Cognitive effects of short-term use of raloxifene: a randomized clinical trial.

Two questions regarding findings from the Women's Health Initiative are (1) What is the effect of various hormonal regimens including selective estrogen receptor modulators? and (2) Is the negative effect on cognitive functioning related to the older age (65+ years) of the women? This study addresses these two questions in a short-term randomized trial of the effects of raloxifene versus alendronate on cognition. The study found only one significant interaction where the raloxifene and alendronate group changed differently across the two testing occasions. Hence, raloxifene does not have any impact, positive or negative, on short-term cognitive functioning when compared to alendronate.

Dhea supplementation and cognition in postmenopausal women.

Previous work has suggested that DHEA supplementation may have adverse cognitive effects in elderly women. This article analyzed 24-h measurements of DHEA, DHEAS, and cortisol to determine if cognitive decrease with treatment is mediated by DHEA's impact on endogenous cortisol. It was found that DHEA administration increased cortisol at several hours during the day. In the treatment group, cortisol was positively associated with cognition at study completion. An increase in negative associations between DHEA(S) levels and cognition was found at completion. Increased cortisol does not explain the cognitive deficits associated with DHEA, suggesting a direct negative effect of exogenous DHEA on cognition.

Pregnancy history and cognition during and after pregnancy.

An increasing body of literature confirms anecdotal reports that cognitive changes occur during pregnancy. This article assessed whether prior pregnancy, which alters a woman's subsequent hormonal environment, is associated with a specific cognitive profile during and after pregnancy. Seven primigravids and nine multigravids were compared, equivalent for age and education. No differences between groups were found during pregnancy. After delivery, multigravids performed better than primigravids on verbal memory tasks. After controlling for mood, a significant difference in verbal memory remained. A neuroadaptive mechanism may develop after first pregnancy that increases the ability to recover from some cognitive deficits after later pregnancies.

Pregnancy and post partum: changes in cognition and mood.

Steroidal hormones are increasingly recognized as highly relevant in multiple aspects of brain functioning. While basic science has actively worked to advance understanding of fundamental steroid mechanisms within the brain, investigation of the neurobehavioral outcomes of reproductive hormone actions on the human brain has received less attention. We argue that the dramatic steroidal hormone changes seen in human reproduction must be systematically studied and may provide novel explanations of cognitive and mood disorders associated with reproductive events. This chapter provides a review of current literature establishing a role for a variety of steroids on neuroactivity, and evidence from a variety of observational and experimental paradigms linking hormones and clinical aspects of cognition and mood in humans. The specific hormonal changes of pregnancy are described and discussed in relation to concomitant alterations in cognition and mood across the peri-natal period. A review of studies that have systematically observed cognitive and affective changes both during pregnancy and the post-partum period is presented, as well as new data that follow a small cohort of women for an extended period of time after delivery. We conclude that women may show specific areas of cognitive changes during and after pregnancy, notably deficits in verbal learning and memory. Mood appears to be impacted as well. While steroidal hormones show a pattern of associations with mood during and after pregnancy, no such pattern is evident for cognition. The embryonic state of our knowledge regarding reproductive hormones and neurobehavioral functioning is evident, as are the scientific and public health reasons to redress this lacuna.

Psychological factors and hyperemesis gravidarum.

Hyperemesis gravidarum (HG) is a condition of severe, intractable nausea and vomiting during pregnancy. It has long been held that HG is a psychosomatic illness reflective of a long-term psychological trait, that is, conversion disorder. We investigated this possibility by conducting a two-phase study: (1) a comparison of women with (n = 9) and without (n = 10) HG during pregnancy and (2) a comparison of nonpregnant women who did (n = 10) and did not (n = 12) have HG during their most recent pregnancies. The pattern of findings differed between experiments 1 and 2. During pregnancy, women with HG scored significantly higher on three scales associated with conversion disorder (all p values <0.01) than did women without HG. There were no significant differences between HG subjects and controls after pregnancy. We find no support for the theory that HG is a psychosomatic condition. Rather, it appears to be a complex interaction of biological, psychological, and sociocultural factors.

Anosognosia and Alzheimer's disease: the role of depressive symptoms in mediating impaired insight.

The relation between anosognosia and dementia severity in Alzheimer's disease (AD) has been unclear. We constructed a measure that quantified the difference between the perceptions of deficits of patients with AD (n = 23) and ratings from a knowledgeable informant as a measure of anosognosia. There was no correlation between dementia severity and anosognosia. However, dementia severity was positively correlated with the degree of anosognosia after controlling for depressive symptomatology (p =.03). Post-hoc analyses, also controlling for depressive symptoms, indicated that higher levels of anosognosia were associated with lower performance on specific cognitive tasks. These results suggest depressive symptoms may confound the relationship between anosognosia and dementia severity.

