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.     

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.     

Multiple cognitive deficits in amnestic mild cognitive impairment

OBJECTIVE: To determine if more widespread cognitive deficits are present in a narrowly defined group of patients with the amnestic form of mild cognitive impairment (MCI). METHODS: From a larger sample of patients clinically diagnosed as meeting the criteria of Petersen et al. for amnestic MCI, we selected 22 subjects who had Clinical Dementia Rating scores of zero on all domains besides memory and orientation. These MCI subjects with presumably isolated memory impairments were compared to 35 age-matched normal controls and 33 very mild Alzheimer's disease (AD) patients on a battery of neuropsychological tests. RESULT: In addition to the expected deficits in episodic memory, the amnestic MCI group performed less well than the controls but better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Over half the amnestic MCI group (vs. none of the normal controls) scored at least 1 standard deviation below control means on 4 or more of the nonmemory cognitive tasks. CONCLUSIONS: Isolated memory impairment may be fairly uncommon in clinically diagnosed amnestic MCI patients, even when the criteria for amnestic MCI are fairly narrow. Additional cognitive impairments are likely to include fluency and executive functioning. These more diffuse deficits argue for comprehensive cognitive assessments, even when the patient and family are reporting only memory decline, and are consistent with the increase in attention paid to the heterogeneity of MCI.     

Naming of objects, faces and buildings in mild cognitive impairment

Accruing evidence suggests that the cognitive deficits in very early Alzheimer's Disease (AD) are not confined to episodic memory, with a number of studies documenting semantic memory deficits, especially for knowledge of people. To investigate whether this difficulty in naming famous people extends to other proper names based information, three naming tasks – the Graded Naming Test (GNT), which uses objects and animals, the Graded Faces Test (GFT) and the newly designed Graded Buildings Test (GBT) – were administered to 69 participants (32 patients in the early prodromal stage of AD, so-called Mild Cognitive Impairment (MCI), and 37 normal control participants). Patients were found to be impaired on all three tests compared to controls, although naming of objects was significantly better than naming of faces and buildings. Discriminant analysis successfully predicted group membership for 100% controls and 78.1% of patients. The results suggest that even in cases that do not yet fulfil criteria for AD naming of famous people and buildings is impaired, and that both these semantic domains show greater vulnerability than general semantic knowledge. A semantic deficit together with the hallmark episodic deficit may be common in MCI, and that the use of graded tasks tapping semantic memory may be useful for the early identification of patients with MCI.     

Intentional and automatic measures of specific-category effect in the semantic impairment of patients with Alzheimer's disease

The breakdown of semantic knowledge relative to living and non-living categories was studied in patients with Alzheimer's disease (AD). The same living and non-living items were used in a semantic battery and in a semantic priming paradigm exploring automatic access to the semantic system. Although AD patients showed a semantic deficit on the intentional semantic battery, they demonstrated normal semantic facilitation on the priming task. In the AD group as a whole, the semantic impairment did not preferentially affect the living category either in the intentional or automatic condition. Instead, a prevalent deficit for the living category was found in three AD patients (14% of the group) on the intentional semantic tasks, but not on the automatic one. These findings support the view that the category effect may not be a generalised phenomenon in AD but may be restricted to a limited number of patients. The intentional/automatic dissociation of the semantic breakdown demonstrated by AD patients is discussed in relation to different theories regarding the organisation of semantic memory.     

Learning and forgetting new names and objects in MCI and AD

We studied how subjects with mild cognitive impairment (MCI), early Alzheimer's disease (AD) and age-matched controls learned and maintained the names of unfamiliar objects that were trained with or without semantic support (object definitions). Naming performance, phonological cueing, incidental learning of the definitions and recognition of the objects were tested during follow-up. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, suggesting that the MCI patients’ preserved semantic memory can compensate for impaired episodic memory. The MCI group performed equally well as the controls in the tasks measuring incidental learning and recognition memory, whereas the AD group showed impairment in this respect. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that word learning is compromised in both MCI and AD, whereas long-term retention of newly learned words is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI.     

