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.     

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.     

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。     

Influence of memory strategies on memory test performance: A study in healthy and pathological aging

ABSTRACT

The ability to generate memory strategies is a key factor in the performance of episodic memory tasks. Whether the ability to generate memory strategies exerts an influence in the performance of memory tests in the elderly population is still a matter of debate. Here we present results from an experimental memory task (Test of Memory Strategies, TMS), comprised of five lists of words starting from an incidental learning task, and four more lists which progressively gain in their external organization of the material, reducing the necessity of mobilizing complex memory strategies. TMS has been applied to four groups of elderly patients (amnestic Mild Cognitive Impairment – aMCI, multidomain (mMCI), and Vascular Cognitive Impairment – VCI and Depression) and a healthy aging group. In conditions with low organization of the material, the mMCI and VCI groups (both showing a greater executive function impairment) have shown lower performance. However, as the material was progressively organized, they improved their performance. The aMCI group showed similar performance to the control group at the lower level of external organization but did not improve performance in conditions with a high level of external organization. The mMCI and VCI groups showed lower performance on all TMS conditions compared with controls. Discriminant analysis revealed 90% sensitivity and specificity to differentiate between groups based on TMS conditions. These results indicate how executive functions influence performance on memory tasks in elderly subjects with different neuropsychological profiles.     

血管性认知功能障碍与胰岛素抵抗关系的临床研究

探讨在血管性认知功能障碍（vascular cognitive impairment,VCI）的发病机制中胰岛素抵抗（insulin resistance,IR）的作用及二者之问的关系。比较41例VCI患者与80例健康对照组中空腹血糖（FPG）等13个因素之间是否存在差异,及VCI的发生与上述各因素之间的关系。VCI组FPG、FINS、HOMA-IR、ISI、FIB、TC、TG、LDL明显高于对照组（P〈0．01或P〈0．05）;其中FINS、HOMA-IR、LDL为VCI发生的危险因素;MMSE评分与ISI呈显著正相关（rs=0．56,P〈O．01）。VCI中存在IR,IR是VCI发生的危险因素之一,VCI的严重程度与IR呈正相关。     

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。     

活动参与在认知损害中的延缓作用

认知损害有关的病理机制、危险因素研究由来已久,但尚未找到有效治疗认知损害的途径,认知损害的保护性因素研究进而成为研究者们关注的热点。前人的研究显示活动参与对认知损害具有积极的影响,可能是认知损害的重要保护性因素,但活动参与对认知损害的影响机制以及各活动之间存在的交互作用仍不明确。未来的研究可着重探讨不同活动类型及其交互作用同认知损害的关系,并分析活动参与对认知损害起保护作用的公共因子。     

Modeling and estimating recall processing capacity: Sensitivity and diagnostic utility in application to mild cognitive impairment

We investigate the potential for using latency-based measures of retrieval processing capacity to assess changes in performance specific to individuals with mild cognitive impairment (MCI), a reliable precursor state to Alzheimer’s Disease. Use of these capacity measures is motivated in part by exploration of the effects of atrophy on a computational model of a basic hippocampal circuit. We use this model to suggest that capacity may be a more sensitive indicator of the underlying atrophy than speed of processing, and test this hypothesis by adapting a standard behavioral measure of memory (the free and cued selective reminding test, FCSRT) to allow for the collection of cued recall latencies. Participants were drawn from five groups: college-aged, middle-aged, healthy elderly, those with a diagnosis of MCI, and a sample of MCI control participants. The measure of capacity is shown to offer increased classificatory sensitivity relative to the standard behavioral measures, and is also shown to be the behavioral measure that correlated most strongly with hippocampal volume.     

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。     

Subjective cognitive complaint in healthy older adults: Identification of major domains and relation to objective performance

This study analyzed complaints across a range of memory domains in middle-aged and older adults, as well as assessed their relationship with objective cognitive performance and personal characteristics. A total of 115 community-dwelling, healthy adults between the ages of 45 and 87 completed the Self-Evaluation Questionnaire (QAM) and were tested with a comprehensive neuropsychological battery. A principal component analysis identified seven dimensions of complaint. Difficulty inhibiting internal and external sources of interference when learning or remembering something was the main area of complaint and it was correlated with word-list recall and Digit Symbol. We identified complaints related to a set of memory failures that appear to be more detrimental to autonomy and safety. These were correlated with a measure of functional autonomy and might, therefore, indicate more severe difficulties. Overall, this study provides indications regarding the main domains of memory complaints and identifies which complaints are most reflective of objective cognitive problems.     

Functional Mobility in a Divided Attention Task in Older Adults With Cognitive Impairment

ABSTRACT. Motor disorders may occur in mild cognitive impairment (MCI) and at early stages of Alzheimer's disease (AD), particularly under divided attention conditions. We examined functional mobility in 104 older adults (42 with MCI, 26 with mild AD, and 36 cognitively healthy) using the Timed Up and Go test (TUG) under 4 experimental conditions: TUG single task, TUG plus a cognitive task, TUG plus a manual task, and TUG plus a cognitive and a manual task. Statistically significant differences in mean time of execution were found in all four experimental conditions when comparing MCI and controls (p < .001), and when comparing MCI and AD patients (p < .05). Receiver-operating characteristic curve analyses showed that all four testing conditions could differentiate the three groups (area under the curve > .8, p < .001 for MCI vs. controls; area under the curve > .7, p < .001 for MCI vs. AD). The authors conclude that functional motor deficits occurring in MCI can be assessed by the TUG test, in single or dual task modality.     

