Memory In Postmenopausal Women Research Articles

Brain volumetric changes in menopausal women and its association with cognitive function: a structured review.

The menopausal transition has been proposed to put women at risk for undesirable neurological symptoms, including cognitive decline. Previous studies suggest that alterations in the hormonal milieu modulate brain structures associated with cognitive function. This structured review provides an overview of the relevant studies that have utilized MRI to report volumetric differences in the brain following menopause, and its correlations with the evaluated cognitive functions. We performed an electronic literature search using Medline (Ovid) and Scopus to identify studies that assessed the influence of menopause on brain structure with MRI. Fourteen studies met the inclusion criteria. Brain volumetric differences have been reported most frequently in the frontal and temporal cortices as well as the hippocampus. These regions are important for higher cognitive tasks and memory. Additionally, the deficit in verbal and visuospatial memory in postmenopausal women has been associated with smaller regional brain volumes. Nevertheless, the limited number of eligible studies and cross-sectional study designs warrant further research to draw more robust conclusions.

ODP406 Effects of hormone replacement therapy on memory cognitive function in postmenopausal women: a systematic review and meta-analysis

Abstract Objective To investigate the effect of hormone replacement therapy (HRT) on memory cognitive function in postmenopausal women. Methods PubMed, Cochrane, Embase, Chinese Biomedical Literature Database (CBM)and web of ClinicalTrials.gov were systematically searched for randomized controlled trials comparing the effect of HRT on memory function in postmenopausal women to Placebo. The primary outcome of interest is memory cognitive function (measured by tests used in the study). We assessed pooled data by using random-effects model. Results Ten studies with 2818 participants were finally eligible for inclusion in the analysis. Compared with placebo, HRT showed no significant differences on logical memory including both immediate (weighted mean difference [WMD] 0.34, 95% CI: -0.73, 1.40) and delayed(0.99, 95% CI: -0.51, 2.48) recall in postmenopausal women, also no differences on short-delay (-0. 00, 95% CI: -0.37, 0.37) or long-delay (-0.19, 95% CI: -0.69, 0.31) recall of California Verbal Learning Test, but yielded an a mean reduction in digit span forward of -0.20 (95%CI: -0.36,-0. 03), with no significant difference in digit span total scores (-0.67, 95% CI: -1.58, 0.24) or backward (-0.10, 95%CI: -0.26, 0. 05). In women within 5 years of menopause, HRT still shows no harmful or beneficial effects on immediate (WMD 0.45, 95% CI: -0.75, 1.65) or delayed recall (WMD 1. 03, 95% CI: -0.93, 3. 00) of logical memory, but no detrimental effects on digit span forward (WMD -0.11, 95% CI: -0.72, 0.50). Conclusion This review suggests that HRT do not improve verbal memory in postmenopausal women, may even impair some domains of short-term memory. HRT may thus not be a potential therapeutic strategy to prevent memory decline in postmenopausal women. Presentation: No date and time listed

Menopausal hormone therapy does not improve some domains of memory: A systematic review and meta-analysis.

BackgroundAged women appear to be at a higher risk of developing memory impairment than men. Whether menopausal hormone therapy (MHT) could improve memory in postmenopausal women remains unclear. We thus conducted a meta-analysis to investigate the potential effect of MHT on memory, especially verbal memory, in postmenopausal women.MethodsPubMed, Cochrane, Embase, Chinese Biomedical Literature Database, and web of ClinicalTrials.gov were systematically searched for randomized controlled trials comparing MHT versus placebo in postmenopausal women. Our primary outcome of interest is memory function.ResultsWe included 10 studies with 2,818 participants in the final analysis. There was no significant differences in immediate recall (weighted mean difference [WMD] 0.34, 95% confidence interval [CI]: -0.73, 1.40), delayed recall (WMD 0.99, 95% CI: -0.51, 2.48), short-delay (WMD -0.00, 95% CI: -0.37, 0.37), and long-delay (WMD -0.19, 95% CI: -0.69, 0.31) recall between WMT and placebo. WMT was associated with a lower digit span forward (mean reduction -0.20, 95% CI: -0.36, -0.03). In women within 5 years of menopause, MHT did not differ in immediate (0.45, 95% CI: -0.75, 1.65) or delayed recall (1.03, 95% CI: -0.93, 3.00), and digit span forward (-0.11, 95% CI: -0.72, 0.50), when compared with placebo.ConclusionThis meta-analysis suggested that MHT had no effect on verbal memory in postmenopausal women, and may impair some domains of short-term memory. Current available evidence does not support MHT for improving memory in women less than 60 years, even in recently menopausal women.Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO, identifier CRD42021233255.

