Semantic interference in mild Alzheimer disease: preliminary findings.

OBJECTIVE: The authors evaluated the usefulness and psychometric properties of the Semantic Interference Test (SIT) in patients with mild Alzheimer disease (AD). METHODS: Subjects were first presented with 10 common objects to be learned over three trials. Proactive interference was assessed by having subjects recall 10 new objects that were semantically related to the previous ones. Retroactive interference was assessed by having subjects recall the original 10 objects. RESULTS: Controlling for overall memory impairment, very mildly impaired AD patients demonstrated significantly greater proactive and retroactive interference effects than the normal, community-dwelling comparison group. The proactive score alone and the combined proactive-plus-retroactive score index were more effective than traditional neuropsychological measures of delayed recall in distinguishing between the very mildly impaired AD group and the normal-comparison group. CONCLUSION: The authors discuss the potential usefulness of the SIT in identifying vulnerability to semantic interference in early AD.     

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。     

Everyday memory impairment of patients with mild cognitive impairment

We evaluated everyday memory impairment in 24 patients with mild cognitive impairment (MCI) with the Rivermead Behavioral Memory Test (RBMT) and compared the scores with those of 48 age-, sex- and education-matched normal controls (NC) and 48 age-, sex- and education-matched Alzheimer disease (AD) patients. Overall everyday memory was impaired in MCI patients but the severity was milder than that in AD patients. The MCI patients showed impairment of everyday memory tasks requiring delayed recall. But they could normally perform tasks immediately after memorizing, except for recalling and retracing a simple new route. The total Profile score correctly classified 100% of the MCI patients and 91.7% of NC, thus demonstrating the usefulness of the RBMT for diagnosing MCI patients. Prospective memory tasks were not useful for detecting the patients with MCI.     

Episodic and semantic memory in mild cognitive impairment

Little is known about episodic and semantic memory in the early predementia stage of Alzheimer's disease (AD), which is referred to as mild cognitive impairment (MCI). To explore person knowledge, item recognition and spatial associative memory, we designed the Face Place Test (FPT). A total of 75 subjects participated: 22 patients with early AD, 24 with MCI and 29 matched controls. As predicted, AD patients showed significant deficits in person naming, item recognition and recall of spatial location (placing). Surprisingly, subjects with MCI were also impaired on all components. There was no significant difference between AD and MCI except on the placing component. Analysis of the relationship between semantic (naming) and episodic (recognition and placing) components of the FPT revealed a significant association between the two episodic tasks, but not between episodic and semantic performance. Patients with MCI show deficits of episodic and semantic memory. The extent of impairment suggests dysfunction beyond the medial temporal lobe. The FPT might form the basis of a sensitive early indicator of AD.     

Using different memory cutoffs to assess mild cognitive impairment.

OBJECTIVE: Although mild cognitive impairment (MCI) is characterized by performance on memory and other measures below expected normative values, neither a scientific rationale nor a consensus exists regarding which measures have the most use or the optimal cutoffs to use to establish impairment. METHODS: Different memory measures were administered to 80 normal community-dwelling subjects divided into two age groups. This provided conormed data on eight different memory indices by which to compare 23 nondemented clinically diagnosed patients with MCI who met all other criteria for Alzheimer disease (AD). RESULTS: On immediate memory for passages, delayed visual reproduction, object memory, and a measure sensitive to semantic interference, 70%-78% of patients with MCI were identified as impaired at 1.5 standard deviations or greater below expected levels. Conditional logistical regression for age-matched samples indicated that consideration of raw scores for these neuropsychologic tests in combination did not significantly change the odds of MCI diagnosis. When impairment relative to the total normal elderly sample was calculated based on one or more impairments at a 1.5 or greater cutoff, specificity fell below acceptable levels when more than three memory measures were considered. CONCLUSION: An array of widely used neuropsychologic measures demonstrated utility in distinguishing patients with MCI-AD from cognitively normal community-dwelling elders. The appropriateness of more or less stringent cutoffs was highly influenced by the number of measures considered. These findings have important implications regarding the choice of cut points for impairment used for the diagnosis of MCI in both research and clinical settings.     

