Copyright is owned by the Author of the thesis. Permission is given for a copy to be downloaded by an individual for the purpose of research and private study only. The thesis may not be reproduced elsewhere without the permission of the Author. HORMONE REPLACEMENT THERAPY USE AND EVERYDAY MEMORY IN MID-AGED NEW ZEALAND WOMEN YOLANDE M HAMIL TON 2000 Hormone Replacement Therapy Use and Everyday Memory in Mid-Aged New Zealand Women A Thesis Presented in Partial Fulfilment of the Requirements for the Degree of Masters of Arts in Psychology at Massey University, Palmerston North, New Zealand Yolande M Hamilton 2000 ABSTRACT There continues to be inconsistent evidence as to the extent that Hormone Replacement Therapy (HRT) may preserve memory performance in menopausal women. The Rivermead Behavioural Memory Test-Extended Version (RBMT-E) is a new measure of everyday memory developed for normal populations. The RBMT-E was used to test the everyday memory in a sample of 104 mid-aged New Zealand women (53 HRT users & 51 non-users) . Measures of mood, affect, stress, general health and menopausal symptoms as well as age and education were also taken to control for possible confounds. Results showed significant differences (p< 0.5) between the groups for three sub-tests: 'Story Immediate', 'Story Delayed ', and 'Message Delayed '. After calculation of a total profile score and adjustments for age and IQ, HRT users scored more highly than non HRT users on the RBMT-E overall measure of Everyday Memory. Conclusions suggest that HRT use does show a relationship with verbal memory, and that the potentially beneficial effect may assist in the performance of everyday memory tasks. ii ACKNOWLEDGEMENTS The completion of this thesis would not have been achieved without the support and encouragement of a number of people. To the women of Christchurch who so willingly came forward to participate in the study, expressing their desire to help, and giving their precious time from their ever busy lives, thank you . I would like to express my gratitude and appreciation to my supervisor, Dr. Chris Stephens, whose pragmatism and patience helped curb my often , impatient desire to be done. I would also acknowledge the support from the special people in Christchurch who unstintingly gave me their time and wisdom during the difficult times. I would like to express my thanks to Jim Pollard for his willingness to listen , and to Fred Knewstubb , who came to the rescue so often when the computer would not comply with my requests to deliver what I had written the day before. Finally, I would like to pay tribute to my Mother who passed away before the completion , but who was unwavering in her belief that it would be done, and to my Dad , who stayed the distance and walked the extra mile. TABLE OF CONTENTS Page Number Abstract Acknowledgements Table of Contents List of Tables List of Figures List of Appendices Chapter 1. Introduction 2. The Evidence of a Relationship between Memory and HRT use II Ill v VII viii 1 3 Biological Mechanisms Involving Estrogen 3 3. 4. Menopause 5 Hormone Replacement Therapy (HRT) . 6 Memory and Menopause 8 The Effect of HRT on Memory and Cognitive Function 9 Summary 16 Memory and its Measurement Memory Constructs of Memory Measures of Memory Menopause and Memory - Related Variables Summary Purpose and Formulation Aims of the Present Study Hypotheses Design 18 18 19 23 25 32 34 34 35 35 iii iv Page Number 5. Method 36 Participants 36 Measures 39 Procedure 53 6. Results 58 Preparation of Data & Preliminary Analyses 58 Hypotheses 1 63 Hypotheses 2 65 Hypotheses 3 65 Hypotheses 4 68 Hypotheses 5 70 Results of RBMT-E Utility Assessment 73 7. Discussion 75 Hypotheses Testing 75 Limitations 79 Future Research 79 The Utility of RBMT-E 80 Conclusion 86 References 87 v LIST OF TABLES Table Page Number 1. Demographic and Health Characteristics of HRT Use Groups 37 and Total Sample. 2. NART Error and Estimated IQ Classification for Total Sample. 38 3. Personal Medical History of HRT Use Groups and Total Sample. 38 4. Concomitant Medications Use by HRT Use Groups and Total 39 Sample. 5. The Variables that were significantly, differently, distributed 59 between the HRT Use Groups, showing the Number and Percentage in Each Group. 6. Digit Span Means and Standard Deviations for HRT Use Groups. 60 7. Sub-score Means and Standard Deviations from Women 's 60 Health Questionnaire for both HRT Use Groups 8. Profile of Mood Scores for HRT Use Groups. 61 9. Positive and Negative Affect Mean and Standard Deviation 62 Scores for HRT Use Groups. 10. Evaluation of Health , Functional Status and Wellbeing 62 sub-scale scores from the Short-Form (SF 36) Health Survey. 11. Means and Standard Deviations scores achieved on the 63 Social Readjustment Rating Scale. 12. Sub-test mean Raw Scores on the Rivermead Behavioural 64 Memory Test - Extended Version (RBMT-E) for HRT Use Groups. 13. RBMT -E Sub-test and Total Profile Scores: Means and 65 Standard Deviations. 14. Results of Hierarchichal Regression of RBMT-E Sub-test Profile 66 Scores on Age, HRT Use. and Agehrt. 15. Means of HRT Use Groups on RBMT-E sub-tests showing 67 Interaction Effect between Age and HRT use. 16. Correlations between RBMT-E and POMS and PANAS Mood 69 sub-scale scores. vi - List of Tables continued - 17. Results of Regression of RBMT-E sub-test scores on 70 Depression and Tension sub-scale scores of Profile of Moods Questionnaire. 18. Mean scores of the HRT Use Groups on RBMT-E 71 sub-tests when regressed on Depression and Tension sub-scales of the Profile of Mood Questionnaire. 19. Comparison Mean Scores with the RBMT-E Development 73 Study. 20. Frequency of Maximum and Minimum Achievable Scores 74 for RBMT-E sub-tests. LIST OF FIGURES Figure Page Number 1. The form of the interaction between 'age' and 'HRT 67 use' on RBMT-E sub-test, 'Second Names'. 2. The form of the interaction between 'Depression' 72 and 'HRT use' on the RBMT-E sub-test, 'Messages Immediate'. 3. The form of the interaction between 'Tension ' 72 and 'HRT use' on RBMT-E sub-test, 'Route Immediate'. vii LIST OF APPENDICES Appendix 1. Advertisement 2. Rivermead Behavioural Memory Test-Extended Version Profile of Mood Scale Positive and Negative Affect Scale Women's Health Questionnaire Short Form Health Survey (SF-36) Life Events Questionnaire Digit Span North American Reading Test (NART-2) . Demographics Questionnaire 3. Information Sheet Consent Form viii 1 CHAPTER 1 INTRODUCTION This study investigates the possible relationship between Hormone Replacement Therapy (HRT) and the everyday memory performance of mid-aged women . Building on a neuroscientific platform that has demonstrated a positive effect of hormone replacement on memory in animals, there is now supportive evidence of a similar effect on verbal memory in mid-aged menopausal women . In addition , more recent research has suggested that the effect of hormone replacement may extend to other aspects of memory. Menopause is a transition period that occurs in all women at mid-age, and in addition to the loss of natural estrogen and the cessation of periods, is associated with various symptoms including complaints of memory loss. Hormone Replacement therapy is advocated by medical professionals as a compensation for the lack of estrogen , and for the alleviation of accompanying symptoms. The medicalisation of menopause and the subsequent prescription of HRT is not without controversy. The inconsistent and often contradictory findings of studies that have endeavoured to unravel the nature of the HRT effect, have extended this controversy. Alongside this evolution has emerged a continuing debate as to how memory should be measured. Questions about the validity of naturalistic versus laboratory research have highlighted the difficulty in obtaining memory measures that accurately portray how an individual may perform in everyday life. With the suggestion that the effect of hormone replacement may extend to other aspects of memory, it follows that there is need to ensure that such a measure accurately reflects how women's memory functions in everyday experience. 2 The Rivermead Behavioural Memory Test is designed to be an ecologically valid measure of everyday memory and has proven reliability and validity. The Rivermead has recently been further developed to create an extended version that is said to allow the assessment of 'normal , younger, individuals'. The present study utilises the Rivermead Behavioural Memory Test-Extended Version , to investigate the relationship of HRT with everyday memory performance in mid­ aged New Zealand women . Chapter 2 of this thesis examines the evidence for a relationship between memory and HRT. Chapter 3 describes the current understanding of the constructs of memory, including the concept of everyday memory. Next, how memory has been measured is discussed. The relationship of memory to menopause follows, with a description of the many confounding variables such as age, education , health , sleep , stress and mood that have often made it difficult to clarify the role HRT may play in memory performance. Chapter 4 describes the formulation and design of the project and outlines the specific hypotheses tested . CHAPTER 2 THE EVIDENCE FOR A RELATIONSHIP BETWEEN MEMORY AND HORMONE REPLACEMENT THERAPY 3 The review of the evidence for a relationship between memory and hormone replacement therapy commences with support from the field of neuroscience. Highlights of recent findings from this arena have set the stage for past, and present investigations of whether memory is maintained by estrogen . Our current understanding of menopause, and the hormonal changes that accompany it are described next. A review of the research regarding hormone replacement therapy (HRT) follows and this includes evidence for the benefits of HRT, (those well established and those still inconsistent and contradictory) , as well as the recognised risks and contraindications for particular women. Over the past decade, research has endeavoured to establish that the estrogen loss associated with menopause does indeed impair aspects of memory. In addition , research findings that HRT users often exhibit a better performance in memory function than HRT non-users is discussed. BIOLOGICAL MECHANISMS INVOLVING ESTROGEN In recent years there has been an increasing interest in the role the central nervous system (CNS) plays in the control of menopause, and in turn , what effects the hormone estrogen may exert on the CNS during this time (Richards, Kuh , Hardy & Wadsworth, 1999). Estrogen appears to have an organisational and activational influence affecting the development and function of the CNS, and may also be responsible for the sexual differentiation of tissues in specific areas of the brain (Sherwin, 1998). 