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.     

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.     

The nature of lexico-semantic processing deficits in mild cognitive impairment

Lexico-semantic impairments in Alzheimer disease (AD) have been attributed to abnormalities in both intentional and automatic access to semantic memory. However, the order in which these impairments appear during the course of the disease is unclear. We sought to answer this question by documenting lexico-semantic impairments in 61 subjects with mild cognitive impairment (MCI), a pre-AD stage, and by comparing them to those of 39 AD and 60 normal elderly (NE) subjects. All subjects were tested with intentional access tasks (picture naming and semantic probes), automatic access tasks (lexical decision and priming), and executive function tasks (Stroop and Stroop-Picture naming). Results indicated that the MCI group was only impaired on tasks of intentional access relative to the AD group who was impaired on both types of tasks. Because most MCI subjects eventually develop AD, these results suggest that intentional access to semantic memory is impaired before automatic access. Further, impairments on the Stroop-Picture naming task but not on the Stroop task, suggest that lexico-semantic impairments in the MCI group may be related to inhibition deficits during semantic search. Findings are discussed in light of executive dysfunctions within the framework of semantic memory theories.     

The cognitive and neural expression of semantic memory impairment in mild cognitive impairment and early Alzheimer's disease

Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge.     

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.     

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.     

Hippocampal formation alterations differently contribute to autobiographic memory deficits in mild cognitive impairment and Alzheimer's disease

Autobiographical memory (AM) is part of declarative memory and includes both semantic and episodic aspects. AM deficits are among the major complaints of patients with Alzheimer's disease (AD) even in early or preclinical stages. Previous MRI studies in AD patients have showed that deficits in semantic and episodic AM are associated with hippocampal alterations. However, the question which specific hippocampal subfields and adjacent extrahippocampal structures contribute to deficits of AM in individuals with mild cognitive impairment (MCI) and AD patients has not been investigated so far. Hundred and seven participants (38 AD patients, 38 MCI individuals and 31 healthy controls [HC]) underwent MRI at 3 Tesla. AM was assessed with a semi‐structured interview (E‐AGI). FreeSurfer 5.3 was used for hippocampal parcellation. Semantic and episodic AM scores were related to the volume of 5 hippocampal subfields and cortical thickness in the parahippocampal and entorhinal cortex. Both semantic and episodic AM deficits were associated with bilateral hippocampal alterations. These associations referred mainly to CA1, CA2‐3, presubiculum, and subiculum atrophy. Episodic, but not semantic AM loss was associated with cortical thickness reduction of the bilateral parahippocampal and enthorinal cortex. In MCI individuals, episodic, but not semantic AM deficits were associated with alterations of the CA1, presubiculum and subiculum. Our findings support the crucial role of CA1, presubiculum, and subiculum in episodic memory. The present results implicate that in MCI individuals, semantic and episodic AM deficits are subserved by distinct neuronal systems.     

Extent and neural basis of semantic memory impairment in mild cognitive impairment

An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted.     

Lack of semantic priming effects in famous person recognition in Mild Cognitive Impairment

IntroductionGrowing evidence indicates that individuals with Mild Cognitive Impairment (MCI) manifest semantic deficits that are often more severe for items that are characterized by a unique semantic and lexical association, such as famous people and famous buildings, than common concepts, such as objects. However, it is still controversial whether the semantic deficits observed in MCI are determined by a degradation of semantic information or by a deficit in intentional access to semantic knowledge. Here we used a semantic priming task in order to assess the integrity of the semantic system without requiring explicit access to this system. This paradigm may provide new insights in clarifying the nature of the semantic deficits in MCI.MethodsWe assessed the semantic and repetition priming effect in 13 individuals with MCI and 13 age-matched controls who engaged in a familiarity judgment task of famous names. In the semantic priming condition, the prime was the name of a member of the same occupation category as the target (Tom Cruise–Brad Pitt), while in the repetition priming condition the prime was the same name as the target (Charlie Chaplin–Charlie Chaplin).ResultsThe results showed a defective priming effect in MCI in the semantic but not in the repetition priming condition. Specifically, when compared to controls, MCI patients did not show a facilitation effect in responding to the same occupation prime-target pairs, but they showed an equivalent facilitation effect when the target was the same name as the prime.ConclusionThe present results provide support to the hypothesis that the semantic impairments observed in MCI cannot be uniquely ascribed to a deficit in intentional access to semantic information. Instead, these findings point to the semantic nature of these deficits and, in particular, to a degraded representation of semantic information concerning famous people.     

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。     

The Semantic Object Retrieval Test (SORT) in amnestic mild cognitive impairment.

