The effects of acute and repeated doses of moclobemide on psychomotor performance and cognitive function in healthy elderly volunteers

The effects of moclobemide, a new selective and reversible MAO-A inhibitor, on cognitive function and psychomotor performance were measured in 12 healthy elderly male volunteers (with a mean age of 72.5 years). Subjects received moclobemide 200 mg, amitriptyline (positive internal control) 25 mg or placebo twice daily and were assessed on a battery of psychometric tests on the mornings following the first (acute) day and seventh (sub-chronic) day. The tests were: Choice Reaction Time; Tracking; Critical Flicker Fusion Threshold; Memory Scanning; Continuous Attention Task; the Leeds Sleep Evaluation Questionnaire and a Visual Line Analogue Rating Scale. The results show that amitriptyline produced impairment of cognitive and psychomotor functions. Moclobemide, however, did not disrupt sleep or cause daytime sedation, and remained neutral in the assessment of behavioural toxicity.     

The Effect of Desensitization Protocols on Human Splenic B-Cell Populations In Vivo

Rituximab, intravenous immunoglobulin (IVIG) and rabbit antithymocyte globulin (rATG) all have been suggested to have an effect on antibody producing cells, however, supporting data are lacking. To assess the impact of these agents on splenic B‐cell populations in vivo, we retrospectively examined 25 spleens removed from patients treated with these agents as part of desensitization protocols in either ABO incompatible or positive crossmatch living donor kidney transplantation. These were compared to control (CTL) spleens removed for trauma. CTLs and spleens removed at transplant after multiple pretransplant plasmaphereses (PP) plus low‐dose IVIG showed similar large numbers of naïve B cells (CD20⁺ and CD79⁺), plasma cells (CD138⁺) and memory B cells (CD27⁺ cells). Adding rituximab to this PP/IVIG regimen reduced the number naïve B cells, but had no effect on memory or plasma cells. Combination treatment (PP/IVIG, rituximab and rATG) showed a trend toward the reduction of CD27⁺ cells, but again plasma cells were unchanged. We conclude that none of these protocols reduces splenic plasma cells in vivo. PP/low‐dose IVIG does not alter splenic B cells, but the addition of rituximab decreases mature B cells. Memory B cells may be affected by combination therapy including rATG and requires further study.     

Maturation of executive function in autism.

BACKGROUND: Executive dysfunction has been reported at different ages in autism. It is not clear however, when this impairment emerges or how its expression is affected by development. METHODS: 61 non-mentally retarded autism participants (AUT) and 61 age, gender, and IQ matched typically developing participants (CON) were assessed with two oculomotor executive function tasks, the oculomotor delayed response task (ODR) and the antisaccade task (AS), as well as a visually-guided saccade sensorimotor task (VGS). RESULTS: The AUT group demonstrated impairments in response inhibition and spatial working memory at all ages tested. Developmental improvements in speed of sensorimotor processing and voluntary response inhibition were similar in both groups indicating sparing of some attentional control of behavior. Developmental progression in the speed of initiating a cognitive plan and maintaining information on line over time, however, was impaired in the AUT group indicating abnormal development of working memory. CONCLUSIONS: These results indicate that while executive dysfunction is present throughout development, there is evidence for both typical and atypical developmental progression of executive functions in autism. The plasticity suggested by the developmental improvements may have implications regarding appropriate developmental epochs and types of interventions aimed at enhancing cognitive capacities in individuals with autism.     

Mood state and cerebral metabolism in persons with age-associated memory impairment

People undergoing medical procedures sometimes experience feelings that may influence the results. In this study, we explore the relationship between changes in mood state self-ratings and cerebral glucose metabolism during positron emission tomography (PET) in persons with age-associated memory impairment (mean age 59.4±9.8 years). Brain regions of interest involved in both mood and memory were examined. Mood ratings of increased boredom correlated significantly with mesial temporal and parietal asymmetry and decreased parietal metabolism. Mood ratings of increased fatigue correlated with basal ganglia asymmetry and the right basal ganglia and left mesial temporal metabolism. These findings suggest that subjective mood state changes during PET may influence metabolism in brain regions implicated in emotion and memory function in people with age-related memory complaints.     