4 Animal studies have shown multiple sites of estrogen action, some of which play important roles in learning and memory function. These include the cerebral cortex, hypothalamus, amygdala, thalamus, the preoptic area , anterior pituitary, basal forebrain and the CA 1 region of the hippocampus (Woolley & McEwen, 1993; McEwen, Alves , Bulloch & Weiland , 1997). Estrogen is also known to influence several neurotransmitter systems, including acetycholine, noradrenaline, serotonin and dopamine (Henderson , 1997). Estrogen enhances cholinergic function that is known to be deficient in Alzheimer's disease by increasing the enzyme acetyltransferase in several areas of the brain , including the CA 1 area of the hippocampus (Rice, Graves , Mccurry & Larsen , 1997). The neuronal atrophy that occurs in both the aging rat and human brain is expressed predominately in these cholinergic-rich regions of the CNS, including the basal forebrain , hippocampus and amygdala (Birge, 1996). Estrogen is thought to be responsible for stimulating neuronal repair, assisting in neuronal suNival and function through neurotrophic growth factors (NGF) (Birge, 1996). For example, adult rats , at 28 weeks after ovariectomy, have been shown to perform poorly on tasks of memory and learning , as well as exhibiting a decline in cholinergic neuronal activity in both frontal cortex and hippocampal regions. This deterioration appears to be prevented by the administration of estrogen replacement. It has been suggested that certain neuronal elements of the CNS (in particular those affected by memory loss disorders such as Alzheimers) are likely to be dependent on estrogen for their survival and function (Birge, 1996). The stimulation of neuronal regeneration and neurotropic growth factors evidenced by estrogen replacement has been shown to enhance learning (Birge, 1996). Estrogen effects are also suggested in the mitigation of neurotoxic effects of stress-induced release of corticosteroids (Henderson, 1997). An increase in Glucocorticoid Hormones appear to be able to damage hipppocampal neurl (Luine, 1994) and may be an additional mechanism through which estrogen influences hippocampal aging (Nappi et al. , 1999). This has important implications in furthering our understanding of the effects of stress on memory performance. Sherwin (1998), has rightly placed an important caveat on the assumption that changes in rats immediately apply to humans. The application of such findings requires replication or at least validation with human populations. With this caveat in mind , the findings from neuroscience described above clearly illustrate that estrogen, in addition to playing an important role in both the timing and organisation of menopause, may also exert a far wider effect on a variety of mechanisms including the preservation of cognitive function . MENOPAUSE The menopause is recognised as a universal event in women's life cycle . Menopause has been considered a process of many months or even years (Stevens-Long & Common, 1992), but is now more universally defined as the cessation of menses for longer than six months (Pearlstein, 1995). In the western world , menopause occurs at the average age of 50.8 years, and marks a period of transition for women as they move from a reproductive to a non-reproductive phase of the life cycle (Sherwin , 1994). Menopause is thought to be a multifactorial process involving both neural and ovarian factors. At menopause, as well as age-related alterations in hypothalamic function , the ovarian follicle supply is finally exhausted leading to a decrease in the production of estrogen (Sherwin , 1994). Prior to the approximate age of 40 years during the premenopausal phase, the ovaries are responsible for the secretion of 95 per cent of the estrogen that enters 6 the circulation (Sherwin , 1994). After this age, due to a continued diminishing number of oocytes, the ovaries produce decreasing amounts of estrogen, until finally there is insufficient hormone to sustain the monthly menstrual cycle. At this stage, the ovary no longer secretes estrogen and a dramatic decrease in plasma levels can be seen (Phillips & Sherwin, 1992). At this point, estrone, an estrogen that is a much weaker steroid , and that arises from a peripheral conversion from androstenedione becomes the predominant estrogen (Sherwin , 1994 ). Certain physical symptoms are common during this period . These include hot flushes , night sweats and vaginal dryness. Complaints of memory problems together with an inability to concentrate are also among symptoms that have been associated with menopause (Phillips et al. , 1992). There is some evidence that suggests that menopause may be a fairly benign event for most women , and also that the transition can often represent an active reorganisation of life goals and attitudes (Slaven & Lee, 1998). However, from a biological perspective, there is increasing support for the implication of estrogen loss in being responsible for a wider decremental effect on the cognitive functioning of women in old age (McEwen et al. , 1997). HORMONE REPLACEMENT THERAPY (HRT) The decline of the natural estrogens during the menopausal transition and the appearance of associated symptoms has led to the development and use of HRT to compensate for this decline. Prior to the onset of the menopause, three major types of natural female estrogens are produced . Estradiol is the more potent form , which is primarily produced during reproductive years. During menopause, estrone (a less active estrogen) becomes the more dominant estrogen and is produced by the conversion of androgens in adipose tissue. Estriol is the third and weakest of the natural estrogens (Coney, 1991 ). 7 The culmination of the increased knowledge about the decline in the amount of natural estrogens, and a greater awareness of the disruptive nature of symptoms, resulted in a medicalisation of menopause that introduced a theory of estrogen deficiency (Coney, 1991 ). As a result , efforts to limit both the menopausal symptoms, and an increased incidence of associated diseases, have contributed to the design of hormone replacement therapy (Coney, 1991 ; Mayeaux & Johnson, 1996). There are three basic HRT regimens: Hormone Replacement Therapy (HRT) is defined as a combination of estrogen and progesterone therapy that is prescribed for women who show evidence of, and seek relief for, menopausal symptoms. This regimen can involve the estrogen and progesterone supplied simultaneously or sequentially (Coney, 1991 ). Estrogen replacement therapy (ERT) is a term used to describe estrogen therapy alone, or unopposed estrogen. This treatment is now generally reserved for those women who no longer have their uterus, as it has been strongly linked to endometrial hyperplasia and uterine cancer (Mayeaux et al. , 1996). For the purpose of this thesis , the definition HRT will include both treatments unless indicated otherwise. To date, the primary reason for the prescription of HRT for mid-aged women has been to alleviate a wide range of reported possible symptoms (Consensus Development Conference, 1993). The determination of which women are actually prescribed HRT depends to a large extent on the severity of the symptoms, the women's acceptance of their doctor's advice, and the amount of personal knowledge about HRT. The acknowledged risks of HRT use include endometrial and breast cancer and regular screening for these risks is recommended (Mayeaux et al., 1996). HRT has been developed from estrogens that were first derived from pregnant mares' urine and this continues to be the major source. In addition to oral tablet form, administration of HRT can also occur by the application of transdermal 8 patches, subcutaneous implants and intravaginal creams, although the latter does not appear to have a major effect in menopausal symptom relief except in large or long-term doses (Mayeaux et al., 1996). Following its development and inception , HRT has proved to be a valuable treatment in the reduction of long term disease (e.g. , osteoporosis , cardiac events and mortality outcomes) (Newman, 1999). Together with the support of neuroscience and empirical studies, evidence has also emerged that suggests that HRT use may also be implicated in the maintenance and possible enhancement of memory (Sherwin , 1998), and as a protective factor against various types of dementias (e.g. , Alzheimers , Vascular type) (Birge, 1997). Although these recent findings may sharpen the focus of research, the inconsistency of much of the evidence serves notice that the issues of 'if' and 'how' HRT acts is at present unclear. These issues have become increasingly complex to investigate, with definite conclusions remaining elusive. However, the importance of such a determination can not be understated . If HRT use can and does exhibit enhancement and protective factors to older women , it is important to investigate the 'face validity' of such claims and demonstrate clearly what the practical outcomes of HRT use for menopausal women may be. This is essential in order to allow women a fully informed choice as to how HRT use may benefit particular individual women. MEMORY AND MENOPAUSE The relationship of cognitive and memory decline to changes that occur during the menopausal transition, has been largely based on the evidence of behavioural studies in animals. These studies have established a correlation of changes in neural architecture with hormone levels (McEwen et al., 1997). However, although there is also indirect evidence that estrogen has positive effects on cognitive 9 function in postmenopausal women (Sherwin , 1994) , data on the effect of estrogen loss on cognitive performance in untreated women are few. It does not necessarily follow that the loss of ovarian function and the correspond ing reduction in estrogen will result in a decline in memory function in all menopausal women . There is evidence that some women experience little or any decline at all in memory function (Birge, 1996). Furthermore, a recent study of both male and female mid­ aged participants, failed to find any gender differences in the decline of cognitive function (Barrett-Connor & Kritz-Silverstein , 1999). This suggests that the estrogen deficiency associated with menopause may not be strongly associated with memory losses reported . On the other hand , memory loss does appear to be a prominent compla int of postmenopausal women (Anderson , Hamburger, Liu , & Rebar, 1987). In support of the association of menopause and memory loss, a more recent study (Nappi et al. , 1999) found that both surgical menopause and physiological menopause exerted a negative effect on short-term memory, whereas long-term memory, attention and psychomotor performances were largely unaffected . In addition , surgical menopause appeared to produce a more negative effect on short-term verbal memory than physiological menopause. The EFFECT of HRT on MEMORY and COGNITIVE FUNCTIONING In recent years there have been substantial reviews of research that has investigated the effect of HRT on women's cognition at menopause and in later life (Erkkola , 1996; Haskell , Richardson & Howitz, 1997; Rice et al. , 1997; Sherwin , 1997; 1998; Yaffe, Sawaya, Lierberburg & Grady, 1998; Newman, 1999). While supporting the plausibility of the biological mechanisms that suggest an estrogen effect on memory, and noting the data that provides evidence of a positive relationship between the two (Rice et al. , 1997; Yaffe et al. , 1998), conclusions remain imprecise. Criticisms have included: 10 "Insufficiently investigated , poorly investigated" (Erkola et al., 1996, S30); "not sufficient evidence to recommend widespread use" (Haskell et al., 1997, p.1251 ; Newman, 1999, p.1268); "inadequate evidence, trials too inadequate to recommend for treatment of dementing disorders" (Yaffe et al. , 1998, p.694); "evidence remains controversial with a need for more data and further elucidation of specific cognitive domains that may respond to estrogen" (Rice et al., 1997, p. 26S) . On the other hand , Sherwin (1998) , suggests that despite the methodological problems that have impinged on the conclusions drawn, there is an "overwhelming finding that estrogen serves to maintain or enhance verbal memory whereas it has little effect on visual or spatial memory in women" (p.21 ). Of particular note and interest, is the fact that the women who received placebo treatment in these studies (Sherwin , 1988; 1990) did in fact complain more spontaneously of memory deficit, than those women who were using HRT. Research investigating any possible effects of estrogen on memory and cognition in mid aged women has used both experimental and observational studies. Observational studies have in general focused on the association of estrogen with performance on cognitive and/or memory tests (Newman, 1999). These studies have mostly used cross sectional data and compared HRT current users with non HRT users. As a result, findings have been somewhat inconsistent. After matching for age and education , Kampen & Sherwin (1994) found significant improvement only on one test, paragraph recall. Similarly, Robinson, Freidman, Marcus, Tinklenberg & Yesavage (1994), found significant improvement in HRT users for