Disrupting cannabinoid receptor interacting protein 1 rescues cognitive flexibility in long-term estrogen-deprived female mice

Hormone therapy (HT) has failed to improve learning and memory in postmenopausal women according to recent clinical studies; however, the reason for failure of HT in improving cognitive performance is unknown. In our research, we found cognitive flexibility was improved by 17β-Estradiol (E2) in mice 1 week after ovariectomy (OVXST), but not in mice 3 months after ovariectomy (OVXLT). Isobaric tags for relative and absolute quantitation (iTRAQ) revealed increased cannabinoid receptor interacting protein 1 (CNRIP1) in E2-treated OVXLT mice compared with E2-treated OVXST mice. Adeno-associated virus 2/9 (AAV2/9) delivery of Cnrip1 short-hairpin small interfering RNA (Cnrip1-shRNA) rescued the impaired cognitive flexibility in E2 treated OVXLT mice. This effect is dependent on CB1 function, which could be blocked by AM251—a CB1 antagonist. Our results indicated a new method to increasing cognitive flexibility in women receiving HT by disrupting CNRIP1.

Vasomotor symptoms are associated with episodic memory in postmenopausal women

Vasomotor symptoms are associated with episodic memory in postmenopausal women

The intensity of menopausal symptoms is associated with episodic memory in postmenopausal women

Objective: The adaptation of the brain to aging is subject to the impact of psychological and environmental factors and possibly climacteric symptomatology. We aimed to determine the association of climacteric symptomatology with different aspects of episodic memory in a sample of Greek menopausal women.Methods: This cross-sectional study included 39 postmenopausal women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT) and the revised Brief Visuospatial Memory Test (BVMT), assessing verbal and visuospatial episodic memory, respectively. We evaluated general cognitive status using the Mini-Mental State Examination (MMSE) and the Clock Drawing Test. Menopausal symptoms were assessed using Greene’s Climacteric scale.Results: In the multivariate approach, vasomotor symptoms predicted independently HVLT (retained percentage and delayed recall: b-coefficient = −0.568, p = 0.009 and b-coefficient = −0.563, p = 0.012, respectively). Psychological symptoms predicted independently MMSE (b-coefficient = −0.391, p = 0.024); and in combination with free estrogens (logFEI), psychological symptoms predicted BVMT (total and delayed recall: b-coefficient = −0.558, p = 0.001 and b-coefficient = −0.474, p = 0.005) and HVLT discrimination index (b-coefficient = −0.390, p = 0.023). Combined symptomatology predicted independently MMSE (b-coefficient = −0.457, p = 0.006) and HVLT total (b-coefficient = −0.557, p = 0.034); combined symptomatology predicted in combination with logFEI scores of BVMT total (b-coefficient = −0.593, p < 0.001), BVMT delayed recall (b-coefficient = −0.492, p = 0.002).Conclusion: The intensity of psychological, vasomotor and combined climacteric symptoms predicted cognitive performance in this sample of postmenopausal women. A differential contribution of vasomotor symptoms to episodic memory is described, with the negative impact being more pronounced in visuospatial rather than verbal episodic memory.

Effect of vestibular stimulation on memory in postmenopausal Women with Osteoporosis

Effect of vestibular stimulation on memory in postmenopausal Women with Osteoporosis

Salivary cortisol and explicit memory in postmenopausal women using hormone replacement therapy

Circulating cortisol levels are known to influence explicit memory in humans and other primates. The present study investigated salivary cortisol and its association with explicit memory performance in 99 postmenopausal women (64 treated with conjugated equine estrogens or estradiol, and 35 matched controls not using any form of hormone therapy). Controls were compared with treated women taking estrogens alone (n=39), or taking estrogens in combination with a progestin (n=25). Mean time on hormone therapy was approximately 5 years, with initiation of treatment in close proximity to the onset of menopause. Explicit memory was assessed with the California Verbal Learning Test (CVLT). Saliva was collected before (basal or resting sample) and after (post-test sample) completing a set of cognitive tasks. Cortisol was measured using a high-sensitivity radioimmunoassay. Treated women were found to have higher resting cortisol concentrations than controls matched for time of day. Basal cortisol was a modest predictor of learning and memory on the CVLT. Higher cortisol was associated with better recall and fewer memory errors, which is consistent with experimental studies examining explicit memory under small increases in circulating cortisol load. Potential cumulative effects on the central nervous system of sustained exposure to mildly increased cortisol in conjunction with the long-term use of oral estrogens are discussed in the context of aging and dementia.

