Focused attention deficits in patients with Alzheimer's disease and mild cognitive impairment

Reaction time (RT) tasks take various forms, and can assess psychomotor speed, (i.e., simple reaction time task), and focused attention (i.e., choice reaction time (CRT) task). If cues are provided before stimulus presentation (i.e., cued choice reaction time (CCRT) task), then a cueing effect can also be assessed. A limited number of studies have addressed the nature of focused attention impairments in Alzheimer's disease (AD). Additionally, it is unknown whether similar impairments occur in Mild Cognitive Impairment (MCI). The current study used three RT tasks to address the nature of focused attention impairments in AD and MCI subjects. The results suggest that there were significant CRT and CCRT differences in AD subjects when compared to NECs. Furthermore, slowed RTs were also present in the MCI group, which provides evidence for impaired focussed attention and the inability to benefit from a cue in both the MCI and AD groups. The implications of the impairments related to the MCI group could potentially prove useful in early diagnosis of cognitive impairments in the elderly.     

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.     

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.     

Neuropsychological Differences Between Frontotemporal Dementia and Alzheimer's Disease: A Review

This paper surveys the similarities and differences between frontotemporal dementia (FTD) and Alzheimer's disease (AD). The review covers findings primarily from neuropsychological studies on memory, language, attention/executive function, and visuospatial abilities. However, neuropsychiatric and neuroimaging data are also briefly discussed. Distinguishing features of both FTD and AD are described in order to present a comprehensive clinical picture of these dementing diseases, which is essential for the process of differential diagnosis. The cause of specific cognitive deficits is also considered. Our comprehensive review of the empirical literature reveals that AD is characterized by early memory loss and visuospatial problems, while among the main features of FTD are behavioral abnormalities and executive dysfunctions.     

Cognitive Deficits in the Early Stages of Alzheimer's Disease

ABSTRACT— Evidence from longitudinal, experimental, and neuroimaging studies converge to indicate that psychological functions other than episodic memory are affected very early in the course of Alzheimer's disease and, indeed, may predate or influence the apparent memory deficits. Changes in personality and difficulty in executive function, especially in terms of attentional and inhibitory control, are especially prominent. Deficits in other types of memory (i.e., semantic memory, conditioning) can also be detected in the early stages of the disease. It is time to update existing diagnostic criteria for this form of dementia in terms of current knowledge of multiple and interacting brain systems.     

The attribute priming effect in patients with Alzheimer's disease

Experiments with semantic priming (SP) paradigms have documented early hypopriming in patients with AD when concepts are used as primes and attribute concept features as targets, suggesting that concept attributes are vulnerable to damage very early in the disease course. The aims of this study were to confirm early priming reduction in the attribute condition in patients with AD and to determine which of several semantic indexes (such as the level of distinctiveness, correlation or feature dominance of concept features) best predicts the priming effect size in AD. We administered an SP attribute condition paradigm to 20 mildly demented patients with AD and to 10 NCs. We used concept–attribute pairs for which normative data of semantic indexes relative to both concept primes (i.e., number, type, mean level of dominance, distinctiveness and correlation of features constituting the concepts) and target features (i.e., level of feature dominance, correlation and distinctiveness) were available. Results showed that compared to NCs, the AD group obtained very reduced priming facilitation. Furthermore, the item regression analyses showed that the priming decrement in the AD group was predicted by the feature dominance of the target in the related pairs; that is, the lower the target feature dominance, the lower the priming effect elicited. These results confirmed hypopriming in the attribute condition from the very early phase of AD and support the view that attributes which are more salient for the identification of a given concept are also those most resistant to semantic memory degradation in AD pathology.     

