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Screening for Alzheimer's disease: the memory impairment screen versus the conventional three-word memory test.

OBJECTIVES: To improve screening for Alzheimer's disease (AD) with the Memory Impairment Screen (MIS), a 4-minute, four-item delayed free and cued recall memory test with controlled learning and high discriminative validity. To assess the discriminative validity of the MIS for AD and to compare it with the conventional three-word memory test, a delayed free recall task, widely recommended as a dementia-screening test in clinical practice. DESIGN: Cross-sectional validation study nested within a longitudinal study of aging and dementia. The MIS and the standard three-word memory task were administered as part of a comprehensive neurological and neuropsychological evaluation. SETTING: Einstein Aging Study at the Albert Einstein College of Medicine, Bronx, New York. PARTICIPANTS: Two hundred forty community-dwelling older adults. MEASUREMENTS: Sensitivity, specificity, and positive predictive value (PPV) were calculated for the MIS and three-word memory test as screening tests for AD. RESULTS: In comparison with the three-word memory task, the MIS had higher sensitivity (.86 vs.65), higher specificity (.97 vs.85), and greater PPV (.80 vs.37) as a screen for AD. CONCLUSIONS: The MIS had high discriminative validity as a screening test for AD and substantially outperformed the three-word memory task. Given its validity and brevity, the MIS has important advantages as an AD screen for use in primary care.

Aged↗

Negotiating false memories: interviewer and rememberer characteristics relate to memory distortion.

In a recent study, more than half of the participants were led to create a partial or complete false memory for an emotional childhood event (e.g., serious animal attack). Using a subsample from that study, we examined the hypothesis that memory distortion is related to characteristics of interviewers and rememberers. The relations between susceptibility to memory distortion and (a) dissociation (Dissociative Experiences Scale) and (b) personality traits (NEO-Five Factor Inventory) were investigated. Results indicated that participants who exhibited memory distortion scored significantly higher on the dissociative scale than their counterparts who did not exhibit memory distortion. Further, susceptibility to memory distortion was associated with higher extraversion scores in interviewers and lower extraversion scores in participants. This pattern of findings suggests that false memories may derive from a social negotiation between particular interviewers and rememberers.

Adult↗

Spatial memory formation and memory-enhancing effect of glucose involves activation of the tuberous sclerosis complex-Mammalian target of rapamycin pathway.

The tuberous sclerosis complex-mammalian target of rapamycin (TSC-mTOR) cascade integrates growth factor and nutritional signals to regulate the synthesis of specific proteins. Because both growth factor signaling and glucose have been implicated in memory formation, we questioned whether mTOR activity is required for long-term spatial memory formation and whether this cascade is involved in the memory-augmenting effect of centrally applied glucose. To test our hypothesis, we directly administered rapamycin (an inhibitor of mTOR), glucose, 5-aminoimidazole-4-carboxamide-1beta-4-ribonucleoside (AICAR; an activator of AMP kinase), or glucose plus rapamycin into the dorsal hippocampus after we trained rats in the Morris water maze task. The results from these studies indicate that glucose enhances, whereas AICAR and rapamycin both impair, long-term spatial memory. Furthermore, the memory-impairing effect of targeted rapamycin administration could not be overcome by coadministration of glucose. Consistent with these behavioral results, biochemical analysis revealed that glucose and AICAR had opposing influences on the activation of the TSC-mTOR cascade, as indicated by the phosphorylation of ribosomal S6 kinase (S6K) and 4E binding protein 1 (4EBP1), targets of mTOR. Together, these findings suggest that memory formation requires the mTOR cascade and that the memory-enhancing effect of glucose involves its ability to activate this pathway.

Aminoimidazole Carboxamide↗

New learning and remote memory in the same and different domains of experience: implications for normal memory and amnesia.

This study investigated the correlation between new and remote memory ability in normal young subjects and evaluated whether using tests that tapped different domains of experience had any effect on the relationship between new and remote memory. Remote memory was assessed using a famous face test and new memory was evaluated using both novel faces and words. The main finding was a significant correlation between New and Remote face familiarity scores. A correlation was obtained when both tests tapped the same domain of memory, whereas when tests tapped different domains, there was no Remote-New correlation. Remote-New correlations may only exist between tests tapping the same domain of memory. This has implications for the interpretation of previous amnesic literature and for future investigations.