Homocysteine and cognitive disorders of postmenopausal women measured by a battery of computer tests--central nervous system vital signs.

The purpose of the study was the analysis of cognitive functions in postmenopausal women having different status of homocysteine levels by a battery of computer tests-central nervous system vital signs (CNS-VS). We examined whether homocysteine increases the risk of cognitive decline and which cognitive domains are more affected. We showed that the considerably better neurocognitive index was obtained by women with low homocysteine levels in comparison with those with hyperhomocysteinemia (p = 0.0017). Similarly, results were obtained in the field of executive functioning (p = 0.0011), complex attention (p = 0.0106), cognitive flexibility (p = 0.0016), and memory (p = 0.0145). Verbal memory and visual memory did not differ considerably among the studied groups. Also, we demonstrated that ε4/ε4 genotype was the most common (15.5%) in women with hyperhomocysteinemia than in groups of patients with low (0%) or normal (1.9%) homocysteine levels. In summary, hyperhomocysteinemia was related with increased risk of decline in executive functioning, complex attention, cognitive flexibility, and memory in postmenopausal women.

Do soy isoflavones improve cognitive function in postmenopausal women? A meta-analysis.

Several studies have demonstrated that soy isoflavone (SIF) supplementation can improve aspects of cognitive function. However, these findings remain controversial. We aimed to quantify the effects of SIF supplementation on improving cognitive function in postmenopausal women. Databases and relevant Websites were searched for relevant studies up to March 2014. Two reviewers independently verified all potentially suitable randomized controlled trials (RCTs) using inclusion and exclusion criteria, and the quality of identified RCTs was assessed using the Jadad scale and the Risk of Bias Tool from the "Cochrane handbook for systematic reviews of interventions." Any disagreement on study quality or data extraction was resolved by consensus; a third reviewer was consulted if needed. Standardized mean differences (SMDs) in cognitive function test scores were calculated between SIF-treated and placebo-treated groups. We conducted a meta-analysis of 10 placebo-controlled RCTs of SIF supplementation (1,024 participants; treatment duration of 6 wk to 30 mo). The overall SMD in summary cognitive function test scores (0.08) was statistically significant (95% CI, 0.02-0.15; P = 0.014). The summary SMD for visual memory (0.10) was statistically significant (95% CI, 0.02-0.18; P = 0.016). In subgroup analyses, the statistically significant SMDs were as follows: 0.12 (95% CI, 0-0.25; P = 0.044) for non-US countries; 0.16 (95% CI, 0.05-0.28; P = 0.004) for mean age younger than 60 years; and 0.15 (95% CI, 0.03-0.27; P = 0.011) for treatment duration less than 12 months. SIF supplementation seems to have a positive effect on improving summary cognitive function and visual memory in postmenopausal women. There may be a critical window of opportunity in initiating SIF use at an earlier age in postmenopausal women, and geography and treatment duration seem to be factors influencing the effects of SIF supplementation. All individuals in the included studies should be followed up to observe the incidence rates of Alzheimer's disease and dementia, and future studies should report any adverse effects of SIF supplementation.

Transdermal testosterone improves verbal learning and memory in postmenopausal women not on oestrogen therapy

The aim of this study was to examine the effects of testosterone on verbal learning and memory in postmenopausal women. Randomized, placebo-controlled trial in which participants were randomized (1:1) to transdermal testosterone gel 300mcg/day, or identical placebo, for 26weeks. Ninety-two postmenopausal women aged 55-65years, on no systemic sex hormone therapy. The primary outcome was the score for the International Shopping List Task (ISLT) of CogState. Secondary outcomes included other CogState domains, the Psychological General Well-Being Index (PGWB) and safety variables. Eighty-nine women, median age 60years, were included in the primary analysis. Testosterone treatment resulted in statistically significantly better performance for the ISLT (improved verbal learning and memory) compared with placebo, adjusted for age and baseline score (mean difference 1·57; 95%CI 0·13, 3·01) P=0·03). There were no significant differences for other CogState domains or the PGWB scores. At 26weeks, the median total testosterone was 1·7nm (interquartile range (IQR) 1·1, 2·4) in the testosterone group and 0·4nm (IQR 0·3, 0·5) in the placebo group. The small but statistically significant effect of testosterone treatment on verbal learning and memory in postmenopausal women provides the basis for further clinical trials.