Development and validation of the Parental Intrusiveness Rating Scale among bulimic and comparison women.

OBJECTIVE: Based on hypotheses generated during clinical interviews with 80 women with a lifetime history of bulimia nervosa (BN), we designed an instrument for assessing the extent to which women with BN report parental intrusiveness and breakdown of appropriate role boundaries during their adolescent development. METHOD: Through an iterative process of item generation and scale administration, the Parental Intrusiveness Rating Scale (PIRS), consisting of 20 maternal items and 20 paternal items, was developed. Maternal subscales include Invasion of Privacy, Jealousy and Competition, and Overconcern with the Daughter's Eating, Weight, and Shape. Paternal subscales include Invasion of Privacy, Seductiveness, and Overconcern with the Daughter's Eating, Weight, and Shape. We validated the instrument using a subset of the above BN and comparison women (ns = 55 and 33, respectively), as well as an independent sample of women with BN and college comparison subjects (ns = 31 and 540, respectively). RESULTS: Parental intrusiveness scores were significantly positively correlated with disturbed relationships in the family of origin of our initial cohort. Reliability analyses, both test-retest and item-scale correlations, revealed adequate to strong statistical associations in the combined sample. CONCLUSION: The PIRS promises to enrich our understanding of problematic parental behaviors among women who develop BN and allows us to broaden the conceptualization of familial risk factors for this disorder.

Associations between circulating sex steroid hormones and cognition in normal elderly women.

OBJECTIVE: To provide exploratory analyses of associations between levels of several sex hormones and cognitive performance in elderly women. BACKGROUND: Sex steroid hormones are implicated in the cognitive processes of the adult brain. Comparing cognitive performance across or between conditions associated with different hormone levels, such as phases of the menstrual cycle, surgical menopause, and estrogen replacement therapy suggests conditions with higher levels of estrogen are associated with better verbal memory and possibly worse visuospatial ability. METHOD: The authors measured circulating sex hormone levels in 39 highly educated, nondemented, predominantly white elderly women. Levels were correlated with neuropsychological performance, controlling for age, education, frequency of prior testing, use of estrogen replacement, and depression. RESULTS: High estradiol levels were associated with better delayed verbal memory and retrieval efficiency, whereas low levels were associated with better immediate and delayed visual memory. Levels of testosterone were related positively to verbal fluency. Levels of progesterone and androstenedione were unrelated to cognitive performance. CONCLUSIONS: Both estrogen and testosterone showed associations with cognitive performance. Estrogen may enhance, and depress, specific cognitive skills.

Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease.

Carriers of the apolipoprotein E (APOE) epsilon4 allele show significantly higher risk of Alzheimer disease (AD). The aim of this present study was to test the hypothesis that a significant interaction exists between APOE genotype and gender on AD. Interactions of epsilon4 by gender, although indicated in the literature, require further verification. A total of 195 past or current control or AD participants in an ongoing longitudinal study of aging and dementia were genotyped. All subjects were at least 60 years old; demented subjects met clinical or pathologic criteria for late-onset AD. Logistic regression analysis and proportional hazard models were used to evaluate joint effects of APOE and gender. A significant statistical interaction between APOE and gender was shown (p = 0.04) in logistic regression analysis. Women carrying one or more APOE-epsilon4 allele were more likely to develop AD [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 3.2-19. 1]. For men, the presence of the APOE-epsilon4 allele was not associated with a statistically significant increased risk (OR = 1.6, 95% CI = 0.5-5.3). The interaction term in the proportional hazards model neared (p = 0.07) statistical significance, and a similar but reduced gender effect was shown. The analysis suggests that the presence of one or more APOE-epsilon4 allele confers a substantially greater risk of AD to women than to men. These findings in part may account for reports of increased risk of AD faced by women.

Social support, social adjustment, and recovery status in bulimia nervosa.