Procedural memory stimulation in Alzheimer's disease: impact of a training programme

The study evaluates the efficacy of a procedural memory stimulation programme in mild and mild-moderate Alzheimer's disease (AD). Twenty basic and instrumental activities of daily living have been selected, and divided into two groups, comparable for difficulty. Ten normal elderly subjects (age 68.0±4.8 years; MMSE score: 28.7±0.9; education: 7.6±3.5 years) were asked to perform the two groups of daily activities and the time required to perform the tasks of each group was recorded and used as a reference. Ten mild and mild-moderate AD patients (age 77.2±5.3 years; MMSE score: 19.8±3.5; education: 7.3±4.7 years) without major behavioural disturbances constituted the experimental group. Patients were evaluated in all 20 daily activities and the time employed was recorded at baseline and after a 3-week training (1 h/d, 5 d/week) period. Five patients were trained during the 3 weeks on half of the 20 daily activities and the other five patients were trained on the remainder. This procedure was adopted in order to detect separately the improvement in "trained" and "not trained" activities, allowing to control better the effects of the intervention. The assessment of the functional impact of the training was directly measured, through the variation of time employed to perform tasks before and after training. After 3 weeks of training a significant improvement was observed for the trained activities, from 3.6 to 1.9 standard deviations below the performance of the normal elderly controls ( P <0.05). AD patients improved also in not-trained activities from 3.5 to 2.7 standard deviations below the controls'performance ( P <0.05). The rehabilitation of activities of daily living through developing procedural memory strategies may be effective in mild and mild-moderate AD patients.     

Memory outcome at 5 years post-childhood traumatic brain injury

Primary objective: This study seeks to extend previous findings by documenting memory performance in a sample of 70 children at 5 years post-injury. It was anticipated that increasing injury severity would be associated with decreased performance on working and complex memory tasks. It was also expected that injury severity would significantly predict memory, but that the time from insult to subsequent testing would be associated with an increased relationship to non-injury factors.

Research design: Participants were assessed at 5 years post-injury, aged between 6-14 years, using measures of immediate, working and complex memory.

Methods and procedures: The sample comprised 18 children who had sustained a severe TBI, 24 with a moderate TBI, 11 with a mild TBI and 17 healthy controls, matched for age, gender and socio-economic-status.

Results: Results indicated that severe TBI was associated with decreased complex auditory-verbal memory performance, although children with TBI did not display impairment on immediate, working or complex visual-spatial memory. While injury severity significantly predicted complex memory outcome, non-injury factors failed to significantly predict either working or complex memory performance.

Conclusions: Future research should be engineered towards further clarifying what influences recovery from childhood TBI in the elongated post-injury period.     

Peripheral clonal deletion of antiviral memory CD8+ T cells

Antiviral cytotoxic memory CD8⁺ T cells adoptively transferred to mice which are persistently infected with lymphocytic choriomeningitis virus WE or DOCILE initially proliferated extensively; they either caused the death of the recipient or, alternatively, disappeared within a few days. Apparently, the complete and coordinated induction and stimulation by widely distributed viral antigen caused these memory T cells to die before virus had been eliminated from the host. Thus memory T cells are as susceptible to peripheral exhaustion/deletion as unprimed T cells. These results indicate possible limitations of exclusively CD8⁺ T cell-mediated adoptive immunotherapy against viral infections or tumors.     

P300 and Long-Term Memory: Latency Predicts Recognition Performance

The study-test paradigm was used to investigate memory acquisition processes and the effects of repetition on long-term recognition memory. In this procedure, subjects are presented with a list of words (“targets”) to be memorized (Study series). They are later tested for recognition on a word list comprised of the target words mixed randomly with an equal number of new, distractor words (Test series). Both reaction time and the P300 component of the event-related brain potential were used as measures of processing time. During the Study series, large P300s were elicited despite a word category probability of 1.0. When the words from the Study series were divided on the basis of recognition performance, words that were subsequently recognized elicited P300s with shorter latencies than unrecognized words. P300 amplitude to words in the Study series increased with repetition while maintaining a constant latency. During the Test series, P300 latency and reaction time decreased with repetition for both target and distractor words. P300 amplitude to all words increased substantially over Test repetitions with target words eliciting larger P300s than distractor words. Words that were recognized more consistently during the Test series elicited larger and earlier P300s than words that were recognized less consistently. The P300 amplitude and latency results from both the Study and Test series are interpreted as reflecting the increased discriminability of the target words as the memory trace increases in strength.