Publications (91)417.78 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Thyroid hormones (THs) play a critical role in differentiation, growth, and metabolism of animal and human organ systems, including the brain. Although associations between normal levels of THs and cognitive functions in healthy elderly individuals have been reported, the findings are inconsistent, possibly due to differences in study designs. Because thyroid disease occurs more frequently in women, the goal of the present study was to examine the relationship between levels of THs and performance on neuropsychological tests in 122 healthy, euthyroid women whose mean age was 51 years. Higher levels of free T3 were positively associated with longer completion times (slower performance) on Trail Making Test - Part A (p = 0.006) and Part B (p = 0.032) and on the Tower of London test (p = 0.002). Higher levels of thyroglobulin antibodies (TgAb) were positively correlated with more errors on the Trail Making Test Part B (p = 0.000), on the Word Fluency test (p = 0.023), and on the Design Fluency test (p = 0.045). No significant correlations between TH levels and scores on mood, verbal memory, or working memory measures were observed. The findings point to a possible link between THs and cognitive processes that are mediated primarily by frontal cortex, areas associated with executive function tasks, and suggest that elevations in levels of free T3 and TgAB within the normal range may negatively influence executive functions.
- [Show abstract] [Hide abstract] ABSTRACT: Extant research findings allow several conclusions regarding the relationship between estrogen and cognitive functioning across the female life span. First, performance on tests of verbal memory fluctuates in concert with physiological changes in ovarian hormone production during the menstrual cycle and during pregnancy and the postpartum period. Estrogen therapy (ET) prevents the decrease in verbal memory when administered immediately following the surgical removal of both ovaries in premenopausal women. Some, but relatively little evidence is available to support the idea that ET, initiated at the time of a natural or a surgical menopause for a few years, may protect against cognitive decline 30 years later and more research in this area is urgently needed. Finally, the evidence to date strongly suggests that the initiation of ET decades after the menopause has occurred does not protect against cognitive decline or dementia. Taken together, these findings support the so-called "window of opportunity" hypothesis which holds that ET will be neuroprotective only when administered closely in time to a natural or surgical menopause.
- [Show abstract] [Hide abstract] ABSTRACT: This chapter discusses the estrogen and cognitive functioning in women, relying on the Critical Period Hypothesis (CPH). Memory, a critical aspect of cognition, is composed of numerous component processes that localize to different anatomical sites. Certain neurotransmitters and brain structures, along with neural pathways and projections, are also critical for cognitive function. The integrity of some brain areas is more vulnerable than others to aging processes. Longitudinal designs involve the recruitment of a group of women who are estrogen users and a group who are non-users selected from the same community. Ovarian estrogen production begins to decline a few years before menopause, and levels of E2 decrease to very low levels about 2 years following cessation of ovarian function. The period between the onset of the waning of ovarian function to almost total cessation of ovarian estrogen production is known as the perimenopause or the menopausal transition, and roughly encompasses the period 48-52 years of age.
- [Show abstract] [Hide abstract] ABSTRACT: This longitudinal study investigated the possible influence of estradiol (E₂), progesterone (P), testosterone (T), cortisol (CORT), and prolactin (PRL) levels on cognitive functioning during late pregnancy and the early postpartum period. The performance of 55 pregnant women on a battery of neuropsychological tests, tested once during the third trimester of pregnancy and once during the early postpartum period, was compared with that of 21 nonpregnant controls matched for age and education. Women in the pregnancy group had significantly lower scores than the controls during both the pre- and postpartum visits on tasks of verbal recall and processing speed. CORT levels were significantly associated, in an inverted-U function, with verbal recall scores at both the pregnancy and at postpartum periods and with spatial abilities at postpartum only. During pregnancy, PRL levels were associated in both a linear and an inverted-U function with scores on tests of paragraph recall and in a linear function with scores on tests of executive function. At postpartum, E₂ and CORT were negatively associated in a linear fashion with attention scores. These findings provide new evidence that fluctuating hormone levels during late pregnancy and early postpartum may modulate selected cognitive abilities.