Utility of a modified Mini-Mental State Examination with extended delayed recall in screening for mild cognitive impairment and dementia among community dwelling elders

The objective of this study was to test the utility of additional delayed recall of the three recall items of the Folstein Mini Mental State Evaluation (MMSE) as a screening measure for mild cognitive impairment and dementia in the elderly. It used a cross-sectional study of subjects, who were administered a brief memory screening battery which included the MMSE and extended delayed recall of the three MMSE recall items at 5 minute intervals. The criteria for cognitive status was determined on the basis of the neurological and neuropsychological evaluation. One hundred and two elderly persons who were recruited through a memory screening program were diagnosed as cognitively normal (N=52), mild cognitively impaired (N=24), or demented (N=26). The observed sensitivity of 83.3% and specificity of 90.4% was achieved across three delayed recall trials in differentiating cases with mild cognitive impairment (without dementia) from individuals with normal cognition and was superior to the total MMSE score alone (sensitivity/specificity: 70.8%/84.6%). Cumulative recall for the three MMSE items across only two delayed recall trials demonstrated a sensitivity of 96.2% and specificity of 90.4% in differentiating between cases of dementia versus cases diagnosed with no cognitive impairment. The three trial delayed recall score enhanced prediction of mild cognitive impairment in at-risk elderly living with the community and may have promise in the development of future screening batteries.     

Evaluation of a computerized test system to screen for mild cognitive impairment

Background: Mild cognitive impairment (MCI) refers to the clinical condition between normal aging and Alzheimer's disease (AD) and has a high probability of developing into AD. Early detection of MCI is important because early detection and appropriate follow‐up treatment can prevent the disease from progressing. Therefore, MCI is an important candidate for screening and possible intervention. Methods: We have developed a computerized screening test system to identify cognitive decline. This system consists of six tests (age and year‐of‐birth validity test, three‐word memory test, time orientation test, first modified delayed‐recall test, visual working memory test and second modified delayed‐recall test). The scores obtained from three groups (MCI patients, AD patients and healthy control subjects) were analyzed to evaluate the sensitivity and specificity required for the screening of MCI. Results: The system was well accepted by the patients. All of the test procedures were completed within 5 min. Significant group differences in all test results were found. The system has sensitivity and specificity values of 82% and 87%, respectively, when used as a screen for MCI. Conclusion: The system is useful for the screening of cognitive disorders.     

Semantic knowledge in mild cognitive impairment and mild Alzheimer's disease

The aim of this study was to investigate memory in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Ten patients with MCI, 11 with AD and a group of age and education matched healthy control participants were assessed on a comprehensive battery of semantic memory tests, including traditional semantic memory measures and a non-verbal test of knowledge of object use. The MCI group was impaired on tests of category fluency and all three conditions of an object knowledge test (matching to recipient, function and action), plus a difficult object-naming test. The mild AD group showed additional impairments on traditional measures of semantic memory, including naming high frequency items, comprehension and semantic association. Together these findings suggest that semantic memory impairments occur early in the course of AD, more specifically in patients with "amnesic" MCI, and provide further evidence that impaired category fluency reflects semantic breakdown.     

Comparison between the story recall test and the word-list learning test in Korean patients with mild cognitive impairment and early stage of Alzheimer's disease

Among verbal memory tests, two that are commonly used to measure the ability of verbal memory function in cognitive impairment are story recall tests and word-list learning tests. However, research is limited regarding which test might be more sensitive in discriminating between normal cognitive aging and patients with Alzheimer's disease (AD) in the Korean population. The purpose of the current study was to compare the word-list learning test (Seoul Verbal Learning Test; SVLT) and the story recall test (Korean Story Recall Test; KSRT) to determine which test is more sensitive in discriminating between individuals with normal cognitive aging and patients with mild cognitive impairment (MCI) and early stage of AD in Korea. A total of 53 healthy adults, 127 patients with MCI, and 72 patients with early stage of AD participated in this study. The receiver-operating characteristic (ROC) curve and area under the curve (AUC) were evaluated to compare these two tests. The results showed that the AUC of the SVLT was significantly larger than the AUC of the KSRT in all three groups (healthy adults vs. MCI and early stage of AD; healthy adults vs. MCI; healthy adults vs. early stage of AD). However, in comparison of patients with MCI and early stage of AD, the AUC of SVLT and the AUC of KSRT were not significant. The word-list learning test is a more useful tool for examining verbal memory function for older adults in Korea than the story recall test.     

Patterns of verbal memory performance in mild cognitive impairment, Alzheimer disease, and normal aging.

OBJECTIVE: Individuals with mild cognitive impairment (MCI) typically demonstrate memory loss that falls between normal aging (NA) and Alzheimer disease (AD), but little is known about the pattern of memory dysfunction in MCI. METHOD: To explore this issue, California Verbal Learning Test (CVLT) performance was examined across groups of MCI, AD, and NA. RESULTS: MCI subjects displayed a pattern of deficits closely resembling that of AD, characterized by reduced learning, rapid forgetting, increased recency recall, elevated intrusion errors, and poor recognition discriminability with increased false-positives. MCI performance was significantly worse than that of controls and better than that of AD patients across memory indices. Although qualitative analysis of CVLT profiles may be useful in individual cases, discriminant function analysis revealed that delayed recall and total learning were the best aspects of learning/memory on the CVLT in differentiating MCI, AD, and NA. CONCLUSIONS: These findings support the position that amnestic MCI represents an early point of decline on the continuum of AD that is different from normal aging.     

