Relación entre atrofia cortical difusa y desempeño cognitivo : estudio en población mayor de 60 años en un hospital universitario en la ciudad de Bogotá

El presente trabajo tuvo como objetivo evaluar la existencia de la relación entre la atrofia cortical difusa objetivada por neuroimagenes cerebrales y desempeños cognitivos determinados mediante la aplicación de pruebas neuropsicológicas que evalúan memoria de trabajo, razonamiento simbólico verbal y memoria anterógrada declarativa. Participaron 114 sujetos reclutados en el Hospital Universitario Mayor Méderi de la ciudad de Bogotá mediante muestreo de conveniencia. Los resultados arrojaron diferencias significativas entre los dos grupos (pacientes con diagnóstico de atrofia cortical difusa y pacientes con neuroimagenes interpretadas como dentro de los límites normales) en todas las pruebas neuropsicológicas aplicadas. Respecto a las variables demográficas se pudo observar que el grado de escolaridad contribuye como factor neuroprotector de un posible deterioro cognitivo. Tales hallazgos son importantes para determinar protocoles tempranos de detección de posible instalación de enfermedades neurodegenerativas primarias.

Structure and function of declarative and nondeclarative memory systems

This article reviews recent studies of memory systems in humans and nonhuman primates. Three major conclusions from recent work are that (i) the capacity for nondeclarative (nonconscious) learning can now be studied in a broad array of tasks that assess classification learning, perceptuomotor skill learning, artificial grammar learning, and prototype abstraction; (ii) cortical areas adjacent to the hippocampal formation, including entorhinal, perirhinal, and parahippocampal cortices, are an essential part of the medial temporal lobe memory system that supports declarative (conscious) memory; and (iii) in humans, bilateral damage limited to the hippocampal formation is nevertheless sufficient to produce severe anterograde amnesia and temporally graded retrograde amnesia covering as much as 25 years.

Le blocage de la consolidation et de la reconsolidation des souvenirs émotionnels chez l'humain à l'aide du propranolol

Une récente théorie de la mémoire a proposé que lorsqu'un souvenir déjà bien consolidé est réactivé, il redevient labile et susceptible aux modifications avant d'être restabilisé (reconsolidé) en mémoire à long terme. Ce nouveau modèle réfute le modèle classique de la consolidation qui propose qu'une fois consolidés, les souvenirs soient permanents et donc résistants aux effets des agents amnésiques. Les études validant la théorie de la reconsolidation abondent chez les animaux, mais encore peu d'études ont été réalisées chez les humains. L'objectif de cette thèse est de vérifier, dans une population de sujets sains et de sujets souffrant de trouble de stress post-traumatique (TSPT), l'efficacité d'un agent pharmacologique, le propranolol (un β-bloquant noradrénergique) à atténuer des souvenirs émotionnels nouvellement acquis ou déjà bien consolidés. Plus spécifiquement, nous avons mené un essai clinique contrôlé à double insu chez des sujets sains en leur administrant du propranolol (vs du placebo) lors de l'acquisition d'un nouveau souvenir et une semaine plus tard, lors de sa réactivation. L'objectif du premier article était d'évaluer l'efficacité du propranolol à diminuer la consolidation et la reconsolidation d'un souvenir émotionnel. Par ailleurs, puisque les études chez les animaux ont démontré que ces deux processus mnésiques s'effectuent à l'intérieur d'une fenêtre temporelle précise, le moment de l'administration du propranolol fut pris en considération. Les résultats ont démontré que le propranolol est en mesure de diminuer la consolidation et la reconsolidation d'une histoire émotionnelle tel que démontré par un pourcentage de bonnes réponses plus faible que le groupe contrôle lors des rappels. Toutefois, pour que cet effet soit observé, le propranolol doit être administré une heure avant la présentation des stimuli, pour la consolidation et une heure avant leur réactivation, pour la reconsolidation. En outre, les études portant sur la consolidation et la reconsolidation chez les animaux et chez les humains obtiennent parfois des résultats contradictoires. Ceci pourrait s'expliquer par le type de stimuli utilisé. Ainsi, l'objectif du second article était de préciser quel type d'information est le plus susceptible d'être affecté par le propranolol lors de son acquisition (consolidation) et lors de sa réactivation (reconsolidation). Pour ce faire, les éléments de l'histoire émotionnelle ont été divisés en fonction de leur valence (émotionnel ou neutre) et de leur centralité (central ou périphérique). Les résultats ont démontré le propranolol affecte l'ensemble des informations centrales lors du blocage de la consolidation, mais qu'il affecte plus spécifiquement les éléments émotionnels centraux lors de la reconsolidation. Notre groupe ayant précédemment démontré que le traitement avec le propranolol est en mesure de réduire les symptômes de TSPT chez une population clinique, nous nous sommes interrogés sur son efficacité à diminuer la mémoire implicite d'un événement traumatique. Le propranolol a été administré aux participants à 6 reprises (une fois par semaine sur une période de 6 semaines) lors de la réactivation de leur trauma. Les résultats ont révélé que le traitement avec le propranolol est en mesure de diminuer la réponse psychophysiologique des participants à l'écoute du compte rendu de leur trauma une semaine et 4 mois suivant la fin du traitement. En somme, cette thèse démontre que le propranolol est en mesure de bloquer la consolidation et la reconsolidation de souvenirs émotionnels chez l'humain lorsqu'il est administré une heure avant l'acquisition ou la réactivation des souvenirs. Il arrive en outre à atténuer un souvenir déclaratif émotionnel chez des sujets sains, mais également un souvenir implicite chez des sujets souffrant de TSPT. Ainsi, ces résultats ouvrent la voie à la création de nouveaux traitements pour les psychopathologies ayant comme étiologie un souvenir émotionnel intense.

