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Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers.

Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia.

Adult↗

Effect of memory support and elicited production on fast mapping of new words by adolescents with Down syndrome.

PURPOSE: The purpose of this study was to determine whether memory support and elicited production differentially benefited fast mapping of new vocabulary (comprehension, production accuracy, and speed) in adolescents with Down syndrome (DS) compared with typically developing (TD) children matched for syntax comprehension. The study also examined predictors of individual difference within groups. METHOD: The ability of 19 adolescents with DS to fast map new noun vocabulary was compared with 18 TD children matched for syntax comprehension. The effects of memory support (5 examiner repetitions of the novel word vs. 1) and elicited production (2 repetitions by child vs. none) were evaluated in a repeated-measures design with counterbalancing of tasks. RESULTS: For novel word comprehension, low memory support impaired the TD but not DS participants. DS participants were slower to respond correctly in all conditions but benefited more from memory support than TD participants in speed of response. For novel word production, high memory support benefited all participants in the no-elicited-production condition. Elicited production improved performance equally in the 2 memory conditions. Standard comprehension measures predicted fast-mapped comprehension: vocabulary in the case of the DS group, syntax in the case of the TD group. Auditory short-term memory measures predicted fast-mapped production in the TD group but not the DS group. Hearing and grammatical morpheme comprehension predicted novel word production in the DS group. CONCLUSIONS: DS participants' speed of comprehension of fast-mapped words was differentially increased compared with the TD syntax-comprehension-matched group, by memory support. Elicited production improved production fast-mapping for all participants, and memory support improved it in the absence of elicited production. Comprehension predicted individual differences in fast-mapped comprehension in DS; in addition, hearing predicted production.

Adolescent↗

Memory systems analyses of mnemonic disorders in aging and age-related diseases.

The effects upon memory of normal aging and two age-related neurodegenerative diseases, Alzheimer disease (AD) and Parkinson disease, are analyzed in terms of memory systems, specific neural networks that mediate specific mnemonic processes. An occipital memory system mediating implicit visual-perceptual memory appears to be unaffected by aging or AD. A frontal system that may mediate implicit conceptual memory is affected by AD but not by normal aging. Another frontal system that mediates aspects of working and strategic memory is affected by Parkinson disease and, to a lesser extent, by aging. The aging effect appears to occur during all ages of the adult life-span. Finally, a medial-temporal system that mediates declarative memory is affected by the late onset of AD. Studies of intact and impaired memory in age-related diseases suggest that normal aging has markedly different effects upon different memory systems.

Adult↗

Organizational and visual memory deficits in schizophrenia and bipolar psychoses using the Rey-Osterrieth complex figure: effects of duration of illness.

Verbal declarative memory deficits in schizophrenia are well documented whereas visual declarative memory is less studied. Moreover, there are limited data on whether organizational and visual memory deficits are specific to schizophrenic psychoses. We compared visual memory and organizational function in patients with chronic schizophrenia (n=79) and chronic bipolar psychotic disorder (n=14), and in healthy controls (n=84) using the Rey-Osterrieth Complex Figure (ROCF), testing whether organizational impairments (i.e., executive dysfunctions) account for the visual memory deficit. Groups were comparable on age, handedness and expected intellectual ability (based on single word reading). Using analyses of covariance with sex, parental SES and ethnicity as co-variates, patients with schizophrenia were significantly more impaired than controls on copy accuracy, on recall accuracy, and on percent accuracy of recall. Patients with schizophrenia used a more detail-oriented style on copy and recall and had significantly worse recognition memory. After co-varying IQ, copy organization was also significantly different between the groups. Results for accuracy of copy and recall were not significantly attenuated when controlling for copy organization. Duration of illness was associated with visual memory. Bipolar patients performed at an intermediate level between controls and patients with schizophrenia. The data suggest that in schizophrenia, patients have a visual memory disorder characterized by both organizational processing impairments and retention difficulties, and that there is a decline in visual memory functions with duration of illness. Further research is required to determine whether similar mechanisms underlie the neurocognitive deficits in these psychotic disorders.

Adult↗

Memory skills elders want to improve.

While many research studies have investigated memory training for elders, none have asked which specific memory skills elders would like to improve. This study investigates two related questions. First, which memory skills elders would like to improve? Second, is there a common set of these memory skills? Elders completed a three-part questionnaire. First, it asked for subject demographics. Second, it asked for the first, second, third, and then all other memory skills they would most like to improve. Finally, it asked elders to rate the importance of 10 specific memory skills. The results indicate that elders share a common set of memory skills they wish to improve. They are: (a) people's names, (b) important dates, (c) location of household objects, (d) recent and past events, (e) meetings and appointments, (f) information and facts, (g) general improvement, and (h) medication. One conclusion from these findings is that at least some memory training research should focus on these specific memory skills.