Imaging Brain Effects of APOE4 in Cognitively Normal Individuals Across the Lifespan

The ε4 allele of the apolipoprotein E (APOE4) is associated with an increased risk of developing Alzheimer’s disease (AD). Hence, several studies have compared the brain characteristics of APOE4 carriers versus non-carriers in presymptomatic stages to determine early AD biomarkers. The present review provides an overview on APOE4-related brain changes in cognitively normal individuals, focusing on the main neuroimaging biomarkers for AD, i.e. cortical beta-amyloid (Aβ) deposition, hypometabolism and atrophy. The most consistent findings are observed with Aβ deposition as most studies report significantly higher cortical Aβ load in APOE4 carriers compared with non-carriers. Fluorodeoxyglucose-positron emission tomography studies are rare and tend to show hypometabolism in brain regions typically impaired in AD. Structural magnetic resonance imaging findings are the most numerous and also the most discrepant, showing atrophy in AD-sensitive regions in some studies but contradicting results as well. Altogether, this suggests a graded effect of APOE4, with a predominant effect on Aβ over brain structure and metabolism. Multimodal studies confirm this view and also suggest that APOE4 effects on brain structure and function are mediated by both Aβ-dependent and Aβ-independent pathological processes. Neuroimaging studies on asymptomatic APOE4 carriers offer relevant information to the understanding of early pathological mechanisms of the disease, although caution is needed as to whether APOE4 effects reflect AD pathological processes, and are representative of these effects in non-carriers.     

An attenuation of the 'normal' category effect in patients with Alzheimer's disease: a review and bootstrap analysis

There is a consensus that Alzheimer's disease (AD) impairs semantic information, with one of the first markers being anomia i.e. an impaired ability to name items. Doubts remain, however, about whether this naming impairment differentially affects items from the living and nonliving knowledge domains. Most studies have reported an impairment for naming living things (e.g. animals or plants), a minority have found an impairment for nonliving things (e.g. tools or vehicles), and some have found no category-specific effect. A survey of the literature reveals that this lack of agreement may reflect a failure to control for intrinsic variables (such as familiarity) and the problems associated with ceiling effects in the control data. Investigating picture naming in 32 AD patients and 34 elderly controls, we used bootstrap techniques to deal with the abnormal distributions in both groups. Our analyses revealed the previously reported impairment for naming living things in AD patients and that this persisted even when intrinsic variables were covaried; however, covarying control performance eliminated the significant category effect. Indeed, the within-group comparison of living and nonliving naming revealed a larger effect size for controls than patients. We conclude that the category effect in Alzheimer's disease is no larger than is expected in the healthy brain and may even represent a small diminution of the normal profile.     

Word association in early Alzheimer's disease

The hypothesis that Alzheimer's disease (AD) degrades semantic representations predicts that AD qualitatively alters spontaneous thoughts. In two experiments contrasting free associations to words with strong (e.g., bride-groom) versus weak (e.g., body-leg) associates participants with AD produced less common responses (e.g., bride-pretty) than normal controls but only for words with strong associations, and only on the first (but not on second or third) association response. Furthermore, all participants produced fewer semantically related responses to words with weak associates. Because strong associations should be retrieved more easily than weak associations these results are problematic for retrieval-based accounts of AD. Instead we propose that AD entails a semantic deficit, and that strong associations involve more semantic processing than weak associations (in all speakers).     

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.     

The missing link between faces and names: Evidence from Alzheimer's disease patients

Retrieval of proper names is a cause of concern and complaint among elderly adults and it is an early symptom of patients suffering from neurodegenerative diseases such as Alzheimer's disease (AD). While it is well established that AD patients have deficits of proper name retrieval, the nature of such impairment is not yet fully understood. Specifically, it is unknown whether this deficit is due to a degradation of the links between faces and proper names, or due to deficits in intentionally accessing and retrieving proper names from faces. Here, we aim to investigate the integrity of the links between famous faces and proper names in AD while minimizing the impact of the explicit retrieval. We compare the performances of AD patients and elderly controls in a face-name priming task. We assess the integrity of the link between faces and names at two different levels: identity level - the name and face belong to the same person; and semantic level - the name and face belong to the same category (e.g., politicians). Our results reveal that AD patients compared with controls show intact semantic priming but reduced priming for person identity. This suggests that the deficits in intentionally retrieving proper names in AD are the result of a partial disruption of the network at the identity level, i.e., the links between known faces and proper names.     

