Le Test des cinq mots dans les formes légères de maladie d’Alzheimer : comparaison du score total,du Score Total Pondéré, du Score d’apprentissage et du Score de mémoire dans trois classes d’âge (60 ans, 70 ans, 80 ans)

IntroductionThe five-word test (5WT) is a serial verbal memory test with semantic cuing. It is proposed to rapidly evaluate memory of aging people and has previously shown its sensitivity and its specificity in identifying patients with AD. It measures the efficacy of free and cued recalls during a procedure of immediate and delayed recalls.MethodsThe 5WT was compared in a group of 202 normal subjects and a group of 302 mild AD patients (MMS of 20 or more) aged from 60 to 92 years, in three age classes (60 years, 70 years, 80 years). Nine scores were measured (Total Score, Total Weighted Score, Free Immediate Recall, Learning Score = total of Immediate Recalls, Free Delayed Recall, Memory Score = total of Delayed Recalls, Forgetting Rate, Percentage of Immediate Cuing, Percentage of Delayed Cuing) as well as the presence of intrusions. For each age class, Receiver Operating Characteristic curves determined the most significant cut-off scores.ResultsFor each score of the 5WT, AD patients differed significantly from controls. The cut-off scores were not the same according to age. For the Total Score, the cut-off scores were 10 (60 years), 9 (70 years) and 8 (80 years), whereas the cut-off scores of the Total Weighted Score were 17 (60 years), 16 (70 years) and 14 (80 years). As suggested by Cowppli-Bony et al. (2005), the Total Weighted Score (which gives a higher coefficient to free recalls) was better than the Total Score for discriminating mild AD. The 5WT is useful to discriminate normal controls and mild AD patients. Normal aged subjects displayed good encoding, efficient stocking and consolidation (few forgetting, efficient cued recall), intrusions were rare. Mild AD patients were characterized by weak encoding of words and severe deficit for stocking and consolidation (important forgetting, impaired cued recall), they made numerous intrusions. This psychometric profile is characteristic of the amnestic hippocampal syndrome found in AD.ConclusionThe 5WT is a simple and reliable test for investigating memory in elderly people above 60 years old. According to age, different cut-offs are needed for the Total Score and the Total Weighted Score, the latter appearing more discriminating than the Total Score for the diagnosis of mild AD. It is also interesting to evaluate the presence of intrusions. Lastly, it is important to consider the forgetting rate (between Learning and Memory Scores) in order to confirm the presence of a hippocampal amnesia.     

老年轻度认知障碍记忆损害特点的研究

目的探讨老年轻度认知障碍患者的记忆损害特点,比较不同神经心理学测验对诊断和发现轻度认知障碍的敏感性,筛选临床实用的简捷敏感的神经心理学测验工具。方法轻度认知障碍患者20例,轻度阿尔茨海默病患者26例,健康老年人30名。应用词语回忆测验、图片回忆测验、数字广度测验、本顿视觉保持测验C式A法及D式D法进行测试。结果轻度认知障碍组在图片回忆分、视觉保持测验D式D法正确分及持续错误分上的成绩较正常对照组差(P<0．05);轻度认知障碍组视觉保持测验D法成绩明显差于A法(P<0．01)。结论轻度认知障碍患者对具体视觉形象的记忆能力及对无意义图形的视觉记忆能力受损,存在即刻记忆和延迟记忆障碍,且延迟回忆较即刻回忆损害明显,短时记忆更新的可塑性差;图片回忆测试、本顿视觉保持测验的延迟回忆测试或与即刻回忆联合测试有助于轻度认知障碍的早期发现。     

Delayed recognition memory in Parkinson's disease: a role for working memory?

Immediate and delayed recognition memory for words was examined in a sample of 16 non-demented patients with Parkinson's disease and 16 normal control participants of equivalent age and educational attainment. The patients, relative to control participants, had intact immediate but impaired delayed recognition memory performance. Patients were also impaired on tests of free and cued recall, working memory and a measure of psychomotor processing speed. Processing speed was a significant covariate for delayed recognition, free and cued recall and working memory performance, but not for immediate recognition performance. These results suggest that the same cognitive processes which support performance on tests of recall and working memory also support performance on tests of delayed recognition.     

