Functional Mobility in a Divided Attention Task in Older Adults With Cognitive Impairment

ABSTRACT. Motor disorders may occur in mild cognitive impairment (MCI) and at early stages of Alzheimer's disease (AD), particularly under divided attention conditions. We examined functional mobility in 104 older adults (42 with MCI, 26 with mild AD, and 36 cognitively healthy) using the Timed Up and Go test (TUG) under 4 experimental conditions: TUG single task, TUG plus a cognitive task, TUG plus a manual task, and TUG plus a cognitive and a manual task. Statistically significant differences in mean time of execution were found in all four experimental conditions when comparing MCI and controls (p < .001), and when comparing MCI and AD patients (p < .05). Receiver-operating characteristic curve analyses showed that all four testing conditions could differentiate the three groups (area under the curve > .8, p < .001 for MCI vs. controls; area under the curve > .7, p < .001 for MCI vs. AD). The authors conclude that functional motor deficits occurring in MCI can be assessed by the TUG test, in single or dual task modality.     

Working Memory Demands and Semantic Sensitivity for Prose in Mild Alzheimer's Disease

The debate continues with regard to whether degradation of semantic knowledge or deficits in information processing lead to impaired memory performance in patients with Alzheimer's disease (AD). This study examined the effects of semantic content and working memory demands on the recall and recognition abilities of patients with mild AD. Nineteen patients with probable AD and 19 demographically matched normal control participants were asked to remember prose passages that varied in semantic content (high, medium, and low level of idea importance) and working memory demands (narrative and expository passages). Compared to the controls, patients with mild AD lost the ability to recall prose in a manner consistent with the semantic structure of the passages as the demands on working memory increased. Furthermore, as the demands on working memory increased, patients recognized information in a manner that suggested their initial processing was of isolated details rather than by semantic structure. This study provides support for the hypothesis that information processing deficits contribute to impaired semantic processing in patients with mild AD.     

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.     

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.     

In vivo neuroanatomy of Alzheimer's disease: evidence from structural and functional brain imaging

In vivo structural (CT, MRI) and functional (SPECT, PET) brain imaging techniques have been widely used to study the neuroanatomy and neurophysiology of Alzheimer's disease (AD) and to identify definite biological markers of the disease. We used meta-analytic methods to synthesize this literature to determine what neuroanatomical structures best differentiate patients with AD from healthy normal controls. A total of 125 studies published between 1984 and 2000 that included 3543 patients with AD and 1698 normal healthy controls met inclusion criteria. We found that measures of the temporal cortices, including the amygdala, hippocampus, and inferior temporal lobes, along with the anterior cingulate cortex, associated with the largest magnitudes of effects and, hence, could serve as the most useful structures to help clinicians differentiate AD from healthy normal aging.     

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.     

Dependence on Visual Feedback During Motor Skill Learning in Alzheimer's Disease

Three experiments examined the role of visual feedback on the performance of a fine motor task, namely the rotary pursuit, in patients with Alzheimer's disease (AD) and healthy older adults. After extensive practice tracking a fully visible target, participants in Experiments 1 and 2 were tested under restricted vision (RV) conditions. In both experiments, the two groups showed a drop in performance when vision was restricted, with AD patients showing a significantly larger decline. Tracking improved significantly in normal controls, but not AD patients across the RV trials after the initial drop. When difficulty of the rotary pursuit task was manipulated in Experiment 3 without restricting vision, AD patients and normal controls showed identical patterns of performance. Consequently, it could be concluded that AD patients in the first two experiments were relying more heavily on visual information for accurate performance of the tracking task than their healthy peers.     

Differential impacts of age of acquisition on letter and semantic fluency in Alzheimer's disease patients and healthy older adults

The degree to which the typical age of acquisition (AoA) of words and word frequency have separable influences on verbal production tasks has been strongly debated. To examine the overlap between these factors in verbal fluency tasks, the performance of Alzheimer's disease (AD) patients (N?=?34) and normal elderly controls (N?=?36) was compared on semantic (e.g., vegetables) and letter (e.g., words that begin with F) fluency tasks. These comparisons revealed that words generated for the semantic fluency task had an earlier AoA while words generated for the letter fluency task had a higher word frequency. Differences in AoA between AD patients and controls were larger for semantic than letter fluency. These results suggest that AoA has an effect on verbal production that is independent of word frequency and that AoA has a semantic locus.     

