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Focal retrograde amnesia: a long term clinical and neuropsychological follow-up.

A patient (E.D.) who had displayed a selective retrograde amnesia in association with transient amnesic episodes (Kapur et al., 1986) was reexamined five years after initial assessment. At the clinical level, his transient amnesic attacks continued, but some of these had clear epileptic features. In addition, EEG investigation indicated temporal lobe abnormality, more prominent in the left temporal region, and supported a clinical diagnosis of temporal lobe epilepsy. Both CT scanning and magnetic resonance imaging were unable to detect the presence of any structural lesion. At the neuropsychological level, there was no evidence of dementia in the form of generalized cognitive dysfunction nor significant deterioration in cognitive functioning since the earlier assessment. Our patient continued to show marked memory loss for public events over the past 20-30 years, in the context of normal or near normal performance on most tests of anterograde memory functioning. While memory for famous scenes and famous faces was markedly impaired, our patient's memory for famous cars was within normal limits and his memory for autobiographical events showed only patchy impairment. Although E.D. performed at an average or above average level on most standard tests of anterograde memory functioning, our patient did show evidence of significant memory loss for public events which had occurred over the past ten years (i.e. since the onset of his illness). The possibility is raised that E.D.'s memory disorder may represent a form of disconnection syndrome.

Aged↗

Memory abilities in children with Williams syndrome.

Williams syndrome (WS) is a rare genetic condition characterised by intellectual disability, typical facial dysmorphology and several medical anomalies. A specific neuropsychological profile with a dissociation between language (relatively preserved) and visuo-spatial abilities (more seriously impaired) has been hypothesised in these children. Memory abilities of these patients have not been adequately investigated, although they may substantially contribute to better understanding their neuropsychological profile. The present study aimed at investigating verbal and spatial memory in patients with WS (N = 16). Their performance was compared with that of normally developing children on tasks of verbal and spatial span and immediate and delayed recall of verbal and visuo-perceptual materials. Memory abilities of WS children appear to be characterised by defective visuo-spatial memory, both in the short-term and long-term domain, and a dissociation between normal short- but deficient long-term verbal learning. Results are interpreted by supporting the thesis that intellectual disability reflects the defective functioning of a complex system in which some cognitive competencies may be disrupted more than others (Detterman, 1987; Vicari, Albertini and Caltagirone, 1992).

Child↗

Effects of starvation in infancy (pyloric stenosis) on subsequent learning abilities.

The model of starvation in this study was the medical condition of congenital hypertrophic pyloric stenosis. Pyloric stenosis involves a period of brief starvation in early infancy, is unrelated to socioeconomic conditions, and is easily correctable. A number of specific learning abilities together with the general adjustment of 50 subjects, 5 to 14 years old, who had PS were studied and compared to those of 44 siblings and 50 matched controls. Learning ability was negatively correlated with the degree of severity of the starvation. Starvation resulting in reduction of more than 10% of the expected body weight in infancy was associated with poorer learning abilities, especially those involving short-term memory and attention.

Adolescent↗

Cognitive change in motor neurone disease/amyotrophic lateral sclerosis (MND/ALS).

A motor neuronopathy complicating frontotemporal dementia (FTD) has been recognised and designated FTD/motor neurone disease (MND). FTD is characterised by profound character change and altered social conduct, and executive deficits, reflecting focal degeneration of the frontal and temporal neocortex. The motor neuronopathy comprises bulbar palsy and limb amyotrophy. The major histological change is typically of microvacuolation of the cerebral cortex, with atrophy of the bulbar neurones and anterior horn cells of the spinal cord. Ubiquitinated inclusion bodies occur in large pyramidal cortical neurones and in surviving cranial nerve nuclei and anterior horn cells. Evidence is emerging that some patients with classical MND/amyotrophic lateral sclerosis (ALS), who are thought not to be demented, develop cognitive deficits in the realm of frontal executive functions. Moreover, frontal lobe abnormalities have been demonstrated by neuroimaging. The findings point to a link between FTD/MND and cMND/ALS and suggest that a proportion of patients with cMND/ALS go on to develop FTD. Patients with cMND/ALS may not be equally vulnerable. The hypothesis is that patients who present with bulbar palsy and amyotrophy, rather than corticospinal and corticobulbar features, may be most susceptible to the development of FTD.

Amyotrophic Lateral Sclerosis↗

Deficits of working memory during mental calculation in patients with Parkinson's disease.