Exercise and cognitive functions in Parkinson's disease: Gender differences and disease severity

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cognitive functioning in the schizophrenia prodrome

In the last decade, there has been an increasing interest in cognitive alterations during the early course of schizophrenia. From a clinical perspective, a better understanding of cognitive functioning in putative at-risk states for schizophrenia is essential for developing optimal early intervention models. Two approaches have more recently been combined to assess the entire course of the initial schizophrenia prodrome: the predictive "basic symptom at-risk" (BS) and the ultra high-risk (UHR) criteria. Basic symptoms are considered to be present during the entire disease progression, including the initial prodrome, while the onset of symptoms captured by the UHR criteria expresses further disease progression toward frank psychosis. The present study investigated the cognitive functioning in 93 subjects who met either BS or UHR criteria and thus were assumed to be at different points on the putative trajectory to psychosis. We compared them with 43 patients with a first episode of psychosis and to 49 help-seeking patient controls. All groups performed significantly below normative values. Both at-risk groups performed at intermediate levels between the first-episode (FE) group and normative values. The UHR group demonstrated intermediate performance between the FE and BS groups. Overall, auditory working memory, verbal fluency/processing speed, and declarative verbal memory were impaired the most. Our results suggest that cognitive impairments may still be modest in the early stages of the initial schizophrenia prodrome and thus support current efforts to intervene in the early course of impending schizophrenia because early intervention may prevent or delay the onset of frank psychosis and thus prevent further cognitive damage.

Efeito agudo do exercício físico associado a praxias ideomotoras sobre as concentrações séricas de cortisol e memória declarativa em indivíduos com idade entre 51 e 74 anos

