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Biomedical subjects

O T Wolf

Publications and source records attributed to O T Wolf.

At least 19 recordsLinked to original sources
PubMed2003

HPA axis and memory.

The hormones of the hypothalamus-pituitary-adrenal (HPA) axis influence memory in situations of acute and chronic stress. The present review tries to summarize the current state of knowledge by describing the enhancing as well as the impairing effects of stress or glucocorticoid (GC) treatment documented in animals and humans. GCs secreted during the acquisition of a stressful task facilitate consolidation. However, acute stress (or GC treatment) unrelated to the task impairs performance. The effects of acute stress are additionally modulated by gender, age and the emotional valence of the learning material. Chronic stress in rodents has mostly impairing effects on memory and hippocampal integrity. However, other regions of the brain, such as the prefrontal cortex, are also sensitive to stress. In humans, similar observations have been reported in several patient populations as well as in older subjects. The potential to reverse these effects using behavioural or pharmacological approaches needs to be explored.

Aging↗
PubMed2003

Cognitive functions and sex steroids.

In humans, levels of adrenal (DHEA(S)) and gonadal (estradiol, testosterone) sex steroids decline with age. Studies in rodents have demonstrated that these hormones can have neuro-excitatory and neuro-protective effects in the central nervous system (CNS). Behavioural studies repeatedly have reported enhanced memory performance of rats and mice after acute or sub-chronic treatment with sex steroids. The current review summarizes human studies on this topic conducted by the author as well as other groups. Epidemiological as well as experimental studies have in general shown that estradiol replacement improves cognition, especially verbal memory in menopausal women. Similarly positive effects of testosterone replacement in older men have been reported in several, but not all studies. Cognition enhancing effects of DHEA replacement in older healthy humans in contrast could not be demonstrated with short (weeks) or prolonged (months) treatment regimes. Even though most results support the notion that estradiol in women and testosterone in men can enhance cognition in older healthy humans, more research is needed before recommendations for the clinical practice can be made.

Aged↗
PubMed2002

Volumetric structural magnetic resonance imaging (MRI) of the rat hippocampus following kainic acid (KA) treatment.

An in vivo MRI study employing a high field (7T) magnet and a T1- and T2-weighted imaging sequence with subsequent histopathological evaluations was undertaken to develop and evaluate MRI-based volumetric measurements in the rat. The brain structures considered were the hippocampus, the cingulate cortex, the retrosplenial granular cortex and the ventricles. Control (n=3) and kainic acid (KA; n=4) treated rats were scanned 10 days following the manifestation of stage four seizures. The MRI images exhibited anatomical details (125 microm in-plane resolution) that enabled volumetric analysis with high intra-rater reliability. Volumetric analysis revealed that KA-treated rats had significantly smaller hippocampi, and a significant increase in ventricular size. The cingulate cortex and the retrosplenial granular cortex did not differ in volume between the two groups. The histological observations supported the MRI data showing neuronal loss and neuronal degeneration in CA1 and CA3 of the hippocampus, which was accompanied by strong microglia activation. These data demonstrate a reliable and valid method for the measurement of the rat hippocampus in vivo using MRI with a high field magnet, thereby providing a useful tool for future studies of rodent models of neuro-degenerative diseases.

Animals↗
PubMed2002

Volumetric measurement of the hippocampus, the anterior cingulate cortex, and the retrosplenial granular cortex of the rat using structural MRI.

MRI imaging of the rodent brain is a rapidly growing field in the neurosciences. Relatively limited information is available for regional volume determination. The present paper describes a reliable method for the assessment of the hippocampus, the anterior cingulate cortex, the retrosplenial granular cortex and the ventricles in rats. MRI scans were acquired using a 7 T magnet. The anatomical sampling method was found to be highly reliable with an intra-rater reliability of greater than 0.93. The current protocol should facilitate future in vivo neuroimaging research using animal models of neurodegenerative diseases.

Animals↗
PubMed2001

Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET).

Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[(18)F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal.

Aged↗
PubMed2001

Volumetric analysis of the pre-frontal regions: findings in aging and schizophrenia.

