Reading lexically without semantics: evidence from patients with probable Alzheimer's disease

Recent modifications of the lexical model of oral reading make the prediction that under conditions where sublexical reading processes alone cannot achieve the target pronunciation (i.e., when words have exceptional spellings or when sublexical processes are impaired), patients with severe semantic impairment should have more difficulty reading aloud semantically impaired words than semantically retained words. In a battery of lexical-semantic and reading tasks, two neurologically normal control subjects and two subjects with probable Alzheimer's disease (AD) and only moderate semantic impairment read aloud all words accurately. One AD subject with severe semantic impairment was impaired in word reading but demonstrated no difference in reading words with regular and exceptional spellings. Another AD subject with severe semantic impairment read aloud without error virtually all regular and exception words. Neither severely impaired AD subject demonstrated any relationship between oral reading accuracy and semantic knowledge of exception words. These findings support a model of word reading incorporating lexical, nonsemantic processes by which lexical orthographic input representations directly activate lexical phonological output representations without the necessity of semantic mediation.     

EEG spectral abnormalities and psychosis as predictors of cognitive and functional decline in probable Alzheimer's disease

We examined whether either psychotic features (e.g., delusions and hallucinations) or EEG abnormalities are associated with more rapid progression of Alzheimer's disease (AD). AD patients with psychosis have exhibited more EEG abnormalities than those without psychosis, and both abnormal EEG and psychosis have been noted to be predictors of functional and cognitive decline in AD. Ninety-five probable AD patients participating in a longitudinal study of dementia had an EEG and a semistructured psychiatric interview at baseline. Using EEG spectral analysis, we classified records as normal/abnormal based on the parasagittal mean frequency. Patients with abnormal EEGs were more functionally (e.g., Blessed Rating Scale for activities of daily living) and cognitively (e.g., Mini-Mental State) impaired than patients with normal EEG. AD patients with psychosis were only more functionally impaired than patients without psychosis. A two-factor analysis showed no interaction between abnormal EEG and psychosis. In addition, using a Cox proportional hazard model adjusted for age and education, the presence of an abnormal EEG or psychotic symptom at study entry was associated with higher risk of reaching severe cognitive and functional impairment during follow-up. Neither abnormal EEG nor the presence of psychosis predicted death. These results indicate that both abnormal EEG and psychosis are independent predictors of disease progression but not of physical survival.     

Selection Ability in Alzheimer's Disease: Investigation of a Component of Semantic Processing.

Selection ability (selecting a response from several competing semantic and/or lexical representations) was tested in 21 participants with Alzheimer's disease (AD) and 28 control participants to help clarify the nature of semantic impairments in AD. Selection demands were manipulated in 3 tasks (lexical fluency, comparison, and verb generation). In each, high-selection conditions required response selection from competing alternatives, whereas low-selection conditions had a reduced need for selection. Patients with AD were disproportionately impaired on the high-selection conditions of all tasks, even when this condition was easier. Selection deficits on verb generation were evident only relative to nonspeeded controls. Overall results indicate impaired semantic selection abilities in AD, which may contribute to poor performance on some semantic tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conceptual priming in perceptual identification for patients with Alzheimer's disease and a patient with right occipital lobectomy.

Two experiments examined explicit recognition memory and perceptual and conceptual contributions to implicit perceptual-identification repetition priming for patients with Alzheimer's disease (AD) and Patient M.S. with right-occipital lobectomy. Participants read words (perceptual encoding) and generated words (conceptual encoding) from a definition and letter cue (e.g., "a vehicle for moving the injured—a"). AD patients demonstrated impaired explicit and intact implicit memory for both perceptually and conceptually encoded words. M.S. demonstrated the opposite pattern: intact explicit and impaired implicit memory in both encoding conditions. The double dissociation between AD and M.S. on implicit and explicit memory tasks is discussed in terms of a putative visual memory mechanism in the right-occipital cortex that interacts with lexical mechanisms to yield perceptual-identification priming after perceptual and conceptual encoding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of attention in a spatial memory task in Alzheimer disease patients

Memory and attention are interrelated cognitive processes that most likely influence the functioning of each other, yet they are often difficult to distinguish in psychological experiments. Young, aged adults, and patients with Alzheimer disease (AD) were tested on a delay response task measuring spatial memory that also placed high demands on attentional resources. Aged adults performed as well as young, suggesting that neither attentional nor memory abilities were exceeded in either group. However, AD subjects were severely impaired on this task. Two further experiments with AD patients examined the relative contribution of attentional and memory deficits in the performance of this population. Both memory and attentional impairments were found; however, errors due to memory factors were more closely related to severity of disease as measured on the Folstein Mini-Mental State Examination than were errors of attentional origin. These studies demonstrate the necessity of accounting for attentional components in studies examining memory, especially in patients with AD.     