Semantic organization and verbal episodic memory in patients with mild and moderate Alzheimer's disease

The objective of the present research was to investigate the relationship between semantic organization and cue utilization in mildly and moderately demented patients with Alzheimer's disease (AD). In Experiment 1, subjects were presented with two lists of words: a list with semantically unrelated words and a list with words from four semantic categories presented randomly intermixed. Free recall was assessed and following the organizable list, subjects received a cued recall test. Normal controls, as opposed to mildly and moderately demented patients, showed higher performance in the organizable list as compared to the random list. In addition, normal controls and mildly demented patients benefited from semantic cues in the organizable list and performed at a higher level in total recall as compared to free recall. In Experiment 2, subjects were presented with two lists of words: a list with words from four semantic categories presented randomly intermixed and a list with words from four semantic categories presented clustered, together with information about the organization of the list. Free recall and cued recall, with the category names serving as cues, were assessed. Free recall performance of normal controls was higher in the clustered than in the organizable list, whereas no such effect was observed for the AD patients. Normal controls and mildly demented patients performed at a higher level in total as compared to free recall in both lists, whereas this effect was present only in the clustered list for the moderately demented patients. The overall pattern of results indicates that there are conditions under which memory facilitation from semantic organization may be obtained in AD.     

The 5-word test in 37 depressed patients compared with 36 normal controls and 35 patients with mild Alzheimer's disease

Objectives

Patients with major depression (MD) express frequent memory complaints leading to consultations in memory clinics. The 5-word test (5WT) is a verbal memory test with semantic cueing, which has shown its sensitivity and its specificity in identifying patients with Alzheimer's disease (AD). Our objective was to evaluate memory performances of aged patients with MD compared with controls and AD patients.

Methods

Characteristics of the 5WT were investigated in a sample of 37 patients with MD (66.8 ± 7.5 years) compared with 36 normal controls (67.3 ± 6.8 years) and 35 mild AD patients (67.5 ± 6.1 years).

Results

Duration of depression was 15.3 ± 11.5 years. Memory complaints of MD patients were ancient (4.6 ± 5.5 years) and severe (McNair memory questionnaire = 47.6 ± 20.7). The Total score of MD patients did not differ from controls but was greater than those of AD patients. Learning and Memory scores of MD patients were significantly lower than those of controls and significantly greater than those of AD patients. Forgetting rate between Learning and Memory scores was more important in AD (72.4%) than in controls (2.8%) and MD (13.6%). No intrusions were recorded in controls, three MD patients each made one intrusion, whereas 80% of AD patients made between one to six intrusions (mainly during cued delayed recall). Receiver operating characteristic curves determined the most significant cut-off scores of the Total score. It appeared easy to discriminate AD patients from controls (cut-off = 9, sensitivity = 94.3%, specificity = 100%) or MD patients (cut-off = 8, sensitivity = 88.5%, specificity = 89.2%) whereas it was more difficult to discriminate MD patients from controls (cut-off = 10, specificity = 88.9%, sensitivity = 37.8%).

Discussion

MD patients had significant difficulties with the 5WT as compared to controls, without being of the magnitude of those observed in AD patients.

Conclusion

The 5WT allows a reliable evaluation of memory in MD patients. The presence of true memory deficits with the 5WT could not be ascribed to depression but to other pathological conditions. Consequently, further memory testing should be conducted.     

Patterns of confidence loss in the cued recall of normal people with attenuated recognition memory: their relevance to a similar amnesic phenomenon

Amnesics show relatively good cued recall (but very poor recognition memory) yet display little confidence in the accuracy of their cued recall responses. In the two studies reported here a similar pattern of results was found in normal subjects who were either tested after a long retention interval or after being given inadequate time to learn target words, i.e. cued recall was relatively unaffected whereas both yes/no recognition of words and confidence in cued recall were much impaired. The finding of equivalent impairment in recognition and confidence in cued recall suggests that these forms of memory are mediated by common memory mechanisms. These mechanisms must be impaired in amnesics and, in normal subjects, are very sensitive to delay and learning exposure manipulations. In contrast, cued recall depends largely on a different form of memory spared in amnesics, and which in normal subjects is less susceptible than recognition memory to delay and brief exposure manipulations.     

