Memory Impairment In Alzheimer's Disease Research Articles

Premorbid proneness to distress and episodic memory impairment in Alzheimer’s disease

Background: Chronic stress has been associated with impaired episodic memory, but the association of premorbidly experienced distress with memory function in Alzheimer’s disease is unknown. Objective: To investigate the link...

The dynamic time course of semantic memory impairment in Alzheimer's disease: clues from hyperpriming and hypopriming effects.

The nature of semantic memory deficit in Alzheimer's disease is still a matter of controversy. To clarify this issue, we examined the evolution of semantic memory impairment in 24 Alzheimer's disease patients by means of a longitudinal study. We used two semantic tasks, one explicit and the other implicit, to evaluate the integrity of the same concepts. The explicit task was a semantic knowledge task composed of naming and questions, involving superordinate and attribute knowledge of concepts. The implicit task, a lexical decision task, assessed semantic priming and allowed a very pure measurement of semantic memory. In this task, related pairs of words had coordinate (e.g. "tiger-lion") or attribute ("tiger-stripe") relationships. In the coordinate relation between two words, the semantic priming performances were at first paradoxical: they increased abnormally (hyperpriming) before falling down, whereas in the attribute condition, the priming effects were first normal and then started to decrease in the final sessions (hypopriming). Compared with the semantic knowledge performance, these apparently disconcerting results reflect a coherent pattern of semantic memory degradation in Alzheimer's disease that is a progressive deterioration starting with specific attribute information. The data reveal in an astonishing yet striking manner the dynamic semantic memory degradation in Alzheimer's disease through the apparently paradoxical semantic priming effects.

Cognitive Rehabilitation in Old Age

Back to table of contents Previous article Next article Book Forum: Geriatric PsychiatryFull AccessCognitive Rehabilitation in Old AgeWILLIAM W. BEATTY, PH.D., WILLIAM W. BEATTYSearch for more papers by this author, PH.D., Oklahoma City, Okla.Published Online:1 Sep 2002https://doi.org/10.1176/appi.ajp.159.9.1611-aAboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail As the proportion of old and very old people in industrialized societies steadily increases, the impact on health care systems of the cognitive losses associated with normal and pathological aging grows greater as well. In this brief volume, the editors and authors review the current possibilities for ameliorating these deficits.The book is organized into four parts. Part 1 considers theoretical and methodological issues in research on cognitive rehabilitation in the elderly. Part 2 reviews research on memory training in normal aging. Part 3 reports the influences of lifestyle factors on cognitive rehabilitation in the elderly, including chapters on the impact of physical exercise, smoking, depression, and loss of executive function. Part 4 contains three chapters on the assessment and rehabilitation of cognitive and psychosocial problems in dementia and one concerned with cognitive rehabilitation after stroke.Parts 1 and 2 will probably be of interest to memory researchers and gerontologists, but less so to readers seeking more practical guidance. The authors of these chapters detail (with a fair amount of redundancy) several strategies employed to enhance memory in the normal elderly, which, if they work at all, rarely generalize beyond the specific conditions of practice. Furthermore, many of the studies used mnemonic techniques that were literally invented by the ancient Greek orators. These techniques require considerable practice to learn and a fair amount of cognitive capacity to deploy successfully. Not only do the elderly fail to make use of these procedures outside the laboratory, neither do the memory researchers themselves.As an outsider to the field, I was struck by one author’s description of “the contrast between high performance in daily life and less than optimal performance in the laboratory” of the normal elderly participants in his research. Clearly, much research in this area has assumed practical consequences of laboratory-based “deficits” in the elderly that may not exist. Researchers have sought the causes of every age-related deficit, apparently in a Ponce de Léon–like quest to restore cognitive youth. Evidently, little if any attention has been directed at teaching the elderly basic skills required for everyday living, such as money management.The four chapters on lifestyle influences are more useful. The chapter on smoking presents the physician’s predicament well. Smoking is bad for health, but it is a difficult habit to break, even for the young. Furthermore, nicotine is a cognitive stimulant. Should an elderly person with marginal cognitive function attempt to quit? The other chapters in this section are well done except for two problems. There is almost no consideration of the impact of medications in general and psychiatric medications in particular on cognitive function. This is a glaring weakness, because the elderly are major consumers of prescription and over-the-counter medications. A second omission is the failure to consider the impact of mentally stimulating leisure activities on cognitive aging. In fairness, most of this work appeared after the present volume went to press.The final section considers psychological and environmental treatments for dementia and stroke. Remarkably, there is no mention of cholinesterase inhibitor therapy for memory impairment in Alzheimer’s disease. There is some useful information in the chapters on psychosocial rehabilitation of dementia patients and the treatment of stroke.In summary, this volume will not be very useful to psychiatrists and geriatricians, although it may be valuable to geropsychologists.Edited by Robert D. Hill, Lars Bäckman, and Anna Stigsdotter-Neely. New York, Oxford University Press, 2000, 299 pp., $55.00. FiguresReferencesCited byDetailsCited byNone Volume 159Issue 9 September 2002Pages 1611-a-1612 Metrics History Published online 1 September 2002 Published in print 1 September 2002