Visual synchrony affects binding and segmentation in perception

The visual system analyses information by decomposing complex objects into simple components (visual features) that are widely distributed across the cortex. When several objects are present simultaneously in the visual field, a mechanism is required to group (bind) together visual features that belong to each object and to separate (segment) them from features of other objects. An attractive scheme for binding visual features into a coherent percept consists of synchronizing the activity of their neural representations. If synchrony is important in binding, one would expect that binding and segmentation are facilitated by visual displays that are temporally manipulated to induce stimulus-dependent synchrony. Here we show that visual grouping is indeed facilitated when elements of one percept are presented at the same time as each other and are temporally separated (on a scale below the integration time of the visual system) from elements of another percept or from background elements. Our results indicate that binding is due to a global mechanism of grouping caused by synchronous neural activation, and not to a local mechanism of motion computation.     

Opposite roles of apolipoprotein E in normal brains and in Alzheimer's disease

We have characterized the interaction between apolipoprotein E (apoE) and amyloid beta peptide (Abeta) in the soluble fraction of the cerebral cortex of Alzheimer's disease (AD) and control subjects. Western blot analysis with specific antibodies identified in both groups a complex composed of the full-length apoE and Abeta peptides ending at residues 40 and 42. The apoE-Abeta soluble aggregate is less stable in AD brains than in controls, when treated with the anionic detergent SDS. The complex is present in significantly higher quantity in control than in AD brains, whereas in the insoluble fraction an inverse correlation has previously been reported. Moreover, in the AD subjects the Abeta bound to apoE is more sensitive to protease digestion than is the unbound Abeta. Taken together, our results indicate that in normal brains apoE efficiently binds and sequesters Abeta, preventing its aggregation. In AD, the impaired apoE-Abeta binding leads to the critical accumulation of Abeta, facilitating plaque formation.     

Categorization of novel animals by patients with Alzheimer's disease and corticobasal degeneration.

We taught a novel animal category by rule-based and similarity-based processes to participants with Alzheimer's disease (AD), corticobasal degeneration (CBD), and healthy age-matched participants. Healthy participants successfully categorized by either process. AD patients' rule-based categorization was impaired, while their similarity-based categorization resembled that of healthy participants. Correlations of AD patients' performance with measures of executive functioning suggested a deficit in the cognitive resources necessary for engaging rule-based categorization. The contribution of limited executive resources to categorization difficulty in AD was further demonstrated in a second experiment in which features determining category membership were of lower salience. CBD patients were relatively impaired at similarity-based processing, suggesting that qualitatively distinct categorization processes can be selectively compromised in patients with focal neurodegenerative diseases. Moreover, AD patients' impaired categorization correlated with performance on a measure of semantic memory, implicating this categorization deficit in AD patients' semantic memory difficulty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anti-laminin reactivity and glomerular immune deposition by in vitro recombinant antibodies

Growing evidence suggests that recombinatorial events prior to antigen contact can generate pathogenic autoantibodies in the nonautoimmune individual, thus providing potential disease mediators if conditions arise that permit bypass of tolerance and activation of autoreactive lymphocytes. To examine the disease potential of selected germline antibody genes, Ig were created de novo by in vitro recombination of Ig H and L chains. H chain loss variant (i.e., L-chain only) cell lines were transfected with a DNA construct encoding the variable region and regulatory sequences (LamH) of a nephrotropic murine lupus anti-laminin Ig, and the resultant Ig were examined for in vitro antigen reactivity and in vivo glomerular immune deposition. The results indicate that two light chains, LamL (Vk8, Jk5) and 238L (Vk4, Jk5), expressing unrelated germline V1 genes, combine with LamH to generate Ig that bind basement membrane laminin in vitro, diverge in their capacity to bind ssDNA, and produce two distinct patterns of glomerular immune deposits in vivo: dense mesangial matrix (LamH/LamL) and dramatic linear glomerular basement membrane (LamH/238L) deposits. The Ig genes used by both LamH and 238L are present in nonautoimmune mice as well as in lupus-prone strains. We conclude that certain unmutated Ig genes can contribute to multiple distinct disease associated specificities, including binding to intrinsic kidney antigens, and that mutation is not essential to generate these Ig. Collectively, these observations suggest that pathogenic autoantibodies can be generated in the normal preimmune repertoire by random recombinatorial and somatic events in the absence of mutation.     

