Deregulated semantic cognition contributes to object‐use deficits in Alzheimer's disease: A comparison with semantic aphasia and semantic dementia

Executive control is impaired from the early stages of Alzheimer's Disease (AD) and this produces deregulated semantic cognition (Corbett, Jefferies, Burns, & Lambon Ralph, 2012 ; Perry, Watson, & Hodges, 2000 ). While control deficits should affect semantic retrieval across all modalities, previous studies have typically focused on verbal semantic tasks. Even when non‐verbal semantic tasks have been used, these have typically employed simple picture‐matching tasks, which may be influenced by abnormalities in covert naming. Therefore, in the present study, we examined 10 patients with AD on a battery of object‐use tasks, in order to advance our understanding of the origins of non‐verbal semantic deficits in this population. The AD patients’ deficits were contrasted with previously published performance on the same tasks within two additional groups of patients, displaying either semantic degradation (semantic dementia) or deregulation of semantic retrieval (semantic aphasia; Corbett, Jefferies, Ehsan, & Lambon Ralph, 2009 ). While overall accuracy was comparable to the scores in both other groups, the AD patients’ object‐use impairment most closely resembled that observed in SA; they exhibited poorer performance on comprehension tasks that placed strong demands on executive control. A similar pattern was observed in the expressive domain: the AD and SA groups were relatively good at straightforward object use compared to executively demanding, mechanical puzzles. Error types also differed: while all patients omitted essential actions, the SA and AD groups’ demonstrations also featured unrelated intrusions. An association between AD patients’ object use and their scores on standard executive measures suggested that control deficits contributed to their non‐verbal semantic deficits. Moreover, in a task specifically designed to manipulate executive demand, patients with AD (and SA) exhibited difficulty in thinking flexibly about the non‐canonical uses of everyday objects, especially when distracted by semantically related objects. This study provides converging evidence for the notion that a failure of regulatory control contributes to multimodal semantic impairment in AD and uniquely demonstrates this pattern for the highly non‐verbal domain of object use.     

Lexical and semantic fluency discrepancy scores in aMCI and early Alzheimer's disease

Episodic memory is compromised in amnestic mild cognitive impairment (aMCI), but lesser deficits in other cognitive domains are also commonly observed and may be helpful in identifying this group. The relative difference in performance on lexical and semantic fluency tasks may be a sensitive and specific measure in aMCI and early Alzheimer's disease (AD). We compared four groups of participants, 35 early AD, 47 aMCI, 24 healthy controls, and 18 depressive out‐patient controls, on semantic and lexical fluency as well as other neuropsychological tests. Early AD and aMCI patients showed a distinct pattern of semantic impairment in the two fluency measures compared with the healthy and depressive controls. The findings implicate early failure of the semantic memory system in aMCI and AD and suggest that consideration of the discrepancy in performance on semantic and lexical fluency measures may help in the early identification of AD.     

Analysis of the conceptual structure of natural and artifactual categories in Alzheimer's disease patients

This work has two goals, the first one is to study in detail the conceptual structure of some natural and artifactual categories, by using multidimensional scaling (MDS). According to our theoretical approximation, conceptual structure is composed of semantic features, and these features have different entities and nature. As an index of relevance in mental representation of semantic categories, we took the frequency of production of semantic features on a free verbal production task. Our second goal was to compare the structure of conceptual representations in two populations, healthy elderly and Alzheimer's disease (AD) patients, assuming that conceptual representation is impaired in this last population. We assume that the impairment in the conceptual representations of AD patients will show, when the disease reaches a determined level, loosing specific features. This impairment will have serious consequences in the whole conceptual structure.     