name recall, but not for word recall. Both of these studies involved post menopausal women and excluded those who were currently being treated for depression. Kimura (1995) employed 10 cognitive tests and a test of mood and subsequently described "overall" improvement. However, formal adjustment for 11 age and years of education was not undertaken and specific test results not reported. More recently, Schmidt et al. (1996) , used a cross-sectional design to determine any beneficial effect of estrogen on demanding cognitive tests , and to investigate if this benefit was due to the prevention of silent ischemic brain damage. A positive association was found between HRT and cognitive functioning and a lower rate of clinically unsuspected ischemic brain damage in post-menopausal women. Similar to previous studies, this study was limited by a relatively small sample size (70 participants using HRT) , and may not have been truly representative of the entire population despite the use of random selection. The mean age of the women was 59 years and was somewhat younger than the previously mentioned studies. In contrast to observational studies that have illustrated improvement only in paragraph recall and proper name recall, Schmidt et al. (1996) found evidence of improvement on tasks measuring complex problem solving and psychomotor speed as well as visuospatial and verbal memory. No evidence was found for group difference on mood. In a more recent cross-sectional observational study, Steffens et al. (1999), investigated the association between the history of estrogen use and cognitive function in a large sample of community-dwelling older women (65 years and older). However, no specific measures of memory were undertaken in this study. Cognitive assessment in this study consisted only of the administration of the modified Mini-Mental State Examination (3 MMSE), and did not allow identification of what specific aspects of cognition may have been influenced by estrogen. In addition , the scores for all user groups were all in the normal range which may indicate that a ceiling effect was reached (Newman, 1999). Although the effect of estrogen was reported as a positive one, the effect was quite small and it remains difficult to discern whether this effect was really due to estrogen use or some other design factor (Newman, 1999). 12 In a later, longitudinal study with a larger sample than most observational studies (727 participants), Jacobs et al. (1998), evaluated the relationship between a history of estrogen use and cognitive test performance. Measures of cognitive functioning here included standardised tests of memory, language, and abstract reasoning. Similar to other studies, HRT users were found to score higher at baseline, but in addition , scores on verbal memory improved over time. This study is important in that it suggests that estrogen benefits may extend to more global cognitive domains such as abstract reasoning and language as well . In contrast to the positive findings of the above observational studies, there are others that have reported an apparent nil effect of estrogen on memory and cognitive function in women (Barrett-Connor & Kritz-Silverstein , 1993, 1999; Matthews, Cauley, Yaffe, & Zmuda, 1999). Two of these studies have utilised large samples and appear methodologically sound (Barrett-Connor et al. , 1993; Matthews et al. , 1999). Matthews et al. (1999) , evaluated a cross-sectional and longitudinal association of HRT and cognitive function . Education , next to age was found to be the more powerful predictor of cognitive function than HRT use. Past and current estrogen users did not consistently perform better on cognitive tests. However, there were no specific tests of verbal memory, and because of drop out, longitudinal data only included the better functioning group. This study also demonstrated the possibility that a selection bias may be operating where education and HRT have been shown to be associated with higher cognitive function . The Jacobs et al. (1998) and Barrett et al. (1993) studies are similar in that both employed large samples and standardised measures, although the tests used were different. It is possible that the contrasting results could reflect cohort differences. Barrett-Connor et al. (1993) reported data from a highly educated and exclusive sample, whereas Jacobs et al. (1998) was ethnically diverse, but of limited educational attainment. 13 In a more recent study, Barrett-Connor et al. (1999) , used a cross-sectional study of men and women to examine gender differences specifically with memory. This study hypothesised that if estrogen deficiency is associated with memory loss in post-menopausal women , men should have less memory loss with age than women . However, similar patterns of decline were found with men after adjustments for age, depression and estrogen use. The authors conclude that the absence of sex differences in decline indicates a lack of association between estrogen deficiency and a decline in cognitive function . This finding is important as this is the first study that has attempted to determine whether there are sex differences in cognitive functions in age matched groups of elderly men and women . The Barrett-Connor (1999) study supports the suggestion that the aging process itself may account for cognitive decline and so act independent of any hormonal effect (Sherwin, 1997). Further research is needed in the future to elucidate the individual contributions of the aging process and hormones and areas of possible interaction . A consistent trend in the research has reported positive benefits of estrogen use, and furthermore suggest that the benefit may be specific to verbal memory (Sherwin, 1988; Sherwin et al ., 1992). However, this finding may be due to a lack of specific measures of visuospatial memory, or insufficient power. A more recent cross-sectional , observational study found that women receiving HRT had fewer errors on a specific measure of short term visual memory, visual perception and constructional skills (Benton Visual Retention Test - BVRT) (Resnick, Metter & Zonderman, 1997). A longitudinal analysis in this same study also showed that HRT users maintained their performance over time, whereas non HRT users showed the typical age related increase in memory errors. This finding has been further supported by a study that utilised positron emission tomography (PET), and neuropsychological assessments to examine brain 14 structure and function in individuals 55 years and older (Resnick, Maki , Golski , Kraut & Zonderman, 1998). HRT users showed better performance on neuropsychological tests of verbal and figural memory, and also showed significant differences in PET activation patterns during memory tasks. The findings of this study are not only credible from the point of their use of sophisticated imaging techniques , but also for the substantial battery of valid, reliable neuropsychological tests employed . Five cognitive domains were assessed : verbal knowledge, language, learning and memory, visuospatial abilities and perceptual speed . In addition , three items from the Rivermead Behavioural Memory Test were used to measure prospective memory. Unfortunately, data specific to this test were not reported . The major drawback of the study is that it is observational , and again, as in previous studies, differences may reflect baseline differences in the characteristics of women who choose to receive H RT. Randomised , controlled trials have also provided empirical data to analyse the effects of HRT on cognition and serve to control issues of bias and confound (Rice et al. , 1997). On the whole , experimental studies have found a positive relationship between estrogen use and cognition and more specifically verbal memory in both post surgical and natural menopausal women (Sherwin et al. , 1988, 1990, 1992; Fedor-Freybergh , 1977; Wolf et al. , 1999). However, as with the observational studies, there are studies of equal merit that provide contradictory data (Ditkoff, Crary, Cristo, & Lobo, 1991 ; Vanhulle & Demo, 1976; Polo-Kantola, Partin , Helenius, lrjala & Erkkola, 1998). In both the observational and experimental studies, methodological problems are recognised as being responsible for the inconsistencies (Sherwin , 1992). Sample sizes have typically been small . In addition , samples are often obtained from other surveys (e.g. , Barrett-Connor et al. , 1993) and may include the confounding effects of underlying disease or medications that may counter any positive effect of estrogen (Polo-Kantola et al., 1998). 15 As mentioned above, various types of tests that measure different aspects of cognitive functioning have been employed which make comparisons of results difficult. Validity and reliability of these tests is not always available (Sherwin , 1998). Also tests may tap specific functions of memory that are not affected by estrogen levels (Sherwin , 1998). A further methodological difficulty that has been evident in previous studies is that different types and differing doses of estrogen preparations have been used, and circulating hormones not always measured (Sherwin , 1997). The path to a more definitive explanation for how HRT may act to preserve memory funct ion has not always been clear. This is due in large part to the different regimens of HRT prescribed , and the differing effects these may have on individual women (Sherwin , 1998). Recently, the particular dose, type and route of administration of estrogen preparations has been under scrutiny (Steffens et al. , 1999). It is thought that these differences may alter the impact that estrogen may have on memory functioning . This degree of impact is likely due to a differential absorption and metabolisation by the liver, as well as the degree of diffusion of the different estrogens into the brain (Sherwin , 1997). A dose response relationship of estradiol to memory enhancement has been observed in plasma levels. There is also evidence that the brain remains sensitive to estrogens after a considerable period of low plasma estradiol concentrations (Wolf, Kudielka, Hellhammer, Torber, McEwen & Kirschbaum 1999). However, in contrast, Steffens et al. (1999) found no evidence of a dose-response relationship when measuring Mini-Mental Status Exam Scores (3MMSE). Despite the sharpened focus that the measuring of estrogen levels bring to the investigation of an HRT effect on cognition , the findings remain inconsistent. Also , the demonstrated effect of estrogen on verbal memory to date appears to be modest. Although the small degree of 'better performance' on a number of demanding neuropsychological tests may indicate a positive effect of estrogen , the 16 clinical relevance of these findings has yet to be addressed (Sherwin , 1998). Replicated data does not necessarily mean that untreated surgically menopausal women may be clinically impaired in a way that might affect their daily functioning in the real world (Sherwin, 1998). Despite this conundrum, menopausal and post-menopausal women do spontaneously complain of memory deficits and to date, research has not examined what impact HRT use may have those on aspects of memory utilised in the performance of everyday tasks. Furthermore, the ecological validity of the types of tests used to assess the effect of HRT on memory performance has not been established. As a consequence, there remains a need to examine the relationship between HRT use and memory ability in everyday functioning. SUMMARY There is now accumulated evidence from neuroscience that provides an empirical basis for the view that estrogen exerts effects in areas of the CNS that are known to be involved with the production of memory and learning (Birge, 1997). Estrogen mechanisms also appear to be involved in the mediation of NGF and neurotransmitters that are known to be associated with memory pathology. In addition , animal studies have shown that lowered levels of circulating estrogen do contribute to neuronal loss and also, that these