Implicit memory in Alzheimer's disease: A meta-analysis.

Meta-analysis was performed on 33 articles (36 experiments involving 564 Alzheimer's disease [AD] patients and 592 controls). Overall, AD patients were significantly impaired on implicit memory tests, r?=?.163 (a difference of .329 SDs from normal performance). They were impaired on nonverbal tests (e.g., fragmented pictures), word stem completion, classical conceptual tests (e.g, free association), and on word-based perceptual tests with long delays. However, they performed normally on word-based perceptual tests (e.g., perceptual identification of words) with short study test delays. They also performed normally on word stem completion if they were older than 75, possibly because their age-matched controls were also impaired. These results are neither qualified by study list length nor patient mental status. None of the theories in the field is compatible with the results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conceptual implicit memory performance in Alzheimer's disease.

Alzheimer's disease (AD) patients often exhibit deficits on conceptual implicit memory tests such as category exemplar generation and word association. However, these tests rely on word production abilities, which are known to be disrupted by AD. The current study assessed conceptual implicit memory performance in AD patients and elderly control participants using a conceptual priming task that did not require word production (i.e., semantic decision). Memory performance was also examined using a category exemplar generation test (i.e., a conceptual priming task that required word production) and a recognition memory test. AD patients exhibited deficits on the semantic decision task, the category exemplar generation task, and the recognition memory task. The results indicate that the conceptual memory deficits observed in AD patients cannot be attributed completely to word production difficulties. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

How does feature-based attention affect visual processing?

Five experiments are reported from which it is concluded that attending on the basis of a stimulus feature (e.g., red) does not directly affect the sensory quality of stimuli that possess that feature. Feature-based attention was manipulated in a visual search task by providing information about the probability that the target would possess a given feature (e.g., "The target has a 1.0 probability of being red when present.") Feature-based attention failed to aid performance under "data-limited" conditions (i.e., those under which performance was primarily affected by the quality of the stimulus) but did affect performance under conditions that were not data limited (Experiments 1-3). If attending to a feature had affected the sensory quality of stimuli, performance should have been aided under all conditions. Experiments 4 and 5 provided converging support for this conclusion.     

Motion integration with dot patterns: effects of motion noise and structural information

To better understand how local motion detectors merge their responses so as to permit the global determination of objects' movements in the visual field, direction discrimination of performance was measured using a flexible class of moving dots--two sets of dots translating sinusoidally 90 deg out of phase along orthogonal axes. When dots' velocities are combined, a global motion along a circular trajectory emerges, clockwise or counter-clockwise depending on the sign of the phase lag. However, the results of the present experiments indicate that dot patterns are segregated into distinct, but interacting, streams when each dot motion can be accurately determined. In contrast, perceptual coherence of the global motion occurs when each local motion signal is "blurred" by a "motion noise". Direction discrimination performance then increases regularly with both noise amplitude and noise frequency, i.e., noise speed. Performance also increases when relative motion between dots is added. Testing different dot configurations indicates that performance is better for spatial arrangements that display structural properties (a square shape), as compared to overlapping random distributions. Interestingly, when the delay between stimulus onset and motion onset increases up to 300 msec, performance improves when dot patterns convey come form of structural organization but not when the dots are distributed at random. Relations of these results to existing models of motion integration are considered.     

Amnestic mild cognitive impairment: Difference of memory profile in subjects who converted or did not convert to Alzheimer's disease.