The link between knowledge and remembering in Alzheimer’s disease

Current research on the influence of cognitive support (e.g., activation of task-relevant prior knowledge, item organizability, retrieval cues) on episodic remembering in normal aging and Alzheimer’s disease (AD) is reviewed. Examining the effects of cognitive support on memory may shed light on the relationship between knowledge and remembering, and also provides relevant information pertaining to the development of cognitive intervention procedures. A series of studies from our own and other laboratories reveal a number of interesting empirical regularities. First, AD results in problems in utilizing cognitive support for improving memory. Conceivably, this reduction in cognitive reserve capacity is due to both the overall severity of the episodic memory impairment in AD, as well as to dementia-related deficits in the semantic network that guides encoding and retrieval of information. Nevertheless, AD patients are able to utilize cognitive support in episodic memory tasks, although they typically need more support than their healthy aged counterparts to show memory facilitation. Specifically, it is critical to provide support at both encoding and retrieval in order to demonstrate performance gains in AD. Moreover, successful utilization of retrieval support in this disease is most likely to occur when the encoding requirements force the individual to engage in elaborative cognitive activity (e.g., generation of task-relevant knowledge, categorical organization). Finally, a reduction in cognitive reserve capacity occurs later in the pathogenesis of AD than a generalized episodic memory impairment. This observation reflects the insidious nature of AD, and suggests that the transition from normal aging to AD may be continuous rather than discrete.     

Association Between Gait and Dual Task With Cognitive Domains in Older People With Cognitive Impairment

The authors investigated whether impaired gait and dual-task performances are associated with specific cognitive domains among older people with preserved cognition (PC), mild cognitive impairment (MCI), and mild Alzheimer's disease (AD). The sample comprised 40 older adults with PC, 40 with MCI, and 38 with mild AD. The assessment consisted of gait (measured by 10-m walk test and Timed Up and Go Test [TUGT]), dual task (measured by TUGT associated with a cognitive-motor task of calling a phone number), and cognition (domains of the Addenbrooke Cognitive Examination–Revised and Frontal Assessment Battery [FAB]). For data analysis, the Pearson product-moment correlation and the backward stepwise linear regression were conducted. Language, fluency, and visuospatial domains predicted the 10-m walk test measure specifically in PC, MCI, and AD groups. Only the visuospatial domain was independently associated with the TUGT measure in the MCI and AD groups. FAB score, language domain, and FAB score and fluency domain were the strongest predictors for the isolated cognitive-motor task measure in the PC, MCI, and AD groups, respectively. The visuospatial domain was independently associated with the dual-task test measure in all 3 groups. The study findings demonstrate the influence of specific cognitive domains in daily mobility tasks in people with different cognitive profiles.     

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

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

The contribution of executive control to semantic cognition: Convergent evidence from semantic aphasia and executive dysfunction

Semantic cognition, as described by the controlled semantic cognition (CSC) framework (Rogers et al., 2015 , Neuropsychologia, 76, 220), involves two key components: activation of coherent, generalizable concepts within a heteromodal ‘hub’ in combination with modality‐specific features (spokes), and a constraining mechanism that manipulates and gates this knowledge to generate time‐ and task‐appropriate behaviour. Executive–semantic goal representations, largely supported by executive regions such as frontal and parietal cortex, are thought to allow the generation of non‐dominant aspects of knowledge when these are appropriate for the task or context. Semantic aphasia (SA) patients have executive–semantic deficits, and these are correlated with general executive impairment. If the CSC proposal is correct, patients with executive impairment should not only exhibit impaired semantic cognition, but should also show characteristics that align with those observed in SA. This possibility remains largely untested, as patients selected on the basis that they show executive impairment (i.e., with ‘dysexecutive syndrome’) have not been extensively tested on tasks tapping semantic control and have not been previously compared with SA cases. We explored conceptual processing in 12 patients showing symptoms consistent with dysexecutive syndrome (DYS) and 24 SA patients, using a range of multimodal semantic assessments which manipulated control demands. Patients with executive impairments, despite not being selected to show semantic impairments, nevertheless showed parallel patterns to SA cases. They showed strong effects of distractor strength, cues and miscues, and probe–target distance, plus minimal effects of word frequency on comprehension (unlike semantic dementia patients with degradation of conceptual knowledge). This supports a component process account of semantic cognition in which retrieval is shaped by control processes, and confirms that deficits in SA patients reflect difficulty controlling semantic retrieval.     

