Biomedical subjects

W J Riedel

Publications and source records attributed to W J Riedel.

9 recordsLinked to original sources

PubMed2000

Tryptophan depletion impairs memory consolidation but improves focussed attention in healthy young volunteers.

Animal and human studies have provided evidence for serotonergic modulation of cognitive processes. However, the exact nature of this relationship is not clear. We used the acute tryptophan depletion (ATD) method to investigate the effects of lowered serotonin synthesis on cognitive functions in 17 healthy young volunteers. The study was conducted according to a placebo-controlled, double-blind, crossover design. Cognitive performance and mood were assessed at baseline and 5 and 9 h after administration of ATD. A specific impairment of word recognition, without effects on short-term memory, occurred during ATD. No memory deficits were seen if ATD was induced after acquisition of new words. The Stroop Test and dichotic listening task demonstrated a modality independent improvement of focussed attention after ATD. Fluency was also improved after ATD. ATD did not alter speed of information processing, divided attention or planning functions. These results indicate that serotonin is essential in the process of long-term memory consolidation, primarily in the first 30 min after acquisition. Improvement of specific cognitive processes by lowered 5-HT function may be linked to the removal of inhibitory actions of 5-HT in the cortex.

Adult↗

PubMed1999

Mood effects of 24-hour tryptophan depletion in healthy first-degree relatives of patients with affective disorders.

BACKGROUND: Acute tryptophan (TRP) depletion was evaluated in healthy volunteers with or without a family history of major affective disorder (FH+ versus FH-). METHODS: Twenty-seven subjects (16 FH+, 11 FH-) received 100 g of an amino acid mixture with and without TRP according to a placebo-controlled, double-blind cross-over design and a diet devoid of TRP for the next 24 hours. RESULTS: The ratio TRP/large neutral amino acids declined to 22% of baseline values after 6 hours, and increased during the night reaching 85% of baseline after 24 hours. Overall, after 6 hours, TRP depletion lead to a lowering of mood, but after 24 hours, these changes were no longer detected. Mood changes and gastrointestinal side effects were significantly more evident in FH+ subjects than in FH- subjects. CONCLUSIONS: Our data support the hypothesis that subjects with a positive family history for depression are predisposed to increased vulnerability to the adverse consequences of serotonergic imbalance.

Adolescent↗

PubMed1999

Specificity of the tryptophan depletion method.

Thirteen healthy subjects were subjected to tryptophan (TRP) depletion, lysine (LYS) depletion, and a placebo condition in a double blind cross-over study. The aim of the study was to test the specificity of psychological effects induced by TRP depletion. Subjects ingested a 100 g amino acid mixture with or without TRP or LYS. Six hours later, plasma TRP levels had decreased by 77% in the TRP depletion test and LYS levels by 51% in the LYS depletion condition. After 6 h of TRP depletion, subjects reported significantly more tiredness and lowering of mood, compared to subjects in the placebo group, and memory performance declined. After 6 h of LYS depletion, no significant differences in mood and memory compared to placebo were found. We conclude that the effects of TRP depletion on mood and memory are specific for the depletion of TRP and are not caused by the depletion of an amino acid per se. This supports the hypothesis that TRP depletion affects brain serotonin metabolism and not only brain protein metabolism in general.

Adolescent↗

PubMed1999

Tryptophan depletion in normal volunteers produces selective impairment in memory consolidation.

Serotonin (5-hydroxytryptamine; 5-HT) circuits may play a role in cognitive performance, particularly in learning and memory. Cognitive impairment is often seen in depressed patients, in whom 5-HT turnover in the brain is thought to be lowered. A possible human pharmacological model to study the involvement of the serotonergic system in cognitive impairment is to reduce central 5-HT synthesis through L-tryptophan depletion in healthy subjects. In this study, the cognitive effects of tryptophan depletion were assessed and whether genetically or developmentally determined vulnerability factors were predictive of the cognitive impairment induced by tryptophan depletion. Sixteen healthy volunteers with a positive family history of depression and 11 without were given 100 g of an amino acid mixture with or without tryptophan, according to a double-blind, cross-over design. Tryptophan depletion specifically impaired long-term memory performance in all subjects: delayed recall performance, recognition sensitivity, and recognition reaction times were significantly impaired after tryptophan depletion relative to placebo. Short-term memory and perceptual and psychomotor functions were unchanged. There were no differences between groups with a positive and a negative family history for depression. On the basis of these results, it is concluded that tryptophan depletion specifically impairs long-term memory formation, presumably as a result of an acute decrease in 5-HT turnover in the brain.

Adolescent↗

PubMed1999

Caffeine improves cognitive performance after strenuous physical exercise.

The effects of three carbohydrate electrolyte solutions (CES) containing different amounts of caffeine on cognitive function and the combined effects of these drinks and exercise on cognitive functions were investigated in a double-blind, cross-over study. On five separate occasions, fifteen endurance trained male athletes (23.3 years) received water placebo, CES placebo (68.8 g/l), and three CES drinks containing low, medium and high dosages of caffeine (150, 225 and 320 mg/l). Each occasion, 8 ml/kg of the drink was consumed before -- and 6 ml/kg of the drink was consumed during an all-out 1 hour time trial on a bicycle ergometer. Cognitive (attentional, psychomotor, and memory) tests were carried out immediately before and immediately after exercise. Before exercise, long term memory was improved by CES plus low dose caffeine compared to both placebos. Immediately after exercise, all cognitive functions were improved by CES plus low- and medium-dose caffeine compared to placebo. These results comprise the first practical demonstration of the cognition improving effects of low amounts of caffeine in CES after strenuous physical exercise.