Using the dual task paradigm, previous studies have suggested that working memory (WM) deficit is due to depleted attention resources in patients with Parkinson's disease (PD). The aim of this study is to establish whether the WM problems in PD are due to reduced attentional set-shifting resources rather than depletion of attention resources. The task design attempts to eliminate confounding of the deficits in dealing with novel material, a problem documented in PD, by concentrating on WM tasks of mental calculation that are familiar to subjects in daily living. We also administered attention tasks, the Trail Making Test (TMT) that relies primarily on attentional set-shifting and the Kana (Japanese syllabogram) Pick-out Test instead primarily depending on depleted attention resources for allocation. A total of 24 patients with PD and 24 normal controls participated in this study. The PD group showed deficits in mental calculation span and in attentional set-shifting in the TMT-b.Considering the common deficits in alternating processing of mental calculation and TMT-b in PD, the results suggested that the central executive dysfunction in PD during mental calculations was due to reduced attentional set-shifting resources for rapidly alternating operations, rather than the depletion of attentional resources.

Adult↗

Striatal transplants prevent AF64A-induced retention deficits.

The relevance of the cholinergic system in mnemonic processes has been repeatedly demonstrated. In addition to the cholinergic systems that project to the telencephalon, there are subcortical nuclei with intrinsic cholinergic cells which appear to be involved in memory consolidation; among these is the striatum. Intrastriatal administration of anticholinergic drugs, as well as excitotoxic and electrolytic lesions have been shown to disrupt the acquisition and retention of instrumentally conditioned behaviors. In the present study male Wistar rats were used to confirm the reported detrimental effects of striatal lesions produced by the cholinotoxin AF64A on long-term retention (LTR) of inhibitory avoidance and spontaneous locomotor activity, to determine its effects on short-term retention (STR) and to investigate whether intrastriatal homotopic transplants can reverse the AF64A-induced behavioral deficits. AF64A-striatal lesions did not interfere with STR but disrupted LTR of the inhibitory avoidance task, and striatal transplants prevented this deficit. Spontaneous locomotor activity increased after the lesion but promptly returned to baseline levels. These results support previous findings showing striatal involvement in long-term but not short-term retention and indicate that homotopic transplants induce behavioral recovery of a learning task in striatal lesioned rats.

Acetylcholinesterase↗

WAY 100635, a 5-HT1A receptor antagonist, prevents the impairment of spatial learning caused by blockade of hippocampal NMDA receptors.

We studied the effect of WAY 100635, a 5-HT1A receptor antagonist, on the impairment of spatial learning caused by intrahippocampal injection of 3-((R)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive NMDA receptor antagonist, in a two-platform spatial discrimination task. CPP, 3 and 10 ng/microl, administered bilaterally into the CA1 region of the dorsal hippocampus 10 min before each training session, dose-dependently reduced choice accuracy in the two-platform spatial discrimination task with little or no effect on choice latency and errors of omission. A volume of 10 ng/microl intrahippocampal CPP did not affect choice accuracy or latency of a non-spatial visual discrimination task. Subcutaneous doses of 0.3 and 1 mg/kg WAY 100635 did not modify the choice accuracy, but prevented the impairment caused by 10 ng/microl intrahippocampal CPP. A dose of 20 ng/microl WAY 100635 into the dorsal hippocampus prevented the deficit caused by 10 ng/microl CPP administered in the same region. The results suggest that blockade of 5-HT1A receptors can compensate the loss of NMDA-mediated excitatory input to pyramidal cells in the hippocampus. These findings may have clinical relevance for the symptomatic treatment of memory disorders associated with reduced glutamate transmission mediated by NMDA receptors.

Animals↗

Contributions of the entorhinal cortex, amygdala and hippocampus to human memory.

Recent studies have indicated that, in the monkey, the rhinal cortex (consisting of the entorhinal and perirhinal cortices) is more important to visual recognition memory than the hippocampus or amygdala. The present study investigated the role of the entorhinal cortex in humans using memory scores from surgical epilepsy patients classified according to their mesial temporal lobe pathology. The temporal lobe removals included 4-5 cm of neocortex, amygdala, rhinal cortex and 2-3 cm of the hippocampus and parahippocampal gyrus. Compared to autopsied control subjects, all of the patients showed significant gliosis in the amygdala, but they differed as to whether or not there were entorhinal and/or hippocampal abnormalities. Both preoperatively and one or more years postoperatively, the patients performed tests of verbal recall (Wechsler Memory Scale Logical Memory), visual recall (Rey Figure), verbal recognition and visual recognition (Warrington Recognition Memory Test: Words and Faces, respectively). Preoperatively, patients with hippocampal pathology showed deficits in visual recall. Postoperatively, a significant drop in verbal and visual recall was seen only for patients who lost intact hippocampal tissue, irrespective of the condition of the excised entorhinal cortex. Together, the results argue that the hippocampus is more important than the entorhinal cortex for the recall of newly learned information.