Health numeracy and cognitive decline in advanced age

ABSTRACT

The study aimed at investigating health numeracy in cognitively well performing healthy participants aged from 50 to 95 years as well as in participants with cognitive impairment, but no dementia (CIND). In cognitively well performing participants (n = 401), demographic variables and cognitive abilities (executive functions, reading comprehension, mental calculation, vocabulary) were associated with health numeracy. Older age, lower education, female gender as well as lower cognitive functions predicted low health numeracy. The effect of older age was partly mediated by executive functions and calculation abilities. Participants with CIND (n = 51) performed significantly lower than healthy controls in health numeracy. The findings suggest that cognitively well performing old individuals have difficulties in understanding health-related numerical information. The risk of misunderstanding health-related numerical information is increased in persons with CIND. As these population groups are frequently involved in health care decisions, particular attention has to be paid to providing numerical information in comprehensible form.     

常态脑老化认知功能障碍及相关代谢机制研究进展

常态脑老化（NBA ）是老年期痴呆的首要危险因素,与病态性脑老化有相似的病理基础,但并不完全相同。虽然单一的“脑老化”因素并不足以成为导致老年期痴呆的独立原因,但脑老化状态确实使得大脑对外界负性刺激的敏感性增加,进而使老年人更容易发生认知障碍。阿尔茨海默病等老年痴呆症状的治疗方面尚无逆转的方法,而是重在预防。因此,我们将重点放在痴呆发生之前更早的阶段---常态脑老化阶段,就常态脑老化状态下与认知功能障碍的表现、发生机理及代谢相关机制进行综述,旨在为早期寻找措施防止老年期痴呆性认知功能下降提供理论基础。     

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     

Production of Inflected Novel Words in Older Adults With and Without Dementia

While cognitive changes in aging and neurodegenerative disease have been widely studied, language changes in these populations are less well understood. Inflecting novel words in a language with complex inflectional paradigms provides a good opportunity to observe how language processes change in normal and abnormal aging. Studies of language acquisition suggest that children inflect novel words based on their phonological similarity to real words they already know. It is unclear whether speakers continue to use the same strategy when encountering novel words throughout the lifespan or whether adult speakers apply symbolic rules. We administered a simple speech elicitation task involving Finnish-conforming pseudo-words and real Finnish words to healthy older adults, individuals with mild cognitive impairment, and individuals with Alzheimer's disease (AD) to investigate inflectional choices in these groups and how linguistic variables and disease severity predict inflection patterns. Phonological resemblance of novel words to both a regular and an irregular inflectional type, as well as bigram frequency of the novel words, significantly influenced participants' inflectional choices for novel words among the healthy elderly group and people with AD. The results support theories of inflection by phonological analogy (single-route models) and contradict theories advocating for formal symbolic rules (dual-route models).     

负启动效应的认知神经科学研究

近几年,对负启动效应的神经机制研究发现,干扰项抑制与情节提取都是引起负启动的原因,究竟哪种机制起主要作用与实验任务有很大的关系。从现有的研究结果来看,位置负启动与前额皮层有关,EPR上表现为P1和N1波幅减小或N2波幅的增大,支持抑制机制。特性负启动P3成分仍存在不一致的结果,脑区的广泛激活模式使得研究者越来越倾向采取整合的观点。     

Response to Algarabel et al., 2012 “Recognition memory deficits in mild cognitive impairment”. Reconsidering claims of familiarity disruptions in mild cognitive impairment

There is some debate over the relative impairment of recollection and familiarity in mild cognitive impairment (MCI). A recent publication by Algarabel et al. (2012, Recognition memory deficits in mild cognitive impairment, Aging, Neuropsychology, and Cognition, 19, 608–619) claims to undermine previous studies reporting preserved familiarity in patients with MCI. Here, we respond to their main criticisms, concluding that they are not sufficiently supported by the data presented. The role of recollection and familiarity in MCI remains unresolved and further work will be required to disentangle the mixed literature.     

Neuropsychological function in a group of patients 25 years after sustaining minor head injuries as children and adolescents

Previous studies suggest that neuropsychological impairment following mild to moderate pediatric head injury may become persistent and interrupt the normal course of intellectual development. In this study 45 subjects were assessed with a standardized neuropsychological test battery 25 years after sustaining mild to moderate head injury as children. Although the group scores in the normal range, significant relations between head injury severity and current neuropsychological function were found. The most important predictor of poor outcome was length of PTA at injury, EEG pathology, and loss of consciousness at injury. No significant influence of pre- and post-injury risk factors on current neuropsychological function was evident. The findings support the view that complicated mild and moderate paediatric head injury may heighten the risk of developing subtle neuropsychological problems later in life.     

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。