impairment (aMCI) are reported. A modified repetition-lag training procedure with extended encoding time and strategy choice was used. The training required discriminating studied words from non-studied lures that were repeated at varying intervals during the test phase. Participants were assessed pre/post using untrained measures of cognition and self-report questionnaires. Primary outcome measures were recall of unrelated word pairs both immediately following presentation and following a delay. Secondary outcomes were a measure of attention, cognitive flexibility, and visual working memory. Participants were also asked to report on the frequency of cognitive failures and mood before and after training. Participants (N = 31) were randomized into either the treatment or a no-contact control group and attended the clinic twice per week over a four week period. Twenty-four participants completed the study (twelve in each group). Results indicated that the training group improved at recalling unrelated word pairs after a delay. There were no significant effects of training on other outcomes, self-reported cognitive failures or mood. The results are discussed along with suggestions for future research.     

Alterations in working memory networks in amnestic mild cognitive impairment

Patients with amnestic mild cognitive impairment (aMCI) show preserved or mildly impaired working memory, despite their deficits in episodic memory. We aimed to identify performance and/or neural differences between aMCI patients and matched controls on a standard working memory fMRI task. Neuropsychological assessment demonstrated aMCI impairments in verbal and visual episodic long-term memory, with intact IQ and executive function. Participants completed a standard three-level N-back task where patients were unimpaired. Functional activations in the control group were found in expected areas, including the inferior parietal lobule and dorsolateral prefrontal cortex. Group differences were found in the insula and lingual gyrus and, in a region of interest analysis, in the hippocampus. In all cases, these were caused by an absence of task-related deactivations in the aMCI group. The results are consistent with reports of failure in task-related deacivations in aMCI and could be early indications of pathology.     

轻度认知损伤重复效应脑电研究：范式及应用

“语义一致性加重复”范式（congruity-plus-repetition paradigm）在早前重复范式的基础上增加了早期语义情境用以控制重复效应的前期成份N400和后期成份P600之间的相互干扰。作者回顾了这种范式在轻度认知损伤（mild cognitive impairment,MCI）的事件相关电位研究领域的应用,并分析了该范式在MCI的识别及预测其向痴呆转归方面的优越性。提示效应的组合更能标记正常认知老化向痴呆的动态过渡;能产生两个或多个效应组合的实验范式将是该领域未来研究方向之一。     

Exploring mechanisms that affect retrograde memory for public events in amnestic mild cognitive impairment: A longitudinal update

Here, we examined mechanisms that affect retrograde memory in amnestic mild cognitive impairment (a-MCI) as a function of longitudinal clinical outcome. 8 a-MCI who converted to Alzheimer's dementia (AD) during the subsequent 3-year follow-up (converter a-MCI) and 10 a-MCI who remained clinically stable during the same period (stable a-MCI) were compared at the baseline evaluation (i.e., when they were diagnosed as a-MCI) using a remote memory questionnaire for public events that allows disentangling the differential contribution of storage and retrieval mechanisms to performance accuracy. Results suggest that deficits in remote memory are primarily explained by impaired retrieval abilities in stable a-MCI and by impaired storage in converter-to-AD a-MCI. This distinction between retrograde amnesia due to defective trace utilisation in stable a-MCI and trace storage in converter a-MCI is consistent with the temporal unfolding of declining anterograde memory over the course of disease progression to AD.     

The free and cued selective reminding test for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: A prospective longitudinal study

Amnestic mild cognitive impairment (aMCI) patients carry a greater risk of conversion to Alzheimer's disease (AD). Therefore, the International Working Group (IWG) on AD aims to consider some cases of aMCI as symptomatic prodromal AD. The core diagnostic marker of AD is a significant and progressive memory deficit, and the Free and Cued Selective Reminding Test (FCSRT) was recommended by the IWG to test memory in cases of possible prodromal AD. This study aims to investigate whether the performance on the FCSRT would enhance the ability to predict conversion to AD in an aMCI group. A longitudinal study was conducted on 88 aMCI patients, and neuropsychological tests were analysed on the relative risk of conversion to AD. During follow‐up (23.82 months), 33% of the aMCI population converted to AD. An impaired FCSRT TR was significantly associated with the risk of conversion to dementia, with a mean time to conversion of 25 months. The FCSRT demonstrates utility for detecting AD at its prodromal stage, thus supporting its use as a valid clinical marker.     