Adolescent↗

Intact temporal memory in amnesic patients.

Current theories propose that amnesia is caused by an inability to encode the temporal properties of recent events and/or to associate information across time. The present investigation tested this postulation by manipulating the recency effect which is theorized to be caused by the encoding of temporal information. The continual-distractor paradigm was used to vary the temporal properties of recently presented lists. Amnesics' recall responded normally to the temporal manipulations in lists ranging from 18-54 s. In contrast, overall recall was impaired compared to normals in all conditions and across all positions, including the final position. These findings dissociate memory for temporal information from overall levels of recall. They suggest that the amnesic patient's memory deficit is not caused by an inability to encode temporally associated information.

Aged↗

The dependence of span and delayed-response performance on prefrontal cortex.

Theoretical and empirical research on the cognitive functions of the prefrontal cortex have established that this region mediates what have been called 'executive' processes that can influence working and long-term memory. Despite the accumulation of such empirical evidence, the dependence of purely mnemonic portions of memory tasks on PFC remains unresolved. To address this issue, we performed an analysis of reports of performance on tests of working memory of patients with lesions of the dorsolateral prefrontal cortex, focusing on published reports in the literature of simple span and delayed-response tasks. We found that none of the eleven studies of forward verbal and spatial span in patients with prefrontal cortical lesions that we reviewed (reflecting the performance of 166 individual patients) demonstrated a statistically significant deficit relative to normal controls. In contrast, our review of the delayed-response literature indicated that there are conditions under which PFC lesions disrupt delayed-response performance. Based on the results of our review of the literature, we present testable hypotheses about the working memory functions of the PFC.

Attention↗

Working memory deficits in BXSB mice with neocortical ectopias.

Approximately 40-60% of BXSB/MpJ-Yaa mice exhibit neocortical ectopias, which are misplaced clusters of neurons in layer I of cortex. These ectopias are usually located in the prefrontal and/or motor region of cortex in BXSB mice, and are similar in appearance to those found in postmortem analyses of the brains of dyslexic humans. Several within-strain learning differences between mice with ectopias and those without have been reported. In particular, ectopic BXSB mice exhibited superior reference memory learning, but inferior working memory learning in several studies from our laboratory. This study used the Morris water maze delayed matching-to sample task and the water radial-arm maze to asses working memory in female BXSB mice with and without ectopias. In the delayed matching-to sample task, a hidden escape platform remained in a constant position for each four-trial session, but changed position between sessions. Trial 2 was the measure of working memory, i.e., how well did the mouse remember where the platform was located for that session. In the water version of the eight-arm radial maze, hidden escape platforms were located in four of the eight arms, and each platform was removed from the maze once found. This enabled us to assess working and reference memory simultaneously. Ectopic mice demonstrated working memory deficits during the first part of the delayed matching-to sample task compared to nonectopics. Similarly, ectopics made more working memory errors during the latter half of radial-arm maze testing, while not differing from nonectopics in reference memory performance. Additionally, there were significant correlations between measures of working memory in the radial-arm maze and working memory in a delayed matching-to-sample task. These findings are in agreement with other studies demonstrating working memory deficits in ectopic BXSB mice.

Animals↗

Brief retention deficits associated with cyclically recurring left hemisphere events.

In the chick, brief episodes of enhanced recall ("retrieval events") recur approximately every 25 min in recall via the right hemisphere, and every 16 min in recall via the left. These events coincide with, and probably cause, the numerous transitions between memory phases described in the chick.; The most important of these is the transition to long-term memory, which is sometimes held to occur in chicks at about 50 min after learning, a transition picked out as unique by a variety of effects of amnesia-inducing agents, and by a brief impairment ("dip") in recall at 55 min. We used a single trial passive avoidance task, involving bead pecking, to show that in chicks using only one eye, such dips occur not only at 55 min (in right-eyed chicks only) but also after each of the subsequent series of left hemisphere events (in left-eyed chicks only). Dips in recall appear to result when processes that are initiated by left hemisphere retrieval events result in hemispheric interaction, with one hemisphere (which can be either left or right) holding an inadequate trace (e.g., as a result of monocular training). Recall tests under such conditions may involve both the adequate and the inadequate trace, so that performance is impaired.

Animals↗

GM1 produces attenuation of short-term memory deficits in Hebb-Williams maze performance after unilateral entorhinal cortex lesions.