changes can be reversed by the administration of estrogen (Luine, 1994; McEwen et al., 1997). This finding further contributes to the evidence that estrogen loss may affect memory. However, the generalisation of these observed changes in rats to the possibility of similar changes occurring in humans needs to be made with care (Sherwin, 1998). Menopause in human beings is recognised as a universal event, a process that involves neural and ovarian factors and is associated with a corresponding decrease in estrogen . Currently, HRT is prescribed to compensate for this loss of estrogen and to assist in the alleviation of symptoms. Although estrogen loss at 17 menopause is well documented and circulating estrogen levels have been shown to be associated with memory function (Wolf et al ., 1999), studies that have investigated the effect of HRT on memory continue to produce contradictory and in some part, unconvincing evidence. This is possibly due to methodological problems including different measures of memory, small samples and a bias in the self selected nature of the sample. Modest evidence for a positive association of HRT use with verbal memory and more recently, visual and more complex cognitive functioning has been shown. As yet though , there is not enough evidence to recommend HRT for enhancement of memory in older women . In addition , the clinical relevance of such evidence is unclear. This lack of clarity is due in part to a lack of ecological validity in the research to date. 18 CHAPTER 3 MEMORY AND ITS MEASUREMENT MEMORY Memory is just one component of an individual's cognitive abilities which arise from a complex central nervous system (Sherwin , 1998). Memory itself, is also not a unitary system , but composed of processes involved in the reg istration , storage and retrieval of information acquired through the senses (Lezak, 1995). Everyday Memory has been defined as: "memory that is involved in the performance of everyday life tasks and measured either outside of the laboratory, or using simulated everyday life tasks , inside the laboratory" (Tomer, Larrabee & Crook, 1994, p.606). The term 'everyday memory' originated from an address by Neisser (1978) that sharply criticised the sterility of memory research undertaken in the laboratory, arguing that it failed to capture , or to represent memory as it occurred in the real world . A spirited discussion concerning issues of generalisability and theoretical worth followed this address (Banjai & Crowder, 1989; Ceci & Bronfenner, 1991 ). What has emerged out of an ongoing debate since that address, is a wide acceptance that it is possible, and helpful to study memory outside the laboratory. However, there is acknowledgement that issues of control (e.g. , material to be remembered , circumstances of presentation and participant's motivation) , as well as issues of reliability and validity remain problematic (Gathercole & Collins, 1992; de Wall , Wilson & Baddeley, 1994). With the development of the 'everyday' approach , the study of memory has incorporated memory events that more closely correspond to the 'everyday' memory tasks and can be considered more ecologically valid. . .. _ 19 Methods used to assess everyday memory have included natural observations, simulations of work activities and self-report questionnaires (Pollina, Greene, Tunick & Puckett, 1992). More recently, attempts to study everyday memory have developed an approach that resembles a bridge between laboratory assessment and assessment obtained by questionnaire and observation (e.g., The Rivermead Behavioural Memory Test; Wilson , Cockburn , Baddeley & Hiorns, 1989). Aside from the controversy mentioned above, the concept of everyday memory at present seems to embrace and reflect specific aspects of memory (de Wall , Wilson & Baddeley, 1994) that have been established in the laboratory. Those aspects of memory that have been identified as being implicated in the impaired performance or failure of everyday tasks include short-term memory (immediate or delayed recall) , visual and non verbal memory, recall and recognition memory, and prospective memory. How these aspects of memory are measured (i.e., the tasks employed) , and the factors that are known to affect the memory are now described. CONSTRUCTS OF MEMORY Short-term memory (STM) deals with memory that has just been presented and is still in the individual's conscious awareness. STM tasks that involve holding the material passively have been defined as primary memory, whereas the manipulation of information while being held is referred to as working memory (Craik, Anderson, Kerr & Li , 1995). STM decays in milliseconds, is attention dependent and can be stored from approximately 30 seconds to one hour (Lezak, 1995). The capacity of STM is recognised as equivalent to the number of items that a person can hold in mind at the same time. This is usually measured by a "span", such as the longest number of digits or words that can be reproduced accurately. Working memory has been described as a system that allows the temporary holding and manipulation of information while other cognitive tasks are performed 20 (Baddeley, 1997). Theoretical components of working memory are thought to be · responsible for the strategies that are employed to manage incoming information , and for the maintenance and alteration of attention (Baddeley, 1997). Selective, sustained and divided attention are thought to be mediated by working memory and it appears difficulties in these aspects of attention have been identified as early occurrences in Alzheimer's-type dementia (Glass, 1999). In addition to the distinction of STM, there are memories that appear to be specific to the nature of the information to be learned (e.g., verbal and non-verbal information) (Lezak, 1995). Verbal memory tasks utilise tasks that measure the length of digit span (i.e., the immediate recall of numbers) , word list recall , and story recall (immediate and delayed) (Lezak, 1995). Long-term memory (L TM) refers to the ability to store information and involves tasks that require memory for material that has left conscious awareness from anything from seconds to years ago (Lezak, 1995; Craik & Jennings, 1992). As described above, LTM is therefore defined as by default (i.e ., anything that is not currently in consciousness) , and is made apparent by the ability to recall information after a delayed interval (Glass, 1999). However, it may not always be possible to clearly establish whether information presented 20 minutes earlier and subjected to a delayed recall is actually from L TM (Groeger, 1997). Theories have also established distinctive components of L TM, including episodic (involving the encoding and retrieval of specific autobiographical events) ; semantic (context independent) and more recently implicit (memory requiring the performance of a task) and explicit memory (memory for information is required) (Craik et al. , 1995). Non-verbal or Visual Memory can be defined as memory for pictures, faces and spatial information (Craik et al., 1995). Visual memory tasks include face, picture, line drawing or object recognition and recall (Lezak, 1995). Another type of non­ verbal information is the recall of personal behaviours that may be performed on an everyday basis. Tasks include performing a sequence of activities such as 21 retracing a route around a room and observing retention levels (Hess & Pullen, 1996; Wilson et al. , 1999). Furthermore, non verbal spatial information that allows the navigation around , and the location of objects in an individual's environment, is assessed by tasks that test location recall of objects that are visually presented on display. Familiarity and the use of effective strategies appear to affect the performance of these tasks (Hess et al ., 1996). The effectiveness of memory is dependent on retrieval which involves both recognition and recall aspects (Lezak, 1995). Recognition memory occurs when a similar stimulus triggers awareness. Assessment involves either the individual making a decision about a previous occurrence, or distinguishing between items previously encountered (Lezak, 1995). Most studies assess accuracy in a way that takes into account both accurate and inaccurate (i .e., false negatives; Hess et al ., 1996). Tasks include recognition of faces , pictures or words such as the Warrington Recognition Memory Test (1984)(Lezak, 1995) and can be cued or uncued. Faces are often paired with a name which is later used as a cue for recall. In contrast, recall memory occurs when information is retrieved as a result of an active complex search process (e.g., "Who is the President of the USA?" ; Lezak, 1995). Recall involves 'free memory' and is assessed by using only a general cue (Banich , 1997). However, assessment of recall can also involve the use of direct cues, for example, "One of the photos had something to do with cooking - Can you remember what it depicted?" Recall memory is generally thought to be more difficult than recognition memory and involve more effortful processing (Craik & McDowd, 1987). Apart from aging , factors that affect recall and recognition appear to be the strength of the cue, familiarity, and context (Hess et al ., 1996). In addition , although the evidence is not clear, depression has been associated with deficits in both recall and recognition (Baddeley, 1990). 22 Prospective Memory is defined as the ability to remember to perform activities in the future (e.g ., remembering to keep an appointment or to give someone a message) and is in contrast to retrospective memory which is memory for past events (remembering someone's name) (Einstein & McDaniel , 1990). Data collected from both naturalistic and laboratory settings (Cherry & Lecompte, 1999) have identified a number of factors that affect impairment in prospective memory tasks. Data from both settings have also highlighted specific age-related paradox and difficulties with the research of this memory task (Rendell & Thomson , 1999). Typical procedures for testing prospective memory have involved asking subjects to perform some action in naturalistic settings at specified times in the future (e.g. , telephone the researcher, or send a postcard) (Einstein et al. , 1990). The use of naturalistic experiments raised concern about the loss of control of a number of varying factors (e.g., memory strategies employed by participants, compliance, motivation). Laboratory tasks have also been criticised as not allowing for any contextual integration by the participant (Einstein , McDaniel, Richardson , Guynn & Confer, 1995). In a laboratory task, participants may be presented with lists of words for learning after being instructed to perform an action whenever a particular target word appeared (Einstein, Holland, McDaniel & Guynn, 1992). It has been suggested that the findings from laboratory studies may not transfer to the real world , due to the high degree of sensitivity to the methodology used (Cohen , 1996). There is evidence that there may be two types of prospective memory tasks. One of these has been described as event-based, where prospective memory is spontaneously cued by the occurrence of a specific external event. A second , time-based memory occurs as a result of a cue following the passage of time (Einstein et al. , 1995). Any observance of effects on prospective memory is thought to depend on the type of prospective task (Cherry et al., 1999). Aside from age-related decline in prospective memory (discussed below), ability (i.e., years of education), working memory span and recognition have been shown to account for 23 small, but significant proportions of variance in prospective memory (Cherry et al., 1999). MEASURES OF MEMORY Neuropsychological tests allow for the impairment in distinctive components of memory to be identified (Lezak, 1995). One noticeable result of these attempts to measure the performance of separate memory functions has been the proliferation of testing instruments (Lezak, 1995). A further sequel to such