Adult↗

PubMed1999

Lithium induced cognitive side-effects in bipolar disorder: a qualitative analysis and implications for daily practice.

Qualitative analysis of the literature on cognitive side-effects of lithium in patients with a bipolar disorder identified four of 17 studies that fulfilled criteria of adequate methodological quality. Analysis of these four studies showed that lithium had a negative effect on memory and speed of information processing, often without subjective complaints or awareness of mental slowness. The consequences of these findings for daily practice are discussed, in particular with respect to driving performance. When neurocognitive complaints or deficits are present, lithium plasma level, thyroid functions and degree of mood disturbance should be assessed. In cases where all these parameters are within normal limits and neurocognitive complaints still persist, dose reduction of lithium, thyroid hormone addition, prescription of a slow release preparation or replacement of lithium by another moodstabiliser should be considered. Guidelines are suggested with respect to further neuropsychological screening.

Antimanic Agents↗

PubMed1998

Nutrients, age and cognitive function.

Many nutrients or indices of nutritional status are associated with cognitive functioning, although the size of the effects on cognitive performance may be small. Results from recent studies, however, seem consistently to indicate that supplementation with beta-carotene and alpha-tocopherol, substances that promote antioxidant vitamins A and E, respectively, can be beneficial to cognitive function in elderly people. Folate rather than vitamin B12 appears to be associated with cognitive functioning. Furthermore the daily intake of ginkgo biloba extract can enhance cognitive performance and has been proved to delay cognitive decline in dementia. A proper dietary composition with regard to the ratio of carbohydrates to proteins, as well as the inclusion of sufficient micronutrients, seems to be favourable in the maintenance of cognitive function in the elderly. Glucose can enhance cognitive function, but a rapid decline of glucose levels may impair cognitive function or may induce feelings of lack of energy. Low doses of caffeine may also enhance cognitive function, although most studies on caffeine and cognition, as with studies on glucose and cognition, have not been carried out in elderly individuals. The effects of nutritional supplements are modest but do not seem to be very different from those of medicinal or investigational cognition-enhancing or anti-dementia drugs.

Aged↗

PubMed1996

Cognition enhancers in age-related cognitive decline.

A review of recently published studies on the effect of cognition enhancers in non-demented human study participants is presented. The heterogeneity of the therapeutic target, age-associated cognitive decline, can be improved by separately treating groups in whom age-extrinsic factors may underlie cognitive pathology. Standardisation of cognitive assessments is necessary, since many different tests are applied to answer the same question. Modelling cognitive dysfunction, either by pharmacological or nonpharmacological means, in humans is highly recommended since it allows hypotheses to be tested in a clearly operationalised way. Predictive validity of the currently applied models for the clinical situation remains a problem, however. The scopolamine (hyoscine) model has, to a reasonable extent, predictive validity for the cholinergic agents. The results of 67 single-dose studies and 30 multiple-dose studies are summarised. All single-dose studies and 14 multiple-dose studies were carried out in young or elderly human volunteers. In 45 of 81 volunteer studies, models of cognitive dysfunction were employed. The scopolamine model was the most used (n = 21); the other studies induced cognitive dysfunction by means of benzodiazepines (8), hypoxia (7), alcohol (5) and sleep-deprivation (4). The remaining 16 multiple-dose studies were clinical trials of a duration varying between 2 weeks and 1 year (average duration was 14 weeks). In these trials, the effects of cognition enhancers were assessed in elderly people in whom impairment of memory, psychomotor performance or cognitive function was determined. These included age-associated memory impairment (AAMI) and age-associated cognitive decline (AACD). There were many studies in which the cognition enhancing properties of substances in humans were reliably demonstrated. The cognition enhancing properties of substances that are widely used, such as caffeine, nicotine and vitamins, may already be active against AACD. New developments such as serotonin (5-hydroxytryptamine3; 5-HT3) antagonists and N-methyl-D-aspartate (NMDA) antagonists have provided marginal and disappointing results in AAMI. There is no cognition enhancer that has reliably and repeatedly been demonstrated to be efficacious for the treatment of AACD. However, this situation may change as the selectivity, specificity and adverse effect profiles of substances that are being developed for the treatment of AD may be expected to be improved in the future.

Aged↗

PubMed1995

Cognitive impairment in elderly people. Predisposing factors and implications for experimental drug studies.

The consequences for cognitive functioning of normal aging, depression and dementia are well known. However, the borderline between normal and pathological cognitive aging is less well understood. Recently, it has been found that it is important to differentiate between 'successful', 'usual' and pathological cognitive aging. This article reviews existing views on this borderline. Recently, it has been found that health-related factors, or biological life events, may determine the rate of cognitive aging. Various different, but similar, diagnostic descriptions of age-related cognitive dysfunction exist simultaneously: benign senescent forgetfulness, malignant senescent forgetfulness, age-associated memory impairment, age-consistent memory impairment, late-life forgetfulness, mild cognitive changes (subthreshold) and cognitive impairment disorders are some examples of different diagnostic categories. There are also various diagnostic tools to obtain these experimental diagnoses; for example, the Global Deterioration Scale, the Clinical Dementia Rating Scale and the Cambridge Mental Disorders of the Elderly Examination. A diagnosis is considered important for the early detection of dementia. Pharmacological treatments are still in the experimental stage. Improvement of cognitive function has particularly been studied in clinical trials with groups of patients with Alzheimer's disease as well as patient groups with age-associated memory impairment. Future strategies may orient more towards treating symptoms of cognitive dysfunction, probably also on the basis of diagnosis of health-related factors, in age-related cognitive decline and depression.

Aged↗