Sensory cortical interactions in aging, mild cognitive impairment, and Alzheimer's disease.

Progressive declines in memory function accompany normal aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD). Neuropathological studies suggest that damage to neurons providing connections between cortical areas may contribute to memory impairments in AD. Because AD develops slowly, similar neuropathological changes, to a lesser degree, may be present in MCI and some asymptomatic elderly subjects. In this study we tested the hypothesis that corticocortical interactions between sensory regions are impaired in aging, MCI, and AD, as compared with young subjects. When sensory cortical evoked potentials are elicited by pairs of stimuli the amplitudes of potentials to the second stimulus are attenuated. Corticocortical interactions were assessed by presenting stimulus pairs in different modalities (auditory/visual). There were significant group differences in the degree that a visual stimulus attenuated subsequent auditory potentials (young > healthy elderly > MCI > AD). Control experiments indicated equivalent amplitude reductions for all groups to the second stimulus for stimulus pairs having the same modality. These findings are compatible with progressive declines in corticocortical processing in aging, MCI, and AD.

The neural substrates of verbal episodic memory impairment in Alzheimer's disease (AD): shift of resting CMRGLC correlations from hippocampus to neocortex with memory deterioration

The neural substrates of verbal episodic memory impairment in Alzheimer's disease (AD): shift of resting CMRGLC correlations from hippocampus to neocortex with memory deterioration

Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease.

Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease.

A Study of Remote Memory Impairment in Alzheimer’s Disease by Using the Family Line Test

We evaluated remote autobiographical memory impairment in 25 patients with probable Alzheimer’s disease (AD) and 25 sex-, age- and education-matched healthy subjects by using a newly developed, highly effective assessment tool for remote memory, the Family Line Test (FLT). The FLT yields a total score, scores for 3 lifetime periods and the duration of remote memory impairment. In the patients with AD, the total score was significantly lower and the duration of remote memory impairment was significantly longer than in the healthy controls. A prominent temporal gradient in remote memory impairment was documented in the patients with AD. The total FLT score and duration of remote memory impairment correlated with recent memory and general cognitive dysfunctions.

Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease.

Content and contextual memory for remote public figures and events was assessed with a modified version of the Presidents Test in patients with Alzheimer's disease (AD) or Parkinson's disease (PD). Contributions of executive functioning, semantic memory, and explicit anterograde memory to remote memory abilities were also examined. The AD group had temporally extensive deficits in content and contextual remote memory not accountable for by dementia severity. The PD group did not differ from the control group in remote memory, despite anterograde memory impairment. These results support the position that different component processes characterize remote memory, various mnemonic and nonmnemonic cognitive processes contribute to remote memory performance, and anterograde and remote memory processes are dissociable and differentially disrupted by neurodegenerative disease.