Frontal lobe dysfunction is thought to be involved in schizophrenia and age-associated cognitive decline. Frontal lobe volume changes have been investigated in these conditions using MRI, but results have been inconsistent. Few volumetric MRI protocols exist that divide the pre-frontal cortex into its sub-regions. In the present article, we describe a new method, which allows assessment of the superior, middle and inferior frontal gyrus, as well as the orbitofrontal and cingulate regions. The method uses multiple planes to help guide the anatomical decisions and combines this with a geometric approach utilizing readily apparent anatomical landmarks. Using this protocol, the frontal lobe volumes in young healthy subjects were contrasted with those of young schizophrenic patients and elderly healthy subjects (nine male subjects per group). The results showed that the method could be reproduced with high reliability (r(icc)> or =0.88-0.99). Schizophrenic as well as old subjects had specific significant reductions in the superior frontal gyrus and orbitofrontal regions compared with the young group. However, old and schizophrenic subjects did not differ from each another. No volume differences were observed in the other three regions assessed. Whether or not these volume reductions reflect a common pathological process remains to be investigated in future studies.

Adult↗
PubMed2001

The relationship between stress induced cortisol levels and memory differs between men and women.

Epidemiological as well as experimental studies in elderly subjects have suggested that postmenopausal women are more susceptible to the memory impairing effects of elevated cortisol levels than elderly men. Little is known however about gender differences in the susceptibility to acute stress in young subjects. In the present study a total of 58 healthy young subjects learned a word list, with recall being tested after a brief distraction task. Twenty-two subjects had to learn the list after exposure to a psychosocial stressor (Trier Social Stress Test: TSST), while the remaining subjects served as controls. Free cortisol was determined via saliva samples taken before and 10 minutes after stress. Subjects exposed to the stressor, did not show impaired memory performance per se when compared to the control group. However the cortisol increase in response to the stressor was negatively correlated (r=-0.43, P<0.05) with the memory performance within the stressed group (i.e., subjects showing a larger cortisol response recalling less words than subjects showing only a small cortisol increase). Additional analysis revealed, that this correlation was solely caused by the strong association observed in men (r=-0.82, P<0.05), while no association was observed in women (r=-0.05, P=ns). Our data suggests, that gender modulates the association between cortisol and memory after stress. Whether these differences reflect activational effects of sex steroids or developmentally-programmed sex differences awaits to be determined.

Adult↗
PubMed2001

Cortisol differentially affects memory in young and elderly men.

Nine young and 11 elderly men participated in this placebo-controlled, double-blind, crossover study (0.5 mg/kg cortisol or intravenous placebo). Participants learned a word list before cortisol administration, and delayed recall was then tested. A 2nd word list was learned and recalled after drug administration. In addition, the Paragraph Recall Test and tests measuring working memory (Digit Span), attention (timed cancellation), and response inhibition (Stroop Color and Word Test) were administered at 2 time points after drug administration. Cortisol reduced recall from the word list learned before treatment in both groups but did not influence recall of the list learned after treatment. In contrast, Digit Span performance was decreased by cortisol in young but not elderly participants. The possibility that differential age-associated brain changes might underlie the present results is discussed.

Adult↗
PubMed2000

Testosterone and cognition in elderly men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory.

BACKGROUND: The relevance of the age-associated decline in testosterone for cognition in elderly men is still poorly understood. One hypothesis is that testosterone enhances spatial abilities, while it might impair verbal skills. METHODS: Thirty elderly men received a single testosterone (250 mg testosterone enanthate) or placebo injection. Cognitive performance was tested before and 5 days after treatment using spatial as well as verbal tests. RESULTS: Five days after injection, testosterone and estradiol levels were still in the supraphysiologic range. In the verbal fluency task, the placebo group, but not the testosterone group, showed a practice effect. Therefore, the testosterone group performed significantly worse than the placebo group after treatment. No effects of testosterone were observed in the other verbal and spatial tasks. CONCLUSIONS: The present finding, that testosterone blocks the practice effect in verbal fluency, partly supports the general idea that sex steroids modulate performance in tests with known gender differences. Moreover it demonstrates that these effects can occur rapidly. However, beneficial effects on spatial cognition or memory might need more time to develop and/or might only occur when a less pronounced testosterone increase is induced.

Aged↗
PubMed1999

MRI volume of the amygdala: a reliable method allowing separation from the hippocampal formation.