Aged↗

Simulating episodic memory deficits in semantic dementia with the TraceLink model.

Although semantic dementia is primarily characterised by deficits in semantic memory, episodic memory is also impaired. Patients show poor recall of old autobiographical and semantic memories, with better retrieval of recent experiences; they can form new memories, and normal performance on pictorial recognition memory has been demonstrated. As these abnormalities in episodic memory are virtually a mirror image of those seen in the amnesic syndromes, semantic dementia poses a challenge to extant models of remote memory and amnesia. Here, we show that one such model, TraceLink, can reproduce some of the principal findings on episodic memory in semantic dementia. A loss of nodes and connections within the trace system, which can be identified with the temporal neocortical memory storage sites implicated in semantic dementia, simulates without further assumptions the findings reported above.

Amnesia↗

Loss of memory for people following temporal lobe damage.

A 40-yr-old woman, K.S., is reported, who shows a severe loss of memory for people following a history of epilepsy and right anterior temporal lobectomy. Despite this memory problem, K.S. is not clinically amnesic, has a Memory Quotient of 122 on the Wechsler Memory Scale in line with her IQ of 119, and performs well on conventional tests of recognition and recall. She does not have a generalized semantic memory deficit for living things, but her deficit extends beyond people to include famous animals, buildings and product names. Autobiographical memory is good, except where memory for people is concerned. The nature of the memory store that is impaired in K.S. is discussed, as are the implications of her case for theories of the organization of long-term memory.

Adult↗

Sleep, memory, and learning.

The relationship of sleep to memory and learning is complex. Sleep affects memory, and memory must be present for learning to occur. A number of studies have been conducted to increase our understanding of their relationship. In addition to the numerous scientific investigations of each concept separately, sleep, memory, and learning have been studied together to determine (a) the effect of sleep on memory and learning, (b) the effect of sleep deprivation in general on memory and learning, (c) the effect of rapid eye movement (REM) sleep deprivation on memory and learning, (d) the effect of memory and learning on REM sleep, and (e) the effect of non-REM sleep loss on memory and learning. Neuroanatomic correlates have been pursued as well with most attention to the hippocampus. Despite considerable efforts to date, many of the studies reveal contradictory or inconclusive findings. Much remains unknown, and additional work is needed. Implications for nursing include those that have a direct effect on the patient, the nurse, and nursing science.

Health Promotion↗

Memory, language, and ageing.

This overview provides both theoretical and empirical reasons for emphasizing practice and familiar skills as a practical strategy for enhancing cognitive functioning in old age. Our review of empirical research on age-related changes in memory and language reveals a consistent pattern of spared and impaired abilities in normal old age. Relatively preserved in old age is memory performance involving highly practised skills and familiar information, including factual, semantic and autobiographical information. Relatively impaired in old age is memory performance that requires the formation of new connections, for example, recall of recent autobiographical experiences, new facts or the source of newly acquired facts. This pattern of impaired new learning versus preserved old learning cuts across distinctions between semantic memory, episodic memory, explicit memory and perhaps also implicit memory. However, familiar verbal information is not completely preserved when accessed on the output side rather than the input side: aspects of language production, namely word finding and spelling, exhibit significant age-related declines. This emerging pattern of preserved and impaired abilities presents a fundamental challenge for theories of cognitive ageing, which must explain why some aspects of language and memory are more vulnerable to the effects of ageing than others. Information-universal theories, involving mechanisms such as general slowing that are independent of the type or structure of the information being processed, require additional mechanisms to account for this pattern of cognitive aging. Information-specific theories, where the type or structure of the postulated memory units can influence the effects of cognitive ageing, are able to account for this emerging pattern, but in some cases require further development to account for comprehensive cognitive changes such as general slowing.

Adult↗

Assessment of short-term verbal memory impairments in adolescents and adults with ADHD.

The purpose of this study was to determine whether a brief measure of verbal memory can assess short-term verbal memory impairments relative to verbal abilities in adolescents and adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and to ascertain whether significant differences between short-term verbal memory and verbal abilities are more common among persons with ADHD than in the general population. One hundred seventy-six adolescents and adults diagnosed with ADHD (DSM-IV criteria) were assessed with a measure of short-term verbal memory. The short-term verbal memory score of each subject was compared with the verbal abilities on two measures. Percentages of ADHD subjects with "significant discrepancy" between verbal IQ and short-term verbal memory were compared with the standardization sample for the verbal memory measure. A majority of adolescents and adults diagnosed with ADHD demonstrated significant discrepancy between performance on the short-term verbal memory measure and verbal IQ. The percentage of ADHD subjects with a significant discrepancy between these two measures greatly exceeded the percentage of persons in the general population showing such a discrepancy. This brief measure of short-term verbal memory may be a useful measure to include in a comprehensive assessment for ADHD symptoms in adolescents and adults. Replication in other groups of ADHD patients is needed to test the generalizability of the findings.