Phonological and articulatory impairment in Alzheimer's disease: a case series

We demonstrate that phonological and articulatory impairments may occur at presentation or early in the course of Alzheimer's disease, contrary to claims that these aspects of language production are relatively preserved until the final stages of this disease. Six patients with pathologically confirmed Alzheimer's disease (AD) and four patients with clinically diagnosed dementia of the Alzheimer's type (DAT) presented with one of five different clinical profiles: nonfluent progressive aphasia, mixed progressive aphasia, progressive aphasia diagnosed as DAT from neuropsychological assessment, initial amnestic syndrome with prominent phonological errors, and biparietal syndrome. Analysis of their conversational speech, single-word production, and performance of highly familiar series speech tasks such as counting revealed false start errors, phonological paraphasias, and/or articulatory difficulty. Neuropathological changes were located in left perisylvian regions consistent with speech and language impairment but atypical for Alzheimer's disease.     

Directed forgetting of autobiographical memory in mild Alzheimer's disease

Using the autobiographical directed forgetting method (Barnier et al., 2007), the present paper addressed the intentional inhibitory processes of episodic and semantic autobiographical memory in Alzheimer's disease (AD). Mild AD patients and healthy elderly people were instructed to either forget or to continue remembering previously generated autobiographical events. In a later recall test they were asked to reconstruct the early-generated memories regardless of the forget/remember instruction. Autobiographical reconstruction was further distributed into episodic and semantic memories. Results showed no forget instruction effect on episodic or semantic autobiographical recall with AD patients, whereas healthy elderly people were able to inhibit only episodic autobiographical memories. The findings suggest an impairment of the intentional inhibitory processes in autobiographical memory with AD and a relative preservation of these mechanisms with normal ageing. They also demonstrate an earlier decline in the intentional inhibitory processes compared to the autobiographical deterioration in AD.     

Memories defining the self in Alzheimer’s disease

ABSTRACT

There is a debate over the extent to which personal identity or the self is preserved in patients with Alzheimer’s disease (AD). Autobiographical memory deficits at early stages of AD could contribute to altering patients’ self. However, the nature of the relationship between autobiographical memory deficits and the self in AD has not been much investigated experimentally. In the present study, we aimed to investigate the integrative meaning of self-defining memories (SDMs) in early stages of AD and to analyse its relationship with the self-concept. The results showed that, when compared to the control group, AD patients less frequently extracted meaning from their SDMs and the meaning was less frequently tied to the self. Patients exhibited some altered aspects of the self-concept (i.e., complexity and strength), though some other components still persisted (i.e., valence and certainty). Correlation analyses showed that the impaired integrative meaning in the AD group was correlated with some changes in self-concept. We suggest that integrative meaning may act as a bridge between autobiographical memories and the self-concept, with reduced integration abilities appearing as a potential mechanism for the deterioration of the self-concept in AD.     

A rule-based categorization deficit in Alzheimer's disease?

This study examined the categorization processes that Alzheimer's disease (AD) patients use during assessments of semantic memory. Rule-based categorization involves the careful, analytic processing of strict criteria to determine category membership, particularly for items from graded categories with ambiguous category membership; similarity-based categorization requires an overall comparison of a test stimulus with a prototype or remembered exemplar of the category and is relatively effective for the rapid categorization of items with unambiguous category membership. To assess these processes in AD, patients were asked to decide the category membership of test stimuli for categories with poorly defined or fuzzy boundaries (e.g., VEGETABLE) and for categories with well-defined boundaries (e.g., FEMALE) and then to judge the representativeness of the test stimulus for its chosen category. A subgroup of AD patients demonstrated a typical pattern of impaired semantic memory compared to healthy control subjects; that is, difficulty deciding the category membership of test items from fuzzy categories. Among these patients, we found no deficit in category membership decisions about items taken from well-defined categories. We also found that AD patients and healthy controls do not differ in their representativeness judgments of items within a correctly judged category. These findings are most consistent with the hypothesis that rule-based categorization difficulty limits semantic memory in AD.     