proliferation , is the current lack of systematic comparisons between many of these different tests . This means that their interchangeability and relative usefulness is questionable (Lezak, 1995). This is particularly applicable in studies that to date, have attempted to measure the effect of HRT on memory in post-menopausal women. Numerous and very different neuropsychological tests have been employed throughout the period of study, and this variety of measures may have contributed to the confused and inconsistent findings (Sherwin , 1998). Aging , environmental influence and psychosocial variables interact in important ways to affect cognitive decline (Moscovitch & Wincour, 1992). With particular regard to the literature that has assessed the effect of HRT on memory, not all studies have measured or controlled for the numerous variables that may impact on memory performance (Sherwin , 1998). There has also been inconsistency in the approach to , (lleasuring memory. Although most studies have employed reliable and valid measures of cognitive functioning, not all studies have included comprehensive memory assessment (Sherwin, 1998). Furthermore, even some of the more comprehensive memory measures that have been utilised in the research and that are widely accepted and employed, offer several issues of concern. For example, the Wechsler Memory Scale-Revised 24 (WMS-R) and the Luria Nebraska Neuropsychological Battery Memory Scale (LNNB-M), have been criticised for lacking ecological validity (Makatura, Chows, Leahy, Castillo & Kalpakjian , 1999). Almost all of the studies that have investigated the possible effects of HRT in women have used these, or similar measures (Barrett-Connor et al. , 1993, 1999; Schmitt et al. , 1996; Henderson, Watt & Buckwalter, 1996). More recently, a new approach that utilises computerised methods that can examine the speed of information processing has been developed (Polo-Kantola et al. , 1998). However, again , the issue of ecological validity emerges. The age-related losses revealed by these tests may also fail to accurately reflect the degree of interference in everyday tasks in the real world (Rybash , Hoyer & Roodin , 1986). In the past, empirical data supporting a correlation between test performance on these earlier measures and performance in everyday functioning has been limited (Wilson , 1993). As a result , a fueled debate as to whether the findings that result from such testing are of any significance has arisen . Little or any functional representation may actually occur, as any compensations that individuals may make in everyday memory tasks are not always accounted for by these assessment measures (Rybash et al. , 1986). Everyday Memory has been described earlier as "memory that is evidenced in everyday life tasks .. . " (Tomer et al. , 1994, p.606). Makatura et al. (1999) argue that the psychometric instruments mentioned above tend to focus on how memory works rather than what an individual can do with the capacity. As a result, these types of instruments may fail in the assessment of areas that are often critical to everyday functioning . A compelling argument exists to suggest that the testing of memory in ways that simulate realistic everyday tasks, may provide more accurate information. Over the past few decades, there has been a rising concern regarding the lack of measures available for the assessment of the function of memory under realistic conditions. The result of such concern has seen the development of standardised 25 measures that present more emphasis on ecological relevance (Wilson, Cockburn & Baddeley, 1985; de Wall et al. , 1994). One of these, the Rivermead Behavioural Memory Test (RBMT) (Wilson et al., 1985), has been shown to be superior to the WMS-R in assessing everyday functioning when compared with behavioural observations (Makatura et al. , 1999). An extended version of the RBMT, the RBMT-E (Wilson et al., 1999) has recently been developed in order to enhance the original test's sensitivity in the detection of mild deficits. This extended version allows the opportunity to assess the everyday memory problems from a 'normal' and much younger sample and so will establish a starting point for future longitudinal studies. It is predicted to be a promising and ecologically valid measure of everyday memory in normal adults (de Wall et al. , 1994). MENOPAUSE and MEMORY - RELATED VARIABLES Aging Cognitive difficulties observed in mid aged women may be accounted for by an aging process that may operate independent of estrogen effect (Sherwin, 1998). Memory loss, particularly the encoding and retrieval of new information is a common concomitant of aging (Barrett-Connor et al. , 1999), although impairment in memory function can occur as a result of brain pathology and emotional disturbances as well as the aging process (Lezak, 1995). Longitudinal results report modest, gradual cognitive decline with aging , with an inflection point of around 60 years of age (Youngjohn & Crook, 1993). Age related deficits appear to develop in specific areas of memory (Lezak, 1995; Sherwin, 1997). These include short-term memory (with the increased difficulty in encoding and retrieval of information), memory for activities, recognition, free/cued recall, visual/non verbal memory, and prospective memory (Smith & Earles, 1996). In general, older adults also demonstrate poorer performance on recall , recognition, memory for short paragraphs, while memory for remote past events remains intact (Lezak, 1995). Age differences also appear to be larger in tasks that are more 26 difficult and that involve more deliberate or effortful processing , while in contrast age differences do not appear on semantic memory tasks (Smith et al. , 1996). Working memory also shows evidence of an age-related decrease in speed and accuracy. The differences appear to be directly related to the processing efficiency which is facilitated by the speed with which operations can be successfully executed (Smith et al., 1996). In general, the measure of digit span declines only slightly with age, whereas word span shows a greater age decrement (Craik et al. , 1995). However, when memorisation includes an amount longer than immediate storage capacity (e.g., as in story recall) , aging decrements are observable with larger decrements found in a delayed recall test as age increases (Lezak, 1995). Age differences occur in the ability to learn a new route (e.g ., non-verbal , visuospatial memory) , with older participants demonstrating a poorer performance. It does not appear that the context or the distinctiveness of materials used in the testing procedure impacts on the extent of the age differences observed , although the age effects have been found to be smaller when meaningful or familiar contexts are used (Hess et al. , 1996). Recognition Memory performance shows age-related impairments that may be due to a failure to encode, however, the age decrements are smaller than test of recall (Craik et al. , 1987; Hess et al., 1996). Cross sectional studies have demonstrated these decrements as a gradual decline from as early 50 years of age. The poor performance appears to be related to the higher rates of false positives which may be due to encoding strategies (Hess et al., 1996). Age differences in the recognition of photographed scenes are typically slight, but age related deficits are found when free recall or cued recall is the measure (Craik et al., 1995). Prospective memory studies have highlighted paradoxical age-related differences between naturalistic and laboratory tasks, with the latter producing an age-related decline, while naturalistic prospective memory tasks failed to show age differences 27 (Rendell et al., 1999). A likely explanation for this paradox is thought to arise from differences in the nature of the everyday tasks that are utilised by the different methods (Rendell et al. , 1999). Prospective memory that has been shown to decline with age, appears to occur especially in situations where the environment may offer few clues as reminders (Craik et al. , 1992). In addition , age decrements have been found on time-based tasks , although age differences appear to be minimal on simple prospective memory tasks (Einstein et al. , 1992). This is thought to be due to the degree of self-initiation required which may be susceptible to aging effects (Einstein et al. , 1995). More recently, there also appears to be a robust age-related decline in event­ based prospective memory tasks , especially when the tasks are sufficiently demanding , as occurs when the number of cues are increased (West & Craik, 1999). In the past, it has been suggested that these more complex prospective tasks are especially difficult for older participants, because of an increase in the difficulty of the retrospective memory component that exists within the prospective memory task (Einstein et al. , 1992). Failures in prospective memory have also recently been linked to an age-related decline in cue accessibility (i .e. , the amount of processing required to activate the prospective cue-action schema) . The decline in cue accessibility may reflect a reduced ability of adults to maintain an integrated representation of the context (West et al., 1999). Altogether, the extent to which age differences emerge in prospective memory tasks depends on the type and complexity of the prospective memory task and the accessibility of cues (West et al. , 1999). Everyday memory as a concept, has been considered to be relatively stable throughout adulthood until the later decades of life (Youngjohn et al., 1993). Furthermore, age-related decline has not been evidenced in activities that are 28 dependent on everyday experiences (Poon et al. , 1992). However not all studies have utilised a formal measure of everyday memory (Glass, 1999). Other possible confounding variables such as age, education , health , sleep, stress and mood are also likely to be involved in the possible effect of the menopause process on memory. It is likely that biological aging , environmental influence, psychosocial variables all interact in important ways to affect cognitive decline (Moscovitch et al. , 1992). Furthermore, chronological age has previously been found to be the least influential factor in accounting for total variance in memory performance (Arbuckle, Gold & Andres , 1986 cited in Moscovitch et al. , 1992). Studies have shown that medical history, educational level and lifestyle can contribute to significant differences in cognitive abilities among individuals within the same age range (Moscovitch et al. , 1992). However, in contrast, other studies have not provided any evidence that health factors or education account for age differences in memory (Salthouse, Kausler & Saults, 1990; Earles, Brannon & Hill , 1993). A possible explanation for the disparate findings with education is the changes that have occurred in the quality of education offered to different cohorts (Smith et al. , 1996). Sleep Sleep difficulties have been associated with menopause in that higher levels of difficulty are reported at later stages of the menopause transition (Slaven et al. , 1998). Concentration and memory lapses have been associated with sleep deprivation , although performance nas generally been found to be better than anticipated (Weiten, 1995). However, increased interruptions in sleep have been shown to be associated with increased disruptions of mood and a reported decrease in general wellbeing (Peterson & Schmidt, 1999). However, it has not been clearly established whether some of the psychological symptoms that occur during menopause (e.g ., mood disruption and less satisfaction in daily tasks) are 29 due to lowered estrogen and progesterone levels, or are a function of disrupted sleep (Peterson et al. , 1999). Stress Stress is an acknowledged factor in the disruption of attention that also leads to impairment in a variety of functions including cognitive functioning (Weiten , 1995). Women enter the menopause transition at an age where it is highly likely that they have experienced or are currently experiencing divorce, death of spouse or parent, loss of employment, children leaving home and other major life events (McKinlay, McKinlay & Brambilla , 1987). There is now evidence from longitudinal studies that appears to add some weight to the hypothesis that these changes in life events may be associated with the observable psychological distresses noted during menopause (Slaven et al ., 1998). Mood Emotional !ability, depression and a decreased sense of well-being are common complaints during the menopausal transition (Mayeaux et al ., 1996). Controversy exists as to whether these observed changes in mood constitute a menopause­ related mood disorder, and there does not appear to be clear evidence of any increase in depression that is related to the menopausal years (Ballinger, 1990). However, there is the suggestion that women with known histories of depressive symptoms may be at increased risk during menopause which may indicate an increased risk for this group of women (Pearlstein , 1995). Alteration in mood has been associated with the reduction of estrogen that occurs at menopause. Two neurotransmitters (serotonin and norepinephrine) are involved in the regulation of mood , and biochemical evidence now suggests that estrogen effects may influence this regulation of mood (Halbreich, 1997). 