Adolescent↗

MRI hippocampal volumes and memory function before and after temporal lobectomy.

We investigated the relationship between preoperative MRI hippocampal volumes and clinical neuropsychological memory test data obtained before and after temporal lobectomy and amygdalohippocampectomy for intractable epilepsy in 44 left (LTL) and 36 right (RTL) temporal lobectomy patients. In LTL patients, the difference (right minus left hippocampal volume) between hippocampal volumes (DHF) was significantly (p < 0.001) correlated (r = 0.61) with postoperative verbal memory change as measured by a delayed memory percent retention score from the Wechsler Memory Scale-Revised, Logical Memory subtest. DHF was also positively associated with postoperative memory for abstract geometric designs in LTL patients (r = 0.49, p < 0.005). Resection of a relatively nonatrophic left hippocampus was associated with poorer verbal and visual memory outcome. In RTL patients, larger right adjusted (for total intracranial volume) hippocampal volume was associated with decline in visual-spatial learning, but not memory, following surgery. MRI hippocampal volume data appear to provide meaningful information in evaluating the risk for memory impairment following temporal lobectomy.

Adult↗

Forgetting, reminding, and remembering: the retrieval of lost spatial memory.

Retrograde amnesia can occur after brain damage because this disrupts sites of storage, interrupts memory consolidation, or interferes with memory retrieval. While the retrieval failure account has been considered in several animal studies, recent work has focused mainly on memory consolidation, and the neural mechanisms responsible for reactivating memory from stored traces remain poorly understood. We now describe a new retrieval phenomenon in which rats' memory for a spatial location in a watermaze was first weakened by partial lesions of the hippocampus to a level at which it could not be detected. The animals were then reminded by the provision of incomplete and potentially misleading information-an escape platform in a novel location. Paradoxically, both incorrect and correct place information reactivated dormant memory traces equally, such that the previously trained spatial memory was now expressed. It was also established that the reminding procedure could not itself generate new learning in either the original environment, or in a new training situation. The key finding is the development of a protocol that definitively distinguishes reminding from new place learning and thereby reveals that a failure of memory during watermaze testing can arise, at least in part, from a disruption of memory retrieval.

Amnesia, Retrograde↗

Molecular approaches to learning and memory.

We are now at the stage of neurophysiology where learning and memory can be subjects of studies at a strictly molecular level, on the basis of the well-established finding that these higher nervous activities are sustained by, and formed in, the physicochemical events of specified neural mechanisms in the brain. As for the neurophysiological process of memory, much evidence has shown that short-term memory and long-term memory probably result from different molecular events in the brain, i.e., the former from reversible chemical modification of the synapses concerned, and the latter from reorganization of the synapses following synthesis of protein and its axonal transport, which causes the enduring consolidation of memories. How does the experience of individual organisms trigger the protein synthesis in the brain required for long-term memory? What is the role of protein molecules thus formed? What is the mechanism for the regulation of gene expression in the reorganization of neuronal circuits? Many such difficult problems need to be solved. Recently, cholinergic and glutamatergic neuron networks have attracted much attention because there is a strong possibility that they play a critical role in memory. The clinical implication of these findings in human memory deficit, as exemplified in senile dementia, further emphasizes the importance of neurobiological elucidation of the molecular mechanism for learning and memory.

Animals↗

[Effects of acute mild and moderate hypoxia on human short memory].

OBJECTIVE: To investigate the effects of acute mild and moderate hypoxia on human short memory. METHOD: Tests of pattern memory, scanning memory, continuous recognition memory and space memory were conducted on 18 healthy young male subjects during exposure to 300 m (control), 2800 m, 3600 m and 4400 m altitude in hypobaric chamber. RESULT: Compared to control group, only the performance of continous recognition memory decreased significantly after exposure to 2800 in for 1 h(P < 0. 05); total reaction time in all tests increased significantly (P < 0.0 1) and performance decreased after exposure to 3600 in for 1 h, but the error rates in memory scanning and space memory test were unchanged (P > 0.05); during exposure to 4400 in performance of all tests decreased further to about 90.4%, 93.7%, 83.3% and 80.7% of the control values (P < 0.01), respectively,and error rate increased significantly too (P < 0.05). CONCLUSION: Performance of human short memory decreased after exposure to acute mild and moderate hypoxia for 1 h, and these effects were aggravated with the increase of altitude. Characteristic and threshold of the effect on the various performance tests were different, but increase of reaction time was the first to appear in all cases.

Aerospace Medicine↗

Nitric oxide is necessary for multiple memory processes after learning that a food is inedible in aplysia.