Studies of MRI-derived volume of the amygdala have been mostly performed on coronal sections where its boundaries with the hippocampus and the entorhinal cortex are indistinct. To date, all reports of in vivo amygdala volume have consistently overestimated the size of the structure. We have developed a method for the MRI-based in vivo measurement of the amygdala volume which allows a better separation of the amygdala from the adjoining hippocampal formation. In nine normal volunteers we obtained three-dimensional spoiled gradient recalled acquisition, 1.3-mm thick, T1 weighted sagittal MR images and created electronically linked reformatted images in the coronal and axial planes. On the original sagittal and the reformatted axial planes, where it is more readily apparent, we delineated the boundaries between the amygdala and the hippocampus and the amygdala and the hippocampo-amygdala transition area, respectively. We then projected those markings onto the coronal plane, where the other boundaries of the amygdala are more easily seen. Using these markings as a guide and utilizing extra-amygdalar coronal landmarks for the anterior end, we outlined the whole amygdala on the coronal plane and determined its volume. We observed that 45% of the coronal slices that contained amygdala also contained some hippocampus. The amygdala measurement had high test-retest reliability, with an intra-class correlation coefficient (rICC) of 0.99 for the total volume and an rICC of 0.93 for the measurement at the level of the individual slice. The average amygdala volume was 1.05 +/- 0.17 cm3 on the right and 1.14 +/- 0.15 cm3 on the left. Our amygdala volumes are in agreement with those reported in postmortem studies, which provides the reported method with face validity.

Adult↗
PubMed1999

Actions of dehydroepiandrosterone and its sulfate in the central nervous system: effects on cognition and emotion in animals and humans.

Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, exert multiple effects in the rodent central nervous system (CNS). Most of them seem to be mediated through their non-genomic action on several neurotransmitter receptors. DHEA(S) increases neuronal excitability, enhances neuronal plasticity and also has neuroprotective properties. In line with these observations DHEA(S) treatment in rodents enhances memory in several paradigms. Even more studies show antiamnestic effects of the steroids. However, DHEA(S) has also anxiolytic and anti-aggressive properties. In humans cross-sectional and longitudinal studies suggest that DHEAS might be associated with global measures of well-being and functioning; however, a relationship with cognition could not be detected to date. Moreover, studies investigating DHEAS levels in neurodegenerative diseases have produced conflicting results. Experimental studies in elderly humans have revealed preliminary evidence for mood enhancing and antidepressant effects of DHEA treatment, while positive effects on measures of memory and attention could not be found. However, electrophysiological studies demonstrated that DHEA treatment has effects on the human CNS. Several reasons for the discrepancy between data obtained in rodents and humans are discussed and research perspectives are outlined which might help to improve interpretation of results obtained in the two species.

Aged↗
PubMed1999

Two weeks of transdermal estradiol treatment in postmenopausal elderly women and its effect on memory and mood: verbal memory changes are associated with the treatment induced estradiol levels.

The present randomized double blind study investigated the effects of a 2 week transdermal estradiol treatment on memory performance in 38 healthy elderly women. Cognitive performance was tested at baseline and after 2 weeks of estradiol or placebo treatment using verbal, semantic, and spatial memory tests as well as a mental rotation task and the Stroop. Initial results showed no differences after treatment between placebo or estradiol treated subjects. However, within treatment group analysis revealed that estradiol treated subjects who reached higher estradiol levels (larger than 29 pg/ml) performed significantly better after treatment in the delayed recall of the paired associate test (verbal memory) than subjects who reached lower estradiol levels (P < 0.05). A nonsignificant trend was observed for the immediate recall condition (P < 0.10). These findings were strengthened by correlations between treatment-induced estradiol levels and changes in verbal memory performance. In addition, there was an association between estradiol levels and mood changes. However mood changes were not significantly associated with changes in verbal memory performance (P > 0.20). The present study supports the idea that estradiol replacement has specific effects on verbal memory in healthy postmenopausal women, with delayed recall being more affected. It suggests that these effects can occur relatively rapidly, and that there may be a dose response relationship of estradiol to memory enhancement. Furthermore, the fact that these results were obtained in women who had been menopausal for an average of 17 years before entering the study indicates that the brain maintains a sensitivity for estrogens even after years of low estradiol plasma concentrations.

Administration, Cutaneous↗
PubMed1998

Opposing effects of DHEA replacement in elderly subjects on declarative memory and attention after exposure to a laboratory stressor.