Phytoestrogen α-zearalanol improves memory impairment and hippocampal neurogenesis in ovariectomized mice.

Estrogen is known to provide robust protection of memory in postmenopausal women, but the fact that estrogen may increase the incidence of uterine and breast tumors has undoubtedly limited the clinical use of estrogen. In the present study, the effect of α-zearalanol (α-ZAL), a plant-derived phytoestrogen with low side-effect on uterine and breast, on memory has been evaluated in ovariectomized (OVX) mice when using 17β-estradiol (17β-E2) as an estrogen positive control. Our findings demonstrated that OVX resulted in impaired spatial learning and memory and reduced numbers of newborn neurons in the dentate gyrus of the hippocampus, while 17β-E2 or α-ZAL treatment significantly improved memory performance and restored hippocampal neurogenesis. We also found the reduction of brain derived neurotrophic factor (BDNF) and TrkB expression in OVX mice, which were ameliorated by 17β-E2 or α-ZAL supplementation. These results indicated that α-ZAL may improve memory impairments induced by OVX and modulate the expression of BDNF-TrkB benefit to neurogenesis which may be involved in the memory protection from α-ZAL, in a manner similar to that of 17β-E2. The present findings suggested that α-ZAL may be a plausible substitute of 17β-E2 in improving memory in postmenopausal women.

Administration of dehydroepiandrosterone (DHEA) increases serum levels of androgens and estrogens but does not enhance short-term memory in post-menopausal women

The current study examines the effect of administering dehydroepiandrosterone (DHEA) on short-term memory. This experiment used a double-blind placebo-controlled cross-over design to explore the effects of a four week regimen of 50 mg oral DHEA on performance on the digit span, verbal span, and modified Sternberg (Oberauer) tasks. The results demonstrate that the current regimen of drug administration significantly increases serum levels of DHEA, DHEAS, testosterone and estrone and substantially alters the patterns of correlations among the serum levels of these hormones. Despite this substantial change in the hormonal milieu, DHEA administration produced no beneficial effects on cognitive performance in the digit span, verbal span, or modified Sternberg paradigm tasks. Ancillary analyses of the relation between hormone levels and cognitive performance demonstrated a strong positive correlation between DHEA levels and performance on digit span forward/backward and verbal span forward in the placebo drug condition, but not in the DHEA condition. We interpret the juxtaposition of the null results of DHEA administration and the correlation of DHEA levels and performance in the placebo condition to indicate that the referenced correlations arise because a third variable (i.e., age) is associated with both performance and DHEA levels. Additional analyses supported this hypothesis.

Estradiol treatment altered anticholinergic-related brain activation during working memory in postmenopausal women

Estradiol has been shown to affect cholinergic modulation of cognition in human and nonhuman animal models. This study examined the brain-based interaction of estradiol treatment and anticholinergic challenge in postmenopausal women during the performance of a working memory task and functional MRI. Twenty-four postmenopausal women were randomly and blindly placed on 1mg oral 17-β estradiol or matching placebo pills for three months after which they participated in three anticholinergic challenge sessions. During the challenge sessions, subjects were administered the antimuscarinic drug scopolamine, the antinicotinic drug mecamylamine, or placebo. After drug administration, subjects completed an fMRI session during which time they performed a visual verbal N-back test of working memory. Results showed that scopolamine increased activation in the left medial frontal gyrus (BA 10) and mecamylamine increased activation in the left inferior frontal gyrus (BA 46). Estradiol treatment compared to placebo treatment significantly reduced the activation in this left medial frontal region during scopolamine challenge. Estradiol treatment also increased activation in the precuneus (BA 31) during mecamylamine challenge. These data are the first to show that estradiol modulated antimuscarinic- and anitnicotinic-induced brain activity and suggest that estradiol affected cholinergic system regulation of cognition-related brain activation in humans.