Gesturing helps memory encoding in aMCI

Encoding in episodic memory is a step often impaired in patients with amnestic Mild Cognitive Impairment (aMCI). However, procedural memory processes are still relatively preserved. In line with previous research on the enactment effect, we investigated the potential benefit of encoding words combined with imitative gestures on episodic memory. Based on the Grober and Buschke’s free/cued recall procedure, we developed the Symbiosis test in which 13 patients with aMCI and 16 healthy elderly participants learned 32 words belonging to 16 different semantic categories either in a verbal encoding (A) or a bimodal (B; verbal and motor imitation) condition, using a blocked ABBA/BAAB procedure. Overall, memory retrieval was better in healthy participants than in patients with aMCI, and better for cued retrieval in the bimodal encoding (gesture cues) than the verbal encoding (category cues) condition, but there was no interaction effect between group and encoding conditions. These results show that performing concomitant gestures can enhance cued episodic memory retrieval in patients with aMCI and in healthy elderly controls. The Symbiosis test broadens the scope of the enactment effect, from action phrases to isolated words learning in patients with aMCI. Future work should investigate how bimodal encoding provides novel perspectives for memory rehabilitation in patients with aMCI.     

Interference and conflict monitoring in individuals with amnestic mild cognitive impairment: A structural study of the anterior cingulate cortex

Amnestic mild cognitive impairment (aMCI) is a clinical condition characterized by memory impairment in the absence of any other cognitive impairment and is commonly associated with high conversion to Alzheimer's disease. Recent evidence shows that executive functions and selective attention mechanisms could also be impaired in aMCI. In this study, we investigated performance differences (i.e., reaction times [RTs] and accuracy) between a group of aMCI participants and a group of age‐matched healthy individuals on the attentional network task (ANT) focusing on situations with increased interference. In particular, we assessed the relationship between interference and conflict effects and grey matter volumes (GMVs) of the anterior cingulate cortex (ACC)/pre‐supplementary motor area in the entire sample because of its crucial role in conflict monitoring. When compared with controls, aMCI participants were less accurate on the ANT, showing increased interference and conflict effects, but no differences in RTs. In addition, aMCI participants exhibited lower GMV in the ACC than controls. While better accuracy for interference and conflict effects was associated with an increase of GMV in the ACC for both groups, RTs from the interference effect were negatively correlated with GMV of the ACC only in aMCI participants. In other words, lower GMV values of the ACC were paralleled with significantly impaired performance in terms of interference resolution. In conclusion, our study suggests the presence of a selective impairment in interference and conflict monitoring in aMCI, which in turn is associated with decreased GMVs in the ACC.     

Spatial Working Memory in Aging and Mild Cognitive Impairment: Effects of Task Load and Contextual Cueing

ABSTRACT

Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically aging older adults and 15 amnestic MCI patients as to their working-memory capacities for object-location information and potential differential effects of memory load and additional context cues. An age-related deficit in visuospatial working-memory maintenance was found that became more pronounced with increasing task demands. The MCI group additionally showed reduced maintenance of bound information, i.e., object-location associations, again especially at elevated memory load. No effects of contextual cueing were found. The current findings indicate that working memory should be considered when screening patients for suspected MCI and monitoring its progression.     