Aging is accompanied by a continuous decline of the adrenal steroid hormone DHEA and its ester DHEAS. Results from studies in rodents have demonstrated that DHEA(S) administration can enhance memory in several test paradigms. However studies from this laboratory did not find positive effects of DHEA treatment on cognitive performance in young and elderly humans. With respect to a possible mechanism of DHEA activity, effects on several neurotransmitter receptors as well as a possible antiglucocorticoid action are discussed. For high levels of glucocorticoids, a disruptive effect on hippocampal mediated memory is documented in rodents and humans. Therefore it was speculated that, if an antiglucocorticoid action of DHEA would underlie the observed beneficial effects of DHEA on memory, these effects might only be detectable if subjects are stressed (and therefore have high cortisol levels). To test this hypothesis 75 elderly women and men participated in a placebo controlled experiment. Subjects took DHEA (50 mg/day) or placebo for 2 weeks (double blind). Thereafter they participated in a standardized psychosocial laboratory stressor (Trier Social Stress Test; TSST). Before and after stress exposure subjects completed two declarative memory tests (visual-verbal and spatial) as well as one attention test. In addition recall of visual material learned before stress was assessed after stress. Baseline DHEAS levels were significantly lower compared with young adults. DHEA replacement increased DHEAS levels into ranges found in young subjects. DHEA-substituted subjects showed a trend towards a larger cortisol stress response. In the visual memory test subjects under DHEA recalled less items after stress which they had learned before stress. In the attention test however subjects under DHEA performed better than subjects from the placebo group after stress. No interaction between stress and DHEA was found for the spatial memory task. The effects of DHEA substitution on memory and attention after stress exposure seem to be heterogenous. While recall of previously learned material seems to be impaired, attention is enhanced. These results do not support the idea of a direct antiglucocorticoid or anti-stress effect of DHEA on hippocampal mediated memory functions.

Aged↗
PubMed1998

Effects of dehydroepiandrosterone replacement in elderly men on event-related potentials, memory, and well-being.

BACKGROUND: In humans, concentrations of the adrenal steroid hormone dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decline with age. Results from studies in rodents have suggested that DHEA administration can improve memory performance as well as neuronal plasticity. However, a first study from our laboratory could not demonstrate beneficial effects of DHEA substitution on cognitive performance and well-being in elderly subjects. To further evaluate whether DHEA replacement has effects on the central nervous system, an experiment using event-related potentials (ERPs) was conducted. METHODS: In this placebo-controlled crossover study, 17 elderly men (mean age, 71.1 +/- 1.7 yr; range 59-81 yr) took placebo or DHEA (50 mg/day) for 2 weeks (double blind). After each treatment period subjects participated in an auditory oddball paradigm with three oddball blocks. In the first two blocks subjects had to count the rare tone silently, whereas, in the third block they had to press a button. In addition, memory tests assessing visual, spatial, and semantic memory as well as questionnaires on psychological and physical well-being were presented. RESULTS: Baseline DHEAS levels were lower compared with young adults. After 2-week DHEA replacement, DHEAS levels rose 5-fold to levels observed in young men. DHEA substitution modulated the P3 component of the ERPs, which reflects information updating in short-term memory. P3 amplitude was increased after DHEA administration, and only selectively in the second oddball block. DHEA did not influence P3 latency. Moreover, DHEA did not enhance memory or mood. CONCLUSIONS: A 2-week DHEA replacement in elderly men results in changes in electrophysiological indices of central nervous system stimulus processing if the task is performed repeatedly. However, these effects do not appear to be strong enough to improve memory or mood.

Aged↗
PubMed1998

Sex differences in endocrine and psychological responses to psychosocial stress in healthy elderly subjects and the impact of a 2-week dehydroepiandrosterone treatment.

Evidence from animal as well as human studies has suggested that significant sex differences exist in hypothalamus-pituitary-adrenal axis (HPA) activity. As gonadal steroids could be important modulators of HPA sex differences, stress responses were investigated in subjects of advanced age after dehydroepiandrosterone (DHEA) or placebo treatment. After a 2-week treatment with 50 mg DHEA daily or placebo, 75 men and women (mean age, 67.6 yr) were exposed to the Trier Social Stress Test (TSST). The TSST is a brief psychosocial stress that consists of a free speech and mental arithmetic task in front of an audience. The results show that the TSST induced significant increases in ACTH, salivary free cortisol, total plasma cortisol, norepinephrine, and heart rates (all P < 0.0001) as well as decreased positive affect in the elderly (P = 0.0009). Men showed larger stress responses in ACTH (P = 0.004), salivary free cortisol (P = 0.044), and plasma total cortisol (P = 0.076) compared to women. No sex differences were observed in norepinephrine, epinephrine, or heart rate responses. In contrast to ACTH and cortisol response differences, women reported that they were significantly more stressed by the TSST than men (P = 0.0051). Women treated with DHEA showed ACTH stress responses similar to those of men, but significantly enhanced compared to those of women taking placebos (P < 0.009). No other stress response differences emerged between DHEA and placebo groups. Finally, DHEA treatment did not result in an improvement of subjective well-being. We conclude that elderly men show larger HPA responses than women to psychosocial stress, as studied in the TSST. Estrogen effects on hypothalamic CRF-producing neurons might be responsible for these sex differences.

Adrenocorticotropic Hormone↗