Testosterone improves verbal learning and memory in postmenopausal women: Results from a pilot study

Objective To explore the effects of testosterone on cognitive performance in healthy postmenopausal women. Study design Open-label pilot study. Nine postmenopausal women on non-oral hormone replacement therapy, aged 47–60 years received transdermal testosterone spray for 26 weeks. A control group of 30 women provided normative data for comparison. Main outcome measures Scores from a computerized cognitive test battery performed pre- and post treatment, at 0 and 26 weeks. Results There were no differences between treatment/normative groups in any parameter at baseline. At week 26 scores for the International Shopping list task including delayed recall (verbal learning and memory) and the continuous paired associate learning task (visual learning and memory) were significantly higher in the treatment group as compared to the normative group ( p < 0.05). Significant improvements from baseline were observed for the International Shopping list delayed recall (verbal learning and memory) and Groton Maze recall tasks (visual learning and memory) for the treatment group (both p < 0.05), after 26 weeks. There were no significant differences between baseline and week 26 in the normative group. In the regression analysis which modeled the score at week 26, and which included a bootstrapping approach, the beta coefficient for the treatment group was statistically significant when age and baseline score were taken into account for the International Shopping list task including delayed recall (both p < 0.02). Conclusion Testosterone improved cognitive performance in the domain of verbal learning and memory in a pilot study of healthy postmenopausal women and is worthy of further exploration in a randomized placebo controlled study.

Differential effects of estrogen and micronized progesterone or medroxyprogesterone acetate on cognition in postmenopausal women

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.

Women’s cognitive health special edition

Women’s cognitive health special edition

Enhanced neuroactivation during verbal memory processing in postmenopausal women receiving short-term hormone therapy

To study the effects of hormone therapy on brain activation patterns during verbal memory in postmenopausal women. A randomized, double-blind placebo-controlled cross-over study was performed. A tertiary care university medical center. Ten healthy postmenopausal women (age range 56-60 years) were recruited from the local community. Women were randomized to the order they received combined hormone therapy, 5 microg of ethinyl E(2) and 1 mg of norethindrone acetate, and placebo. Volunteers received hormone therapy or placebo for 4 weeks, followed by a 1-month washout period, and then received the other treatment for 4 weeks. A functional magnetic resonance imaging (fMRI) was performed at the end of each 4-week treatment using a verbal memory task. Brain activation patterns were compared between hormone therapy and placebo. Hormone therapy was associated with increased activation in the left middle/superior frontal cortex (BA 6,9), medial frontal cortex and dorsal anterior cingulate (BA 24,32), posterior cingulate (BA 6), and left inferior parietal cortex (BA 40) during memory encoding. All regions were significant with correction for multiple comparisons. Hormone therapy increased neural activation in frontal and parietal areas in postmenopausal women during a verbal memory task.

Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: Evidence for the critical period hypothesis

Estradiol has been shown to interact with the cholinergic system to affect cognition in postmenopausal women. This study further investigated the interaction of estradiol and cholinergic system functioning on verbal memory and attention in two groups of healthy younger (ages 50–62) and older (ages 70–81) postmenopausal women. Twenty-two postmenopausal women were randomly and blindly placed on 1 mg of 17-beta estradiol orally for 1 month then 2 mg for 2 months or matching placebo pills after which they participated in three anticholinergic challenge sessions when verbal memory and attention were assessed. Subjects were administered either the antimuscarinic drug scopolamine (SCOP), the antinicotinic drug mecamylamine (MECA), or placebo. After the first challenge phase, they were crossed over to the other hormone treatment for another 3 months and repeated the challenges. Results showed that estradiol pretreatment significantly attenuated the anticholinergic drug-induced impairments on a test of episodic memory (the Buschke Selective Reminding Task) for the younger group only, while estradiol treatment impaired performance of the older group. The results suggest that younger subjects may experience more cholinergic benefit from estradiol treatment than older subjects, supporting the concept of a critical period for postmenopausal estrogen use.

Effects of estrogen and progesterone on spatial memory consolidation in aged females

Interpretation of data illustrating that estrogen, with or without progestin, is detrimental to memory in post-menopausal women is complicated by the fact that little is known about the effects of progestins on memory. The present study examined if estrogen, alone or with progesterone, affects spatial memory consolidation in ovariectomized aged female mice. Mice received eight training trials in a spatial Morris water maze followed immediately by injection of water-soluble 17β-estradiol (E 2; 0.2 mg/kg) or vehicle. Mice were re-tested 24 h later. All mice learned to find the platform on Day 1. On Day 2, the performance of control, but not E 2 mice, deteriorated, suggesting that E 2 enhanced memory for the platform location. In a second experiment, mice were injected with E 2 and 10 or 20 mg/kg water-soluble progesterone. The 10 mg/kg dose of progesterone did not affect estrogen's ability to enhance spatial memory consolidation, but 20 mg/kg blocked this effect. These data indicate that estrogen can improve spatial memory consolidation in aged females and that this effect can be attenuated by progesterone.