Different mechanisms of episodic memory failure in mild cognitive impairment

Mild cognitive impairment (MCI), defined as episodic memory impairment beyond what is expected in normal aging, is often associated with hippocampal atrophy (HA) and may represent incipient Alzheimer's disease. However, recent studies suggest that MCI is very heterogeneous and multiple etiologies likely exist. One possibility is small vessel cerebrovascular disease (CVD). Specifically, we hypothesized that white matter hyperintensities (WMH), an MRI marker for CVD, would lead to impairments in executive control processes critical for working memory that may, in turn, result in episodic memory impairment. To test this hypothesis, we examined a group of subjects clinically diagnosed with MCI and used MRI to further subcategorize individuals as either MCI with severe white matter hyperintensities (MCI-WMH) or MCI with severe hippocampal atrophy (MCI-HA). MCI-WMH, MCI-HA, and matched control subjects each performed a battery of working memory and episodic memory tasks. Results showed that MCI-HA and MCI-WMH were equally impaired on the episodic memory task relative to controls, but MCI-WMH were additionally impaired on tests tapping verbal and spatial working memory abilities and attentional control processes. These results suggest that CVD and hippocampal dysfunction are associated with distinct neuropsychological profiles. Although both syndromes are associated with episodic memory deficits, CVD is additionally associated with working memory and executive control deficits.     

Deficient intentional access to semantic knowledge in patients with severe closed-head injury

Patients after severe closed-head injury (CHI) demonstrate reduced ability to spontaneously utilize semantic memory during word-list memory tests and when requested to answer questions regarding general knowledge. However, they show normal lexical facilitation in both automatic and intentional semantic priming paradigms. The present study was aimed at investigating two alternative hypotheses a) that the deficit in semantic processing after CHI is the result of impaired access to an otherwise normal semantic system or b) that it reflects a loss of knowledge from a deteriorated semantic store. For this purpose, the performance of 15 CHI patients on an automatic Semantic Priming paradigm and on tests of Picture Naming and Semantic Judgment were compared to those of 14 normal controls (NC). Although CHI patients' reaction times were significantly slower than those of NCs, the semantic priming effect was comparable in the two groups. Instead, CHI patients performed significantly worse than NCs in the naming and semantic judgment tasks. These results provide evidence that CHI patients access semantic memory automatically at a normal rate. However, when the task is more demanding in terms of processing requests, then CHI patients' performance becomes defective.     

The use of semantic knowledge in Alzheimer's disease: evidence for impairments of attention

The ability to access and use semantic knowledge was examined in 25 patients with Alzheimer's disease (AD) and 31 healthy controls. The AD patients exhibited intact automatic activation of semantic relationships on a semantic priming task. They also made active use of category information on a recognition memory test. However, the patients did not use semantic information to generate expectations on the semantic priming task and were inconsistent in their use of category information on the memory test. It is suggested that attentional deficits underlie the observed impairments and may in fact help explain the patterns of performance across tasks differing widely in their overt cognitive demands.     

Visual object recognition in early Alzheimer's disease: deficits in semantic processing

OBJECTIVES: The purpose of the present study was to divide visual object recognition into different stages and to reveal which of these stages are impaired in early Alzheimer's disease (AD). METHODS: Performance in object detection, familiarity detection, semantic name and word categorization, and identification with naming were studied by using two-choice reaction-time tasks. Ten patients with newly diagnosed AD and 14 healthy subjects were studied. RESULTS: Patients with early AD had impairments in several stages of the object recognition process. After controlling for the basic visuomotor slowness, they were as fast and as accurate as the controls in object detection, but had difficulties in all stages that required semantic processing. CONCLUSIONS: Semantic memory impairments contribute to the deficits in visual object recognition in early AD. Thus, the semantic memory deficit may be manifested in several ways in the difficulties that AD patients experience in everyday life.     

Multidimensional measures of person knowledge and spatial associative learning: can these be applied to the differentiation of Alzheimer's disease from frontotemporal and vascular dementia?

Patients with early stage Alzheimer's disease (AD) show deficits in person knowledge and spatial associative memory. The current investigation examined the ability of impairment in these domains to differentiate AD from other overlapping conditions. In experiment 1, 14 AD patients, 21 vascular dementia (VaD) patients, 11 frontal variant frontotemporal dementia (fvFTD) patients and 41 controls were administered a graded faces test. VaD patients demonstrated a level of impairment comparable to the AD group on both the naming and person identification elements of the task. A mild naming deficit was revealed in the fvFTD group. In experiment 2, 22 AD patients, 23 patients with mild cognitive impairment (MCI), 11 fvFTD patients, 13 semantic dementia (SD) patients, and 23 elderly controls were administered the face-place test, a newly developed task that combines naming of famous faces, item recognition and spatial location. The naming component of the face-place test clearly differentiated SD patients from all dementia groups. All patient groups, except those with fvFTD, showed substantial deficits in the item recognition and spatial components. Consistency analyses indicated a fairly robust association between the two episodic components (item recognition and placing), but not between semantic and episodic elements of the FPT. Person knowledge deficits are, therefore, not specific to AD and the employment of face stimuli may influence the performance of SD patients on tasks of episodic memory.     

