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.     

Memory profiling in mild cognitive impairment: Can we determine risk for Alzheimer's disease?

Mild cognitive impairment (MCI) is considered a transitional stage between normal ageing and Alzheimer's disease (AD), but not all MCI cases progress to AD and there has been limited focus on how to identify who will progress. Given claims for a characteristic kind of memory impairment in AD involving deficits in encoding and consolidation of information, we propose that ‘memory profiling’ of individuals with MCI may help identify which individuals will progress. We initially set out to establish whether the same characteristic memory profile was present prior to the onset of AD (preAD). Very few studies provided data that allowed us to examine this, but results tentatively supported an encoding/consolidation profile in preAD. A single study tested the clinically important contrast of preAD versus non‐preAD MCI cases and found no difference under any condition or in memory profiles, but interpretation of the findings is limited by short duration of follow‐up, ceiling effects, and task limitations in assessing more complex and qualitative aspects of memory. Although existing data lead to equivocal conclusions, we believe that memory profiling is an endeavour worth pursuing, particularly given the increasing number of people with MCI presenting for clinical assessment. We propose that tests designed specifically to measure memory processes should be sensitive to preAD and are required in prospective longitudinal designs to identify these clinically crucial MCI cases.     

Visual associations to retrieve episodic memory across healthy elderly,mild cognitive impairment,and patients with Alzheimer’s disease

Episodic memory tests need to determine the degree to which patients with moderate to severe memory deficits can still benefit from retrieval support. Especially in the case of Alzheimer’s disease (AD), this may support health care to be more closely aligned with patients’ memory capacities. We investigated whether the different measures of episodic memory of the Visual Association Test-Extended (VAT-E) can provide a more detailed and informative assessment on memory disturbances across a broad range of cognitive decline, from normal to severe impairment as seen in AD, by examining differences in floor effects. The VAT-E consists of 24 pairs of black-and-white line drawings. In a within-group design, we compared score distributions of VAT-E subtests in healthy elderly controls, mild cognitive impairment (MCI), and AD (n = 144), as well as in relation to global cognitive impairment. Paired associate recall showed a floor effect in 41% of MCI patients and 62% of AD patients. Free recall showed a floor effect in 73% of MCI patients and 84% of AD patients. Multiple-choice cued recognition did not show a floor effect in either of the patient groups. We conclude that the VAT-E covers a broad range of episodic memory decline in patients. As expected, paired associate recall was of intermediate difficulty, free recall was most difficult, and multiple-choice cued recognition was least difficult for patients. These varying levels of difficulty enable a more accurate determination of the level of retrieval support that can still benefit patients across a broad range of cognitive decline.     

The free and cued selective reminding test: Validation for mild cognitive impairment and Alzheimer's disease

The International Working Group on Alzheimer's disease (AD) suggested the free and cued selective reminding test (FCSRT) to assess memory, as it showed high sensitivity and specificity in the differentiation of AD from healthy controls and other dementias. The FCSRT involves the use of selective reminding with semantic cueing in memory assessment. This study aims to validate the FCSRT for mild cognitive impairment (MCI) and AD through the analysis of the diagnostic accuracy and the suggestion of cut‐off scores. Patients were classified into two groups according to standard criteria: MCI (n = 100) and AD (n = 70). A matched control group (n = 101) of cognitively healthy subjects was included. The reliability and the validity of the FCSRT were analysed on the immediate (IR) and delayed (DR) recalls. The Cronbach's alpha was 0.915 for the IR and 0.879 for the DR. The total recall measures revealed good areas under the curve for MCI (IR: .818; DR: .828) and excellent for AD (IR: .987; DR: .991). Furthermore, the MCI group was subdivided with respect to a non‐similar/similar AD pattern of impairment, with almost half of the subjects showing an AD‐like decline. This analysis represents a novel contribution regarding the properties of the FCSRT in illustrating the heterogeneity of MCI at baseline. The FCSRT has proved to be a very useful tool in the characterization of the memory impairment of the AD spectrum.     

Visual Imagery Processing and Knowledge of Famous Names in Alzheimer's Disease and MCI

ABSTRACT

The study of memory for famous people and visual imagery retrieval was investigated in patients in the early stages of Alzheimer's disease (AD) and in the prodromal stage of AD, so-called Mild Cognitive Impairment (MCI). Fifteen patients with AD (MMSE ≥23), 15 patients with amnestic MCI (a-MCI) and 15 normal controls (NC) performed a famous names test designed to evaluate the semantic and distinctive physical features knowledge of famous persons. Results indicated that patients with AD and a-MCI generated significantly less physical features and semantic biographical knowledge about famous persons than did normal control participants. Additionally, significant differences were observed between a-MCI and AD patients in all tasks. The present findings confirm recent studies reporting semantic memory impairment in MCI. Moreover, the current findings show that mental imagery is lowered in a-MCI and AD and is likely related to the early semantic impairment.     

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.     

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.     

