Biomedical subjects

Jens C Pruessner

Publications and source records attributed to Jens C Pruessner.

17 recordsLinked to original sources

PubMed2006

Hippocampal volumes are larger in postmenopausal women using estrogen therapy compared to past users, never users and men: a possible window of opportunity effect.

Considerable evidence suggests that estrogen can have neuroprotective effects. However, recent results raised important questions regarding the conditions under which hormone therapy (HT) following menopause can be beneficial. It has been suggested that variables such as time of initiation and duration of HT use are of critical importance for beneficial cognitive effects to be observed. The aim of the present study was to investigate the potential neuroprotective effects of estrogens in aging on brain regions with high levels of estrogen receptors, namely the hippocampus (HC) and the amygdala (AG). In order to better characterize the punctual and long-term effects of estrogens, we tested postmenopausal women currently using estrogen therapy alone (ET), past HT users, never users, and men. Age at menses, age at menopause, HT duration and age were included as covariates in the analysis. Results demonstrate that women using ET had larger left and right HC volumes compared to men, and larger right HC volumes compared to past users and never users. Importantly, we found a significant negative relationship between ET duration and HC volume in this group. The observed effects were region-specific since no significant differences could be observed for the AG. In summary, these findings support a treatment duration dependent neuroprotective role of estrogen on HC volume in aging.

Aged↗

PubMed2006

Comprehensive dissection of the medial temporal lobe in AD: measurement of hippocampus, amygdala, entorhinal, perirhinal and parahippocampal cortices using MRI.

BACKGROUND: Early pathological involvement of specific medial temporal lobe areas is characteristic for Alzheimer's disease (AD). OBJECTIVE: To determine the extent of regional medial temporal lobe atrophy, including hippocampus, amygdala, and entorhinal, perirhinal, and parahippocampal cortices in mild AD patients and healthy controls, and to compare diagnostic accuracy across volumetric markers. METHODS: We studied 34 patients with clinically probable AD and 22 healthy elderly control subjects. Regional volumetric measures were obtained from volumetric T1-weighted MRI scans after accounting for global brain atrophy using affine transformation into standard space. RESULTS: Volumes of medial temporal lobe structures were significantly smaller in AD patients than in controls with exception of the left entorhinal cortex. The degree of atrophy was comparable between all structures. Diagnostic accuracy (number of correctly allocated cases divided by number of all cases) was highest for the right parahippocampal cortex with 85%, but only slightly lower for the right hippocampus and right entorhinal cortex with 82% and 84%. Using a linear combination of markers, the unilateral volumes of the right hippocampus, parahippocampal cortex and perirhinal cortex yielded an accuracy of 93%. CONCLUSION: Extent of atrophy is similar between the different regions of the medial temporal lobe in mild AD.Volume measurements of medial temporal lobe structures in addition to the hippocampus only yield improved diagnostic accuracy if a combination of these structures is used.

Aged↗

PubMed2005

Size versus shape differences: contrasting voxel-based and volumetric analyses of the anterior cingulate cortex in individuals with acute posttraumatic stress disorder.

BACKGROUND: Two studies found morphological differences in the anterior cingulate cortex (ACC) of individuals with chronic posttraumatic stress disorder (PTSD). We sought to replicate and extend these findings in a sample of individuals with acute PTSD. METHODS: The ACCs of individuals with acute PTSD (n = 14) and matched healthy control subjects (n = 14) were compared using voxel-based morphometry (VBM), semi-automated volumetric analyses, and probabilistic maps. Posttraumatic stress disorder diagnosis was ascertained by a psychologist using a structured interview. RESULTS: Voxel-based morphometry analyses revealed significantly less gray-matter density in the right pregenual ACC and in the left insula of the PTSD group. However, volumetric analyses of the ACC revealed no significant differences between groups. Probabilistic maps of the labels of the pregenual ACC indicated that the difference between groups in gray matter density was due to shape differences. CONCLUSIONS: Although there are no volumetric differences in the ACC of acute PTSD individuals compared with normal control subjects, significant shape differences exist, which might indicate volumetric differences in the surrounding structures.

Accidents, Traffic↗

PubMed2005

Self-esteem, locus of control, hippocampal volume, and cortisol regulation in young and old adulthood.