Differential impacts of age of acquisition on letter and semantic fluency in Alzheimer's disease patients and healthy older adults

The degree to which the typical age of acquisition (AoA) of words and word frequency have separable influences on verbal production tasks has been strongly debated. To examine the overlap between these factors in verbal fluency tasks, the performance of Alzheimer's disease (AD) patients (N = 34) and normal elderly controls (N = 36) was compared on semantic (e.g., vegetables) and letter (e.g., words that begin with F) fluency tasks. These comparisons revealed that words generated for the semantic fluency task had an earlier AoA while words generated for the letter fluency task had a higher word frequency. Differences in AoA between AD patients and controls were larger for semantic than letter fluency. These results suggest that AoA has an effect on verbal production that is independent of word frequency and that AoA has a semantic locus.     

Increased regional cerebral glucose metabolism and semantic memory performance in Alzheimer's disease: A pilot double blind transdermal nicotine positron emission tomography study

Nicotinic receptor dysfunction and impaired semantic memory occur early in Alzheimer's disease patients (AD). Previous research implied that nicotine's ability to enhance alertness, arousal, and cognition in a number of nonclinical populations was a function of its ability to stimulate CNS nicotinic cholinergic receptors. In this study it was hypothesized that transdermal administration of nicotine would increase both regional cerebral glucose metabolism (rCMRglc) and semantic memory (as assessed by verbal fluency). Two mild AD and two elderly controls underwent positron emission tomography scanning during a double blind nicotinic agonist verbal fluency challenge procedure. rCMRglc increases occurred in both AD patients, but not controls. In the two AD patients, verbal fluency scores increased by an average of 17%. One elderly control's verbal fluency increased, and the other decreased. These findings suggest that nicotine's effect on metabolism and verbal fluency is due to its ability to stimulate the cholinergic system.     

The update of semantic memories in amnestic mild cognitive impairment

It is still controversial to what extent neocortical consolidated memories are susceptible of change by processes of reconsolidation and transformation throughout experience, and whether the medial temporal lobes are necessary for this update of semantic consolidated memories, as they are for episodic remembering. We hypothesize that patients with amnestic mild cognitive impairment (aMCI) who have deficits in episodic memory may also have difficulties in updating information on added new features of objects. Sixteen participants with aMCI and 20 healthy control participants performed a semantic word-to-picture task, in which they were asked to identify as belonging to a given semantic category NEW objects, that have incorporated novel features, as well as OLD items, semantically and visually SIMILAR items and UNRELATED items. Patients with aMCI made a greater percentage of errors than healthy controls. Participants globally made greater percentages of errors in difficult types of items, namely NEW and SIMILAR, as compared to easier ones, OLD and UNRELATED. Importantly, an item by diagnostic group interaction effect was observed, and post hoc analysis showed that patients with aMCI made a higher percentage of errors than controls in NEW items only. In conclusion, patients with aMCI had a particular difficulty in identifying the NEW items of the word-to-picture task as compared to the control participants, supporting the concept of a flexible and dynamic conceptual knowledge system, involving the update of semantic memories and the integration of new attributes in a constant transformation process, which is impaired in these patients.     

Increased Proportion of Farm Animal Names Generated by Patients with Alzheimer's Disease: What Does it Mean?

Binetti et al. (1995) reported that patients with Alzheimer's disease (AD) produced fewer semantic clusters than controls on the Animals Fluency task; of the clusters produced, 80% involved farm animals for the patients with AD compared to 40% for controls. In the present study we replicated the finding of Binetti et al.; however, the differential distribution of animal names by subcategory for the patients and controls could be accounted for by differences in the overall output and by assuming that word generation was strictly determined by prototypicality of the animal names. Thus, the increased proportion of farm animal names produced by patients with AD can be accounted for simply by postulating impaired access to semantic memory rather than degraded representations, the idea favored by Binetti et al.     

Why do Alzheimer patients have difficulty with pronouns? Working memory, semantics, and reference in comprehension and production in Alzheimer's disease

Three experiments investigated the extent to which semantic and working-memory deficits contribute to Alzheimer patients' impairments in producing and comprehending referring expressions. In Experiment 1, the spontaneous speech of 11 patients with Alzheimer's disease (AD) contained a greater ratio of pronouns to full noun phrases than did the spontaneous speech produced by 9 healthy controls. Experiments 2 and 3 used a cross-modal naming methodology to compare reference comprehension in another group of 10 patients and 10 age-matched controls. In Experiment 2, patients were less sensitive than healthy controls to the grammatical information necessary for processing pronouns. In Experiment 3, patients were better able to remember referent information in short paragraphs when reference was maintained with full noun phrases rather than pronouns, but healthy controls showed the reverse pattern. Performance in all three experiments was linked to working memory performance but not to word finding difficulty. We discuss these findings in terms of a theory of reference processing, the Informational Load Hypothesis, which views referential impairments in AD as the consequence of normal discourse processing in the context of a working memory impairment.     