Mimicking aphasic semantic errors in normal speech production: evidence from a novel experimental paradigm

Semantic errors are commonly found in semantic dementia (SD) and some forms of stroke aphasia and provide insights into semantic processing and speech production. Low error rates are found in standard picture naming tasks in normal controls. In order to increase error rates and thus provide an experimental model of aphasic performance, this study utilised a novel method- tempo picture naming. Experiment 1 showed that, compared to standard deadline naming tasks, participants made more errors on the tempo picture naming tasks. Further, RTs were longer and more errors were produced to living items than non-living items a pattern seen in both semantic dementia and semantically-impaired stroke aphasic patients. Experiment 2 showed that providing the initial phoneme as a cue enhanced performance whereas providing an incorrect phonemic cue further reduced performance. These results support the contention that the tempo picture naming paradigm reduces the time allowed for controlled semantic processing causing increased error rates. This experimental procedure would, therefore, appear to mimic the performance of aphasic patients with multi-modal semantic impairment that results from poor semantic control rather than the degradation of semantic representations observed in semantic dementia [Jefferies, E. A., & Lambon Ralph, M. A. (2006). Semantic impairment in stoke aphasia vs. semantic dementia: A case-series comparison. Brain, 129, 2132-2147]. Further implications for theories of semantic cognition and models of speech processing are discussed.     

Differential memory impairment in dementia with Lewy bodies and Alzheimer's disease

This study was conducted in order to elucidate the functioning of the Central Executive System of Working Memory (WM) and to clarify the status of other cognitive functions in Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Fourteen DLB, 22 AD, and 23 control subjects were assessed with the dual task paradigm and other cognitive tests. When compared with controls, DLB subjects performed more poorly in concurrent conditions on semantic WM tasks, and AD subjects performed more poorly on the spatial WM task. The DLB subjects had an inferior verbal span and AD subjects, an inferior recall on the CVLT. These data suggest relative impairments of verbal and semantic WM in DLB and relative impairments of spatial WM and verbal episodic memory in AD.     

A novel technique for the quantitative assessment of apraxic deficits: Application to individuals with mild cognitive impairment

The purpose of this study was to apply two novel quantitative assessments of apraxia to issues surrounding the cognitive profile of individuals with mild cognitive impairment (MCI) who are at increased risk of Alzheimer's disease (AD). In particular, it was wished to determine whether such quantitative assessment techniques can detect minor degrees of impairment at a stage in the putative disease process before apraxia has become clinically obvious. A total of 23 individuals with MCI and 75 healthy controls were assessed on two 3‐item sequential movement tasks involving either meaningful or meaningless actions. A traditional rating scale assessment of gesture‐to‐command was also administered. MCI patients took significantly longer than control subjects to complete the sequential movement tasks despite unimpaired performance on the traditional gesture production tasks. Furthermore, retrospective analyses revealed that, at the group level, only MCI patients who subsequently proceeded to a clinical diagnosis of AD were significantly slower than controls at the initial assessment. These findings provide the first evidence that the neuropsychological deficits associated with MCI may extend to the domain of praxic functions. Consequently, this work contributes to the growing literature questioning the clinical usefulness of the concept of MCI and the appropriateness of current diagnostic criteria for distinguishing this condition from mild AD.     

Performance of an Adapted Version of the Timed Up-and-Go Test in People with Cognitive Impairments

In clinical practice, older people with cognitive impairment may have difficulties to understand the instructions of the Timed Up-and-Go (TUGT) test and present a bad performance. The purpose of this study was to identify differences in the TUGT performance, in an adapted version, between older adults with preserved cognition (PC), mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to identify the association between the adapted TUGT performance and cognition among groups. A cross-sectional study was conducted with 118 community-dwelling older adults divided in three groups: PC (n?=?40), MCI (n?=?40) and AD (n?=?38). The evaluation was composed by the adapted TUGT and cognitive assessment (Addenbrooke's Cognitive Examination and Frontal Assessment Battery). Only the cadence of TUGT presented significant difference between groups, specifically between AD versus MCI and PC groups. The main correlations were found between time of TUGT with fluency domain and global cognitive function, especially in the AD Group. The findings contribute to the understanding of how cognition interferes on functional mobility in older people with MCI and AD. The adapted TUGT is easy to perform in clinical practice and can be useful when assessing mobility in people with cognitive impairment.     