30 The idea that a reduction in estrogen may predispose post-menopausal women to depression remains controversial and has not always been supported by epidemiological studies (Halbreich, 1997). In addition , empirical data has not always supported estrogen as an effective treatment for major depression , although interestingly, it has been reported to have a positive effect on healthy, non depressed , post-menopausal women (Ditkoff et al. , 1991 ). However, HRT does appear to play a role in the amelioration of some depressive symptoms. Chatel , Fugere, Bossinette & Berube (1996) found depression scores improved, although not significantly, in a group of 57 women attending a menopause clinic. Also , Cagnacci , et al. (1997) found that estrogen use improved depression and anxiety as measured by the Self -Evaluation Depression Scale, although a later study failed to demonstrate any beneficial effect of HRT on depressed mood (Cagnacci , Neri , Tarabusi , Volpe & Facchinetti , 1999). Between these two reported studies, and contributing to a continuing controversy, a meta-analysis of the effect of HRT on depressed mood (Zweifel & O'Brien , 1997) concluded that HRT was effective in reducing depressed mood in menopausal women . In this meta-analysis, methodology, such as controlled design , sample sizes and valid measures of depression were all reported as adequate. A later, more limited review (Archer, 1999) further supports this stance, concluding that there is suggestive evidence that estrogen may be an effective treatment for depression in both perimenopausal and menopausal women . It is possible that the variable definitions of depression and menopause contribute to the disparity of the findings, making interpretation problematic. In addition , sample characteristics, such as women presenting at menopausal clinics being a self-selected population and the likelihood of these women having experienced previous depressive episodes, may further compound interpretation difficulties (Pearlstein, 1995). Thus, research samples may not always be representative of the menopausal population of women. However, on the whole, there is increasing 31 empirical support for a positive effect of HRT on mild to moderate depressive symptoms that may accompany the menopause transition . A link between depression and cognitive abilities such as memory has been acknowledged , although significant memory impairments have not always been associated with depression , and research is often contradictory (Lezak, 1995). For example, no differences have been found between depressed unmedicated women and matched controls (Gas & Russell , 1986). Also , although non depressed participants have demonstrated a trend towards higher scores, significant differences in tests of verbal short term retention or learning have not been found (Marsh, Marsh & Johnson , 1987, cited in Lezak, 1995). In addition , depressed patients have been shown to perform as well as non-depressed patients in tests of speed , recognition memory and abstraction (Cole & Zarit, 1984). However, depressed patients have been shown to demonstrate cognitive impairment and forgetfulness. Impaired performance on attention and immediate memory tasks has also been shown, with the severity of impairment related to the depression (Cohen , Weingarter, Smallberg , Pickar & Murphy, 1982). Facial recognition has been found to be significantly impaired relative to test norms, although verbal learning and memory measures remained at normative values (Sweeney, Wetzler, Stokes & Kocsis , 1989). Difficulties in concentrating , and changes in cognition such as problems in thinking and making decisions, are listed as symptoms of depression in the DSM IV (Kaplan & Sadock, 1998). It is thought that the memory dysfunction demonstrated in association with , or as a result of depression is more likely to be a reflection of poor encoding than a learning problem. Deficits demonstrated in both verbal and visuospatial material have been attributed to retrieval on free recall , rather than learning (Massman, Delius, Butters, Dupont & Gillian, 1992). The above review highlights the complexity of the relationship between mood (in particular depression) and cognitive ability. The association of menopause with 32 mood !ability is well documented, and clinically observed, but remains controversial (Halbriech , 1997; Mayeaux et al ., 1996). Much of the literature, but not all , supports the presence of significant and specific impairments in cognitive ability in clinically depressed individuals (Lezak, 1995). HRT use has been shown to improve mild to moderate depressive symptoms (Cagnacci et al ., 1997; Archer, 1999). In view of the evidence of such an association between mood and cognitive ability, research that investigates the effects of other variables on memory must consider and control for the possible confounding effects of mood . SUMMARY The association between the construct of memory and the processes of aging and menopause is a complex one. The period of menopause has been linked to memory deficits, with women undergoing surgical menopause in particular, showing a negative affect on short-term verbal memory. Generally, the measurement of memory has often lacked both external and ecological validity (i .e., the degree to which tasks used in research are similar to the tasks of everyday life) (Hess et al ., 1996). The presence of a number of confounding variables has increased the difficulty in assigning clear and independent associations of the effect of these variables in previous studies. In particular, the accurate assessment of affect or mood state is important when assessing the memory of mid-life women. Somatic symptoms, such as fatigue , insomnia and changes in weight, that occur during the menopausal transition are frequently used to index depressive or anxious feelings. Thus far, there has been a surprising lack of research investigating the possible effect of HRT on older women's cognitive functioning , particularly in regard to the performance of everyday tasks. Such tasks include the ability to remember names, to recognise faces , to recall where personal belongings have been left, to attend to and remember conversations, and to remember to remem~er. The ability to perform these tasks are all important aspects of everyday memory functioning. Ultimately, the preservation of these abilities determine the quality, and independence of living maintained by women as 33 they continue through, and past the menopause transition. This is of increasing relevance as society prepares for an increased aging population and the projected associated increase in dementia, especially of Alzheimer's type. Investigation of the possible relationship between HRT use and everyday memory tasks is one of the aims of the present study. 34 CHAPTER4 PURPOSE AND FORMULATION This present study was undertaken to assess the relationship between HRT use and mid-aged women's cognitive status. The study was planned in order to establish the suitability and cultural sensitivity of measures that to date, had primarily been used with overseas populations. In particular, the study would pilot the use of The Rivermead Behavioural Memory-Extended Test (a newly created measure of everyday memory tasks) on a New Zealand sample of mid-aged women . The data would also provide some estimates of the relationships between mood, HRT use and memory in a sample of mid-aged New Zealand women . AIMS OF THE PRESENT STUDY • The first aim of the study is to investigate the effect of HRT use on the everyday memory ability of New Zealand women between the ages of 40 and 60 years. More specifically, to test whether there is a significant difference in everyday memory performance between mid-aged women using HRT and women not using HRT, while taking into account the effects of age , mood , education , general health and stress. • A second aim of the study is to evaluate the use of a measure of everyday memory (The Rivermead Behavioural Memory Test-Extended Version) on a sample of mid-aged women. HYPOTHESES • The first hypothesis is that women who use HRT will show better everyday memory ability than those women who do not use HRT, while controlling for 35 age, affect, mood, health, education and stress. In addition , it is expected that verbal memory will show the greatest difference between the two groups. • The second hypothesis predicts that memory ability will decline with increasing age. • The third hypothesis predicts that age will moderate the relationship between HRT use and memory ability. More specifically, it is predicted that differences in memory ability between HRT users and non HRT users will be greatest for older women. • The fourth hypothesis predicts that mood will be positively related memory ability. More specifically, positive mood will be associated with better memory and conversely, negative mood will be associated with poorer memory ability. • The fifth hypothesis predicts that mood will moderate the relat ionship between HRT use and memory ability. DESIGN The study employed a cross-sectional , correlational , between subjects design , comparing a sample of New Zealand women aged between the ages of 40 and 60 years who were either HRT users or non HRT users. 36 CHAPTER 5 METHOD PARTICIPANTS A total of 104 women with an age range of 40-60 years (mean age, 51 .67 years) who volunteered to participate in the project were studied . Of these women , 53 (51 %) were HRT users and 51 (49%) were non-users. Demographic data for the total sample are summarised in Table 1. To avoid duplication and for ease of comparison, data for the two HRT use groups are included . Twenty-six percent considered themselves pre menopausal , 39.4% as menopausal , and 33 .7% identified themselves as post-menopausal. All the women were functioning independently in the community and 76.9 % were employed in a full or part -time work. Seventy per cent reported participating in regular exercise, while 63 .5% of participants were taking some form of prescribed or 'over the counter' medication . Fifty-five percent of the sample had received an excess of 12 years education , and of this group, 60% were being treated with HRT. Participants were recruited by a number of methods including speaking to health professionals (Gerontologists) at a local hospital in Christchurch , and by advertisements (see Appendix 1) placed in local newspapers in Christchurch and Palmerston North . The following inclusion criteria were used: 1. Women aged between 40 and 60 years of age 2. All ethnic groups of New Zealand citizens. 