Self-esteem, the value we place on ourselves, has been associated with effects on health, life expectancy, and life satisfaction. Correlated with self-esteem is internal locus of control, the individual's perception of being in control of his or her outcomes. Recently, variations in self-esteem and internal locus of control have been shown to predict the neuroendocrine cortisol response to stress. Cumulative exposure to high levels of cortisol over the lifetime is known to be related to hippocampal atrophy. We therefore examined hippocampal volume and cortisol regulation, to investigate potential biological mechanisms related to self-esteem. We investigated 16 healthy young (age range 20-26 years of age) and 23 healthy elderly subjects (age range 60-84 years). The young subjects were exposed to a psychosocial stress task, while the elderly subjects were assessed for their basal cortisol regulation. Structural Magnetic Resonance Images were acquired from all subjects, and volumetric analyses were performed on medial temporal lobe structures, and whole brain gray matter. Standardized neuropsychological assessments in the elderly were performed to assess levels of cognitive performance, and to exclude the possibility of neurodegenerative disease. Self-esteem and internal locus of control were significantly correlated with hippocampal volume in both young and elderly subjects. In the young, the cortisol response to the psychosocial stress task was significantly correlated with both hippocampal volume and levels of self-esteem and locus of control, while in the elderly, these personality traits moderated age-related patterns of cognitive decline, cortisol regulation, and global brain volume decline.

Adult↗

PubMed2005

Hippocampal shape analysis using medial surfaces.

In magnetic resonance imaging (MRI) research, significant attention has been paid to the analysis of the hippocampus (HC) within the medial temporal lobe because of its importance in memory and learning, and its role in neurodegenerative diseases. Manual segmentation protocols have established a volume decline in the HC in conjunction with Alzheimer's disease, epilepsy, post-traumatic stress disorder, and depression. Furthermore, recent studies have investigated age-related changes of HC volume which show an interaction with gender; in early adulthood, volume reduction of the HC is found in men but not in women. In this paper, we investigated gender differences in normal subjects in young adulthood by employing a shape analysis of the HC using medial surfaces. For each subject, the most prominent medial manifold of the HC was extracted and flattened. The flattened sheets were then registered using both a rigid and a non-rigid alignment technique, and the medial surface radius was expressed as a height function over them. This allowed for an investigation of the association between subject variables and the local width of the HC. With regard to the effects of age and gender, it could be shown that the previously observed gender differences were mostly due to volume loss in males in the lateral areas of the HC head and tail. We suggest that the analysis of HC shape using medial surfaces might thus serve as a complimentary technique to investigate group differences to the established segmentation protocols for volume quantification in MRI.

Adolescent↗

PubMed2005

Correlation of cerebrospinal fluid levels of tau protein phosphorylated at threonine 231 with rates of hippocampal atrophy in Alzheimer disease.

BACKGROUND: The microtubule-associated tau protein abnormally phosphorylated at threonine 231 (p-tau231) has been investigated as a potential marker of Alzheimer disease. Levels of cerebrospinal fluid (CSF) p-tau231 vary across patients with Alzheimer disease. We hypothesized that these variations partially reflect differences in the degree of neuronal damage and therefore may be used to predict structural disease progression. OBJECTIVE: To investigate whether CSF p-tau231 levels correlate with rates of hippocampal atrophy as an in vivo marker of regional neuronal loss. DESIGN AND PATIENTS: We measured hippocampal volumes on the basis of serial magnetic resonance image examinations in 22 patients with Alzheimer disease. In addition, we determined CSF p-tau231 levels at baseline. RESULTS: Levels of CSF p-tau231 were significantly correlated with baseline hippocampal volumes (P<.001) and rates of hippocampal atrophy (left hippocampus, P<.001; right hippocampus, P = .02), independent of disease duration and severity. CONCLUSION: These findings suggest that variations in p-tau231 levels may be used to predict progression of brain atrophy in patients with Alzheimer disease.

Aged↗

PubMed2005

The Montreal Imaging Stress Task: using functional imaging to investigate the effects of perceiving and processing psychosocial stress in the human brain.