OBJECTIVE: To examine recovery status in bulimia nervosa (BN) and its relation to social support and social adjustment. METHOD: Using a cross-sectional design, we administered the modified Social Support Questionnaire and the Social Adjustment Scale-Self-Report (SAS-SR) to 40 women, each of whom was actively bulimic (ABN), was in remission from BN (RBN), or had no history of eating disturbance (comparison). RESULTS: In terms of social support, relative to RBN and comparison subjects, the ABN group had significantly fewer persons in their friendship and kinship networks available to provide emotional support, although the groups were equivalent in number of persons available to provide things and advice. Relative to the comparison group, both bulimic groups were significantly dissatisfied with the quality of emotional support provided by relatives. On the SAS-SR, women in the ABN group displayed the poorest overall social functioning. The RBN group was functioning significantly better than the ABN group, but significantly more poorly than the comparison group. DISCUSSION: Our results suggest that the social functioning of RBN women lies between ABN women and non-eating-disordered women, indicating both gains relative to the active phase and residual deficits.

Lifelong estrogen exposure and cognitive performance in elderly women.

Fluctuating endogenous and exogenous estrogens influence cognition in women. In this study, cognitive functioning in elderly women was examined by applying methodology used in understanding the effects of chronic estrogen exposure on hormone-sensitive tissue other than the brain. An index, combining menstrual, reproductive, and physical markers associated with estrogen levels, was developed for elderly, nondemented, predominantly Caucasian women (n = 87). This index related to better performance on two verbal factors, one attentional and one global in nature. Findings suggest that estrogen exposure across the life span plays a role in brain aging. Possible physiological mechanisms for this effect are discussed.

Pregnancy, the postpartum, and steroid hormones: effects on cognition and mood.

The effects of pregnancy on cognition and mood were examined using a repeated-measures design. Nineteen women, average age 33, were tested with a comprehensive neuropsychological battery during their last 2 months of pregnancy and again within 2 months of delivery. Blood samples were obtained from all subjects and assayed for a variety of steroid hormones implicated in cognitive and mood functioning. Most participants also completed several self-report measures of mood. In comparison with performance after delivery, women showed significantly more impairment in aspects of verbal memory during pregnancy and also tended to report more negative mood states. Memory deficits were not explained by mood disturbances. No hormone assayed consistently related to cognitive performance during pregnancy. During pregnancy, higher levels of progesterone (P) were associated with greater mood disturbances and higher levels of dehydroepiandrosterone (DHEA) with better mood. After delivery, testosterone (T) was strongly and consistently associated with greater reported mood disturbances. Our results confirm a peripartal memory deficit, which cannot be explained by the dramatic rise in circulating steroid hormones, or by mood status during pregnancy. Steroidal hormones, namely P, DHEA and T, appear to play a role in mood disturbances during, and after, pregnancy. Studies beginning earlier in pregnancy and continuing for an extended period of time after delivery are needed to confirm and expand these observations.

Gender-related cognitive deficits in Alzheimer's disease.

Recent studies have identified cognitive deficits in semantic memory and verbal language abilities among women with Alzheimer's disease (AD). Few studies to date have explored gender differences in episodic memory function in AD. The present study compared the performance of men and women diagnosed with AD on a battery of neuropsychological measures. Results indicated the presence of gender-related cognitive deficits on tasks of confrontation naming, expressive word knowledge, and both episodic and semantic memory for women with AD, relative to findings in men.

Virtual environments in the diagnosis, prevention, and intervention of age-related diseases: a review of VR scenarios proposed in the EC VETERAN Project.

A group of worldwide virtual reality and health-care researchers have decided to combine their efforts in a multidisciplinary project titled VETERAN-virtual environments in the diagnosis, prevention and intervention of age-related diseases. The main goal of the VETERAN project is the tuning and testing of different virtual environments, designed to address the cognitive/functional impairments that may occur due to the aging process and age-related disorders. In particular the developed modules will address the problems commonly found in the following pathologies that have a strong impact on the elderly health care policy: Alzheimer's disease and other senile dementias; stroke and unilateral spatial neglect; mobility-related accidents within specific environments (e.g., falls, shocks). The project will focus on research into clinical aspects of age-related diseases and disorders of high morbidity and specifically target goals of prevention, treatment, or delay in onset. Another goal of the VETERAN project is to define and develop new protocols and tools to be used for general rehabilitation purposes. These tools will aim to provide systematic restorative training within the context of functionally relevant, ecologically valid simulated environments. This approach is hoped to optimise the degree of transfer of training and/or generalisation of learning to the person's real world environment.

Virtual environments for targeting cognitive processes: an overview of projects at the University of Southern California.