- [Show abstract] [Hide abstract] ABSTRACT: To investigate possible differential effects of the coadministration of conjugated equine estrogen (CEE) and a placebo (CEE + PL), CEE and medroxyprogesterone acetate (CEE + MPA), or CEE and micronized P (CEE + MP) on aspects of cognitive functioning in naturally postmenopausal women. Double-blind, randomized, controlled trial. Gynecologic screening occurred at a university hospital, and neuropsychological testing took place in a university laboratory. Twenty-four naturally menopausal women with an intact uterus who had never used hormone therapy were recruited by means of newspaper advertisements. All completed the study. A battery of mood and neuropsychological tests was administered. Women were randomly assigned to receive CEE + PL (n = 7), CEE + MPA (n = 9), or CEE + MP (n = 8). The tests were readministered 12 weeks later. Standardized tests of mood, verbal memory, working memory, spatial abilities, and visual-spatial sequencing, and assays of serum sex hormone levels. Mood improved after treatment in all groups. No changes in scores occurred over time in any cognitive test in the group that received CEE + PL. Only the CEE + MP group had a significant decrease in their delayed verbal memory scores from baseline to after treatment. The CEE + MP-treated women performed significantly better on a test of working memory than women in the other two groups. Coadministration of CEE with MPA or MP caused differential effects on aspects of memory in postmenopausal women. These findings need to be replicated with a larger sample size before their potential clinical implications can be determined.
- [Show abstract] [Hide abstract] ABSTRACT: The precise impact of age-related changes in hormone levels on cognition in men is still unclear due to differing study designs and contradictory findings. This study was undertaken to examine the relationship between endogenous sex hormone levels and cognitive functioning in healthy older men using a comprehensive battery of neuropsychological tests and measurement of serum sex hormone levels. Verbal learning and memory, visual-motor processing, spatial abilities, working memory and attention, and levels of testosterone and estradiol were evaluated in 54 healthy older men. Regression analyses revealed significant curvilinear associations between working memory function and both free and bioavailable testosterone levels, suggesting that an optimal hormone level may exist for maximal performance on tasks of executive/frontal lobe functioning. However, no other relationships were evident between either estradiol or testosterone levels and any of the other cognitive functions evaluated. Hormone assays performed at the end of the study revealed that a considerable portion of the healthy elderly men in our sample met criteria for hypogonadism and suggests that their low hormone levels may have mitigated against discovering other significant hormone-cognition relationships.
- [Show abstract] [Hide abstract] ABSTRACT: The effects of testosterone (T) and estradiol (E2) on cognition in men are confounded in extant studies. This randomized, placebo-controlled trial was undertaken to investigate the possible effects of E2 on cognition in older men. Twenty-five men with prostate cancer (mean age: 71.0 ± 8.8 years) who required combined androgen blockade treatment were enrolled. Performance on cognitive tests was evaluated at pre-treatment baseline and following 12 weeks of treatment with a gonadotropin-releasing hormone analog and the nonsteroidal antiandrogen bicalutamide to determine whether specific cognitive functions would decline when the production of both T and E2 were suppressed. In the second phase of the study, either micronized E2 1 mg/day or an oral daily placebo was randomly added to the combined androgen blockade for an additional 12 weeks to determine whether E2 would enhance performance in specific cognitive domains (verbal memory, spatial ability, visuomotor abilities and working memory). Compared to pretreatment, no differences in scores occurred on any cognitive test following 12 weeks of combined androgen blockade. In the add-back phase of the study (Visit 3), the placebo-treated men, but not the E2-treated men, exhibited a trend towards improvement in their scores on both the immediate (p = .075) and delayed recall (p = .095) portions of a verbal memory task compared to baseline. Moreover, at Visit 3, placebo-treated men performed significantly better than the E2-treated men on both the immediate (p = .020) and delayed recall (p = .016) portions of the verbal memory task. Thus, combined androgen blockade plus add-back E2 failed to improve short- or long-term verbal memory performance in this sample of older men being treated for prostate cancer.
- [Show abstract] [Hide abstract] ABSTRACT: This randomized, placebo-controlled, cross-over study investigated whether estrogen treatment would have a beneficial effect on tests of verbal memory in men with mild cognitive impairment (MCI). Forty-three men newly diagnosed with MCI were administered a battery of neuropsychological tests before randomly receiving 12 weeks of treatment with estrogen or placebo followed by a 12 week cross-over treatment. A significant improvement in the total score, and in two subscale scores of the Buschke Selective Reminding Test occurred following estrogen treatment compared to both pretreatment and post-placebo scores (p<0.05). However, benefit occurred only in the men who had received estrogen for 12 weeks following 12 weeks of placebo. Although these findings tentatively suggest that treatment with estrogen may improve verbal memory in men with MCI, the fact that the improvement occurred only in the group that received estrogen following 12 weeks of placebo and the absence of improvement on every test of verbal memory administered suggests that these findings need to be replicated using a larger sample size.