Cognitive and affective Theory of Mind in mild to moderate Alzheimer's disease

Theory of Mind (ToM) allows one's own and others' cognitive and emotional mental states to be inferred. Although many patients with Alzheimer's disease (AD) display impaired social functioning as their disease progresses, very few studies have investigated ToM in AD. Those that have done so suggest that patients' ToM deficits are the consequence of other cognitive impairments. The aim of this study was thus to investigate changes in both the cognitive and the affective dimensions of ToM in AD, using tasks designed to circumvent the patients' comprehension difficulties. Sixteen mild to moderate AD patients and 15 healthy controls matched on age, sex and education level underwent cognitive (preference judgment and first‐ and second‐order false belief) and affective (Reading the Mind in the Eyes) ToM assessments. Comprehension of false belief stories was verified and an additional neuropsychological examination was undergone. We observed impaired performances by AD patients on all the ToM tasks. While working memory and executive functioning impairments contributed to the deterioration in the more complex aspects of cognitive ToM abilities as highlighted by a correlation analysis, we failed to observe any comprehension difficulties in patients who performed poorly on simple cognitive ToM tasks, which suggests that AD truly affects cognitive ToM.     

A model‐based approach to limb apraxia in Alzheimer's disease

Limb apraxia is a neurological deficit characterized by an inability to pantomime and/or imitate gestures, which can result from neurodegenerative disorders such as Alzheimer's disease (AD). The major goal of the study was to describe comprehensively the apraxia deficits observed in AD patients and to relate those deficits to general cognitive status, measures of daily activity, and other neuropsychological measures. Limb apraxia was assessed on a variety of conceptual and gesture production tasks in 30 AD patients. As a group, AD patients were impaired across gesture production tasks: of note was the greater impairment in imitation, as opposed to pantomime, which was especially pronounced when patients were imitating with a delay. Imitation performance was best predicted by measures of visuospatial processing, while imitation with delay was best predicted by measures of working memory. In addition, pantomime in response to pictures of tools was less accurate than Pantomime to Verbal Command and holding the tool during performance did not decrease the participants' impairment, while introducing a verbal cue during imitation increased the severity of deficits. Furthermore, investigation into patterns of deficits clearly demonstrated that the nature of limb apraxia deficits observed in AD can be quite heterogeneous and that dissociations between the conceptual and the production system exist. Finally, we also report on significant correlations between general cognitive status and limb apraxia.     

Word recognition in Alzheimer's disease: Effects of semantic degeneration

Impairments of word recognition in Alzheimer's disease (AD) have been less widely investigated than impairments affecting word retrieval and production. In particular, we know little about what makes individual words easier or harder for patients with AD to recognize. We used a lexical selection task in which participants were shown sets of four items, each set consisting of one word and three non‐words. The task was simply to point to the word on each trial. Forty patients with mild‐to‐moderate AD were significantly impaired on this task relative to matched controls who made very few errors. The number of patients with AD able to recognize each word correctly was predicted by the frequency, age of acquisition, and imageability of the words, but not by their length or number of orthographic neighbours. Patient Mini‐Mental State Examination and phonological fluency scores also predicted the number of words recognized. We propose that progressive degradation of central semantic representations in AD differentially affects the ability to recognize low‐imageability, low‐frequency, late‐acquired words, with the same factors affecting word recognition as affecting word retrieval.     

Cognitive Effects of HIV-1 Infection

The major neurological complication of human immunodeficiency virus type 1 (HIV-1) infection is cognitive impairment, which can range in severity from a mild subclinical cognitive inefficiency to a severe dementing illness. Mild to moderate cognitive impairment is identified primarily by neuropsychological tests. The prevalence and severity of cognitive impairment associated with HIV-1 infection increases as the disease progresses. Deficits in attention, information processing speed, memory, and motor abilities can occur early in the course of HIV-1 infection, with deficits in abstraction and executive functions observed in later stages of infection. The nature of the cognitive impairment observed is thought to reflect the effects of HIV-1 infection on the integrity of subcortical or frontostriatal brain systems. Issues related to the detection of subclinical to severe cognitive impairment are discussed, along with the clinical significance of mild cognitive impairment as a significant risk factor for mortality in HIV-1 infection. The need to control for possible confounding factors that can influence test performance is also reviewed.     