Adolescent↗

Memory as assessed by recognition and reading time in normal and memory-impaired people with Alzheimer's disease and other neurological disorders.

Three experiments are reported that examine the dissociations in performance on two tests of retention, speeded reading and recognition in young people, home-dwelling and institutionalized elderly people, and people with severe memory disorders. In Experiment 1, subjects read sentences in normal and in geometrically transformed script at initial presentation, 1-2 hr later, and again 4-14 days later. On the latter two occasions, they were required to distinguish old sentences that they had read previously from new ones. In general, the young and elderly subjects could distinguish old from new sentences at the short delay, and all but the institutionalized elderly people could do so at the long delay. Retention as measured by reading speed typically paralleled recognition performance in that those items that were recognized best were read most quickly. The dissociation between these two tests of retention is seen only in people with memory disorders. Although these people could not distinguish old from new items even at short delays (most could not even remember having seen any sentences), their retention as assessed by reading time was similar to that of the other groups. Old sentences were read most quickly, indicating retention of item-specific information, and reading time of new sentences improved, indicating the acquisition and retention of a general skill. Experiment 2 examined what type of item-specific information was retained. Young, elderly, and memory-disordered subjects studied weakly associated word pairs and sentences. A few minutes later they were tested on both recognition and speeded reading of old, new, and recombined pairs and sentences, the last being those in which words from a studied pair or sentence were recombined with words from other such pairs or sentences. The results of both retention tests indicated that young and elderly people could distinguish old from new and recombined items. People with memory disorders, however, again failed on recognition but performed normally on speeded reading. Like the other two groups, they read old items faster than either recombined or new items. In Experiment 3, similar results were obtained even when the word pairs were constructed using randomly associated items. The results of all three experiments suggest that on implicit tests of memory, such as speeded reading, people with memory disorders can be shown to have formed and retained new associations despite failing utterly on explicit tests, such as recognition, that require conscious recollection of a previous episode.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Complexity effects in visuo-spatial working memory: implications for the role of long-term memory.

Several studies have shown that the capacity of visuo-spatial working memory is limited by complexity. Using a variant of the Corsi blocks task, this paper investigates the effect of complexity of the to-be-remembered path on visuo-spatial memory span. Redundancy was determined by three Gestalt principles: symmetry, repetition, and continuation. Experiment 1 revealed an effect of path complexity. The subsequent experiments explored whether the superiority for recall of structured over complex paths can be attributed solely to the operation of visuo-spatial working memory, or whether it also reflects the use of long-term knowledge. Experiment 2 demonstrated that the effect of complexity remained, even when the mechanisms for visuo-spatial coding were removed by a secondary visuo-spatial task. In Experiments 3 and 4 subjects were trained in the recall of complex paths. This led to the creation of long-term memory representations for these paths, as shown by an improvement in their span, and a concomitant lack of transfer to new paths. Finally, Experiment 5 showed that one prior repetition of a complex path was sufficient to produce specific and long-term learning effects. These results point to the involvement of long-term memory processes in the temporary retention of visuo-spatial material for which representations exist in long-term memory. They also suggest that the effect of complexity may provide a tractable technique for investigating the mechanisms underlying the limits of visuo-spatial short-term storage.

Humans↗

Psychosocial stress impairs working memory at high loads: an association with cortisol levels and memory retrieval.

Stress and cortisol are known to impair memory retrieval of well-consolidated declarative material. The effects of cortisol on memory retrieval may in particular be due to glucocorticoid (GC) receptors in the hippocampus and prefrontal cortex (PFC). Therefore, effects of stress and cortisol should be observable on both hippocampal-dependent declarative memory retrieval and PFC-dependent working memory (WM). In the present study, it was tested whether psychosocial stress would impair both WM and memory retrieval in 20 young healthy men. In addition, the association between cortisol levels and cognitive performance was assessed. It was found that stress impaired WM at high loads, but not at low loads in a Sternberg paradigm. High cortisol levels at the time of testing were associated with slow WM performance at high loads, and with impaired recall of moderately emotional, but not of highly emotional paragraphs. Furthermore, performance at high WM loads was associated with memory retrieval. These data extend previous results of pharmacological studies in finding WM impairments after acute stress at high workloads and cortisol-related retrieval impairments.