Insights into spared memory capacity in amnestic MCI and Alzheimer's Disease via minimal interference

Impairment on standard tests of delayed recall is often already maximal in the aMCI stage of Alzheimer's Disease. Neuropathological work shows that the neural substrates of memory function continue to deteriorate throughout the progression of the disease, hinting that further changes in memory performance could be tracked by a more sensitive test of delayed recall. Recent work shows that retention in aMCI patients can be raised well above floor when the delay period is devoid of further material - 'Minimal Interference'. This memory enhancement is thought to be the result of improved memory consolidation. Here we used the minimal interference/interference paradigm (word list retention following 10 min of quiet resting vs. picture naming) in a group of 17 AD patients, 25 aMCI patients and 25 controls. We found (1) that retention can be improved significantly by minimal interference in patients with aMCI and patients with mild to moderate AD; (2) that the minimal interference paradigm is sensitive to decline in memory function with disease severity, even when performance on standard tests has reached floor; and (3) that this paradigm can differentiate well (80% sensitivity and 100% specificity) between aMCI patients who progress and do not progress to AD within 2 years. Our findings support the notion that the early memory dysfunction in AD is associated with an increased susceptibility to memory interference and are suggestive of a gradual decline in consolidation capacity with disease progression.     

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.     

Semantic clustering as a neuropsychological predictor for amnestic-MCI

Recent research has demonstrated that patients with Alzheimer's disease (AD) show deficits in semantic processing when compared to cognitively healthy individuals. This difference is thought to be attributed to losses in higher cortical systems that are predominantly associated with executive functioning. The first aim of the study will be to determine if differences in semantic clustering can accurately differentiate patients with amnestic mild cognitive impairment (aMCI) from cognitively normal (CN) individuals. The second aim will be to determine the extent to which semantic processing might be associated with executive functions. Data from 202 (134 CN, 68 aMCI) participants were analyzed to quantify differences in semantic clustering ratios on the HVLT-R. Study participants ages ranged from 51 to 87 with education ranging from 6 to 20 years. ANCOVA revealed statistically significant differences on semantic clustering ratios (p < .001). Moderate correlations between semantic clustering Category Fluency Test (r = .45) were also found. Statistically significant group differences were also present on Trails-B and WAIS-R Digit Symbol performance (p < .001). Overall, these data indicate that deficits in semantic clustering are present in aMCI patients.     

Lexical but not semantic priming in Alzheimer's disease.

The hypothesis that patients with Alzheimer's disease (AD) have a disturbance in semantic processing was tested using a new lexical-priming task, threshold oral reading. Healthy elderly controls showed significant effects of priming for word pairs that are associatively related (words that reliably co-occur in word association tests) and for word pairs that are semantically related (high-frequency exemplars that belong to the same superordinate category but are not high-frequency associates). AD patients showed effects of priming for associatively related words but not for word pairs that are related only by shared semantic features. These results are consistent with the hypothesis that semantic processing is impaired in AD and suggest that independent networks of relationships among words and among concepts in semantic memory may be differentially disrupted with various forms of brain damage.     

Semantic versus phonological false recognition in aging and Alzheimer's disease

Patients with Alzheimer's disease (AD) have been found to exhibit lower levels of false recognition of semantic associates compared with healthy older adults. Because these patients may show impaired performance of episodic and semantic memory tasks, this finding could be explained by deficits in episodic memory, semantic memory, or both. The authors adapted a paradigm for comparison of semantic versus phonological false recognition. They found that: (a) patients with AD exhibited lower levels of corrected false recognition of semantic, phonological, and hybrid (mixed semantic and phonological) lists than older adults, and (b) patients with AD showed very similar levels of false recognition for all list types. These results suggest that only episodic memory deficits are necessary to explain the lower level of false recognition of semantic associates observed in patients with AD when compared to older adults. Additionally, (c) older adults showed greater levels of semantic, phonological, and hybrid false recognition than younger adults, extending previous false recognition research of semantically related words and categorized colored photographs to phonologically related words.     

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.     

Category size effects in semantic and letter fluency in Alzheimer's patients

Many studies have found that patients with Alzheimer's disease (AD) perform significantly worse than normal controls on verbal fluency tasks. Moreover, some studies have found that AD patients' deficits compared to controls are more severe for semantic fluency (e.g., vegetables) than for letter fluency (e.g. words that begin with F). These studies, however, have not taken category size into account. A comparison of AD patients and age-matched controls on three semantic and three letter categories revealed that both the size and type of a category significantly predicted AD patients' deficits on verbal fluency tasks. These results suggest that the verbal fluency of AD patients will be most attenuated on large semantic categories.