Assessment of free and cued recall in Alzheimer’s disease and vascular and frontotemporal dementia with 24-item Grober and Buschke test

Alzheimer’s disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) are the most common forms of dementia. It is well known that memory deficits in AD are different from those in VaD and FTD, especially with respect to cued recall. The aim of this clinical study was to compare the memory performance in 15 AD, 10 VaD and 9 FTD patients and 20 normal controls by means of a 24-item Grober-Buschke test [8]. The patients’ groups were comparable in terms of severity of dementia. We considered free and total recall (free plus cued) both in immediate and delayed recall and computed an Index of Sensitivity to Cueing (ISC) [8] for immediate and delayed trials. We assessed whether cued recall predicted the subsequent free recall across our patients’ groups. We found that AD patients recalled fewer items from the beginning and were less sensitive to cueing supporting the hypothesis that memory disorders in AD depend on encoding and storage deficit. In immediate recall VaD and FTD showed a similar memory performance and a stronger sensitivity to cueing than AD, suggesting that memory disorders in these patients are due to a difficulty in spontaneously implementing efficient retrieval strategies. However, we found a lower ISC in the delayed recall compared to the immediate trials in VaD than FTD due to a higher forgetting in VaD.     

Verbal Learning Differences in Epileptic Patients with Left and Right Temporal Lobe Foci

A verbal learning test patterned after and using the same format as the Rey Auditory-Verbal Learning Test was administered to the following three groups: (1) patients with left temporal lobe epilepsy (L-TLE) as defined by EEG criteria (n = 11); (2) patients with right temporal lobe epilepsy (n = 10); and (3) normal controls (n = 11). Performance was highly similar for all three groups during the five immediate recall learning trials. The performance of the L-TLE group, averaged across three delayed recall trials (free recall, phonemic cued recall, semantic cued recall), was significantly poorer than that of the other two groups. The L-TLE group showed the worst performance on the phonemic cued recall trial, poor performance on the delayed free recall trial, and relatively intact performance on the semantic cued recall trial. Immediate and delayed free recall and phonemic and semantic cued recall for the distractor list did not discriminate groups. Word frequency, word presentation order, and concrete versus abstract words did not have different effects across groups.     

French adaptation of the Hopkins Verbal Learning Test

INTRODUCTION: A number of tests are currently used in clinical and research settings for the assessment of patients with memory deficits. Among them, the Hopkins Verbal Learning Test (HVLT) is particularly appropriate for the longitudinal follow-up of patients with memory disorders because it exists in six parallel forms, and therefore avoids the risk of learning effect at retest. Since a test with these characteristics is not available in French, we decided to adapt a French version of the HVLT. METHODS: 180 normal subjects participated in the study. Their mean age was 41 years (SD=11), and they had had on average 12 years of schooling (SD=3). The subjects were randomly divided into 6 groups of 30 subjects. One of the six forms of the French version of the HVLT was administered orally to each group of subjects. Each form consisted of a list of 12 words belonging to 3 different semantic categories. For the construction of the French version of the HVLT, we adopted the same procedure as used in the original version of the test taking into account the French lexical and semantic characteristics of the items. In the first part of the test, the list was administered three times to the subjects. Following each administration, subjects were asked for an immediate free recall. Twenty minutes later, used for intercurrent tasks, subjects were asked for a delayed free recall, which was immediately followed by a recognition memory task. In this task, subjects listened to a list of 24 words, 12 belonging to the studied list and 12 were distractors; the subjects were asked to recognize the 12 studied words. RESULTS: The subjects' performance was equivalent in the six forms of the test, except for the immediate recall of Form 3 (which was excluded from the test). No significant difference emerged in free recall, delayed free recall, and recognition across the five remaining forms of the test. CONCLUSION: Our study provides a useful tool for the longitudinal evaluation of patients with memory impairment and may become the test of reference in European longitudinal clinical trials. The French adaptation of the HVLT represents only a first step, because it needs to be standardized, in order to provide norms, and validated, in order to provide values of sensitivity and specificity.     