Introduction: Several modifications are identified as aging, causing more or less limitation imposed by over the years. Among these, one can highlight the different degrees of cognitive decline, particularly memory that can involve the daily activities and the subject functionality. Studies have shown an association between levels of serum cortisol and stress imposed by the exercise on this. However, there are few studies that references the performance on cognitive aspects of declarative memory and cortisol on the exercise in the water with automatic and práxicos movements and moderate. Objective: Check the effect based on the acute physical exercise and práxicos automatic movements on the performance of visual declarative memory and in serum cortisol in subjects aged between 51 and 74 years. Materials and Methods: It builds a survey characterized as cross with a first sample of 32 physically active subjects aged between 51 and 74 years, divided into two exercise groups (March of Automatic Group - MAG and the March of Praxis Group - MPG). We used a probabilistic and random sampling for sample selection. Used the MMSE (Mini Mental State Examination) to check the general cognitive status, visual acuity test - optotypes chart "E" Rasquin and was even used the declarative visual memory test proposed by Nitrini and collaborators (1994), applying before motor stimulation and immediately after, and the day of blood collection with 2 ml for analysis of cortisol hormone. The normality and homogeneity were verified from the Shapiro-Wilk and Levene tests. Thus we adopted a descriptive statistics to characterize the sample. The Split-Plot ANOVA was used along with the paired t-test to verify the identified differences. We adopted a significance level of p <0.05. Results: It was observed that the groups (MAG and MPG) and the anthropometric variables, perceived exertion, education, cognitive assessment and visual acuity showed no significant differences (p > 0.05), showing that the groups are homogeneous, with variables and similar means. After the stimulation session, lasting 30 min, it was observed that the amount of hits for Δ of declarative memory questionnaire visual images increased, presenting significant for both groups (MAG, p < 0.001; MPG, p = 0.042). The same was observed for cortisol concentration with a reduction in the levels immediately after the stimulus (MAG and MPG, p < 0.001). Conclusion: The results showed that the exercises proposed in its acute effect provide significantly memories of gains and also showed a reduction in cortisol levels.

The deferred imitation task as a nonverbal measure of declarative memory.

We tested amnesic patients, patients with frontal lobe lesions, and control subjects with the deferred imitation task, a nonverbal test used to demonstrate memory abilities in human infants. On day 1, subjects were given sets of objects to obtain a baseline measure of their spontaneous performance of target actions. Then different event sequences were modeled with the object sets. On day 2, the objects were given to the subjects again, first without any instructions to imitate the sequences, and then with explicit instructions to imitate the actions exactly as they had been modeled. Control subjects and frontal lobe patients reproduced the events under both uninstructed and instructed conditions. In contrast, performance by the amnesic patients did not significantly differ from that of a second control group who had the same opportunities to handle the objects but were not shown the modeled actions. These findings suggest that deferred imitation is dependent on the brain structures essential for declarative memory that are damaged in amnesia, and they support the view that infants who imitate actions after long delays have an early capacity for long-term declarative memory.

Working memory correlates of three symptom clusters in schizophrenia

Examined whether discrete working memory deficits underlie positive, negative and disorganised symptoms of schizophrenia. 52 outpatients (mean age 37.5 yrs) with schizophrenia were studied using items drawn from the Positive and Negative Syndrome Scale (PANSS). Linear regression and correlational analyses were conducted to examine whether symptom dimension scores were related to performance on several tests of working memory function. Severity of negative symptoms correlated with reduced production of words during a verbal fluency task, impaired ability to hold letter and number sequences on-line and manipulate them simultaneously, reduced performance during a dual task, and compromised visuospatial working memory under distraction-free conditions. Severity of disorganisation symptoms correlated with impaired visuospatial working memory under conditions of distraction, failure of inhibition during a verbal fluency task, perseverative responding on a test of set-shifting ability, and impaired ability to judge the veracity of simple declarative statements. The present study provides evidence that the positive, negative and disorganised symptom dimensions of the PANSS constitute independent clusters, associated with unique patterns of working memory impairment.