Executive Functioning in Older Adults with Mild Cognitive Impairment: MCI Has Effects on Planning,But Not on Inhibition

ABSTRACT

In this study, we compared executive functioning in 32 mild cognitive impairment (MCI) individuals with that of normally aging controls. Cognitive planning tests (Trail Making, Porteus Maze Test, verbal fluency tests) show a group difference favoring the normal controls, but tests for inhibition of prepotent responses (no-go accuracy, two measures of the Stroop effect, and negative priming) failed to uncover a significant group difference. The results indicate that there is no general executive control function impairment in MCI; rather, the deficits found are compatible with the hypothesis that MCI is an accelerated form of normal aging.     

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。     

Memory factors in Rey AVLT: Implications for early staging of cognitive decline

Supraspan verbal list learning is widely used to assess dementia and related cognitive disorders where declarative memory deficits are a major clinical sign. While the overall learning rate is important for diagnosis, serial position patterns may give insight into more specific memory processes in patients with cognitive impairment. This study explored these patterns in a memory clinic clientele. One hundred eighty three participants took the Rey Auditory‐Verbal Learning Test (RAVLT). The major groups were patients with Alzheimer's disease (AD), Vascular Dementia (VD), Mild Cognitive Impairment (MCI), and Subjective Cognitive Impairment (SCI) as well as healthy controls (HC). Raw scores for the five trials and five serial partitions were factor analysed. Three memory factors were found and interpreted as Primacy, Recency, and Resistance to Interference. AD and MCI patients had impaired scores in all factors. SCI patients were significantly impaired in the Resistance to Interference factor, and in the Recency factor at the first trial. The main conclusion is that serial position data from word list testing reflect specific memory capacities which vary with levels of cognitive impairment.     

Response speed, contingent negative variation and P300 in Alzheimer’s disease and MCI

Background

Decreased speed of information processing is a hallmark of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Recent studies suggest that response speed (RS) measures are very sensitive indicators of changes in longitudinal follow-up studies. Insight into the psycho-physiological underpinnings of slowed RS can be provided by measuring the associated event-related potentials (ERP).

Aims

The current study aims to investigate the relation between RS and its psycho-physiological correlates in AD and MCI.

Methods

Fifteen psychoactive drug-naïve AD patients, 20 MCI patients and twenty age-matched, healthy control subjects participated. Response speed was measured during a simple (SRT) and choice reaction time task (CRT). An oddball and contingent negative variation (CNV) paradigm were used to elicit ERP. To evaluate test-retest reliability (TRR), subjects underwent a similar assessment one week after the first.

Results

The SRT and CRT distinguished the patient groups significantly. The P300 amplitude and latency also distinguished the groups and showed a significant correlation with response speed. The CNV amplitude did not reveal a significant difference between groups and also showed a low TRR.The TRR of the SRT, CRT and P300 amplitude and latency in general was moderate to high.The current study suggests that response speed measures on a behavioural and psycho-physiological level deserve attention as a possible marker in the diagnosis and follow-up of AD.     

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     

Correlation between functional mobility and cognitive performance in older adults with cognitive impairment

Association between cognitive impairment and gait performance occurs in mild cognitive impairment (MCI) and Alzheimer‘s disease (AD), particularly under “divided attention” conditions, leading to a greater risk of falls. We studied 36 controls, 42 MCI, and 26 mild AD patients, using the Timed Up-and-Go test (TUG) under four conditions: TUG single – TUG1; TUG cognitive – TUG2; TUG manual –TUG3; TUG cognitive and manual – TUG4. Cognition was assessed using the MMSE, SKT, Exit25, and TMT (A and B). We found significant correlations between cognitive scores and TUG2 [r values (MMSE: –0.383, TMT-A: 0.430, TMT-B: 0.386, Exit25: 0.455, SKT: 0.563)] and TUG4 [(MMSE: –0.398, TMT-A: 0.384, TMT-B: 0.352,Exit25: 0.466, SKT: 0.525)] in the AD group, and between all TUG modalities and SKT in MCI and AD. Our results revealed that functional mobility impairment in cognitive dual tasks correlated to cognitive decline in AD patients and to attention and memory impairment in MCI.     

Dissociations in Visual Attention Deficits among Persons with Mild Cognitive Impairment

ABSTRACT

Impairments in visual attention and visual information processing have been identified as part of the neuropsychological features of Alzheimer's disease (AD), even in its earliest stages. There is increasing recognition that these deficits may be selective rather than global, with some attentional subtypes being more vulnerable than others. The few studies that have investigated attentional deficits in mild cognitive impairment (MCI), a putatively prodromal phase of AD, have not satisfactorily addressed the possible selectivity in attentional deficits in MCI. This study examined potential dissociations in visual attention deficits in MCI using a measure that assesses simple, divided, and selective attention. The results indicated a hierarchy of attentional impairments, with divided attention being the most affected and simple attention the least. Among participants with MCI, 53% showed evidence of impairment in divided attention compared to 19% of controls (OR = 4.81, p < .001). Poorer visual attention was also associated with poorer overall cognitive status. The implications of these findings for early identification of MCI, prevention of functional decline in MCI, and delay/reversal of cognitive degradation in MCI are discussed.     