- [Show abstract] [Hide abstract] ABSTRACT: According to the 'critical period' hypothesis, which attempts to explain the observed discrepancies in the studies on estrogen and cognition, estrogen therapy effectively decreases cognitive decline in aging women when it is initiated around the time of menopause but not when it is started decades later. Here, I review studies in which the timing of the initiation of estrogen therapy was provided, to determine whether their findings support the 'critical period' hypothesis. The vast majority of the reviewed studies support the idea that early but not late initiation of estrogen therapy might prevent or delay cognitive decline in aging women. Nevertheless, numerous design issues, such as the specific drugs and doses that were used, the possible effects of progestins on cognition, and the failure to administer neuropsychological tests of specific cognitive domains that are sensitive to estrogen therapy confound the extant literature. In view of the reanalyzes of the Women's Health Initiative's data that show a beneficial effect of estrogen therapy on cardiac and breast diseases in women aged 50-59 years, more definitive evidence is needed to confirm that the early initiation of estrogen therapy that is continued for a few years provides enduring protection against cognitive aging 15-20 years later.
- [Show abstract] [Hide abstract] ABSTRACT: Ten surgically menopausal women who had been chronically receiving a combined estrogen-androgen preparation as replacement therapy showed an inverse relationship between plasma sex hormone levels and mood (P < 0.02). Our findings also suggest that measurement of sex hormone-binding globulin may be an important factor in explaining differential clinical response to hormone replacement therapy in postmenopausal women. © 1987 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
- [Show abstract] [Hide abstract] ABSTRACT: Although there is now a substantial literature on the putative neuroprotective effects of estrogen on cognitive functioning in postmenopausal women, it is replete with inconsistencies. The critical period hypothesis, posited several years ago, attempts to account for the discrepancies in this literature by positing that estrogen treatment (ET) will protect aspects of cognition in older women only when treatment is initiated soon after the menopause. Indeed, evidence from basic neuroscience and from the animal and human literature reviewed herein provides compelling support for the critical period hypothesis. Although it is not known with certainty why estrogen does not protect cognition and may even cause harm when administered to women over the age of 65years, it is likely that the events that characterize brain aging, such as a reduction in brain volume and in neuronal size, alterations in neurotransmitter systems, and a decrease in dendritic spine numbers, form an unfavorable background that precludes a neuroprotective effects of exogenous estrogen on the brain. Other factors that have likely contributed to the discrepancies in the estrogen-cognition literature include differences in the estrogen compounds used, their route of administration, cyclic versus continuous regimens, and the concomitant use of progestins. This critical analysis attempts to define conditions under which ET may protect aspects of cognition in aging women while also considering the cost/benefit ratio for the treatment of women aged 50-59years. Suggestions for specific future research questions are also addressed.
Article: Hormones, the Brain, and Me[Show abstract] [Hide abstract] ABSTRACT: My research program in psychoneuroendocrinology, a subdiscipline of psychology, has focused on the investigation of three areas of women's health. First, the authors have studied the role of androgen in female sexuality; second, the authors have investigated the effects of estrogen on mood in women, and more recently, the authors have demonstrated the conditions under which estrogen treatment would be neuroprotective with regard to cognitive functioning in aging women. The results of our own and of other researchers' studies in all three areas of psychoneuroendocrinology are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
- [Show abstract] [Hide abstract] ABSTRACT: Although there is evidence from randomized controlled trials that estrogen therapy protects against aspects of cognitive decline that occur with normal aging in women, findings from the Women's Health Initiative Memory Study and from some cross-sectional and longitudinal studies failed to find neuroprotective effects of estrogen in older women. There is growing empirical support for the critical-period hypothesis, formulated in the attempt to resolve these discrepancies. It holds that estrogen therapy has protective effects on verbal memory and on working memory only when it is initiated closely in time to menopause, whereas starting treatment many years following menopause does not protect and may even be harmful. Supporting evidence for this hypothesis from basic neuroscience and from animal and human studies is evaluated for its ability to explain the inconsistencies and to describe the conditions under which estrogen may protect cognitive function in aging women.