37 Table 1. DemograQhic & Health Characteristics of HRT use GrouRS and Total SamRle. HRT use non HRT use Total (n=53) (n=51) (n=104) Age 52 .34 years 50.98 years 51 .67 years (Mean) (Mean) (Mean) Ethnicity NZ European 48 (51 .6%) 46 (48.4%) 90.4% Other Ethnicity 5 (9.4%) 5 (9.8%) 9.6 % Education High School 20 (37.7%) 26 (51 .1%) 44.2% (<11yrs) Diploma!Tertiary 33 (62 .3%) 25 (49.0%) 55.8% (> 12yrs) EmQloyment full/part-time paid 43 (81 .1%) 37 (72.5%) 76.9% full-time unpaid 10 (18 .9%) 14 (25.4%) 23 .1% Exercise 36 (67.9%) 36 (70.6%) 69 .2% Nil exercise 17 (32 .1%) 15 (29.4%) 30.8% History: Head Injury (yes) 10 (18.9%) 9 (17.6%) 18.3% (no) 43 (81 .1%) 42 82.4%) 81 .7% Smoking Never 27 (50.9%) 36 (70.6%) 60.6% Past 21 (39.6%) 12 (23 .5%) 31 .7% Present 5 (9.4%) 3 (5 .9%) 7.7% Family neurological Strokes 14 (26.4%) 12 (23.5%) 25.0% Alzheimer's dementia 5 (9.4%) 6 (11 .8%) 10.6% Other dementia 3 (5 .6%) 2 (3.7%) 4.8% Neu rolog ica I 31 (58.5%) 32 (62.7%) 60.6% 38 An IQ mean (122, SD. 6.35) was established for the total sample from the scores on the NART, a measure of crystallised intelligence. The NART scores yielded a mean of 6.51 (SD. 5.11) errors for the total sample. Ninety-six percent of the entire sample were classified as above average (predicted IQ 111 and above), and 3.2% as average group were classified as average (predicted IQ 90-110) . The high percentage that is classified as above average may not be representative of the population of mid-aged women. Table 2 shows the means and standard deviations of the NART and IQ for the total sample. Table 2. NART Errors and established IQ classification for Sample. NART errors IQ 6.51 122 Mean (SD) (n=104) (5 .11) (6.35) The histories of personal illness for the sample are shown in Table 3. The numbers of women who used concomitant medication are shown in Table 4. Both tables are expressed as a percentage of either the HRT or non HRT group as well as for the total sample. Table 3. Personal Medical History of HRT use Groups and Total Sample. Personal Illness HRT users non HRT users Total (n=53) (n=51) (n=104) Diabetes 2 (3.7%) 2 (1 .9%) High BP 11 (20.7%) 12 (23.5%) 23 (22.11%) Heart Disease 1 (1.9%) 2 (3.9%) 3 (2.88%) Epilepsy 1 (2%) 1 (0.96%) Cancer 4 (7.5%) 5 (9.8%) 9 (8.65%) Depression (history) 16 (30.2%) 5 (9.8%) 21 (20.19%) PMT/symptoms 21 (39.6%) 22 (43.1 %) 43 (41.34%) 39 Table 4. Concomitant Medications Use bY'. HRT use GrouQS and Total SamQle. HRT use non HRT use Total (n=53) (n=51) (n=104) Asthma 4 (7%) 2 (3 .9%) 6 (5 .76%) Anti-inflammatory 5 (1%) 4 (7 .8%) 9 (8.65%) Memory enhancing 6 (11.7%) 6 (5.76%) Antidepressants 4 (7%) 3 (5.8%) 7 (6.73%) Vitamins/Minerals 12 (22.6%) 13 (25.5%) 25 (24 .03% Calcium 10 (18.8%) 5 (9 .8%) 15 (14.42%) BP medication 11 (20.7%) 8 (15.6%) 19 (18.26%) Thyroid 4 (7 .5%) 4 (7 .8%) 8 (7.69%) Peptic ulcer 2 (3.7%) 1 (1.9%) 3 (2 .88%) Sleep 2 (3 .7%) 1 (1.9%) 3 (2 .88%) Pain 1 (1.8%) 1 (0.96%) St. John Wort 1 (1.9%) 1 (0 .96%) MEASURES The following scales (see Appendix 2) , were chosen as a set of measures for the study. As well as the two psychological constructs of everyday memory and mood , scales were chosen to control for the effect of known possible confounding variables. Each will be described in turn . 1. Measuring Everyday Memory The Rivermead Behavioural Memory Test - Extended Version (RBMT-E) . (Wilson , Clare, Cockburn, Baddeley, Tate & Watson , 1999). The RBMT-E has been described as a standardised and reliable measure of everyday memory (Wilson et al., 1999). To date, it has not been used with a New Zealand population. The original Rivermead Behavioural Memory Test (RBMT) (Wilson, Cockburn & Baddeley, 1985) was designed to predict everyday memory 40 problems in people with acquired , non-progressive brain injury, and also to monitor change over time (Wilson et al. , 1999). The RBMT has been shown to be a useful tool in the measurement and prediction of everyday memory problems (van Balen , Westzaan & Mulder, 1996). Inter-rater reliability has been shown to be 100% for both profile and screening scores. Also, parallel-form reliability has been demonstrated between versions A and B, C and D as 0.86, 0.83 and 0.88 respectively (Wilson et al. , 1985). The RBMT has been used with New Zealand populations, has excellent face validity and a recognised ecological validity (Fraser, Glass & Leathern , 1999). Normative data for a New Zealand population of 131 elderly people (60-89) recently established (Fraser et al. , 1996). In addition to issues of reliability and validity, the design of four different versions allowed repeated assessments while minimising practice effects (Wilson et al. , 1989). The extended version of the Rivermead (RBMT-E) has been developed in order to enhance the sensitivity of the RBMT by increasing the difficulty of the test. Versions A and B of the RBMT have been combined to make Version 1 of the RBMT-E, and Versions C and D have been combined to make Version 2 of the RBMT-E. This has resulted in an extension the original RBMT from that of a screening test, to a test providing a sensitive measure of memory within a normal range (de Wall et al. , 1994). The extended version has been designed to follow the original structure so as to capitalise on the established validity and sensitivity of the original RBMT (Wilson et al., 1999). In a pilot study (de Wall et al., 1994) found that the RBMT-E significantly discriminated between a middle-aged (40-55 years) and older group (65-79 years), even when these differences were small as measured by the Warrington Recognition Memory Test (Lezak, 1995). Participants also included 18 individuals from African-Caribbean and Asian origin to ensure cultural appropriateness and sensitivity (de Wallet al., 1994). 41 The RBMT-E (Wilson et al. , 1999) is comprised of two parallel versions that have been shown to be sensitive to age and IQ effects in non-brain participants. Parallel-form reliability was investigated by administering the 2 versions of the test to 191 control subjects aged between 16-76 years. Overall mean scores were very similar between the two versions (Wilson et al. , 1999), although tests of significance were not reported in the manual. The test has been shown to be capable of detecting more subtle memory deficits than the original RBMT. In a comparison of 45 neurologically impaired people on both the original and the RBMT-E , the newly extended version separated the RBMT scores into good, average, poor and impaired subgroups (Wilson et al. , 1999). In discussing the assumption that the RBMT-E is a valid measure of everyday memory, de Wall et al. (1994) cite the ecological validity of the original RBMT. This was firmly established with the use of contrasting groups for whom everyday memory problems were or were not prominent, and then subsequently validated against hours of careful observation . Correlations between therapist observations and scores obtained on the RBMT were significant (=0.75). Materials: The RBMT-E consists of a manual with instructions for administration and scoring of the test. A test materials book contains the sub-tests and allows the tester to read the instructions while the participant views the stimuli. In addition , supplementary items include a large picture card with 15 items (picture recognition) , a message envelope (route & messages) and a timer. A scoring sheet (Appendix 2) , which is also a procedural guide is included. Sub-tests: The RBMT-E is comprised of 11 sub-tests: 42 * Sub-test 1 & 2 - First and Second Names. The participant is shown three photographic portraits and asked to remember the first and second names of all three people in the photographs. The participant is required to recall the names at the end of the test. Each name recalled without a prompt is scored 2, recalled after a prompt is scored 1. * Sub-test 3 - Belongings. Two possessions belonging to the participant are borrowed and secreted in a desk drawer and a cupboard (or suitable alternatives). The participant is requested to ask for the belongings at the end of the test session, and to remember where they have been hidden. Each item recalled without a prompt is scored 2, recalled after a prompt is scored 1. * Sub-test 4 - Appointments. This sub-test assesses response to cueing . The tester sets an alarm for 20 minutes time. The participant is required to ask two questions relating to the near future , when the alarm sounds. For Version 1, the questions are "When do I have to see you again?" and "When does this session end?" For Version 2, the questions are "When will I know the results of the test?" and "What time do we finish today?" The participant is told to remember to ask both questions when the alarm sounds. If the participant does not ask the questions spontaneously when the alarm sounds, prompts are given (e.g. , "What were you going to do when the alarm rings?") . Each question asked spontaneously scores 2, each question after a prompt is scored 1. *Sub-test 5 - Picture Recognition (Presentation) . The participant is shown 20 line drawings simultaneously on a large sheet of card . Participants are requested to memorise as many as they can in 15 seconds, and to recognise these later on from a set of 40. The tester informs the participant of the time after 5 and 10 seconds. At 15 seconds, the tester informs the participant that 43 'time's up'. The raw score is obtained by deducting the number of false positives from the number of original pictures correctly identified. Maximum score=20 *Sub-test 6 - Story (Immediate) . The participant is asked to listen to a short passage of prose being read out, and then to immediately recall as much of it as possible. (The participant is asked to recall the story again later in the testing procedure, without a second reading) . The authors (Wilson et al ., 1999) make particular note that certain names and possibly a few words are culture specific. The tester is advised to change names/words to suit the culture of the participant. Later, after appointments, the tester asks the participant to recall the prose passage (story delayed). For scoring , the story is divided into 21 ideas with each idea that is recalled perfect or close =1 . Guidelines are given in an appendix for scoring 1/2 a point for partial or approximate synonyms. Maximum score 21 . * Sub-test 7 - Face Recognition (Presentation) . The participant is shown pictures of 15 faces , one at a time for 3 seconds each . The participant is asked to decide whether the person in the photo is under or over 40 years old . The participant is later required to select the original 15 from a set of 30. Scoring is obtained by deducting the number of false positives from the number of original faces correctly identified. Maximum score 15. * Sub-test 8 - Route (Immediate) and Sub-test 9 - Messages (Immediate) . The tester traces a short route within the room . The route comprises of 7 sections. The participant is asked to retrace the route immediately. An example is given in the manual - two chairs, a door, a window, a heater, table and noticeboard. After the story delayed , the participant is required to retrace the original route with the messages ('Route' and 'Messages Delayed'). If the message envelope and book are not spontaneously picked up, a prompt is again given (e.g ., "I took two things with me"). Maximum score 15. 