The Virtual Environments Laboratory at the University of Southern California (USC) has initiated a research program aimed at developing virtual reality (VR) technology applications for the study, assessment, and rehabilitation of cognitive processes. This technology is seen to offer many advantages for these aims. The status of two ongoing VR projects will be discussed in this article. The projects outlined are being conducted via cooperative efforts with both the Integrated Media Systems Center and the Information Sciences Institute at USC. These departments consist of a multidisciplinary group of scientists that represents engineering, computer science, communications, information technology, education, and psychology. This mix of expertise has served to facilitate the development of these projects via an integrated approach to VR application development. The first project involves the development of a series of ImmersaDesk-delivered visuospatial tests and training tools that leverage the interactive, dynamic, and 3D assets that are available with current VR technology. The second project involves a head mounted display (HMD) VR system for the study, assessment, and possible rehabilitation of attention disorders. It is believed that these projects target cognitive variables that are well matched to the current strengths and limitations that exist with presently available VR technology.

Gender issues in the use of virtual environments.

Gender differences in cognitive and behavioral performance have been reported throughout the psychological literature. Consequently, gender differences should be considered and controlled for when cognitive research is conducted in virtual environments (VEs). These variables may include gender-related differences in cognitive performance, susceptibility for cybersickness, and the impact of sex hormones on cognition. Such issues are addressed in the context of a recent VE study of the visuospatial ability referred to as mental rotation. The Mental Rotation Test (MRT), a paper and pencil measure, has been shown to produce one of the largest gender differences in the cognitive literature. The outcomes of the MRT are in favor of males. However, results reported from a Virtual Reality Spatial Rotation (VRSR) test demonstrate no gender differences when subjects were able to manually manipulate the stimuli in a VE. Further analysis uncovers gender differences in the patterns of associations between verbal and spatial tasks and performance on VRSR. Results are discussed in terms of dimensionality factors and hemispheric lateralization.

Basic issues in the use of virtual environments for mental health applications.

In order for Virtual Environments (VE) to be efficiently developed in the areas of clinical psychology and neuropsychology, a number of basic theoretical and pragmatic issues need to be considered. The current status of VE's in these fields, while provocative, is limited by the small number of controlled studies that have been reported which apply this technology to clinical populations. This is to be expected considering it's relatively recent development, expense, and the lack of familiarity with the technology by mainstream researchers in these fields. In spite of this, some work has emerged which can begin to provide a basic foundation of knowledge which could be useful for guiding future research efforts. Although much of the work does not involve the use of fully immersive head mounted displays (HMD's), studies reporting PC-based flatscreen approaches are providing valuable information on issues necessary for the reasonable and measured development of VE/mental health applications. In light of this, the following review will focus on basic issues that we see as important for the development of both HMD and non-HMD VE applications for clinical psychology, neuropsychological assessment, and cognitive rehabilitation. These basic issues are discussed in terms of decision-making for choosing to develop and apply a VE for a mental health application. The chapter covers the issues involved with choosing a VE approach over already existing methods, deciding on the "fit" between a VE approach and the clinical population, level of presence, navigation factors, side effects, generalization, and general methodological and data analysis concerns.

Body weight, estrogen and cognitive functioning in Alzheimer's disease: an analysis of the Tacrine Study Group data.

We conducted a retrospective analysis of clinically ascertained Alzheimer's disease subjects, hypothesizing that weight, given its positive relationship to endogenous estrogen levels, would correlate with better cognitive performance among women, but not necessarily men, with this disorder. Baseline (pretreatment) data, collected by the Tacrine Study Group were available from 347 women and 316 men. After controlling for age, duration of dementia, height, and education, we found weight to have a significant, positive relationship with two measures of global cognitive functioning among women. For men, this relationship was smaller and did not reach statistical significance. Post hoc analyses among women found the effect of weight to be independent of concurrent use of estrogen replacement medication. The use of estrogen replacement was independently related to better cognitive performance. Results support the contention that higher body weight - putatively as a reflection of higher levels of endogenous estrogens - has a positive effect on cognitive performance among women with Alzheimer's disease.

Virtual reality and cognitive assessment and rehabilitation: the state of the art.

VR offers the potential to develop human testing and training environments that allow for the precise control of complex stimulus presentations in which human cognitive and functional performance can be accurately assessed and rehabilitated. However, basic feasibility issues need to be addressed in order for this technology to be reasonably and efficiently applied to the neuropsychological assessment (NA) and cognitive rehabilitation (CR) of persons with acquired brain injury and neurological disorders. This chapter will provide an introduction to the basic concepts of neuropsychological assessment and cognitive rehabilitation along with rationales for virtual reality's applicability in these complimentary fields. We review the relevant literature regarding theoretical and pragmatic issues for these applications, and provide a description of our ongoing work developing a mental rotation/spatial skills cognitive assessment and training system. References are provided in each section for further reading in each area reviewed.