Stress-induced cortisol elevations are associated with impaired delayed, but not immediate recall

Glucocorticoids are known to modulate memory functions, with elevated cortisol levels being associated with impaired declarative memory. This specific effect has been shown in several studies using pharmacological doses of cortisol. The present study was designed to assess the effects of stress-induced cortisol elevations on (1) the type of memory processing (encoding, consolidation and retrieval), and (2) on the emotional valence of the material under study. Sixteen healthy females were presented neutral and emotional material (words and paragraphs) before and after a stress challenge. Declarative memory was tested immediately after presentation and 24 h later (delayed recall). Delayed, but not immediate recall of the information presented after the stress challenge was significantly reduced compared with delayed recall of information presented before the stress challenge. In line with this, strong negative correlations were found for delayed recall of words and spatial memory presented after the challenge with post-stress cortisol levels, whereas no significant correlations were found between cortisol levels and delayed recall at day 1. These results suggest that stress-induced cortisol specifically affects long-term consolidation of declarative memories. These findings may have implications for understanding the effects of traumatic stress on memory functioning in patients with stress-related psychiatric disorders.     

A Nine—Word dementia version of the california verbal learning test

Abstract

The validity of an experimental 9-word version of the California Verbal Learning Test (CVLT) was investigated. The construct validity of the 9-word CVLT was assessed with a principal component analysis (PCA) on a sample of nondemented subjects. A three—factor solution, related to immediate free recall, delayed recall and recognition, and intrusion errors was produced. Construct validity was also assessed by comparing subjects with probable Alzheimer's disease (AD), probable ischemic vascular dementia (IVD), and a normal control (NC) group. AD subjects evidenced little learning on immediate free recall test conditions, made no improvement on cued recall or recognition test conditions, and produced copious amounts of intrusion errors. IVD subjects performed similarly to AD subjects on immediate free recall test conditions, but improved on all cued recall and recognition test conditions, and made significantly fewer intrusion errors. The NC group was vastly superior to both groups of demented subjects on all CVLT indices. These results indicate that the 9-word CVLT has good psychometric properties, and that it may be a reasonable alternative to the standard 16-word CVLT among subjects who are obviously impaired.     

How Similar is the Effect of Cueing in Amnesics and in Normal Subjects Following Forgetting?

Verbal recognition and cued recall were compared in normal subjects after intervals of 15 minutes, one week and six weeks. When given cues subjects were encouraged to produce as many appropriate words as possible in a 30 second period and rate the words for familiarity. Guessing controls were used and subjects' skill at generating words without a memory component was also assessed. The results confirmed others in showing that cued recall declines more slowly over time than recognition. Further, although subjects cued well at six weeks they did not feel correctly cued words to be familiar. A similar effect has been noted with amnesic cueing. Also, at the six week interval, correct words tended to be generated later than after the shorter intervals, and there was a correlation between cued recall and cueing skill in general. These findings suggest that normal subjects who have largely forgotten and, probably, also amnesics use cues differently from normal subjects who are tested immediately after learning.     

Rey verbal learning test is a useful tool for differential diagnosis in the preclinical phase of Alzheimer's disease: comparison with mild cognitive impairment and normal aging

OBJECTIVE: To confirm that performance in verbal learning and memory test (Rey's Auditory Verbal Learning Test-RAVLT) is a helpful early neuropsychological marker of dementia of Alzheimer's type (DAT). METHODS: RAVLT was administered as part of a more extensive neuropsychological battery at baseline evaluation in 116 unselected patients referred by subjective memory complaints (SMC). Patients were followed longitudinally for 2 years (average interval of 27.7+/-4 months). Seventy patients were included in the study: 27 developed probable DAT; 17 were diagnosed as cognitively normal persons and 26 were diagnosed with Mild Cognitive Impairment (MCI). Remaining patients abandoned or they did not meet the criteria for DAT, MCI or control. Performance on RAVLT at the baseline evaluation was compared between groups. RESULTS: Patients diagnosed two years later with probable DAT showed lower results, more frequently performed a score of zero at the delayed recall test (Trial 6) and had a percentage of forgetting (difference between Trials 5 and 6) higher than 75%. Score at delayed recall test and percentage of forgetting correlated with functional scales such as MMSE, Geriatric Depression Screening, Informant Questionnaire and Blessed's Dementia Rating. CONCLUSIONS: RAVLT could help to identify those patients with SMC who would progress to DAT over a few years, and also to differentiate between the preclinical phase of Alzheimer's disease, mild cognitive impairment and normal aging. A score of zero at the delayed recall test or a percentage of forgetting > or =75% in patients with SMC is suggestive of probable DAT in the future.     