BACKGROUND: Between 10% and 15% of patients with the amnestic variety of Mild Cognitive Impairment (MCI) convert to Alzheimer disease (AD) per year. OBJECTIVE: Characterize cognitive markers that may herald conversion from MCI to AD and directly assess semantic memory in patients meeting criteria for amnestic MCI. DESIGN: Thirty-five amnestic MCI patients and 121 healthy aging controls enrolled at an Alzheimer Disease Center received a battery of standard neuropsychologic tests, and the Semantic Object Retrieval Test (SORT), a test that we have developed for the assessment of semantic memory and subsequent name production, and that has been shown to be able to differentiate between normals and patients with AD. RESULTS: On the basis of normative data from the SORT, the MCI subjects could be divided into 2 groups: 10 patients (29%) with a significant semantic impairment (SI+) and 25 without a semantic memory deficit (SI-). There was a significant correlation between all SORT variables and performance on the Boston Naming Test. In this MCI population, significantly impaired SORT performance was associated with a relative decrease in performance on tests of frontal lobe functions, although disruption of thalamic-related processes cannot be excluded as an etiology for semantic memory impairment. CONCLUSIONS: The SORT is a specific test of semantic memory, and is a sensitive measure of semantic memory deficits in patients who otherwise meet criteria for amnestic MCI. Using this specific assessment tool, a significant number of MCI patients were found to have semantic memory deficits. As these patients may be early in the course of possible progression toward dementia, the SORT or other tests of semantic memory may provide important diagnostic or prognostic information in patients with MCI.     

Verbal fluency performance in dementia of the Alzheimer's type: a meta-analysis

A meta-analysis of 153 studies with 15,990 participants was conducted to compare the magnitude of deficits upon tests of phonemic and semantic fluency for patients with dementia of the Alzheimer's type (DAT) relative to healthy controls. As has been found for patients with focal temporal cortical lesions (but not for patients with focal frontal cortical lesions), DAT patients were significantly more impaired on tests of semantic relative to phonemic fluency (r=0.73 and 0.57, respectively). Thus, since phonemic and semantic fluency are considered to impose comparable demands upon executive control processes such as effortful retrieval, but the latter is relatively more dependent upon the integrity of semantic memory, these results suggest that the semantic memory deficit in DAT reflects a degradation of the semantic store. Also supporting this conclusion, confrontation naming, a measure of semantic memory that imposes only minimal demands upon effortful retrieval, was significantly more impaired than phonemic fluency (r=0.60 versus 0.55, respectively). However, since semantic fluency was also significantly more impaired than confrontation naming (r=0.73 versus 0.61), deficits in semantic memory and effortful retrieval may be additive. Semantic, but not phonemic fluency, was significantly more impaired than measures of verbal intelligence and psychomotor speed. Thus, the semantic memory deficit in DAT qualifies as a differential deficit, but executive dysfunction as indexed by phonemic fluency does not constitute an additional isolated feature of the disorder. Dementia severity was not significantly related to the relative magnitude of deficits upon phonemic and semantic fluency.     

Gender-related cognitive deficits in Alzheimer's disease

Recent studies have identified cognitive deficits in semantic memory and verbal language abilities among women with Alzheimer's disease (AD). Few studies to date have explored gender differences in episodic memory function in AD. The present study compared the performance of men and women diagnosed with AD on a battery of neuropsychological measures. Results indicated the presence of gender-related cognitive deficits on tasks of confrontation naming, expressive word knowledge, and both episodic and semantic memory for women with AD, relative to findings in men.     

Alzheimer's disease and feeling-of-knowing in episodic memory

Episodic memory feeling-of-knowing (FOK) was examined in 16 patients with Alzheimer’s disease (AD), 16 elderly participants, and 16 younger adults. Participants were given cued recall and recognition tests of 20 critical cue-target words. Subsequently, they judged their FOK for non-recalled words in terms of how likely they thought they would be to recognize the keywords on a subsequent recognition test. The results indicated dementia-related deficits on both the recall and recognition tests. Compared to older adults, AD patients exhibited impaired FOK accuracy. This pattern of outcome indicates that early AD is associated with a deficit in episodic memory and a deficit in memory monitoring for newly learned information. Furthermore, our observation revealed that in AD, episodic memory may be a more important factor than executive function in explaining the FOK inaccuracy.     

The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer's disease: relationship to episodic and semantic memory impairment

The development of cholinergic therapies for Alzheimer's disease (AD) has highlighted the importance of understanding the role of attentional deficits and the relationship between attention and memory in the earliest stages of the disease. Variability in the tasks used to examine aspects of attention, and in the disease severity, between studies makes it difficult to determine which aspects of attention are affected earliest in AD, and how attentional impairment is related to other cognitive modules. We tested 27 patients in the early stages of the disease on the basis of the MMSE (minimal 24-30 corresponding to minimal cognitive impairment, very mild or possible AD in other classifications; and mild 18-23) on a battery of attentional tests aimed to assess sustained, divided, and selective attention, plus tests of episodic memory, semantic memory, visuoperceptual and visuospatial function, and verbal short-term memory. Although the mildly demented group were impaired on all attentional tests, the minimally impaired group showed a preserved ability to sustain attention, and to divide attention based on a dual-task paradigm. The minimally demented group had particular problems with response inhibition and speed of attentional switching. Examination of the relationship between attention and other cognitive domains showed impaired episodic memory in all patients. Deficits in attention were more prevalent than deficits in semantic memory suggesting that they occur at an earlier stage and the two were partially independent. Impairment in visuoperceptual and visuospatial functions and verbal short-term memory were the least common. Although attention is impaired early in AD, 40% of our patients showed deficits in episodic memory alone, confirming that amnesia may be the only cognitive deficit in the earliest stages of sporadic AD.     