OBJECTIVE: We developed a protocol for inducing moderate psychologic stress in a functional imaging setting and evaluated the effects of stress on physiology and brain activation. METHODS: The Montreal Imaging Stress Task (MIST), derived from the Trier Mental Challenge Test, consists of a series of computerized mental arithmetic challenges, along with social evaluative threat components that are built into the program or presented by the investigator. To allow the effects of stress and mental arithmetic to be investigated separately, the MIST has 3 test conditions (rest, control and experimental), which can be presented in either a block or an event-related design, for use with functional magnetic resonance imaging (fMRI) or positron emission tomography (PET). In the rest condition, subjects look at a static computer screen on which no tasks are shown. In the control condition, a series of mental arithmetic tasks are displayed on the computer screen, and subjects submit their answers by means of a response interface. In the experimental condition, the difficulty and time limit of the tasks are manipulated to be just beyond the individual's mental capacity. In addition, in this condition the presentation of the mental arithmetic tasks is supplemented by a display of information on individual and average performance, as well as expected performance. Upon completion of each task, the program presents a performance evaluation to further increase the social evaluative threat of the situation. RESULTS: In 2 independent studies using PET and a third independent study using fMRI, with a total of 42 subjects, levels of salivary free cortisol for the whole group were significantly increased under the experimental condition, relative to the control and rest conditions. Performing mental arithmetic was linked to activation of motor and visual association cortices, as well as brain structures involved in the performance of these tasks (e.g., the angular gyrus). CONCLUSIONS: We propose the MIST as a tool for investigating the effects of perceiving and processing psychosocial stress in functional imaging studies.

Adult↗

PubMed2005

The Douglas Hospital Longitudinal Study of Normal and Pathological Aging: summary of findings.

In 1988, our group initiated the Douglas Hospital Longitudinal Study of Normal and Pathological Aging to assess the association between secretion of the stress hormone cortisol and cognitive performance in a group of 51 older adults. In this paper, we summarize the data obtained in this study to date. We have found that long-term exposure to high endogenous levels of cortisol is associated with both memory impairments and a 14; smaller volume of the hippocampus. We also report on studies showing that in older adults with moderate levels of cortisol over time, memory performance can be acutely modulated by pharmacologic manipulations of cortisol. We describe one participant who was included in the group of older adults presenting with increased cortisol levels over time, memory impairments and reduced hippocampal volume and in whom major depression, followed by Alzheimer's disease, developed during the course of the study. Together, the results of the Douglas Hospital Longitudinal Study of Normal and Pathological Aging show that increased secretion of cortisol in the older human population is significantly associated with impairment of cognitive function during aging.

Aged↗

PubMed2004

Focal decline of cortical thickness in Alzheimer's disease identified by computational neuroanatomy.

Alzheimer's disease (AD) is characterized by a heterogeneous distribution of pathological changes throughout the brain. Magnetic resonance imaging can be used to investigate the regional distribution of cortical atrophy in AD in vivo. One marker for the disease-specific atrophy is the thickness of the cortical mantle across the brain, obtained with automated 3-D image processing. Here, we present data from 36 subjects (17 controls and, 19 patients diagnosed as probable AD) investigated for cortical thickness across the entire brain. We show significant cortical thickness decline in AD in temporal, orbitofrontal and parietal regions, with the most pronounced changes occurring in the allocortical region of the medial temporal lobes, outlining the parahippocampal gyrus, and representing a loss of >1.25 millimeters of cortical thickness. Moreover, focal cortical areas decline with progression of the disease as measured by time from baseline scan as well as the Mini-Mental State Exam. The results demonstrate the ability of this method to detect changes in cortical thickness in AD, across the entire brain, without need of prior anatomical definitions. The regional distribution of changes reported here is consistent with independent findings on the distribution of neuropathological alterations in AD. Using cortical thickness, moreover, we provide a direct quantitative index of atrophy in the disease.

Aged↗

PubMed2004

A voxel-based morphometric study to determine individual differences in gray matter density associated with age and cognitive change over time.

Voxel-based morphometry (VBM) was used to examine the relation between age and gray matter density cross-sectionally and to study the association between gray matter density and longitudinal decline in performance on cognitive tests in healthy, non-demented elderly individuals. Participants were neuropsychologically tested at baseline and again after 3 years. Thirty-seven subjects (mean age 72.5 years) who showed a decline in cognitive test performance at follow-up were compared with 38 individually matched control subjects (mean age 71.8 years) whose performance did not change over time. Magnetic resonance imaging scans were acquired at follow-up and individual differences in regional gray matter density were examined with VBM. The largest age effects were found in various regions in the prefrontal cortex, the (medial) temporal lobes and the striate cortex. Longitudinal cognitive decline was associated with decreased gray matter density in prefrontal areas, the (medial) temporal lobes and the posterior parietal cortex. These findings suggest that prefrontal and temporal cortical regions are of particular relevance both in aging and age-related cognitive decline in healthy elderly individuals.