Recognition memory deficits in mild cognitive impairment

ABSTRACT

There is no agreement on the pattern of recognition memory deficits characteristic of patients diagnosed with mild cognitive impairment (MCI). Whereas lower performance in recollection is the hallmark of MCI, there is a strong controversy about possible deficits in familiarity estimates when using recognition memory tasks. The aim of this research is to shed light on the pattern of responding in recollection and familiarity in MCI. Five groups of participants were tested. The main participant samples were those formed by two MCI groups differing in age and an Alzheimer's disease group (AD), which were compared with two control groups. Whereas one of the control groups served to assess the performance of the MCI and AD people, the other one, composed of young healthy participants, served the purpose of evaluating the adequacy of the experimental tasks used in the evaluation of the different components of recognition memory. We used an associative recognition task as a direct index of recollection and a choice task on a pair of stimuli, one of which was perceptually similar to those studied in the associative recognition phase, as an index of familiarity. Our results indicate that recollection decreases with age and neurological status, and familiarity remains stable in the elderly control sample but it is deficient in MCI. This research shows that a unique encoding situation generated deficits in recollective and familiarity mechanisms in mild cognitive impaired individuals, providing evidence for the existence of deficits in both retrieval processes in recognition memory in a MCI stage.     

Increased sensitivity to proactive interference in amnestic mild cognitive impairment is independent of associative and semantic impairment

Episodic memory deficit is the hallmark of amnestic mild cognitive impairment (aMCI). There is, however, an overlap in performance among patients with aMCI and elderly controls (EC). The memory deficit in aMCI therefore needs to be better characterized. Studies have shown that associative memory is selectively impaired in aMCI, and recent work suggested that aMCI may be hypersensitive to semantic proactive interference (PI). It is not known whether this increased PI is related to associative or semantic impairment. EC (n = 44) and patients with aMCI (n = 30) performed two tasks presenting a gradually increasing PI effect across four lists. One task used semantic cueing, the other phonological cueing. We controlled for associative memory by introducing it as a covariate and by matching our subjects for it. Patients with aMCI had a greater PI effect than EC matched for associative memory, regardless of the type of cueing. The increased PI effect in patients with aMCI is independent of their associative and semantic impairment.     

Association Between Gait and Dual Task With Cognitive Domains in Older People With Cognitive Impairment

The authors investigated whether impaired gait and dual-task performances are associated with specific cognitive domains among older people with preserved cognition (PC), mild cognitive impairment (MCI), and mild Alzheimer's disease (AD). The sample comprised 40 older adults with PC, 40 with MCI, and 38 with mild AD. The assessment consisted of gait (measured by 10-m walk test and Timed Up and Go Test [TUGT]), dual task (measured by TUGT associated with a cognitive-motor task of calling a phone number), and cognition (domains of the Addenbrooke Cognitive Examination–Revised and Frontal Assessment Battery [FAB]). For data analysis, the Pearson product-moment correlation and the backward stepwise linear regression were conducted. Language, fluency, and visuospatial domains predicted the 10-m walk test measure specifically in PC, MCI, and AD groups. Only the visuospatial domain was independently associated with the TUGT measure in the MCI and AD groups. FAB score, language domain, and FAB score and fluency domain were the strongest predictors for the isolated cognitive-motor task measure in the PC, MCI, and AD groups, respectively. The visuospatial domain was independently associated with the dual-task test measure in all 3 groups. The study findings demonstrate the influence of specific cognitive domains in daily mobility tasks in people with different cognitive profiles.     

Visual associations cued recall A Paradigm for Measuring Episodic Memory Decline in Alzheimer’s Disease

Repeated measurements of episodic memory are needed for monitoring amnestic mild cognitive impairment (aMCI) and mild Alzheimer’s disease (AD). Most episodic memory tests may pose a challenge to patients, even when they are in the milder stages of the disease. This cross-sectional study compared floor effects of the Visual Association Test (VAT) and the Rey Auditory Verbal Learning Test (RAVLT) in healthy elderly controls and in patients with aMCI or AD (N = 125). A hierarchical multiple regression analysis was used to examine whether linear or quadratic trends best fitted the data of cognitive test performance across global cognitive impairment. Results showed that VAT total scores decreased linearly across the range of global cognitive impairment, whereas RAVLT total scores showed a quadratic trend, with total scores levelling off for 90% of aMCI patients and 94% of AD patients. We conclude that the VAT shows few if any floor effects in patients with aMCI and mild AD and is therefore a potentially promising cognitive test for monitoring episodic memory impairment.