Memory disorders in acute encephalitis : A neuropsychological study

Acute encephalitis is an inflammation of the brain, mostly caused by viral infection. A variety of cognitive symptoms may persist after the acute stage, and neuropsychological assessment is crucial in evaluation of the outcome. The most commonly reported sequelae are memory deficits. The main aims of this study were to investigate the types of memory impairment in various encephalitides, the frequency of global amnesia following encephalitis, and the changes in the deficits during follow-up. Between 1 January 1985 and 31 December 1994, 77 adult patients under the age of 75 with acute encephalitis but without alcohol abuse, or coexisting or previous neurological diseases were consecutively referred for neuropsychological examination at the Department of Neurology, Helsinki University Central Hospital. The aetiology was established in 44/77 (57%) patients; 17 had Herpes simplex virus encephalitis (HSVE). Transient amnesia (TENA) at the acute stage of the disease was found in 70% of patients. Furthermore, similarly to brain trauma, TENA was found to indicate cognitive outcome. The frequency of persisting global amnesia syndrome with both anterograde and retrograde amnesia in all encephalitic patients was 6%. One patient had isolated retrograde amnesia, which is very rare. In HSVE the frequency of global amnesia was 12.5%, which is lower than expected. As a group, HSVE patients were not found to have a homogeneous pattern of amnesia, instead subgroups among all encephalitic patients were observed: some patients had impaired semantic memory, some had difficulty predominantly with executive functions and some suffered from an increased forgetting rate. Herpes zoster encephalitis was found to result in mild memory impairment only, and the qualitative features indicated a subcortical dysfunction. On the whole, the cognitive deficits were predominantly found to diminish during follow-up. Progressive deterioration was often associated with intractable epilepsy. The frequency of dementia was 12.5%. In conclusion, the neuropsychological outcome, especially in HSVE, was more favourable than has previously been reported, possibly due to early acyclovir medication. Memory disorders after encephalitis should not be considered uniform, and the need for neuropsychological rehabilitation should be considered case-by-case

Oscillatory brain activity in memory disorders

Neuronal oscillations are thought to underlie interactions between distinct brain regions required for normal memory functioning. This study aimed at elucidating the neuronal basis of memory abnormalities in neurodegenerative disorders. Magnetoencephalography (MEG) was used to measure oscillatory brain signals in patients with Alzheimer s disease (AD), a neurodegenerative disease causing progressive cognitive decline, and mild cognitive impairment (MCI), a disorder characterized by mild but clinically significant complaints of memory loss without apparent impairment in other cognitive domains. Furthermore, to help interpret our AD/MCI results and to develop more powerful oscillatory MEG paradigms for clinical memory studies, oscillatory neuronal activity underlying declarative memory, the function which is afflicted first in both AD and MCI, was investigated in a group of healthy subjects. An increased temporal-lobe contribution coinciding with parieto-occipital deficits in oscillatory activity was observed in AD patients: sources in the 6 12.5 Hz range were significantly stronger in the parieto-occipital and significantly weaker in the right temporal region in AD patients, as compared to MCI patients and healthy elderly subjects. Further, the auditory steady-state response, thought to represent both evoked and induced activity, was enhanced in AD patients, as compared to controls, possibly reflecting decreased inhibition in auditory processing and deficits in adaptation to repetitive stimulation with low relevance. Finally, the methodological study revealed that successful declarative encoding and retrieval is associated with increases in occipital gamma and right hemisphere theta power in healthy unmedicated subjects. This result suggests that investigation of neuronal oscillations during cognitive performance could potentially be used to investigate declarative memory deficits in AD patients. Taken together, the present results provide an insight on the role of brain oscillatory activity in memory function and memory disorders.

Java Memory Model aware Software validation

The Java Memory Model (JMM) provides a semantics of Java multithreading for any implementation platform. The JMM is defined in a declarative fashion with an allowed program execution being defined in terms of existence of "commit sequences" (roughly, the order in which actions in the execution are committed). In this work, we develop OpMM, an operational under-approximation of the JMM. The immediate motivation of this work lies in integrating a formal specification of the JMM with software model checkers. We show how our operational memory model description can be integrated into a Java Path Finder (JPF) style model checker for Java programs.

H.M.'s personal crossword puzzles: understanding memory and language.