Adult↗

PubMed2004

Dopamine release in response to a psychological stress in humans and its relationship to early life maternal care: a positron emission tomography study using [11C]raclopride.

Mesolimbic dopamine is thought to play a role in the processing of rewards. However, animal studies also demonstrate dopamine release in response to aversive stressful stimuli. Also, in animal studies, disruptions of the mother-infant relationship have been shown to have long-lasting effects on the mesolimbic dopamine system and the hypothalamic-pituitary adrenal axis. We therefore investigated dopamine release in response to stress in human subjects, considering the relationship to early life parental care. We screened 120 healthy young college students for parental care in early life using a combination of telephone interviews and questionnaires. Five students from the top end and five students from the bottom end of the parental care distribution were then invited for a positron emission tomography study using [11C]raclopride and a psychosocial stress task. The psychosocial stressor caused a significant release of dopamine in the ventral striatum as indicated by a reduction in [11C]raclopride binding potential in the stress versus resting condition in subjects reporting low parental care. Moreover, the magnitude of the salivary cortisol response to stress was significantly correlated with the reduction in [11C]raclopride binding in the ventral striatum (r = 0.78), consistent with a facilitating effect of cortisol on dopamine neuron firing. These data suggest that aversive stressful events can be associated with mesolimbic dopamine release in humans, and that the method presented here may be useful to study the effects of early life events on neurobiological stress systems.

Adult↗

PubMed2004

Effects of self-esteem on age-related changes in cognition and the regulation of the hypothalamic-pituitary-adrenal axis.

Epidemiological studies have demonstrated the effects of self-esteem on global health and life expectancy in normal aging. Endocrinological studies in humans have demonstrated the effects of self-esteem on basal regulation and reactivity of the hypothalamic-pituitary adrenal (HPA) axis. To investigate the effects of differences in self-esteem on age-related changes in cognitive performance and HPA regulation, we investigated 20 healthy elderly subjects (age range 60-84, mean age 69.8 y). We assessed salivary cortisol levels together with neuropsychological assessment, and psychological assessment for self-esteem and locus of control. Across the study sample, age was significantly associated with reductions in cognitive performance and changes in basal cortisol regulation. Self-esteem appeared independent of age. Defining two groups of subjects with high and low self-esteem, age-related changes in cognitive and endocrinological variables became more prominent in the low self-esteem group, whereas age no longer had a significant impact on the variables in the high self-esteem group. These data suggest an effect of self-esteem on cognitive decline with aging. It further suggests an effect on age-related endocrine changes in humans. These results are discussed with regard to potential mechanisms by which the reported association between self-esteem and aging could be mediated.

Aged↗

PubMed2003

Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change.

Study protocols in endocrinological research and the neurosciences often employ repeated measurements over time to record changes in physiological or endocrinological variables. While it is desirable to acquire repeated measurements for finding individual and group differences with regard to response time and duration, the amount of data gathered often represents a problem for the statistical analysis. When trying to detect possible associations between repeated measures and other variables, the area under the curve (AUC) is routinely used to incorporate multiple time points. However, formulas for computation of the AUC are not standardized across laboratories, and existing differences are usually not presented when discussing results, thus causing possible variability, or incompatibility of findings between research groups. In this paper, two formulas for calculation of the area under the curve are presented, which are derived from the trapezoid formula. These formulas are termed 'Area under the curve with respect to increase' (AUCI) and 'Area under the curve with respect to ground' (AUCG). The different information that can be derived from repeated measurements with these two formulas is exemplified using artificial and real data from recent studies of the authors. It is shown that depending on which formula is used, different associations with other variables may emerge. Consequently, it is recommended to employ both formulas when analyzing data sets with repeated measures.

Area Under Curve↗

PubMed2002

Glucocorticoids and hippocampal atrophy after heart transplantation.

The glucocorticoid cascade hypothesis proposes that hippocampal atrophy may result from excessive steroid exposure. Although demonstrated in animal models and some human hypercortisolemic states, hippocampal damage as a possible consequence of posttransplant steroid immunosuppression has not been investigated in human heart transplant recipients. We report a case of a 37-year-old female heart transplant recipient who had the clinical, neuropsychiatric, and neuroimaging findings consistent with hippocampal atrophy after 5 years of steroid exposure.

Adult↗

PubMed2002

Volumetry of temporopolar, perirhinal, entorhinal and parahippocampal cortex from high-resolution MR images: considering the variability of the collateral sulcus.