A comparison of episodic memory deficits in neuropathologically-confirmed Dementia with Lewy bodies and Alzheimer's disease.

Little is known about possible differences in the memory deficits that occur in Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We compared 24 autopsy-confirmed DLB and 24 age-, education-, and MMSE-matched autopsy-confirmed AD patients on the California Verbal Learning Test (CVLT) and the Wechsler Memory Scale-Revised Logical Memory subtest. The DLB and AD groups were similarly impaired on CVLT Total Learning (Trials 15) and Long Delayed Free Recall, but the DLB group demonstrated relative improvement in Savings scores and on recognition testing compared to the AD group. Likewise, the patient groups were equally impaired on Logical Memory immediate and delayed recall, but the DLB group's Saving scores were significantly better than those of the AD patients. These results indicate that while both DLB and AD patients exhibit significant memory impairment, the ability to consolidate information may be less severely impaired in DLB patients than in AD patients.     

Intranasal insulin improves memory in humans

Previous studies have suggested an acutely improving effect of insulin on memory function. To study changes in memory associated with a prolonged increase in brain insulin activity in humans, here we used the intranasal route of insulin administration known to provide direct access of the substance to the cerebrospinal fluid compartment. Based on previous results indicating a prevalence of insulin receptors in limbic and hippocampal regions as well as improvements in memory with systemic insulin administration, we expected that intranasal administration of insulin improves primarily hippocampus dependent declaration memory function. Also, improvements in mood were expected. We investigated the effects of 8 weeks of intranasal administration of insulin (human regular insulin 4 x 40 IU/d) on declarative memory (immediate and delayed recall of word lists), attention (Stroop test), and mood in 38 healthy subjects (24 males) in a double blind, between-subject comparison. Blood glucose and plasma insulin levels did not differ between the placebo and insulin conditions. Delayed recall of words significantly improved after 8 weeks of intranasal insulin administration (words recalled, Placebo 2.92±1.00, Insulin 6.20±1.03, p<0.05). Moreover, subjects after insulin reported signs of enhanced mood, such as reduced anger (p<0.02) and enhanced self-confidence (p<0.03). Results indicate a direct action of prolonged intranasal administration of insulin on brain functions, improving memory and mood in the absence of systemic side effects. These findings could be of relevance for the treatment of patients with memory disorders like in Alzheimer’s disease.     

Free and cued selective reminding test: an Italian normative study

The presence of episodic memory impairment is required for the diagnosis of Alzheimer??s dementia by all current diagnostic criteria. The new research criteria proposed by Dubois et al. (Lancet Neurol 6:734?C746, 2007) require that the impairment should not improve significantly with cueing, recognition testing nor after the control of effective encoding. This is considered to be the core deficit of ??prodromal Alzheimer??s disease??. The Free and Cued Selective Reminding Test (FCSRT) is a memory test that allows in assessing these specific features of memory impairment. Here, we report normative data for an Italian version of the FCSRT. The test is based on the 12 pictorial stimuli, 6 belonging to the living domain, and 6 to the non-living domain. Six scores were derived from the performance of 227 healthy Italian adults, with age, sex and education homogenously distributed across subgroups: immediate free recall (IFR), immediate total recall (ITR), delayed-free recall (DFR), delayed total recall (DTR), Index of Sensitivity of Cueing (ISC), number of intrusions. In multiple regression analyses, age emerged as an influencing factor for both IFR and DFR, with older people obtaining lower scores. Education and gender appear to influence only IFR, with better performance by more educated subjects and females. Adjusted scores were used to determine inferential cutoff scores and to compute equivalent scores.     