Adult↗

Where did I leave my keys? A twin study of self-reported memory ratings using the multifactorial memory questionnaire.

Behavior genetics has convincingly shown the importance of genetic factors in objective tests of memory function. However, self-report memory tests have received little attention. This study used items from the Multifactorial Memory Questionnaire (MMQ) to estimate the heritability of self-reported memory contentment and ability in 909 monozygotic (MZ) and 1034 dizygotic (DZ) twin pairs aged between 20 and 84 years from the St Thomas' Adult UK Twin Register. Heritability estimates ranged between 37% and 64% for contentment (e.g., reporting to worry about one's memory) and approximately 45% for ability (e.g., reporting a tendency to forget keys). Shared family environmental influences (between 32% and 33%) were found for some abilities (e.g., learning to use a new gadget). Given their clinical significance and ease of administration, these tests could prove to be useful in examining memory functioning in large-scale population studies.

Adult↗

Choline supplementation facilitates short-term memory consolidation into intermediate long-term memory of young Sprague-Dawley rats.

Choline is important for the synthesis of acetylcholine, an integral neurotransmitter involved in memory formation. In order to investigate the effect of choline supplementation on memory consolidation, the study utilized a T-maze to facilitate passive avoidance learning and memory in young female Sprague-Dawley rats. Rats were placed in two groups; choline-supplemented that received choline chloride daily for two weeks, and control that received vehicle daily for two weeks. Rats were evaluated to determine their ability to avoid an aversive electric foot-shock (0.1 mA at 60V) when they characteristically entered the preferred dark area (DA) of the T-maze. Both groups of rats showed preference, without significant difference, for entry into DA of the T-maze. However, fifteen minutes after passive avoidance both choline supplemented and control rats avoided entry into DA. This display of DA avoidance 15 minutes after training, suggests that both groups of rats had acquired short-term memory of the aversive stimulus. However, when the test was repeated 24 hours after training, the control group did not avoid entry into DA, whereas the choline-supplemented group either avoided entry or entered after a significantly longer latency period (p < 0.01). These results suggest that supplementation with choline facilitated the consolidation of short-term memory of the avoidance learning into intermediate long-term memory in young rats.

Age Factors↗

Blinking in patients with memory disorders during short term memory tasks.

The occurrence of blinking during short term memory tasks was analyzed for 32 subjects divided into three groups: 12 memory impaired patients, 10 elderly normals (age-matched to the patients), and 10 young normals. The subjects were participating in a study of brain evoked potentials accompanying memory activities. They were instructed not to blink during the performance of the memory tasks for reasons related to the quality of the recorded potentials. In this context, the withholding of blinking can be considered a secondary task. Blinking during the short term memory tasks was inversely related to performance accuracy (r = -.57). Age, mini-mental score and reaction time were also significantly related to the frequency of blinking. Dividing the memory patients into two groups according to the incidence of blinking, ("high-blinking" and "low-blinking"), revealed a significant difference in overall task accuracy with the high-blinking group performing more poorly than the low-blinking group.

Adult↗

Memory functioning in hemiplegics: a neuropsychological analysis of the Wechsler Memory scale.