Researchers in clinical and basic neuroscience frequently target structures of the human medial temporal lobe (MTL) for volumetric analysis with magnetic resonance imaging (MRI). In neurodegenerative diseases, a precise volumetric analysis of MTL structures can assist in differential diagnosis and can be used in guiding early treatment. Also, in functional neuroimaging, exact localization is crucial for the correct interpretation of focal MTL activations with respect to specific memory functions. In presently available protocols, precise and consistent volumetric analysis of MTL structures is compromised in numerous ways. Most importantly, in order to cover all structures of the MTL, the researcher is presently forced to combine independently developed segmentation protocols for different structures from different laboratories. This approach limits anatomical precision because these protocols are based on different anatomical guidelines and descriptions that cannot easily be integrated. The segmentation approach presented in this paper was designed to address this issue by presenting segmentation guidelines for all major structures of the parahippocampal gyrus (PHG). It was developed directly to complement a volumetric protocol for hippocampus and amygdala (Pruessner et al., 2000, Cereb Cortex 10:433-442), thus allowing volumetric assessment of all major MTL structures in an integrated and consistent manner. Furthermore, it takes into consideration the neuroanatomical appearance of the collateral sulcus by presenting a method to correct the volumes of the surrounding cortices for the variability of this sulcus. The protocol was validated using MR images of 40 healthy normal control subjects (20 men and 20 women, age range 18-42 years). Intra- and interrater coefficients are presented, together with mean values for the volumes of all PHG structures, correlations with age and sex, and tests for hemispheric differences.

Adult↗

PubMed2002

Regional frontal cortical volumes decrease differentially in aging: an MRI study to compare volumetric approaches and voxel-based morphometry.

Recent neuroimaging studies suggest that the frontal lobes are the part of the brain most profoundly affected by the aging process. The present study investigated whether subregions within the frontal cortex show different patterns of brain aging. Magnetic resonance images of 57 healthy participants between 21 and 81 years old were used to measure regional frontal gray matter volumes in three ways: a manual tracing method, a semiautomatic "Talairach boxes" volumetric method, and voxel-based morphometry. Seven regions within each hemisphere were manually traced: precentral gyrus, inferior frontal gyrus, dorsolateral frontal cortex, ventral medial region, lateral orbital region, anterior cingulate, and frontal pole. With the semiautomatic approach, four regions were measured: lateral, orbital, and medial frontal regions and frontal pole. Advancing age was strongly associated with decreases in the volume of the whole frontal cortex. Differential age effects on the volumes of frontal subregions were dependent on the method applied. According to the manual approach, age-related volume decreases were strongest in the lateral and orbital frontal gray matter. The semiautomatic and voxel-based analyses found that age effects were most prominent within the lateral frontal and cingulate regions. Overall, it was concluded that although semiautomated and voxel-based methods can provide a reasonable estimate of regional brain volume, they cannot serve as a substitute for manual volumetry.

Adult↗

PubMedDate not supplied

Self-reported depressive symptoms and stress levels in healthy young men: associations with the cortisol response to awakening.

OBJECTIVE: There is evidence that clinical depression and negative mood are associated with elevated basal cortisol levels. Recently, measuring the cortisol response during the first hour in the morning with strict reference to the time of awakening was established as a reliable marker of individual adrenocortical activity. In studies using this marker, a relationship with self-reported stress levels and psychosomatic symptoms has been found. The goal of the present study was to investigate the association of self-reported depressive symptomatology with early morning free cortisol levels and their relationship to measures of stress. METHODS: We assessed the severity of depressive symptoms using the Hamilton Depression Inventory and chronic and acute stress perception in 40 healthy young men. Once a week, for 4 consecutive weeks, subjects provided saliva samples collected at 0, 30, and 60 minutes after awakening. RESULTS: Higher levels of depressive symptomatology were associated with a greater cortisol response after awakening. This association seemed to be stronger when only subjects in the nonclinical range of depression were included. Furthermore, cortisol levels and depressive symptomatology were significantly positively correlated with measures of chronic and acute stress perception. CONCLUSIONS: The present study extends earlier findings of hypothalamus-pituitary-adrenal axis hyperactivity in clinical depression to healthy young men with mild levels of depressive symptomatology. Measuring the cortisol response to awakening is proposed as an economical alternative to traditional approaches for determining basal hypothalamus-pituitary-adrenal axis activity. Associations between depressive symptomatology and chronic stress, as well as implications for future studies, are discussed.

Acute Disease↗