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Biomedical subjects

O T Wolf

Publications and source records attributed to O T Wolf.

27 records · Page 2Linked to original sources
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↗
PubMed1997

Free cortisol levels after awakening: a reliable biological marker for the assessment of adrenocortical activity.

In three independent studies, free cortisol levels after morning awakening were repeatedly measured in children, adults and elderly subjects (total n=152). Cortisol was assessed by sampling saliva at 10 or 15 minute intervals for 30-60 minutes, beginning at the time of awakening for two days (Study 1 and 2) or one (Study 3) day, respectively. In all three studies, free cortisol levels increased by 50-75% within the first 30 minutes after awakening in both sexes on all days. Premenopausal women consistently showed a stronger increase with a delayed peak after awakening compared to men on all days. In Study 2, there was a tendency for lower early morning free cortisol levels for women taking oral contraceptives (p=.10). Stability of the area under the curve (AUC) of the early morning free cortisol levels over the three (Study 1 and 2) or two (Study 3) days ranged between r=.39 and r=.67 (p<.001). Neither age, weight, nor smoking showed an effect on baseline or peak cortisol levels. Sleep duration, time of awakening and alcohol consumption also appeared to be unrelated to early morning free cortisol levels. From these data we conclude that in contrast to single assessments at fixed times, early morning cortisol levels can be a reliable biological marker for the individual's adrenocortical activity when measured repeatedly with strict reference to the time of awakening.

Adrenal Cortex↗
PubMed1997

Effects of a two-week physiological dehydroepiandrosterone substitution on cognitive performance and well-being in healthy elderly women and men.

The levels of dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS decrease with age after a peak around 25 yr. Animal studies as well as the first studies in humans have generated the idea that DHEA replacement in elderly subjects may have beneficial effects on well-being and cognitive functions. In the present experiment 40 healthy elderly men and women (mean age, 69 yr) participated in a double blind, placebo-controlled DHEA substitution study. For 2 weeks subjects took 50 mg DHEA daily, followed by a 2-week wash-out period and a 2-week placebo period. The treatment sequence was randomized in a cross-over design. After 2 weeks of DHEA or placebo, psychological and physical well-being as well as cognitive performance were assessed using several questionnaires and neuropsychological tests. All subjects had low DHEAS baseline levels. DHEA substitution lead to a 5-fold increase in DHEAS levels in women (from 0.67 +/- 0.1 to 4.1 +/- 0.4 micrograms/mL; P < 0.001) and men (from 0.85 +/- 0.1 to 4.5 +/- 0.4 micrograms/mL; P < 0.001). DHEA, androstenedione, and testosterone levels also increased significantly in both sexes (all P < 0.001). No significant changes were observed in insulin-like growth factor I or insulin-like growth factor-binding protein-3 levels. DHEA replacement had no strong beneficial effect on any of the measured psychological or cognitive parameters. Only women tended to report an increase in well-being (P = 0.11) and mood (P = 0.10), as assessed with questionnaires. They also showed better performance in one of six cognitive tests (picture memory) after DHEA. However, after Bonferroni alpha adjustment, this difference was no longer significant. No such trend was observed in men (P > 0.20). Likewise, no beneficial effects of DHEA substitution could be observed in any of the other tests of the neuropsychological test battery in either sex (all P > 0.20). In conclusion, the present data do not support the idea of strong beneficial effects of a physiological DHEA substitution on well-being or cognitive performance in healthy elderly individuals.

Affect↗
PubMed1996

Stress- and treatment-induced elevations of cortisol levels associated with impaired declarative memory in healthy adults.

Two studies investigated the association between cortisol levels and memory performance in healthy adults. In a first study, 13 subjects were exposed to a brief psychosocial laboratory stress ("Trier Social Stress Test") with a subsequent test of declarative memory performance. Results indicated a significant negative relationship between stress-induced cortisol levels and performance in the memory task, i.e. subjects with high cortisol response to the stressor showed poorer memory performance. In a second experiment it was investigated if cortisol, alone, i.e. independent of psychological stress, would also impair memory function. In this study, 40 healthy subjects received either 10 mg cortisol or placebo orally. One hour later they were tested for procedural and declarative memory and spatial thinking. Subjects who received cortisol showed impaired performance in the declarative memory and spatial thinking tasks but not in the procedural memory task. From these results we conclude that in healthy adults elevated free cortisol levels are associated with impaired memory function.

Adult↗