The Wechsler Memory Scale was administered to 60 hemiplegics and 30 amputees who were matched by age, education, and sex. The results indicated that the orientation subtest has diagnostic value in discriminating between left- and right-sided brain damage in patients and that the right hemisphere may play a proportionately larger role for temporal orientation. The mental control and digits backward subtests seem to be measuring a composite of different cortical functions which are not represented equally in both cerebral hemispheres. Optimal performance on these tests requires interhemispheric integration among these cortical functions. Unilateral damage to either side of the brain would interfere with a special part of the composite function subserved by the damaged hemisphere and produce comparable detrimental effects on performance. The logical memory, digits forward, and associate learning subtests measure memory functions which are equipotentially represented in both hemispheres. Damage to either side of the brain would have no effect on the performance of these tasks. In general, the neuropsychological analysis suggests that the Wechsler Memory Scale has diagnostic value in assessing short-term memory impairment in brain damaged patients. However, memory quotient obtained by summing the total subtest scores has very little value in discriminating between left- and right-sided brain lesions.

Adult↗

A new hypothesis on memory - a possible role of local circuits in the formation of the memory trace.

An hypothesis is proposed arguing that local circuits might work as biochemical units involved in synthesis of macromolecules related to the memory processes. Specific sequences in the activation of local circuits should act as a "template" for the synthesis of particular memory molecules, which, in turn, may facilitate the repetition of the original sequences of bioelectrical signals (short-term memory). The resynthesis of the local memory molecules in cell body areas, their flow to terminal areas via axoplasmic transport and their possible passage to other nerve cells via transynaptic transport might be the basis of long term memory. The role of diffuse neuronal systems (e.g. noradrenaline systems) is discussed in the frame of memory recall and consolidation. The suggested hypothesis can be represented in a very effective way by means of the graph theory.

Animals↗

[Memory function of patients with cerebral arteriosclerosis evaluated by Rivermead behavioural memory test].

Using Rivermead behavioural memory test, we examined 142 patients with cerebral arteriosclerosis. The results showed that the rate of anomalies of screening score in patients with cerebral arteriosclerosis were significantly higher than that of the control group (P < 0.01). The patients and control scores were significantly different (P < 0.05) in all items except the picture and face recognition. Comparing the screening score with brain CT scan, we found a relationship between brain damage and behavioural memory declination. Also, many persons of control group got low scores with behavioural memory test, suggesting that the Rivermead behavioural memory test be sensitive to memory declination. With its simplicity and sensitivity the Rivermead behavioural memory test may have some practical value in China.

Aged↗

Sensory-specific and fractional disorders of recent memory in man. I. Isolated loss of visual recent memory.

Two patients who lost, in isolation, visual recent memory following bilateral posterior cerebral artery infarctions are described. Tactile, verbal, and nonverbal auditory recent memory functions were preserved in both patients. Based on computerized tomography scans and behavioral and anatomical data in monkey, isolated loss of visual recent memory in man is best understood as a bilateral disconnection syndrome between the striate cortex and the structures in the medial temporal lobe that are involved with recent memory. The possible existence of two other sensory-specific disorders of recent memory, tactile and auditory, is postulated, and the clinical relationship of prosopagnosia, achromatopsia, and spatial disorientation to visual recent memory loss is discussed.

Adult↗

Multiple memory deficits in patients with multiple sclerosis. Exploring the working memory system.

Some patients with multiple sclerosis (MS) demonstrate impaired memory. A group of 16 patients with MS who were mildly to moderately affected (Kurtzke Expanded Disability Status Scale Score = 3.8) were studied, and they were compared with a matched control group on tests of "working memory." The working memory system was explored by evaluating the amount of information that can temporarily be held in a buffer system during encoding. Results indicated that patients with MS have difficulty in processing information at the level of a hypothesized articulatory loop in working memory. This deficit was correlated with their retrieval of verbal information from long-term memory, as well as how accurately they processed verbal information presented at a rapid rate. There was no significant relationship between ratings of MS severity or number of plaques visualized on magnetic resonance imaging scans and the degree of working memory deficit.

Adult↗

Reevaluation of the origin of CD44(high) "memory phenotype" CD8 T cells: comparison between memory CD8 T cells and thymus-independent CD8 T cells.