Storage and processing working memory functions in Alzheimer-type dementia

A selective deterioration of working memory functions has been suggested as an explanation of the cognitive decay occurring in normal ageing as well as in Alzheimer-type dementia. Recent studies have highlighted that elderly people's limitations in working memory functions may be better interpreted when analysing the specific characteristics of the cognitive process (i.e., passive storage or active manipulation of information). In the present study, we have adapted a procedure used to investigate age-related memory modifications, involving both verbal and visuo-spatial material in tasks tapping passive and active processes, to investigate the deterioration associated with Alzheimer's disease. A group of Alzheimer patients in the early stages of the disease were matched to a control group of healthy elderly. Results show that Alzheimer patients performed less accurately than the control group in all tasks. However, the deficit was maximised in the case of active processes, regardless of the type of material used (verbal or visuo-spatial). These data highlight the importance of considering the amount of active processing as the key variable when interpreting the decay in cognitive functions in the early stages of Alzheimer's disease.     

Alzheimer's disease in Down syndrome: neurobiology and risk

Down syndrome (DS) is characterized by increased mortality rates, both during early and later stages of life, and age-specific mortality risk remains higher in adults with DS compared with the overall population of people with mental retardation and with typically developing populations. Causes of increased mortality rates early in life are primarily due to the increased incidence of congenital heart disease and leukemia, while causes of higher mortality rates later in life may be due to a number of factors, two of which are an increased risk for Alzheimer's disease (AD) and an apparent tendency toward premature aging. In this article, we describe the increase in lifespan for people with DS that has occurred over the past 100 years, as well as advances in the understanding of the occurrence of AD in adults with DS. Aspects of the neurobiology of AD, including the role of amyloid, oxidative stress, Cu/ZN dismutase (SOD-1), as well as advances in neuroimaging are presented. The function of risk factors in the observed heterogeneity in the expression of AD dementia in adults with DS, as well as the need for sensitive and specific biomarkers of the clinical and pathological progressing of AD in adults with DS is considered.     

Normal McCollough effect in Alzheimer's disease and global amnesia

The McCollough effect (ME), a long-lasting, pattern-contingent aftereffect in normal human vision, was examined in persons with known deficits in memory. We induced MEs in 11 subjects, 5 patients with various severities of Alzheimer's disease (AD), H.M. (a patient who has global amnesia due to bilateral medial temporal lobectomy and who has been studied for 35 years since his operation), and 5 control subjects. H.M. and the AD patients showed MEs of strength and duration comparable to those of the control subjects. These results demonstrate a dissociation between learning mechanisms that mediate recall and recognition versus mechanisms that mediate the ME. Furthermore, knowledge about the sites of neuropathology in H.M. and in AD are consistent with other sources of evidence implicating early visual areas, especially V1, as a critical locus of the ME.     

On the nature of the verbal memory deficit in Alzheimer''s disease

Verbal memory was investigated in patients with Alzheimer's disease (AD) with previously documented deficits in word production and comprehension. Procedures were employed to evaluate word recall and recognition within the context of both "multistore" and "levels of processing" models of memory. In addition, memory abilities were evaluated with respect to performance on measures of verbal fluency and language comprehension. As expected, the AD patients performed significantly worse than normal individuals on all tasks. However, in each experiment their pattern of recall across conditions was found to be qualitatively similar to that produced by normal subjects. It was argued that the memory impairment associated with Alzheimer's disease may be largely due to an inability to encode a sufficient number of stimulus features or attributes. Furthermore, this encoding deficit includes, but is not limited to, semantic attributes. Similarities between the performance of the AD patients and reported findings with Korsakoff patients and normal subjects with "weak" memory were discussed.