Evidence for a dissociation of structural and semantic knowledge in dementia of the Alzheimer type (DAT)

Object recognition and naming deficits in dementia of the Alzheimer type (DAT) have typically been attributed to deficits in semantic processing, with only a few studies proposing loci of deficits other than semantic. One possible cause of DAT object recognition impairments could involve deficits in processing structural aspects of visually presented items. In this paper, we assess the performance of a group of mild DAT patients on two tasks of structural access, object decision, and the complete/incomplete task (based on part-whole matching task), as well as on a semantic probes task, designed to assess the patients' semantic knowledge of the same items for which structural knowledge had earlier been assessed. The DAT patients were substantially impaired in their performance on tasks of structural access. Further, no evidence for item-to-item consistency in the DAT patients' errors for the structural and semantic tasks was found, raising the possibility that structural and semantic knowledge may become differentially impaired in DAT.     

Frontal impairment in subcortical ischemic vascular dementia in comparison to Alzheimer's disease

We compared the performance of patients with Alzheimer's disease to that of patients with subcortical vascular dementia (s-IVD) in a set of tasks assessing categorization abilities, sustained and selective attention, and set-shifting and set-maintaining skills. Only the measures of naming and categorization abilities on the Test of Classification and Recall of Pictures (TCRP) proved useful in differentiating AD from s-IVD patients. s-IVD patients showed worse performance than AD on the TCRP categorization measures, while both AD and s-IVD patients were equally impaired in other tasks assessing executive functions (EF). With respect to the naming task, s-IVD patients made significantly more perseverative and unrelated errors than AD patients. Moreover, in the s-IVD group, we found a strong correlation between categorization ability and an attentional test score (Attentional Matrices), while no such correlation emerged in the AD group. These results suggest a dissociated impairment of EF in the 2 dementia groups. In our view, the lack of inhibition and the inability to manipulate complex information are responsible for a greater executive dysfunction in s-IVD patients in comparison with AD patients. The capacity to build up strategies appears more preserved in AD patients, whose impaired performance in executive tasks seems to be related to an impairment of attentional shifting and working memory.     

The effect of encoding condition on free recall in Parkinson's disease: incidental and intentional memory are equally affected

Free recall memory deficits are common at early stages of Parkinson's disease (PD). As most studies have used intentional memory tasks, there is little information on how non-intentional, incidental encoding conditions affect memory performance in PD. We studied possible differences between PD patients and controls on free recall using incidental and intentional visual memory tasks. Free recall was examined in relation to attentive/executive functioning and subjective memory complaints. A total of 29 non-demented, medicated PD patients (age 60, disease duration 19 months) and 29 healthy controls (age 61) participated in the study. Incidental free recall was studied using a memory-modification of the Boston naming test (Memo-BNT) and intentional free recall with the 20 Objects test. There was a significant main effect for group due to worse free recall performances in the PD group. No statistically significant interaction between group and encoding condition was observed. The free recall deficit in the PD group was related to cognitive/psychomotor slowing, but not to attentive/executive task demands, or to subjective memory complaints. The results indicate that PD patients are impaired on free recall irrespective of encoding condition.     

Word-stem completion task to investigate semantic network in patients with Alzheimer''s disease

Semantic impairment in patients with Alzheimer's disease (AD) is revealed by tasks of verbal naming, verbal fluency, and semantic knowledge. Causes of the deficit remain unclear in spite of many studies to investigate whether AD patients suffer from the inability to have voluntary access to an almost intact semantic store or from its break down. Word-stem completion (WSC) tasks have been utilized in healthy subjects in order to study semantic memory and network by exploiting the possibility of the involuntary access to them. Available conflicting data refer to the presence of semantic prime in AD patients. To explore the semantic network in AD, patients were requested to complete with the first word that sprang to their mind a stem submitted immediately after presentation of the word prime, as a WSC task. Stems consisted of the three beginning letters of words that were semantically related to primes. We compared data obtained with this task from patients with mild to moderate AD with those from normal controls (NC). AD patients completed less stems (P<0.001) with the expected words than NC, suggesting a break down of the semantic network rather than a deficit in the access to the semantic store.     

What do Alzheimer's disease patients know about animals? It depends on task structure and presentation format.

Deficits on tasks requiring semantic memory in Alzheimer's disease (AD) may be due to storage loss, a retrieval deficit, or both. To address this question, we administered multiple tasks involving 9 exemplars of the category "animals," presented as both words and pictures, to 12 AD patients and 12 nondemented individuals. Participants made semantic judgments by class (sorting task), similarity (triadic comparison task), and dimensional attributes (ordering task). Relative to control participants, AD patients were impaired on an unstructured sorting task, but did not differ on a constrained sorting task. On the triadic comparison task, the patients were as likely to make judgments based on size as domesticity attributes, whereas control participants made judgments based primarily on domesticity. The patients' judgments were also less consistent across tasks than those of control participants. On the ordering tasks, performance was generally comparable between groups with pictures but not words, suggesting that pictures enable AD patients to access information from semantic memory that is less accessible with lexical stimuli. These results suggest that AD patients' semantic judgments are impaired when the retrieval context is unstructured, but perform normally under supportive retrieval conditions.     