Mild cognitive impairment: deficits in cognitive domains other than memory

Patients with mild cognitive impairment (MCI) typically present with memory complaints, but may have mild deficits in other cognitive domains. We compared the neuropsychological profiles of a series of consecutive MCI patients (n = 116) with a control group of healthy elderly subjects (n = 63). The presence of a memory deficit on delayed recall was consistent in the MCI sample, as it was an inclusion criterion in the study. Impairment on immediate recall was present in 62.6% of the patients on paragraph recall of the logical memory test and in 63.1% of the patients on the word paired-associate learning test. Remarkably, patients with MCI frequently had deficits in cognitive domains beyond memory. As much as 68.7% of the patients had deficits in temporal orientation, 30.2% had deficits in semantic fluency, 33.7% in the Token test, 23.4% in calculation, and 23.9% in motor initiative. If detailed neuropsychological testing is performed, the majority of MCI patients will have deficits in cognitive domains other than memory.     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.     

蒙特利尔认知评估量表在轻度认知功能障碍筛查中的应用

目的 探讨蒙特利尔认知评估量表(MoCA)在轻度认知功能障碍(MCI)患者筛查中的应用.方法 应用简易精神状态检查量表(MMSE)、MoCA对32例MCI患者和50例健康对照者进行神经心理评估,比较二者筛查MCI的效果.结果 以26分为分界值,MoCA筛查MCI的敏感性为96.87%、特异性为76%,MMSE筛查MCI的敏感性为56.25%、特异性为96%;MoCA中除抽象思维、地点定向两项外,其余各亚项的评分在MCI组和对照组间差异均有统计学意义(P＜0.05):MMSE中仅计算与注意力、延迟回忆两项在MCI组和对照组间差异有统计学意义(P＜0.05),其余各项差异均无统计学意义(P＞0.05).结论 MoCA为高敏感性的MCI筛查工具,能全面评估MCI患者的认知功能.且可用于筛查MMSE得分正常的MCI患者.     

Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease

Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). MCI patients experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. An issue currently under investigation is whether MCI represents the preclinical stages of AD or a distinct and static cognitive aetiology. In an attempt to address this issue, the present investigations are adopting a convergent approach to the detection of preclinical AD, where multiple risk factors are considered when making a diagnosis. Currently, one of the most important tools when assessing early cognitive changes is neuropsychological evaluation. MCI subjects typically record neuropsychological performance between that of healthy older individuals and demented patients. Tests assessing new learning, delayed recall and attention/executive function seem to provide valuable information for screening and diagnosis of MCI and early AD if interpreted properly. Recommendations concerning methodological issues and the early management of neuropsychological MCI studies were made.     

FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment

The accurate prediction, at a pre-dementia stage of Alzheimer’s disease (AD), of the subsequent clinical evolution of patients would be a major breakthrough from both therapeutic and research standpoints. Amnestic mild cognitive impairment (MCI) is presently the most common reference to address the pre-dementia stage of AD. However, previous longitudinal studies on patients with MCI assessing neuropsychological and PET markers of future conversion to AD are sparse and yield discrepant findings, while a comprehensive comparison of the relative accuracy of these two categories of measure is still lacking. In the present study, we assessed the global cognitive decline as measured by the Mattis scale in 18 patients with amnestic MCI over an 18-month follow-up period, studying which subtest of this scale showed significant deterioration over time. Using baseline measurements from neuropsychological evaluation of memory and PET, we then assessed significant markers of global cognitive change, that is, percent annual change in the Mattis scale total score, and searched for the best predictor of this global cognitive decline. Altogether, our results revealed significant decline over the 18-month follow-up period in the total score and the verbal initiation and memory-recall subscores of the Mattis scale. The percent annual change in the total Mattis score significantly correlated with age and baseline performances in delayed episodic memory recall as well as semantic autobiographical and category word fluencies. Regarding functional imaging, significant correlations were also found with baseline PET values in the right temporo-parietal and medial frontal areas. Age and right temporo-parietal PET values were the most significant predictors of subsequent global cognitive decline, and the only ones to survive stepwise regression analyses. Our findings are consistent with previous works showing predominant delayed recall and semantic memory impairment at a pre-dementia stage of AD, as well as early metabolic defects in the temporo-parietal associative cortex. However, they suggest that only the latter predictor is specifically and accurately associated with subsequent cognitive decline in patients with MCI within 18 months of first assessment.     