Patterns of impairment in autobiographical memory in the degenerative dementias constrain models of memory

Detailed study of the autobiographical memory (ABM) impairments seen in different forms of degenerative dementia, in particular Alzheimer's disease (AD) and semantic dementia (SD) can inform neuropsychological models of memory. A modified ABM questionnaire which allowed more detailed analysis of episodic and semantic ABM was used to study the pattern of deficits in patients with minimal to mild Alzheimer's disease (AD) and in two patients with mild and moderate semantic dementia (SD). The questionnaire tested both cued and free recall. A group of healthy elderly was also tested. AD patients differed from controls in all measures. There was no clear temporal gradient for episodic ABM, but a modest gradient was observed for semantic ABM. The mild SD patient performed at control level for episodic ABM but showed a deficit within the range of the AD patients for semantic ABM except for the most recent life period. In contrast the moderate SD patient was impaired within the range of the AD patients for both episodic and semantic ABM. The evidence for differential impairment of episodic and semantic ABM retrieval in AD and SD is interpreted as supporting the multiple trace model of memory.     

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.     

Impaired processing of famous faces in Alzheimer's disease is related to neurofibrillary tangle densities in the prefrontal and anterior cingulate cortex

To examine the neuroanatomical correlates of impaired processing of famous faces in Alzheimer's disease (AD), we performed an anterograde clinicopathological study of 25 patients with clinically and neuropathologically confirmed AD. Famous face recognition, identification and naming was assessed using the Famous Face Test. The assessment of neurofibrillary tangle (NFT) and senile plaque (SP) densities was performed in ten cortical areas in both hemispheres, and statistical analysis was made using forward stepwise logistic regression models. A statistically significant relationship was found between NFT densities in Brodmann's areas 9 and 24 in both hemispheres and impaired famous face naming and identification. SP counts did not correlate with any of the neuropsychological parameters. These data suggest that NFT formation in prefrontal and anterior cingulate cortex, two areas involved in semantic memory processes, is a key event in famous face naming and identification deficits. In agreement with previous studies, they also indicate that SP densities are not a good pathological correlate of neuropsychological deficits in AD.     

The underlying mechanisms of semantic memory loss in Alzheimer's disease and semantic dementia

Patients with Alzheimer's disease (AD) and patients with semantic dementia (SD) both exhibit deficits on explicit tasks of semantic memory such as picture naming and category fluency. These deficits have been attributed to a degradation of the stored semantic network. An alternative explanation attributes the semantic deficit in AD to an impaired ability to consciously retrieve items from the semantic network. The present study used an implicit lexical-decision priming task to examine the integrity of the underlying semantic network in AD and SD patients matched for degree of impairment on explicit semantic memory tasks. The AD (n=11) and SD (n=11) patient groups were matched for age, education, level of dementia and impairment on four explicit semantic memory tasks. Healthy elderly participants (n=22) were matched for age and education. Semantic priming effects were evaluated for three types of semantic relationships (attributes, category coordinates, and category superordinates) and compared to lexical associative priming. Healthy controls showed significant priming across all conditions. In contrast, AD patients showed normal superordinate priming, and significant (although somewhat reduced) coordinate priming, but no attribute priming. SD patients showed no priming effect for any semantic relationship. All groups showed significant associative priming. The results indicate that SD patients do indeed have substantial degradation of semantic memory, while AD patients have a partially intact network, accounting for priming in superordinate and coordinate conditions. These findings suggest that AD patients' impairment on explicit semantic tasks is the product of deficient explicit retrieval in combination with a partially degraded semantic network.     

Semantic memory in object use

We studied five patients with semantic memory disorders, four with semantic dementia and one with herpes simplex virus encephalitis, to investigate the involvement of semantic conceptual knowledge in object use. Comparisons between patients who had semantic deficits of different severity, as well as the follow-up, showed that the ability to use objects was largely preserved when the deficit was mild but progressively decayed as the deficit became more severe. Naming was generally more impaired than object use. Production tasks (pantomime execution and actual object use) and comprehension tasks (pantomime recognition and action recognition) as well as functional knowledge about objects were impaired when the semantic deficit was severe. Semantic and unrelated errors were produced during object use, but actions were always fluent and patients performed normally on a novel tools task in which the semantic demand was minimal. Patients with severe semantic deficits scored borderline on ideational apraxia tasks. Our data indicate that functional semantic knowledge is crucial for using objects in a conventional way and suggest that non-semantic factors, mainly non-declarative components of memory, might compensate to some extent for semantic disorders and guarantee some residual ability to use very common objects independently of semantic knowledge.