Nitric oxide (NO) signaling was inhibited via N(omega)-nitro-L-arginine methyl ester (L-NAME) during and after training Aplysia that a food is inedible. Treating animals with L-NAME 10 min before the start of training blocked the formation of three separable memory processes: (1) short-term, (2) intermediate-term, and (3) long-term memory. The treatment also attenuated, but did not block, a fourth memory process, very short-term memory. L-NAME had little or no effect on feeding behavior per se or on most aspects of the animals' behavior while they were being trained, indicating that the substance did not cause a pervasive modulation or poisoning of many aspects of feeding and other behaviors. Application of L-NAME within 1 min after the training had no effect on short- or long-term memory, indicating that NO signaling was not needed during memory consolidation. Treating animals with the NO scavenger 2-phenyl-4,4,5,5-tetramethyl-imidazdine-1-oxy-3-oxide before training also blocked long-term memory. Memory was not blocked by D-NAME, or by the simultaneous treatment with L-NAME and the NO donor S-nitroso-N-acetyl-penicillamine, confirming that the effect of L-NAME is attributable to its effect as a competitive inhibitor of L-arginine for NO synthase in the production of NO rather than to possible effects at other sites. These data indicate that NO signaling during training plays a critical role in the formation of multiple memory processes.

Animals↗

[The profile of memory disturbance in early Lewy body dementia differs from that in Alzheimer's disease].

It may be difficult to distinguish Lewy body dementia (LBD) from Alzheimer's disease (AD) especially at an early stage. Clinical diagnostic criteria for LBD still lack sensitivity. We compared memory performance in early AD and LBD to identify features that may help to distinguish these two conditions. Patients with Mini Mental State scores equal or above 18 were consecutively selected retrospectively from the University Out-patient Memory Clinic database. Probable LBD and AD were respectively diagnosed according to the international consensus criteria and the NINCDS-ADRDA criteria. Short-term memory was assessed with the digit span subtest of the Wechsler Memory Scale and the Corsi block-tapping test. Long term verbal memory was assessed with a French version of the Grober and Buschke test. Long-term visual memory was tested with the recall of four geometric figures of the CERAD battery. There was no difference between the two groups in short-term or long-term visual memory. Except for the immediate and first free recalls, DCL patients performed significantly better than AD patients in all subtests of the Grober and Buschke test. The more striking differences were seen with the third total and delayed total recall. These results highlight the differences of memory impairment pattern in early LBD and AD. Episodic verbal memory is better in LBD patients who benefit more from cues, reflecting the subcortical component of the disease. Such neuropsychological data should be validated prospectively and further be part of the diagnostic criteria.

Aged↗

Estrogen and progesterone improve scopolamine-induced impairment of spatial memory.

This study was conducted to investigate the effects of estrogen and progesterone on spatial memory in ovariectomized female rats, specifically, on memory impaired by the cholinergic antagonist scopolamine. Forty-one female rats were divided into five groups: ovariectomized (OVX), estrogen-treated after ovariectomy (OE), progesterone-treated after ovariectomy (OP), estrogen-progesterone-treated after ovariectomy (OEP), and the sham control group (Control). The animals were trained on an eight-arm radial maze with four arms baited to assess both working and reference memory performances. The OE and OEP groups showed significant improvement in the ability to perform a spatial memory task over the OVX group (P<0.05). Spatial memory in the OP group did not differ from that in the OVX group. After thirty-two trials were conducted and all rats learned the eight-radial maze task, scopolamine hydrobromide (0.2 mg/kg i.p.) was administered prior to retesting. After scopolamine injection, the OVX group showed an increased number of working memory errors, reference memory errors than the other groups (P<0.05). The OE, OEP and OP groups showed significant improvement in spatial impairment induced by scopolamine. These findings suggest progesterone alone or in combination with estrogen, improved scopolamine-induced impairment of working memory and reference memory as effectively as estrogen supplementation.

Analysis of Variance↗

Jian Nao Ning for treatment of memory impairment in patients with mild or moderate multi-infarct dementia.

Forty patients with multi-infarct dementia (MID) were randomly assigned to the treatment group (25 cases) treated with Jian Nao Ning (JNN) and the duxil control group (15 cases). Memory function were assessed at baseline and endpoint using memory subscales of a battery of New Psychometric Tests (Chinese version) including mini-mental state examination (MMSE), verbal memory, and non-verbal memory, etc. After treatment, the mean scores of verbal memory in the Hopkins Verbal Learning Test (P<0.05) and total memory scores of memory items (P<0.001) in JNN group increased significantly; and improvement in episodic memory function including story recall (immediate and delayed), delayed word recall, verbal learning and verbal recognition and visual recognition in the JNN group was better than that in the duxil control group, suggesting that JNN can obviously improve memory function for the patients with mild or moderate multi-infarct dementia.

Aged↗