Exogenous lactate sustains synaptic activity and neuronal viability, but fails to induce long-term potentiation (LTP)

In Alzheimer's disease, brain glucose metabolic ratio decreases, whereas the brain lactate metabolic ratio increases. To investigate possible synaptic dysfunction in Alzheimer's disease, we examined the effects of exogenous glucose deprivation and replacement of glucose with lactate on the synaptic transmission, synaptic plasticity, and the morphological integrity of hippocampal neurons. Synaptic activity was estimated by the amplitude of the population spike (PS) recorded in the granular cell layer in the hippocampal slices from guinea pig and rat. Exogenous glucose deprivation caused the immediate depression of PS. Replacement of glucose with lactate induced transient decrease of PS, followed by spontaneous recovery of synaptic transmission. Neural activity recovered from transient glucose deprivation became resistant to the replacement of glucose with exogenous lactate. Glucose-supported synaptic transmission exhibited approximately 140% enhancement of PS (LTP). However, lactate-supported synaptic activity yielded approximately 110% potentiation of PS. Effects of exogenous glucose and lactate on the cell viability were examined by the propidum iodide uptake and LDH release in the organotypic hippocampal slice cultures. Hippocampal slice cultures incubated in medium containing 10 mM lactate suppressed the cell death during 48 h observation as well as those in the 10-30 mM glucose containing medium. These results indicate that lactate can sustain the neural transmission and support the morphological integrity of hippocampal neurons, but failed to induce LTP, which could at least in part, cause the memory impairment in Alzheimer's disease.

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.

The neural substrates of memory systems impairment in Alzheimer's disease. A PET study of resting brain glucose utilization

The aim of this study was to determine the neuronal basis for memory impairment in Alzheimer's disease by taking advantage of the clinical and metabolic heterogeneity of this pathology. To this end, 19 patients satisfying the NINCDSADRDA criteria for probably Alzheimer's disease of mild-to-moderate severity underwent a detailed examination of the five memory systems according to Tulving's model, together with a PET measurement of resting regional cerebral glucose utilization (CMRGlc). Compared with controls, the patients as a group showed the expected memory and metabolic profiles of impairment. Correlations (corrected for the effects of ageing) were calculated between memory scores and CMRGlc (normalized by the vermis CMRGlc) using two methods: (i) the classic regions-of-interest method, based on a priori hypotheses and individual coregistered structural MRI; and (ii) the statistical parametric mapping method which allows a systematic voxel-by-voxel analysis, in a more descriptive and exploratory way. Significant correlations were above chance levels and largely consistent between the two methods. They were almost exclusively positive (i.e. in the neurobiologically expected direction) and their distribution showed striking differences according to each memory system. Thus, verbal episodic memory impairment was related to changes in a large neuronal network including not only the limbic structures (mesial temporal cortex, thalamus and cingulate gyrus, with left side predominance) but also the parietotemporal and frontal association cortices of the right hemisphere, possibly on a compensatory basis. Regardless of modality, short-term memory tests were mainly correlated with bilateral activity in posterior association cortex, and also with activity in left prefrontal cortex for the visuospatial span, possibly indicating essentially uniform strategies for the performance of the different tasks. As predicted, semantic memory scores correlated with activity in temporoparietal and frontal association cortices of the left hemisphere, and also with activity in left cingulate cortex. Thus, for episodic, short-term and semantic memory, many findings fit classical neuropsychology, while most of the less expected ones were consistent with recent results from functional neuro-imaging in healthy subjects, notably with the hemispheric encoding/ retrieval asymmetry (HERA) model; only few findings suggested possible reorganization processes and/or recourse to unexpected cognitive strategy. Finally, only negative correlations were found for perceptual priming and procedural memory; although they could arise by chance, some of these unexpected findings give rise to interesting hypotheses about the cognitive relationships between the most and least affected memory systems. This study documents the validity and usefulness of our approach in unravelling the neural substrates of cognitive impairment in brain pathology without focal tissue loss such as that seen in neurodegenerative diseases.

Gestural Communication in Alzheimer's Disease

Spontaneous communicative hand-arm gestures were evaluated in elderly patients with probable Alzheimer's disease (AD) and healthy controls (NC). Based on the notion that speech and gestures arise from common semantic-conceptual representations, qualitatively similar linguistic and gestural communicative impairments were expected in association with semantic memory impairment in AD. Despite equal quantity and rate of gesturing, AD and NC groups produced qualitatively different types of gestures. Patients with AD produced proportionately more referentially ambiguous gestures, fewer gestures referring to metaphoric as opposed to concrete contents, and fewer conceptually complex bimanual gestures. Impaired gestural clarity correlated with severity of linguistic/conceptual impairments and disturbed production of pantomimic movements on a test of ideomotor limb apraxia. Results are consistent with the hypothesis that a central semantic-conceptual disorder underlies the similar linguistic and gestural communication impairments in AD.