阿尔兹海默病患者语义记忆障碍特征性研究

目的 探讨阿尔兹海默病(Alzheimer's disease, AD)患者语义记忆障碍的特点,揭示语义知识在大脑中组织的性质。方法 对43例AD患者及28例正常对照者进行一般认知功能测评和语义记忆评估。语义记忆评估选用常见的有生命类及无生命类物体,进行口头图片命名、口头声音命名、图片关联匹配、词语关联匹配测试。统计每一例被试对物体名称和物体语义关联匹配的正确比例,对数据进行群组分析和个体分析。结果 与正常对照组相比,AD组对有生命物体和无生命物体的名称及语义关联匹配均有损伤。10例患者在有生命物体的语义任务上的成绩显著差于在无生命物体的语义任务上的成绩,而另外6例患者在无生命物体的语义任务上的成绩显著差于在有生命物体的语义任务上的成绩。结论 AD患者存在语义记忆障碍,部分AD患者可出现语义范畴特异性损伤,且可出现语义障碍的范畴双分离现象。这表明有生命物体和无生命物体范畴在大脑内相对独立表征,与大脑中语义知识的分布式表征理论一致。     

Heterogeneity in executive impairment in patients with very mild Alzheimer's disease

BACKGROUND/AIMS: The presence of executive impairment in mild Alzheimer's disease (AD) has primarily been demonstrated by means of group comparison. Whether executive dysfunction is a common feature of mild AD or only present in a subgroup of patients remains unclear. The aim of this study was to describe the frequency of impairment on a set of internationally well-known executive tests in patients with very mild AD. METHODS: Thirty-six patients with very mild AD (MMSE scores above 23) and 32 healthy control subjects were administered a battery of 7 executive tests: Trail Making part B, Stroop Interference Test, modified Wisconsin Card Sorting Test (WCST), category- and letter-based verbal fluency, a design fluency task and the Similarities subtest from WAIS. Impairment was defined as a score of 2 SD or more below control means. RESULTS: Executive impairment on at least 1 measure was seen in 76% of the patients, and 50% were impaired on 2 or more tests. Trail Making B and Stroop Interference Test were impaired in more than 40%, whereas only few patients were impaired on Similarities, WCST and design fluency. A wide variation of executive test profiles was seen among the patients. CONCLUSION: Executive impairments are common in early AD and not just a feature characteristic of a subgroup of patients. Complex attentional skills are more frequently affected than other executive functions. There is, however, considerable heterogeneity among AD patients in the pattern of executive dysfunction.     

Effects of automatic/controlled access processes on semantic memory in Alzheimer's disease

This study examines the impact of automatic/controlled access processes on the semantic network in 30 patients with Alzheimer's disease (AD). The AD group was compared with a control group using a battery of neuropsychological tests, a variation of Hodges's semantic testing battery, designed to assess semantic knowledge. The AD group had markedly lower scores than the normal group on each semantic test, but with a different degree of deterioration depending on the nature of the processes (controlled/automatic) in accessing the semantic network. AD patients had poorer performances on the explicit semantic tasks mainly involving controlled-process access (e.g., the WAIS Similarities Subtest) than those involving mainly automatic-process access (e.g., the Verbal Automatism test). Analyses of confidence intervals allowed a gradient of impaired performances in increasing order to be elaborated: a) the Verbal Automatism test, b) the WAIS Vocabulary Subtest, c) the WAIS Information Subtest, d) the Letter Fluency Task, e) Naming as a Response to Definition, f) the Category Fluency Task, g) the WAIS Similarities Subtest, and h) the Oral Denomination 80 Test. The results of our study suggest that explicit semantic tasks needing passive or automatic processes to access semantic memory would be better preserved in AD.     

Verbal learning and memory deficits in Mild Cognitive Impairment

Criteria for amnestic MCI rely on the use of delayed recall tasks to establish the presence of memory impairment. This study applied the California Verbal Learning Test to detail memory performance in MCI patients (n=70), as compared to control subjects (n=92) and AD patients (n=21). Learning across the 5 trials was different among the 3 groups. Learning strategy was also different, the MCI group showing less semantic clustering than the control group. However, both MCI patients and controls could benefit from semantic cueing. This study showed that beyond consolidation deficits, MCI patients have marked difficulties in acquisition and recall strategies.