Vision-fair neuropsychological assessment in normal aging, Parkinson's disease and Alzheimer's disease

We examined performance of healthy older and younger adults and individuals with Alzheimer's disease (AD) and Parkinson's disease (PD) on digit cancellation, a task putatively sensitive to cognitive impairment, but possibly affected by visual impairment, particularly in contrast sensitivity. Critical contrast thresholds were established to create custom stimulus arrays that were proximally matched across individuals. Age- and PD-related differences in search were fully accounted for by the sensory deficit. Increased contrast benefited AD patients, but could not override cognitive impairment. We conclude that visually fair neuropsychological testing can effectively compensate for normal age- and PD-related visual changes that affect cognitive performance. (PsycINFO Database Record (c) 2012 APA, all rights reserved).     

Semantic sensitivity for prose in patients with probable alzheimer's disease

This study examined the sensitivity of patients with probable Alzheimer's Disease (AD) to the inherent semantic structure of prose. Patients and normal controls listened to prose passages and recalled the stories under immediate and delayed conditions. Subjects were also tested with a recognition format. Unlike controls and patients with mild AD, patients with severe AD were unable to differentiate high importance ideas from ideas of lower importance on free recall and recognition. These results suggest relative impairment of semantic processing at the encoding and consolidation process of memory in more advanced AD.     

Influence of education on the pattern of cognitive deterioration in AD patients: the cognitive reserve hypothesis

The cognitive reserve hypothesis proposes that a high educational level could delay the clinical expression of Alzheimer's disease (AD) although neuropathologic changes develop in the brain. Therefore, some studies have reported that when the clinical signs of the disease emerge, high-educated patients may decline more rapidly than low-educated patients because the neuropathology is more advanced. However, these studies have only investigated the decline of global cognition or an isolated cognitive process. To study the differential deterioration pattern of several cognitive processes according to education, the performance of 20 AD patients with a high educational level and a low educational level were compared with the performance of 20 control subjects on a neuropsychological battery. The results showed that cognitive deterioration of AD patients is different according to education, although the global performance was similar in AD patients. The high-educated patients exhibited greater impairment of abstract thinking whereas the low-educated patients showed greater impairment of memory and attentional function. This confirms that some cognitive processes, such as abstract thinking, decline more rapidly in high-educated patients whereas others seem to evolve more slowly if compared to low-educated patients. In this latter case, high-educated patients may still benefit from cognitive reserve after the diagnosis of the dementia.     

Functional decline in the early stages of Alzheimer's disease

At present most reports of functional decline in patients with Alzheimer's Disease (AD) are anecdotal, and few studies have objectively documented the course of the disease. This is a report of a 2-year follow-up of 15 AD patients characterized by mild functional impairment, and 22 age-, sex-, and education-matched control subjects. In a previous cross-sectional study of these 37 subjects and 16 AD patients with moderate functional impairment, we found that measures of memory and attention deficits accounted for much of the impairment observed in functional competence. The current longitudinal study found that these same initial assessments could be used to predict functional decline in the 15 mildly impaired patients. These patients were observed to decline to levels similar to those of the 16 moderate patients. In contrast, the control subjects exhibited little decline during the same period. These results both affirm that it is possible to diagnose AD in its mild form and demonstrate the validity of the initial diagnosis.     

Pantomime recognition impairment in Alzheimer's disease

This study was designed to examine whether 10 AD patients with diffuse lesions and an early semantic deficit could comprehend the meaning of pantomimes and symbolic gestures. We especially wanted to determine the relationship between pantomime recognition and production. The tasks involved naming or showing an understanding (e.g., circumlocutions) of the pantomimes executed by the examiner and producing pantomimes to verbal command or to imitation. The results showed no significant relationship between pantomime comprehension and pantomime production. However, 60% of AD patients performed poorly compared to controls on the Gesture Recognition task. Gesture comprehension was highly correlated with a measure of global cognitive impairment (3MS). The data are consistent with the proposed separation of comprehension and action production systems in a cognitive model of praxis. Gesture comprehension may be diffusely distributed and thus preserved in the early stages of AD as in circumscribed lesions of the left parietal lobe.