抑郁症和早期阿尔茨海默病的记忆和执行功能

目的 研究抑郁症和早期阿尔茨海默病(AD)的神经心理学特征,试图运用神经心理学评估对两者进行鉴别。方法 对32例单相抑郁症、38例早期AD和34例对照进行WHO-UCLA词语学习、词语流畅、复杂图形和逻辑记忆的评估。结果 早期AD组神经心理学测验得分最低,抑郁症组次之,对照组最高,3组之间有显著性差异(P<0.01);抑郁症组仅表现为词语学习和逻辑记忆的自由回忆以及语义流畅的损害(P<0.05),而早期AD组表现为全面的认知功能损害(P<0.01);逐步判别分析提示,复杂图形延迟自由回忆、词语学习长时延迟自由回忆和语义流畅是区分抑郁症组和早期AD组的重要指标。结论 抑郁症和早期AD认知功能损害的特征不同,长时延迟自由回忆、再认和语义流畅能够区分早期AD和抑郁症。     

FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment

The accurate prediction, at a pre-dementia stage of Alzheimer's disease (AD), of the subsequent clinical evolution of patients would be a major breakthrough from both therapeutic and research standpoints. Amnestic mild cognitive impairment (MCI) is presently the most common reference to address the pre-dementia stage of AD. However, previous longitudinal studies on patients with MCI assessing neuropsychological and PET markers of future conversion to AD are sparse and yield discrepant findings, while a comprehensive comparison of the relative accuracy of these two categories of measure is still lacking. In the present study, we assessed the global cognitive decline as measured by the Mattis scale in 18 patients with amnestic MCI over an 18-month follow-up period, studying which subtest of this scale showed significant deterioration over time. Using baseline measurements from neuropsychological evaluation of memory and PET, we then assessed significant markers of global cognitive change, that is, percent annual change in the Mattis scale total score, and searched for the best predictor of this global cognitive decline. Altogether, our results revealed significant decline over the 18-month follow-up period in the total score and the verbal initiation and memory-recall subscores of the Mattis scale. The percent annual change in the total Mattis score significantly correlated with age and baseline performances in delayed episodic memory recall as well as semantic autobiographical and category word fluencies. Regarding functional imaging, significant correlations were also found with baseline PET values in the right temporo-parietal and medial frontal areas. Age and right temporo-parietal PET values were the most significant predictors of subsequent global cognitive decline, and the only ones to survive stepwise regression analyses. Our findings are consistent with previous works showing predominant delayed recall and semantic memory impairment at a pre-dementia stage of AD, as well as early metabolic defects in the temporo-parietal associative cortex. However, they suggest that only the latter predictor is specifically and accurately associated with subsequent cognitive decline in patients with MCI within 18 months of first assessment.     

Verbal serial list learning in mild cognitive impairment: a profile analysis of interference, forgetting, and errors

Using cluster analysis Libon et al. (2010) found three verbal serial list-learning profiles involving delay memory test performance in patients with mild cognitive impairment (MCI). Amnesic MCI (aMCI) patients presented with low scores on delay free recall and recognition tests; mixed MCI (mxMCI) patients scored higher on recognition compared to delay free recall tests; and dysexecutive MCI (dMCI) patients generated relatively intact scores on both delay test conditions. The aim of the current research was to further characterize memory impairment in MCI by examining forgetting/savings, interference from a competing word list, intrusion errors/perseverations, intrusion word frequency, and recognition foils in these three statistically determined MCI groups compared to normal control (NC) participants. The aMCI patients exhibited little savings, generated more highly prototypic intrusion errors, and displayed indiscriminate responding to delayed recognition foils. The mxMCI patients exhibited higher saving scores, fewer and less prototypic intrusion errors, and selectively endorsed recognition foils from the interference list. dMCI patients also selectively endorsed recognition foils from the interference list but performed similarly compared to NC participants. These data suggest the existence of distinct memory impairments in MCI and caution against the routine use of a single memory test score to operationally define MCI.     

Improvement of episodic memory in persons with mild cognitive impairment and healthy older adults: evidence from a cognitive intervention program

The efficacy of cognitive training was assessed in persons with mild cognitive impairment (MCI) and persons with normal cognitive aging. Forty-seven participants were included in this study: 28 with MCI and 17 controls. Twenty-one participants received intervention (20 MCI and 9 controls) and 16 participants (8 MCI and 8 controls) received no intervention (waiting-list group). The intervention focused on teaching episodic memory strategies. Three tasks of episodic memory (list recall, face-name association, text memory) were used as primary outcome measures. Results were analyzed using analyses of variance. The intervention effect (pre- and post-intervention difference) was significant on two of the primary outcome measures (delayed list recall and face-name association). A significant pre-post-effect was also found on measures of subjective memory and well-being. There was no improvement in the performance of groups of individuals with MCI and normal elderly persons who did not receive the intervention. These results suggest that persons with MCI can improve their performance on episodic memory when provided with cognitive training.