- [Show abstract] [Hide abstract] ABSTRACT: Randomized controlled trials (RCTs) and observational and longitudinal studies provide positive, albeit, inconsistent evidence that estrogen might protect against cognitive decline in postmenopausal women. The fact that the Women's Health Initiative Memory Study (WHIMS), the largest RCT to date, failed to find that estrogen therapy (ET) had a protective effect against cognitive aging led to the formulation of the critical period hypothesis which holds that ET will effectively protect against memory decline when it is initiated around the time of menopause but not when considerable time has elapsed since the menopause. Evidence from basic neuroscience, and from rodent, nonhuman primate, and human studies that supports this theory is presented. Although much work remains to be done on the timing of initiation of treatment, on the most effective hormonal compounds and on their routes of administration, the hope is that, eventually, hormonal treatments may be able to attenuate or prevent the decline in aspects of cognition that occur with normal aging.
- [Show abstract] [Hide abstract] ABSTRACT: We investigated the possible influence of testosterone (T) on cognitive functioning in women with polycystic ovary syndrome (PCOS), an endocrine disorder associated with elevated levels of free testosterone (free T). Performance on a battery of neuropsychological tests in 29 women with elevated free T levels due to PCOS was compared to the performance of 22 age- and education-matched, healthy control women with free T levels in the normal female range. Women with PCOS had significantly higher levels of free T (estimated by the free androgen index) and demonstrated significantly worse performance on tests of verbal fluency, verbal memory, manual dexterity, and visuospatial working memory than the healthy control women. No differences between the groups were found on tests of mental rotation, spatial visualization, spatial perception, or perceptual speed. These results suggest that, in women, elevations in free T may be associated with poorer performance on cognitive tasks that tend to show a female advantage.
- [Show abstract] [Hide abstract] ABSTRACT: In a previous study, we found that women with polycystic ovary syndrome (PCOS), an endocrine disorder characterized by chronic hyperandrogenism, performed more poorly than healthy, matched controls on a number of neuropsychological tests, in particular tests of verbal fluency, verbal memory, manual dexterity, and visuospatial working memory. This randomized, placebo-controlled trial was undertaken to investigate whether pharmacologic manipulation of free testosterone (free T) levels in women with PCOS might affect their performance on cognitive tests. Nineteen women with PCOS completed a battery of neuropsychological tests before and after 3 months of treatment with either an anti-androgen (cyproterone acetate) plus estrogen or with a placebo. Hormone treatment of women with PCOS caused a significant reduction in their free T levels but did not affect performance on tests visuospatial ability, verbal memory, manual dexterity, or perceptual speed. Women treated with hormone therapy did, however, demonstrate an improvement in their performance on a test of verbal fluency compared to their pre-treatment scores. These findings suggest that changes in free T levels do not have a significant impact on cognitive performance in women with PCOS, although reductions in free T may be beneficial for verbal fluency.
- [Show abstract] [Hide abstract] ABSTRACT: Women who undergo both natural and surgical menopause experience the loss of cyclic ovarian production of estrogen, but hormonal and demographic differences distinguish these two groups of women. Our objective was to review published evidence on whether the premature cessation of endogenous estrogen production in women who underwent a surgical menopause has deleterious consequences for cognitive aging and to determine whether consequences differ for women if they undergo natural menopause. Studies of estrogen-containing hormone therapy are relevant to this issue. We reviewed evidence-based research, including the systematic identification of randomized clinical trials of hormone therapy with cognitive outcomes that included an objective measure of episodic memory. As inferred from very small, short-term, randomized, controlled trials of high-dose estrogen treatment, surgical menopause may be accompanied by cognitive impairment that primarily affects verbal episodic memory. Observational evidence suggests that the natural menopausal transition is not accompanied by substantial changes in cognitive abilities. For initiation of hormone therapy during perimenopause or early postmenopause when the ovaries are intact, limited clinical trial data provide no consistent evidence of short-term benefit or harm. There is stronger clinical trial evidence that initiation of hormone therapy in late postmenopause does not benefit episodic memory or other cognitive skills. Further research is needed on the long-term cognitive consequences of surgical menopause and long-term cognitive consequences of hormone therapy initiated near the time of surgical or natural menopause. A potential short-term cognitive benefit might be weighed when a premenopausal woman considers initiation of estrogen therapy at the time of, or soon after, hysterectomy and oophorectomy for benign conditions, although data are still quite limited and estrogen is not approved for this indication. Older postmenopausal women should not initiate hormone therapy to improve or maintain cognitive skills.
Montréal, Quebec, Canada
- Department of Psychology