The amnesic patient H.M. has been solving crossword puzzles nearly all his life. Here, we analysed the linguistic content of 277 of H.M.'s crossword-puzzle solutions. H.M. did not have any unusual difficulties with the orthographic and grammatical components inherent to the puzzles. He exhibited few spelling errors, responded with appropriate parts of speech, and provided answers that were, at times, more convincing to observers than those supplied by the answer keys. These results suggest that H.M.'s lexical word-retrieval skills remain fluid despite his profound anterograde amnesia. Once acquired, the maintenance of written language comprehension and production does not seem to require intact medial temporal lobe structures.

Visual memory loss and autobiographical amnesia: a case study.

Amnesia typically results from trauma to the medial temporal regions that coordinate activation among the disparate areas of cortex that represent the information that make up autobiographical memories. We proposed that amnesia should also result from damage to these regions, particularly regions that subserve long-term visual memory [Rubin, D. C., & Greenberg, D. L. (1998). Visual memory-deficit amnesia: A distinct amnesic presentation and etiology. Proceedings of the National Academy of Sciences of the USA, 95, 5413-5416]. We previously found 11 such cases in the literature, and all 11 had amnesia. We now present a detailed investigation of one of these patients. M.S. suffers from long-term visual memory loss along with some semantic deficits; he also manifests a severe retrograde amnesia and moderate anterograde amnesia. The presentation of his amnesia differs from that of the typical medial-temporal or lateral-temporal amnesic; we suggest that his visual deficits may be contributing to his autobiographical amnesia.

Visual memory-deficit amnesia: a distinct amnesic presentation and etiology.

We describe a form of amnesia, which we have called visual memory-deficit amnesia, that is caused by damage to areas of the visual system that store visual information. Because it is caused by a deficit in access to stored visual material and not by an impaired ability to encode or retrieve new material, it has the otherwise infrequent properties of a more severe retrograde than anterograde amnesia with no temporal gradient in the retrograde amnesia. Of the 11 cases of long-term visual memory loss found in the literature, all had amnesia extending beyond a loss of visual memory, often including a near total loss of pretraumatic episodic memory. Of the 6 cases in which both the severity of retrograde and anterograde amnesia and the temporal gradient of the retrograde amnesia were noted, 4 had a more severe retrograde amnesia with no temporal gradient and 2 had a less severe retrograde amnesia with a temporal gradient.

Association of retinal arteriolar dilatation with lower verbal memory::The Edinburgh Type 2 Diabetes Study

Abstract


AIMS/HYPOTHESIS:

Retinal vascular calibre changes may reflect early subclinical microvascular disease in diabetes. Because of the considerable homology between retinal and cerebral microcirculation, we examined whether retinal vascular calibre, as a proxy of cerebral microvascular disease, was associated with cognitive function in older people with type 2 diabetes.

METHODS:

A cross-sectional analysis of 954 people aged 60-75 years with type 2 diabetes from the population-based Edinburgh Type 2 Diabetes Study was performed. Participants underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. The Mill Hill Vocabulary Scale was used to estimate pre-morbid cognitive ability. Retinal vascular calibre was measured from an image field with the optic disc in the centre using a validated computer-based program.

RESULTS:

After age and sex adjustment, larger retinal arteriolar and venular calibres were significantly associated with lower scores for the Wechsler Logical Memory test, with standardised regression coefficients -0.119 and -0.084, respectively (p?<?0.01), but not with other cognitive tests. There was a significant interaction between sex and retinal vascular calibre for logical memory. In male participants, the association of increased retinal arteriolar calibre with logical memory persisted (p?<?0.05) when further adjusted for vocabulary, venular calibre, depression, cardiovascular risk factors and macrovascular disease. In female participants, this association was weaker and not significant.

CONCLUSIONS/INTERPRETATION:

Retinal arteriolar dilatation was associated with poorer memory, independent of estimated prior cognitive ability in older men with type 2 diabetes. The sex interaction with stronger findings in men requires confirmation. Nevertheless, these data suggest that impaired cerebral arteriolar autoregulation in smooth muscle cells, leading to arteriolar dilatation, may be a possible pathogenic mechanism in verbal declarative memory decrements in people with diabetes.