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Medial temporal structures relate to memory impairment in Alzheimer’s disease: an MRI volumetric study

OBJECTIVESMemory impairment is not only the earliest clinical symptom but a central and prominent feature throughout the course of Alzheimer’s disease. Alzheimer related pathological alterations in the medial temporal structures...

A Neural Dissociation within Language: Evidence that the Mental Dictionary Is Part of Declarative Memory, and that Grammatical Rules Are Processed by the Procedural System

Language comprises a lexicon for storing words and a grammar for generating rule-governed forms. Evidence is presented that the lexicon is part of a temporal-parietalhnedial-temporal "declarative memory" system and that granlmatical rules are processed by a frontamasal-ganglia "procedural" system. Patients produced past tenses of regular and novel verbs (looked and plagged), which require an -ed-suffixation rule, and irregular verbs (dug), which are retrieved from memory. Word-finding difficulties in posterior aphasia, and the general declarative memory impairment in Alzheimer's disease, led to more errors with irregular than regular and novel verbs. Grammatical difficulties in anterior aphasia, and the general impairment of procedures in Parkinson's disease, led to the opposite pattern. In contrast to the Parkinson's patients, who showed sup pressed motor activity and rule use, Huntington's disease patients showed excess motor activity and rule use, underscoring a role for the basal ganglia in grammatical processing.

Apolipoprotein E, memory and Alzheimer's disease

Apolipoprotein E (ApoE) ϵ4 is a well-documented risk factor for Alzheimer's disease (AD). Patients with AD show neuronal damage, particularly in the medial temporal lobe structures involved in memory processing. ApoE has been implicated in nerve regeneration following injury, and synaptogenesis in the hippocampus of experimental animals. Recent studies have shown an increased accumulation of βA4 amyloid and an increased deficit in ACh-containing neurons in the brains of AD patients that are homozygous for ApoE ϵ4 compared with those lacking ϵ4. Furthermore, AD patients with two ApoE ϵ4 alleles have more-severe loss in hippocampal volume in magnetic resonance imaging (MRI) scans, and more impairment in tests assessing delayed memory, than AD patients without the ϵ4 allele, in spite of similar global severity of dementia. Minor changes in hippocampal MRI volumetry can also be detected in nondemented elderly, particularly in those with an ϵ4 4 genotype. Data from a population-based study revealed that elderly subjects carrying the ϵ4 allele had worse learning ability than those with the ϵ2 2 or ϵ2 3 phenotypes, whereas these groups did not differ in other cognitive domains. These data suggest that ApoE ϵ4 might influence the magnitude of medial temporal lobe atrophy and memory impairment in AD and also in nondemented elderly. Trends Neurosci. (1996) 19, 224–228

Memory impairment in Alzheimer's disease: replication and extension of the delayed word recall (DWR) test

AbstractObjective: The original DWR test, which measured delayed free recall, was reported to have high predictiveaccuracy in discriminating Alzheimer's disease (AD) patients from control subjects (overall accuracy of 95%).Comparison of differential performance in free recall and recognition of the same material may be of clinical interest. In the present study a delayed recognition component was added to the DWR test and the utility of both measures in discriminating AD patients from control subjects was evaluated.Procedure: This extended version of the DWR test was administered to 66 patients meeting NINCDS/ADRDA criteria for probable AD and 42 control subjects.Results: In a comparison between 42 of these patients (MMSE range 18–29), and 42 age matched healthy controls, both the delayed free recall and recognition measures were highly accurate in distinguishing patients from controls. The free recall measure achieved 98% sensitivity, specificity and overall accuracy, while the recognition measure yielded 98% sensitivity, 95% specificity, and 96% overall accuracy. The recognition performance of all 66 patients, ranging in severity from very mild to severe (MMSE range 11–29), was also evaluated to determine its relationship, if any, to measures of global cognitive impairment. While therecognition measure correlated poorly with MMSE and CAMCOG there was a modest but significant correlation with the CAMCOG memory subscale.Conclusions: In this study of highly selected AD patients both the free recall and recognition measures were sensitive and specific indicators of AD compared to control subjects. Recognition performance appears to be more closely related to degree of amnesia than to degree of global cognitive impairment.

