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O T Wolf

Publications and source records attributed to O T Wolf.

At least 19 recordsLinked to original sources
PubMed2006

Hippocampal volume and cognitive performance in long-standing Type 1 diabetic patients without macrovascular complications.

AIMS: Hippocampal atrophy and memory deficits have been reported in Type 2 diabetes. Whether similar alterations occur in Type 1 diabetes is currently unknown. METHODS: In a case-control design, 13 Type 1 diabetic patients with at least 10 years' duration of disease, but free from clinical signs of macrovascular disease, were compared with age- and gender-matched control subjects. Hippocampal volume and measures of global cerebral cerebrospinal fluid (CSF) were determined from magnetic resonance imaging (MRI) scans. Cognitive functions were assessed using four neuropsychological tests. Mood and depression were measured by questionnaires. RESULTS: Hippocampal volume and memory did not differ between Type 1 diabetic patients and control subjects. However, a significantly increased amount of cerebral CSF suggestive of mild cerebral atrophy was observed in the patients. In addition, deficits in psychomotor speed and selective attention were apparent. Eleven of 13 patients had retinopathy and/or nephropathy. Findings were unrelated to cerebrovascular disease, white matter disease or silent strokes. CONCLUSIONS: Results from our small study in Type 1 diabetic patients do not support findings from previous studies of Type 2 diabetic patients demonstrating reductions in hippocampal volume and impaired memory. On the contrary, we observed evidence for mild cerebral atrophy and impaired psychomotor speed and selective attention. This is in line with some previous studies in Type 1 diabetes. If replicated in larger studies, our findings would support the idea that the effects on brain function and structure differ between Type 1 and Type 2 diabetes.

Adult↗
PubMed2005

Investigating the effects of estradiol or estradiol/progesterone treatment on mood, depressive symptoms, menopausal symptoms and subjective sleep quality in older healthy hysterectomized women: a questionnaire study.

Clinical studies have documented that estrogen treatment often ameliorates mood disturbances and depressive symptoms occurring during the menopausal transition. The relevance of gonadal hormones for mood and well-being in healthy older nondepressed women is less well understood. Fifty-one healthy hysterectomized women (mean age 64) participated in a placebo-controlled double-blind study on the effects of gonadal hormones on cognition. They received either estradiol (2 mg estradiol valerate), estradiol plus progesterone (100 mg micronized progesterone) or placebo. Mood, well being, menopausal symptoms, depressive symptoms and subjective sleep quality were measured at baseline and after 4 and 24 weeks of treatment using three questionnaires. Thirty-five women could be included into the final analysis. Strong increases in estradiol and progesterone levels occurred in response to the treatment. The two hormones, however, had no effects on mood, well-being, menopausal symptoms, sleep quality and depressive symptoms. The current small study suggests that older healthy nondepressed hysterectomized women do not react with positive or negative mood changes to estradiol or estradiol/progesterone treatment.

Adult↗
PubMed2005

A meta-analytic review of the effects of acute cortisol administration on human memory.

Adrenal glucocorticoids (GC) secreted during stress modulate memory. Animal and human studies investigating the effects of acute GC treatment on memory have reported conflicting (enhancing as well as impairing) results. Several theories have been proposed to integrate these contradictory findings. Among the variables discussed are the timing of the GC treatment (before learning or before retrieval) and the time of day (morning versus afternoon). Here we review meta-analytically the results of 16 studies, which experimentally investigated the acute impact of cortisol treatment on human memory. The results revealed that the timing of GC application in the course of a study is a relevant variable which explains a substantial amount of the significant heterogeneity within the effect sizes. The studies which administered cortisol before retrieval (n = 4) reported a significant decrease (average effect size of d = -.49) in memory performance. Studies which administered cortisol before learning (n =12) found on average no effect (d = .08), but there is heterogeneity within these effect sizes. Further analysis on these experiments indicated that studies, which administered cortisol in the morning found a significant memory impairment (d = -.40), while studies conducted in the afternoon observed a small but significant memory enhancement (d = .22). This meta-analysis supports the idea that the timing of GC administration (before learning or before retrieval) is a major determinant of the effects of GCs on human memory. We discuss methodological limitations of the current analysis and suggest several areas for future research.

Adolescent↗
PubMed2005

No changes in event-related potentials with estrogen or estrogen plus progesterone treatment in healthy older hysterectomized women: results from a double-blind, placebo-controlled study.

RATIONALE: The potential to improve cognition in older women with estrogen or estrogen/progesterone therapy is currently a matter of intense debate. Only a few studies conducted so far have used electrophysiological indicators of cognitive information processing as outcome measures in randomised placebo controlled studies. OBJECTIVES: This study was undertaken to measure changes in event-related potentials (ERPs) after short (4 weeks) or prolonged (24 weeks) hormone treatment in older women. METHODS: A randomised, double-blind, placebo-controlled study in hysterectomized older women (aged 58-75 years) was performed (n = 51). The participants received orally estradiol (2 mg estradiol valerate), estradiol plus progesterone (100 mg micronized progesterone) or placebo for 24 weeks. Using four different paradigms, early and late ERPs were assessed at baseline and after 4 and 24 weeks of treatment. RESULTS: Strong hormone increases were observed in the two active treatment groups. However, no significant effects on any of the assessed ERPs were observed in either of the two treatment groups. Similar non-significant findings were obtained for reaction time and error rate. CONCLUSIONS: Estradiol or estradiol/progesterone treatment appears to have no strong effects on several ERP markers of information processing in older hysterectomized women. The current negative findings might suggest a reduced sensitivity of the aged brain to gonadal steroids.

Aged↗
PubMed2004

Cortisol and memory retrieval in humans: influence of emotional valence.

Glucocorticoids secreted in response to stress modulate memory in animals and humans. Studies in rodents suggest that glucocorticoids enhance memory consolidation but impair delayed retrieval. Similar negative effects on memory retrieval have been reported in humans. The human studies so far have not addressed the issue of emotional valence, which conceivably could modulate the effects of cortisol on retrieval. The present mini-review discusses two recent studies from our laboratories that investigate the influence of emotional valence on the retrieval-impairing effects of cortisol. Both studies observed that cortisol impaired retrieval and that emotional valence influenced these effects. For autobiographical memory the impairing effects were stronger for neutral than for emotional items, whereas for word retrieval the opposite pattern was observed (stronger effects on emotional words). Possible reasons for these results are the different memory domains tested as well as the different sex of the subjects. Future studies will address these issues, which are of relevance for psychiatric disorders such as posttraumatic stress disorder or major depression.

Emotions↗
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↗