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.     

Executive functioning in older adults with mild cognitive impairment: MCI has effects on planning, but not on inhibition

In this study, we compared executive functioning in 32 mild cognitive impairment (MCI) individuals with that of normally aging controls. Cognitive planning tests (Trail Making, Porteus Maze Test, verbal fluency tests) show a group difference favoring the normal controls, but tests for inhibition of prepotent responses (no-go accuracy, two measures of the Stroop effect, and negative priming) failed to uncover a significant group difference. The results indicate that there is no general executive control function impairment in MCI; rather, the deficits found are compatible with the hypothesis that MCI is an accelerated form of normal aging.     

Positive and negative affect,depression, and cognitive processes in the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) Trial

ABSTRACT

Objectives: This study examined the relationship between positive and negative affect, depressive symptoms, and cognitive performance. Methods: The sample consisted of 1479 non-demented, postmenopausal women (mean age = 67 years) at increased risk of breast cancer enrolled in the National Surgical Adjuvant Breast and Bowel Project’s Study of Tamoxifen and Raloxifene. At each annual visit, women completed a standardized neuropsychological battery and self-report measures of affect and depression. Data from three visits were used in linear mixed models for repeated measures using likelihood ratio tests. Separate analyses were performed to relate positive/negative affect and depression to each cognitive measure. Results: Higher positive affect was associated with better letter fluency (p = .006) and category fluency (p < .0001). Higher negative affect was associated with worse global cognitive function (p < .0001), verbal memory (CVLT List B; p = .002), and spatial ability (p < .0001). Depressive symptoms were negatively associated with verbal knowledge (p = .004), figural memory (p < .0001), and verbal memory (p’s ≤ .0001). Discussion: Findings are consistent with some prior research demonstrating a link between positive affect and increased verbal fluency and between depressive symptoms and decreased memory. The most novel finding shows that negative affect is related to decreased global cognition and visuospatial ability. Overall, this research in a large, longitudinal sample supports the notion that positive affect is related to increases and negative affect to decreases in performance on distinct cognitive measures.     

Performance on a measure of category fluency in cognitively impaired elderly

ABSTRACT

Measures of verbal fluency are widely used in the assessment of cognitive functioning of the elderly. However, limited research has evaluated patterns (across specific timed intervals) of performance on tasks of language fluency in different forms of dementia. The current study investigated semantic fluency in 488 elderly individuals (249 with Alzheimer's dementia, 97 Vascular dementia, 97 Mild Cognitive Impairment and 45 cognitively intact) across 15-second intervals in an animal naming task using retrospective chart review. Normal controls produced significantly more exemplars and AD patients produced fewer animal names than the other groups. After the first 15- second time interval, the demented groups produced significantly fewer exemplars than the non-demented. At the end of 30 seconds it was possible to differentiate normal aging from MCI who no longer differed from the VaD group. Overall, it appears that the greatest and most clinically meaningful differences between the diagnostic groups were detected in the first three 15-second intervals. The present findings support the use of time intervals and total scores on tasks of verbal fluency in clinical settings and for research purposes.     

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。     

Diagnostic Accuracy of Memory Measures in Alzheimer’s Dementia and Mild Cognitive Impairment: a Systematic Review and Meta-Analysis

With an increasing focus on biomarkers in dementia research, illustrating the role of neuropsychological assessment in detecting mild cognitive impairment (MCI) and Alzheimer’s dementia (AD) is important. This systematic review and meta-analysis, conducted in accordance with PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) standards, summarizes the sensitivity and specificity of memory measures in individuals with MCI and AD. Both meta-analytic and qualitative examination of AD versus healthy control (HC) studies (n = 47) revealed generally high sensitivity and specificity (≥ 80% for AD comparisons) for measures of immediate (sensitivity = 87%, specificity = 88%) and delayed memory (sensitivity = 89%, specificity = 89%), especially those involving word-list recall. Examination of MCI versus HC studies (n = 38) revealed generally lower diagnostic accuracy for both immediate (sensitivity = 72%, specificity = 81%) and delayed memory (sensitivity = 75%, specificity = 81%). Measures that differentiated AD from other conditions (n = 10 studies) yielded mixed results, with generally high sensitivity in the context of low or variable specificity. Results confirm that memory measures have high diagnostic accuracy for identification of AD, are promising but require further refinement for identification of MCI, and provide support for ongoing investigation of neuropsychological assessment as a cognitive biomarker of preclinical AD. Emphasizing diagnostic test accuracy statistics over null hypothesis testing in future studies will promote the ongoing use of neuropsychological tests as Alzheimer’s disease research and clinical criteria increasingly rely upon cerebrospinal fluid (CSF) and neuroimaging biomarkers.