Entorhinal cortex modules of the human brain

Much is known about modular organization in the cerebral cortex, but this knowledge is skewed markedly toward primary sensory areas, and in fact, it has been difficult to demonstrate elsewhere. In this report, we test the hypothesis that a unique form of modules exists in the entorhinal area of the human cortex (Brodmann's area 28). We examined this issue using classic cyto- and myeloarchitectonic stains, immunolabeling for various neurochemicals, and histochemistry for certain enzymes. The findings reveal that the entorhinal cortex in the human is formed by a mosaic of cellular aggregates whose most conspicuous elements are the cell islands of layer II and myelinated fibers around the cell islands, the disposition of glutamic acid decarboxylase-positive neurons and processes, cytochrome oxidase staining, and the pattern of cholinergic afferent fibers. The neuropathology of Alzheimer's disease cases highlights the modules, but inversely so, by destroying their features. The findings are of interest because 1) anatomically defined modules are shown to be present in areas other than the sensory and motor cortices, 2) the modules are morphological entities likely to reflect functions of the entorhinal cortex, and 3) the destruction of entorhinal cortex modules may account disproportionately for the severity of memory impairments in Alzheimer's disease. © 1996 Wiley-Liss, Inc.

Rodent models of memory dysfunction in Alzheimer's disease and normal aging: Moving beyond the cholinergic hypothesis

The Stone maze paradigm has been developed for use as a rat model of memory impairment observed in normal aging and in Alzheimer's disease. Results from several studies have demonstrated the involvement of both cholinergic and glutamatergic systems in acquistion performance in this complex maze task. Although results of clinical studies on the cognitive enhancing abilities of cholinomimetics for treatment of memory impairment in Alzheimer's disease have been inconsistent, new classes of cholinesterase inhibitors offer greater potential for therapeutic efficacy. The physostigimine derivative, phenserine, appears to have marked efficacy for improving learning performance of aged rats or of young rats treated with scopolamine in the Stone maze. Declines in markers of glutamatergic neurotransmission in Alzheimer's disease and in normal aging suggest that pharmacological manipulation of this system might also prove beneficial for cognitive enhancement. Treatment with glycine and/or polyamine aginists is suggested as a strategy for activating the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. In addition, the use of combined pharmacological activation of cholinergic and glutamatergic systems is suggested. Manipulation of signal transduction events should also be considered as a strategy for cognitive enhancement. The influx of Ca 2+ through the channel formed by the NMDA receptor stimulates the production of the oxyradical, nitric oxide (NO·), via the action of nitric oxide synthase (NOS). Compounds that inhibit NOS activity impair acquisition in the Stone maze, suggesting an involvement of NO·. Thus, strategies for inducing NO· production to enhance cognitive performance may be beneficial. Because of the potential neurotoxicity for NO·, this strategy is not straightforward. Although many new directions beyond the cholinergic hypothesis can be suggested, each has its potential benefits which must be weighed against its risks. Nonetheless, an important unifying area for neurobiological research examining mechanisms of normal brain aging and of age-related neuropathology, as observed in Alzheimer's disease, might emerge from the identification of NO· as a simple molecule serving vital physiological functions but representing potential for neurotoxicity.

Differences in verbal memory impairment in Alzheimer's disease and frontal lobe type dementia : F. Pasquier, F. Lebert, L. Grymonprez, L. Souliez, M. Van der Linden, H. Petit. Memory Disorders Unit, Centre Hospitalier Régional et Universitaire, Lille, F-59037 France and University of Liège, Belgium

Differences in verbal memory impairment in Alzheimer's disease and frontal lobe type dementia : F. Pasquier, F. Lebert, L. Grymonprez, L. Souliez, M. Van der Linden, H. Petit. Memory Disorders Unit, Centre Hospitalier Régional et Universitaire, Lille, F-59037 France and University of Liège, Belgium