Episodic long-term, short-term, and implicit memory were investigated in 79 elderly subjects who fulfilled criteria for the amnestic form of mild cognitive impairment (a-MCI; i.e., by having an idiopathic amnestic disorder with absence of impairment in cognitive areas other than memory and without confounding medical or psychiatric conditions) and who developed Alzheimer's disease (AD) after 2 years as well as in 111 subjects affected by a-MCI who did not develop dementia. Results document a memory profile in a-MCI subjects characterized by preserved short-term and implicit memory and extensive impairment of episodic long-term memory. In virtually all episodic memory indexes examined (learning, forgetting, recognition abilities), a-MCI subjects who converted to AD were more severely impaired than were subjects who did not become demented. This memory profile, which closely resembles that exhibited by amnestic patients with bilateral mesial-temporal lobe lesions, confirms a precocious phase in preclinical AD characterized by selective involvement of mesial-temporal areas and worsening of the memory impairment as atrophic changes progress in hippocampal structures. In this context of pervasive episodic memory impairment, tests assessing the free recall of verbal material following a delay interval demonstrated the greater sensitivity to memory deficits of a-MCI subjects who developed AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurotransmitters and memory: Role of cholinergic, serotonergic, and noradrenergic systems.

In Alzheimer's disease (AD), pathological changes are found in the basal forebrain cholinergic system (BFCS), serotonergic raphe (RA), and noradrenergic locus coeruleus (LC) systems. The present study examined the extent to which selective damage in each of these systems individually could produce an impairment of memory, one of the clinical symptoms of AD. Rats were given selective lesions by injecting ibotenic acid into the nucleus basalis magnocellularis and medial septal area (i.e., BFCS); 5,7-dihydroxytryptamine into the medial and dorsal RA; and 6-hydroxydopamine (6-OHDA) into the LC or by ip injections of (2-chloroethyl)N-ethyl-2-bromobenzylamine HCl (DSP4). Rats were tested in a delayed spatial alternation in a T-maze. BFCS lesions impaired choice accuracy with intertrial delays of 5, 30, and 60 s. RA lesions or DSP4 injections impaired choice accuracy only when the intertrial delay was 60 s. LC lesions (by 6-OHDA) did not impair choice accuracy at any delay. The results suggest that the pathological changes in the BFCS and RA are sufficient to produce the types of memory impairments associated with dementia, but the quantitative effects of pathology in these two systems are different. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Deterioration of generic knowledge in patients with Alzheimer's disease: evidence from the Number Information Test

Semantic memory for generic knowledge was assessed in patients with probable Alzheimer's disease (AD; n = 142) and elderly normal control (NC; n = 78) subjects using the Number Information Test (NIT), a test that consists of 24 general knowledge questions that require a single number for an answer (e.g., "How many days are in a year?"). The results showed that patients with AD were impaired, even in the mildest stage of dementia, and that this impairment grew as the severity of their dementia increased over time. In addition, patients with AD were highly consistent in the individual items they missed in subsequent test sessions conducted 1 or 2 years later. These results indicate that semantic memory for generic knowledge is impaired relatively early in AD, deteriorates throughout the course of the disease, and may be due to a loss of knowledge rather than to a retrieval deficit.     

Clinical features of unilateral multicystic renal dysplasia in children

Several recent studies have investigated the effectiveness of various behavioral interventions on the cognitive performance of subjects with Alzheimer's disease (AD). Simulations of Shaw's structured model of the cortex led to the predictions that music might enhance spatial-temporal reasoning. A subsequent behavioral study in college students documented an improvement in scores on a spatial-temporal task after listening to a Mozart piano sonata. In this study, we investigated the enhancement of scores on a spatial-temporal task after a Mozart listening condition in a set of twins who are discordant for AD. After listening to an excerpt from a Mozart piano sonata, the AD twin showed considerable improvement on the spatial-temporal task when compared with pretest scores. Furthermore, no enhancement of scores was seen following either of the control conditions (i.e., silence or 1930s popular tunes). This finding suggests that music may be used as a tool to investigate functional plasticity in Alzheimer's disease and to better understand the underlying pathophysiology.     

The Buddy System: Relationship and contingency conditions in a community intervention program for youth with nonprofessionals as behavior change agents.

Tested the application of the triadic model of therapeutic intervention within a community-based program that trained indigenous nonprofessionals as behavior change agents. Each of 42 youngsters, aged 11-17, referred for behavior and academic problems, received the friendship and companionship of an adult resident in the community. These adult "buddies" attempted to influence their youngsters through their relationship and through the contingent use of social and material reinforcement. School attendance increased when placed on social or social-material contingency, but no change occurred in noncontingent relationship and control conditions. Social-material contingency was also effective in decreasing assorted problem behaviors, e.g., fighting, returning home late, and not doing home chores. However, there were no effects across conditions when academic achievement (i.e., improved grades) was the target behavior. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)