The Hebb-Williams maze was used to examine spatial abilities of adult male Sprague-Dawley rats with unilateral electrolytic entorhinal cortex lesions. The injured rats were treated for 14 days with either saline or ganglioside GM1. Testing was begun 7 weeks following injury, and involved 12 maze problems with independent configurations, with immediate starting replacement used for the six trials per problem. Compared to sham-operated counterparts, the rats with lesion plus saline treatment were impaired in total number of errors, initial entry errors, and repeat errors over 12 consecutive problems. GM1-treated rats showed improved performance, making significantly fewer total and repeat errors, indicating that this substance may be potentially useful as therapy after entorhinal cortex injury.

Analysis of Variance↗

[Trichloroethylene intoxication presenting with temporal seizures].

INTRODUCTION: Trichloroethylene (TCE) is extensively used as a degreasing agent in the metal industry and as a solvent for organic compounds. Its neurotoxicity (with respect to both the peripheral and central nervous systems) is now widely acknowledged. OBSERVATION: Here, we report the case of a 32-year-old male drug addict presenting temporal seizures after "huffing" TCE (i.e. voluntary inhalation). The patient also deve loped a "psycho-organic syndrome" which included cognitive dysfunction (with memory disorders in particular) and personality changes. These disorders had not been noticed by the patient's wife prior to the last episode of inhalation. Four months later, the cognitive disorders had stabilized and no further seizures had been observed. CONCLUSION: The patient's overall clinical picture (notably featuring neuropsychological disorders) and electroencephalographic and brain imaging data argue in favor of a selective effect of TCE on the temporal lobe.

Adult↗

ZTTA, a postproline cleaving enzyme inhibitor, improves cerebral ischemia-induced deficits in a three-panel runway task in rats.

We investigated the effect of N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylaceta l (ZTTA), a novel postproline cleaving enzyme (prolyl endopeptidase, PPCE) inhibitor, on the in vitro activity of rat brain PPCE and memory impairment induced by cerebral ischemia. ZTTA noncompetitively inhibited rat brain PPCE (ki = 2.9 microM). Cerebral ischemia for 5 min increased the number of errors in a working memory task with a three-panel runway paradigm. ZTTA at 6 mg/kg, administered immediately after blood flow reperfusion, significantly reduced the increase in working memory errors expected to occur 24 h after 5 min of ischemia. The antiamnesic action of ZTTA may be ascribable to a neuroprotective effect on the central nervous system due to some neuropeptides that are substrates of PPCE in the brain.

Animals↗

Prolyl oligopeptidase: an unusual beta-propeller domain regulates proteolysis.

Prolyl oligopeptidase is a large cytosolic enzyme that belongs to a new class of serine peptidases. The enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides, which relate to the induction of amnesia. The 1.4 A resolution crystal structure is presented here. The enzyme contains a peptidase domain with an alpha/beta hydrolase fold, and its catalytic triad (Ser554, His680, Asp641) is covered by the central tunnel of an unusual beta propeller. This domain makes prolyl oligopeptidase an oligopeptidase by excluding large structured peptides from the active site. In this way, the propeller protects larger peptides and proteins from proteolysis in the cytosol. The structure is also obtained with a transition state inhibitor, which may facilitate drug design to treat memory disorders.

Amino Acid Sequence↗

Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease.

BACKGROUND: We aimed to determine the specificity, sensitivity, and predictive value of apolipoprotein E (APOE) genotyping in 67 consecutive patients with clinical diagnoses of sporadic Alzheimer's disease (AD) who underwent necropsy. METHODS: We studied patients who attended the Duke Memory Disorders Clinic and were diagnosed as having probable AD. These patients were followed up until they died. APOE genotyping was done during life in most cases, but in some brain tissue obtained at necropsy was used. Members of known AD families were excluded. FINDINGS: After neuropathological examination 57 (85%) of 67 of our patients were confirmed as having AD including all 43 who had at least one APOE-epsilon 4 allele. None of the patients found not to have AD carried an epsilon 4 allele. In this series, the specificity of the epsilon 4 allele was 100%, the sensitivity 75%, the positive predictive value 100%, and the negative predictive value 42%. In this necropsy-confirmed series, the epsilon 4/epsilon 4 genotype predicted AD with 100% accuracy. The epsilon 3/epsilon 4 and epsilon 2/epsilon 4 genotypes were also unexpectedly highly specific for AD. INTERPRETATION: Data from hundreds of necropsy-confirmed non-AD patients in other longitudinal necropsy series will allow the predictive value of APOE genotypes to be assessed with useful confidence limits.

Alleles↗