The association between depressive and cognitive symptoms in amnestic mild cognitive impairment

BACKGROUND: Depressive symptoms are frequently observed in older adults with mild cognitive impairment (MCI). However, little is known regarding the cognitive characteristics of this important subgroup. METHODS: We examined executive functions (controlled inhibition) and verbal episodic memory in 33 healthy older adults (control group), 18 older adults with amnestic MCI plus subclinical depressive symptoms (a-MCI/D+ group), and 26 older adults with amnestic MCI but no depressive symptoms (a-MCI group). RESULTS: Compared to the a-MCI and control groups, patients with a-MCI/D+ showed poor controlled inhibition. Moreover, in verbal episodic memory these patients recalled fewer words than control participants on immediate free, delayed free, and delayed total (free plus cued) recall. Performance on immediate recall suggested a self-retrieval deficit, but delayed performance also revealed the existence of an encoding impairment. In the a-MCI group, participants exhibited normal performance on the executive task, but pervasive memory impairment; the memory deficit concerned free and total recall on both immediate and delayed tasks, suggesting the existence of encoding and self-retrieval disturbances. CONCLUSIONS: This study reveals differences between the pattern of cognitive impairment for a-MCI/D+ and a-MCI subgroups particularly at the level of executive capacities. In terms of memory functioning, the differences between the subgroups were more subtle; more studies are needed in order to better characterize the memory impairment of a-MCI/D+ and a-MCI patients.     

The Category Cued Recall test in very mild Alzheimer's disease: discriminative validity and correlation with semantic memory functions

Episodic memory tests that measure cued recall may be particularly effective in the diagnosis of early Alzheimer's disease (AD) because they examine both episodic and semantic memory functions. The Category Cued Recall (CCR) test provides superordinate semantic cues at encoding and retrieval, and high discriminative validity has been claimed for this test. The aim of this study was to investigate the discriminative validity for this test when compared with the 10-word memory list from Alzheimer's Disease Assessment Scale (ADAS-cog) that measures free recall. The clinical diagnosis of AD was taken as the standard. It was also investigated whether the two episodic memory tests correlated with measures of semantic memory. The tests were administered to 35 patients with very mild AD (Mini Mental State Examination score > 22) and 28 control subjects. Both tests had high sensitivity (>88%) with high specificity (>89%). One out of the five semantic memory tests was significantly correlated to performances on CCR, whereas delayed recall on the ADAS-cog memory test was significantly correlated to two semantic tests. In conclusion, the discriminative validity of the CCR test and the ADAS-cog memory test was equivalent in very mild AD. This may be because CCR did not tap more semantic processes, which are impaired in the earliest phases of AD, than a test of free recall.     

Cued recall and release from proactive interference in Alzheimer's disease

Two tasks were administered to 13 mildly to moderately impaired subjects who met clinical research criteria for AD, and 17 controls matched for age and education. In the first task, subjects were administered a cued recall test (Buschke, 1984). AD subjects were found to be variably impaired in their ability to perform the initial stimulus-processing procedure, which involved matching cues with referents. The subsequent cued recall test did not typically facilitate performance. In the second task, subjects were administered a release from proactive interference (PI) paradigm consisting of semantically related and unrelated word lists. AD subjects did not develop the expected proactive interference effect for the semantically related words or show a resulting "release from PI" on related word list recall compared to normal controls. Results are discussed in terms of the role of semantic processing in episodic memory tasks.     

Screening for dementia by memory testing

Enhanced cued recall provides a simple and clinically useful memory test for identifying dementia in the elderly. Because this test induces semantic processing and coordinates encoding and retrieval for maximum recall, genuine memory deficits due to impairment of specific memory processes can be distinguished from apparent memory deficits due to use of inefficient strategies or impairment of other cognitive processes. Since genuine memory deficits in the elderly are usually associated with dementia, their identification is highly predictive of clinical dementia. The present study validates the use of enhanced cued recall as a screening test for dementia in 70 aged subjects. All but one person with a pure amnesia were correctly classified. Enhanced cued recall correctly classified 97% of the 120 subjects in this and the previous study. Enhanced cued recall shows learning not revealed by free recall, providing more accurate measurement of memory, and distinguishes demented from nondemented elderly more accurately than either free recall or recognition.