CD44(high)CD8 T cells in naive mice, which increase with age, and are often referred to as memory CD8 T cells. However, since thymus-independent CD8 T cells have also been shown to be CD44(high), the origin of the CD44(high)CD8 T cells in naive mice remains unclear. In this study, we compared the characteristics of memory CD8 T cells and thymus-independent CD8 T cells in TCR transgenic mice to clarify the origin of the CD44(high)CD8 T cells in naive normal mice. The memory and thymus-independent CD8 T cells showed differences in surface molecules, spontaneous cell death, cytokine production, and response to IL-2R binding of cytokines. Importantly, the "memory phenotype" CD8 T cells in naive normal mice showed similar characteristics to the thymus-independent CD8 T cells, but differed greatly from "true" memory CD8 T cells in the TCR transgenic mice. Therefore, we conclude that a significant part of the CD44(high) memory phenotype CD8 T cells in naive normal mice represents thymus-independent CD8 T cells, which may participate in age-related changes in immune responses.

Animals↗

Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: To delineate the mechanism of the abnormalities in B cell biology found in patients with primary Sjögren's syndrome (SS). METHODS: The distribution of peripheral B cell subpopulations in 21 patients with primary SS was analyzed by immunofluorescence labeling and flow cytometry. Immunoglobulin rearrangements were analyzed in single B cells isolated from the peripheral blood and parotid glands by fluorescence-activated cell sorting. RESULTS: A significant reduction in the number of peripheral CD27+ memory B cells was found in SS patients, including a significantly reduced number of CD27+/IgD+/IgM+/CD5+ memory B cells. Remarkably, SS patients with secondary lymphoma uniquely exhibited an increase in CD27-expressing peripheral B cells, including CD27(high) plasmablasts. Molecular analysis for mutated Ig gene rearrangements confirmed that CD27 expression distinguished naive and memory cells in SS. In contrast to the peripheral blood, the majority of parotid B cells from 1 patient examined exhibited both the mutational status and phenotype of memory B cells. Accordingly, the mutational frequencies of V(H) rearrangements were significantly greater in parotid B cells than in peripheral blood B cells, whereas the V(H) gene repertoire appeared to be very similar between the compartments. CONCLUSION: These data indicate that there is an accumulation/retention of memory B cells in the inflamed salivary glands of SS patients. It is possible that preferential accumulation of CD27+ memory B cells in the inflamed parotid gland explains their reduction in the peripheral blood.

Adult↗

Neuronal activity related to visual recognition memory: long-term memory and the encoding of recency and familiarity information in the primate anterior and medial inferior temporal and rhinal cortex.

Recordings of the activity of 2705 single neurones were made in entorhinal and perirhinal cortex, area TG of the temporal lobe, and the inferior temporal cortex both during monkeys' performance of a serial recognition memory task using complex pictures and when monkeys were shown objects. Responses of 120 (9.7%) of the visually responsive neurons recorded were significantly smaller to the second than to the first presentations of unfamiliar stimuli. The incidence of such responses was highest in perirhinal cortex plus areas TE1 and TE2 of the temporal lobe, intermediate in lateral entorhinal cortex and areas TE3 and TG, and lowest in other parts of entorhinal and inferior temporal cortex. Response decrements were maintained across 20 or more intervening presentations of other stimuli for the majority of the neurones tested. Responses of 43 (14.4%) of the visually responsive neurones tested were significantly greater to unfamiliar than to highly familiar stimuli. Such differential responses were found only in lateral entorhinal and perirhinal cortex plus areas TG, TE1, TE2 and TE3. For 6 neurones the response difference was significant even when the familiar stimuli had not been seen for more than 24 h: such neurones demonstrate access to information stored in long-term memory for more than 24 h. Seven familiarity neurones signalled information concerning the relative familiarity of stimuli but not information concerning how recently they were last seen; 58 recency neurones signalled information concerning the recency of presentation of stimuli, but not their relative familiarity. Thus certain neurones demonstrate the separable encoding of recency and familiarity information. Neurones signalling information of use for recognition memory are found in cortex close to the rhinal sulcus where lesions result in major deficits in the performance of recognition memory tasks. The conjunction of these findings provides strong evidence for the importance of these neurones and this cortex for processes (recency and familiarity discrimination) necessary for recognition and working memory. The possible relation of the neuronal responses to priming memory is also discussed.

Animals↗