44 *Sub-test 10 & 11 - Orientation and Date. The participant is asked 13 questions pertaining to their present situation (e.g., "what year, month, day, time, date; name of place, city, age and year of birth ; present and previous Prime Ministers, present and previous Presidents of the USA?") . Maximum score= 14, with 2 points awarded if date is correct. After completion of the story, route and messages (delayed) , the original three portrait photographs are represented one at a time. Initial letters are provided as prompts if response is not spontaneous. The test ends with the tester informing the participant, "We have finished this test" as a cue to see of they remember to ask for their belongings, and where they has been placed . If the participant does not request their belongings, the tester prompts with "You were going to remind me to give you some things" . Scoring : Because sub-test raw scores have different minimum and maximum scores , conversion to sub-test profile scores is required . The development study (Wilson et al. , 1999) used box plot analysis for this purpose and further adjustments were made for observed age and IQ effects in this study. In the present study, adjustments were performed as per the manual. Sub-tests that were adjusted for age effects were ; 'Route Immediate' and 'Route Delayed '; sub-tests adjusted for IQ effects were; 'First Names', 'Second Names', 'Story Immediate' and 'Story Delayed'. The raw scores of sub-tests 3 and 4 (i .e., 'Belongings and Appointments') were summed to create a 'Prospective Memory' sub-test before conversion to a profile score. Individual Profile sub-tests have a maximum score of 4 points and are summed to create a total profile score (maximum - 48 points) . In addition , five classifications of an overall profile of memory are calculated. These classifications are; impaired (0-18) , poor (19-27) , average (28-36) , good (37-42) and exceptionally good (43-48)(Wilson et al. , 1999). 45 2. Measuring Mood Mood was operationally defined first as a mild , usually transitory emotion (Chaplin , 1985), and this was measured by the Profile of Moods Questionnaire (McNair, Lorr & Droppleman, 1992). Second, the construct of mood was extended to embrace the two dimensions (positive and negative) of the broader structure:- affect. This was measured by the Positive and Negative Affect Scale (Watson , Clark & Tellegen , 1988). Profile of Moods Questionnaire (POMS). The POMS has been used widely as a measure of transient mood states (Nyenhuis , Yamamoto , Luchetts , Terrien & Parmenter, 1999) and also for depression (Lezak, 1995). The POMS utilises a specific affects approach which emphasises the multiple unique dimensions of mood and includes constructs such as Depression , Tension , Anger, Vigor, Fatigue, and Confusion . Examples of descriptive feelings are Depression , 'unhappy', 'sad ', and 'blue; Tension , 'shaky', and 'panicky'; Anger, 'peeved ' and 'annoyed '; Vigor, 'lively' and 'active; Fatigue, 'worn out', and 'listless'; Confusion , 'muddled ' and 'forgetful '. Participants are asked to rate on a 5 point scale (0 , 'Not at all ', to 4, 'Extremely') (see Appendix 2). The summation of the sub-scale measures (vigor is weighted negatively), allows a description of a total mood disturbance, with a high score indicating a greater mood disturbance (McNair et al. , 1992). The POMS has shown good reliability and validity, and factor analyses have confirmed consistency with reasonably good test-retest correlations (Lezak, 1995). Convergent and discriminant validity has been shown to be good (Nyenhuis et al., 1999), with the POMS scales more highly related to corresponding measures of mood than non-mood scales. Furthermore, the POMS correlated highly with the BDI depression scale, and the visual analogue mood scale. 46 The POMS has been shown to be a reliable and valid measure for mood states in older adults (Gibson, 1997), and has been used in several studies involving menopausal women (Kimura et al. , 1995; Slaven & Lee, 1994, 1997, 1998; Schiffman, Satteley-Miller, Suggs & Graham 1995; Adams, Cartwright, Ostrove, Stewart & Wink, 1998). Positive and Negative Affect Scale (PANAS). The PANAS (Watson , Clark & Tellegen , 1988) is a 20-item scale, developed to measure affect. In particular, the PANAS was designed to capture the two identified , highly distinctive dimensions (positive affect, and negative affect) . Such distinction has been supported by low correlations between the two dimensions (range: -0 .12 to -0.23) (Watson et al. , 1988). The PANAS lists 20 mood descriptions (10 describing a positive affect scale, 'Positive Affect') and (10 describing a negative affect scale, 'Negative Affect') . Participants rate on a 5 point scale (very slightly or not at all , a little, moderately, quite a bit and extremely) , the extent to which they have been experiencing each (see Appendix 2) . Examples of 'Negative Affect' include 'distressed ', 'upset' and 'guilty', while 'Positive Affect ' examples include 'excited ', 'strong ' and 'enthusiastic', with a high score indicating a high degree of positive affect. The positive and negative affect items are summed separately for scoring (range 10-50 for each scale) , to create a 'Positive' and 'Negative' Affect variable label in the present study. High scores mean a greater degree of negativity or positivity. Various time instructions can be used with the PANAS ranging from the present moment to feelings generally. For the present study, participants were asked to indicate the extent of each feeling 'during the past week'. The PANAS also showed good convergent validity with a variety of other brief affect measures (0.76 - 0.92) (Watson et al., 1988). 47 The normative data for the PANAS was gathered in the main from college student population (Watson et al., 1988). In an effort to report generalisability to a non­ student population , 164 non-student adults were also tested . Alpha reliabilities of the 'Positive' and 'Negative Affect' were 0.86 and 0.87 respectively, with a correlation between the scales of .09 and Watson et al. (1988) believe the PANAS is able to offer useful information in adult samples. Mackinnon et al. (1999) , examined the applicability of the PANAS across the life span, with a large sample (n=2651) 18-79 year olds. Factor structure and factor correlations did not appear to change with age. 3. Measuring Confounding Variables Copies of the measures chosen to control for the effect of possible confounding variables are shown in Appendix 2. These included the Women's Health Questionnaire (WHQ) and the Short-Form Health Survey (SF 36). The National Adult Reading Test (Nelson , 1982; Nelson & Williston , 1991) was used in order to provide a pre-morbid estimation of intelligence, and the Digit Span (Wechsler, 1981) as a measure of attention and short-term memory. A measure of the number of life change events, the Social Readjustment Rating Scale (Holmes & Rahe, 1967) was employed to control for the possibility of stress. Women's Health Questionnaire (WHO). The Women's Health Questionnaire was specifically developed by Hunter (1992) to measure the wide range of physical and emotional symptoms experienced by mid­ life women aged 45-65 years. It was designed to identify changes that may occur throughout the menopause transition , and to allow the assessment of the individual effects of symptoms that may arise (Hunter, 1992). The WHO consists of 36-items that reflect somatic, vasomotor, memory, concentration, sexual behaviour, sleep, menstrual, depressed, and anxious mood symptoms which the participant rates on a 4 (0-3) point scale (No, Not at all; No, not much; Yes, sometimes, and Yes, definitely). (see Appendix 2) . Examples of 48 these sub-scales are; somatic, 'My stomach feels bloated'; vasomotor, 'I suffer from night sweats'; memory and concentration, 'my memory is poor' , I have difficulty in concentrating'; sexual behaviour, 'I have lost interest in sexual activity' ; sleep, 'I have difficulty in getting off to sleep', menstrual, 'I have heavy periods'. In the present study, the depressed and anxious factors were omitted as they were thought to be adequately assessed with the POMS and the PANAS. Hunter (1992) acknowledges that not all the scales will be of interest in every study, and that smaller sub-scales may be omitted . Furthermore, the presence of a separate factor to assess sleep difficulties is a particular strength of the WHO when considering the performance of memory in mid-aged women. For scoring, symptom items for each sub-scales were summed and divided by the number of items in each sub-scale. A total score allows an overall measure of well-being with a higher score reflecting more disturbance. Several studies involving menopausal women have utilised the WHO (Wilkund et al., 1992; Greensmith , 1991 ; Slaven et al. , 1997, 1998), and it has been found to be a sensitive measure of response to hormone replacement therapy. Test - retest reliability was assessed after a two-week period and correlations between sub­ scales ranged between 0.69 and 0.96 . Short-Form Health Survey Questionnaire (SF-36). The SF-36 (Ware & Sherbourne, 1992), was constructed to survey health status and designed for use in clinical practice or research, health policy evaluations and general population surveys. The SF-36 is a 36-item questionnaire that measures eight multi-item dimensions tapping functional status, well-being and overall evaluation of health. Functional status evaluates physical and social functioning, as well as role limitations occurring as a result of physical and/or emotional problems. Physical functioning lists 10 activities, and asks the participant to rate how their health limits them on a 3 point scale (Yes, limited a lot; Yes, limited a little, and No, not limited at all). Social functioning asks the participants to rate on a 5 point scale (from all to none), how much time physical health and emotional 49 problems interfered with their social activities. An emotional and physical role limitation scale allow a yes/no rating (range 1-2). The well-being scale assesses general mental health (e.g., 'Have you been a very nervous person ') and bodily pain (very severe to no bodily pain) and vitality (e.g ., Do you feel full of life). A further scale evaluates general health perception , and also includes one non­ scaled item that asks participants about health change over the past year (Jenkinson , Wright & Coulter, 1994). High scores on 'Functional Status ', 'Wellbeing ' and 'Health Evaluation ' indicate the best possible health state. The questionnaire is designed, and has been used successfully for self­ administration , telephone administration , or administration during a personal interview (Ware et al. , 1992). McHorney, Ware, Lu , & Sherbourne (1994) undertook tests of data quality, scaling assumptions and reliability across diverse patient groups, and found that all scales passed tests for item-internal consistency and item-discriminant validity. Reliability coefficients ranged from 0.65 to 0.94 across scales. Jenkinson et al. (1994) found internal consistency to be good , with alpha values > 0.8 for all dimensions of the SF-36 except for the social functioning scale. Jenkinson et al. (1994) also reported the ability of the SF-36 to discriminate between different groups of respondents (those reporting poor to excellent health) . As the authors assert, this suggests that the questionnaire is a suitable instrument for use in homogeneous groups. The validity of the SF-36 has been criticised on the grounds that it does not contain items about sleep (Hunt & McKenna, 1993). To investigate this further, Lyons, Fielder & Littlepage (1993) used the SF 36 in a study on health status, and additionally asked questions of participants regarding any 'problems sleeping' experienced . Participants that reported treatment for a sleeping disorder were found to have lower scores on all the SF 36 variables and Lyons et al. (1993) suggest that the lack of questions about sleep does not detract from the validity. A later study (Zammit, Weiner, Damato, Sillup, & McMillan, 1999) confirmed the findings of Lyons et al. (1993) . Participants with insomnia also obtained lower mean scores on sub-scores of the SF-36 indicating widespread impairment. 50 Although the validity of the SF-36 is confirmed , without specific sleep questions, the association of sleep difficulties with memory performance is difficulty to identify. Sleep difficulties are a common complaint of menopausal women and are also correlated with poor cognitive performance (Hunter, 1992; Weiten , 1995). For the purposes of the current study, sleep difficulties were assessed as a separate factor within the WHO as outlined above. The acceptability, reliability and validity of the SF-36 has been assessed in a N