Postmenopausal estrogen replacement therapy and the risk of Alzheimer disease

BACKGROUND: Previous studies have examined the relation between postmenopausal estrogen replacement therapy (ERT) and the risk of Alzheimer disease (AD). The findings have been inconsistent, since some studies have been interpreted as showing a protective effect while others have reported no effect. OBJECTIVE: To determine whether exposure to ERT is associated with a reduced risk of AD. DESIGN: Population-based nested case-control study. SETTING: The United Kingdom-based General Practice Research Database. PATIENTS: The base cohort consisted of women who were recipients of ERT (n = 112 481) and a similar cohort of women who did not use estrogens (n = 108 925). The 2 cohorts were restricted to women born on or before January 1, 1950. From the 2 cohorts, we identified and verified 59 newly diagnosed cases of AD and 221 matched control subjects. MAIN OUTCOME MEASURE: Prior and current use of ERT in cases compared with controls. RESULTS: Among the 59 newly diagnosed cases of AD, 15 (25%) were current estrogen users, while among the controls, 53 (24%) were current users. The adjusted odds ratio comparing all current estrogen recipients with nonrecipients was 1.18 (95% confidence interval, 0.59-2.37). In estrogen users who took the drug for 5 years or longer compared with nonusers, the odds ratio was 1.05 (95% confidence interval, 0.32-3.44). Odds ratios were similar for estrogen recipients who received estrogens alone and recipients who received combined estrogen-progestin treatment. CONCLUSION: The use of ERT in women after the onset of menopause was not associated with a reduced risk of developing AD.     

Hysterectomy, menopause, and estrogen use preceding Parkinson's disease: an exploratory case-control study.

We studied the association of Parkinson's disease (PD) with type of menopause (natural or surgical), age at menopause, and postmenopausal estrogen replacement therapy using a case-control design. We used the medical records-linkage system of the Rochester Epidemiology Project to identify 72 women who developed PD in Olmsted County, MN, during the twenty years 1976-1995. Each incident case was matched by age (+/- 1 year) to a general population control subject. We collected exposure data through review of the complete medical records of cases and control subjects in the system. PD cases had undergone hysterectomy (with or without unilateral oophorectomy) significantly more often than control subjects (odds ratio [OR] = 3.36; 95% confidence interval [CI] = 1.05-10.77). In addition, PD cases had experienced early menopause (< or = 46 years) more commonly than control subjects (OR = 2.18; 95% CI = 0.88-5.39). Finally, PD cases had used estrogens orally or parenterally for at least 6 months after menopause less frequently (8%) than control subjects (14%; OR = 0.47; 95% CI = 0.12-1.85). However, the findings for early menopause and estrogen replacement therapy were not statistically significant. Despite the limited sample size of this exploratory study, we hypothesize that there is an increased risk of PD in conditions causing an early reduction in endogenous estrogen. This hypothesis needs to be confirmed in a larger study.     

Nulliparity and late menopause are associated with decreased cognitive decline

Changes in Mini-Mental State Examination (MMSE) scores were examined over a median of 12.8 years in a population of 361 community-dwelling postmenopausal women who had never received estrogen replacement therapy. In a linear regression model that took into account age, education, race, surgical versus natural menopause, use of birth control pills, and MMSE score at baseline, it was found that nulliparous women and women who went through menopause later in life had significantly less cognitive decline. These results suggest that greater lifetime exposure to endogenous estrogen may be associated with less age-related cognitive decline.     

Postmenopausal estrogen therapy and Alzheimer disease: overall negative findings

An inverse association between estrogen therapy (ET) and Alzheimer disease (AD) has been reported in some, but not in all studies. We investigated the association between ET and AD in postmenopausal women using a population-based case-control design. Women who developed AD from 1985 through 1989 in Rochester, MN (cases, n=264) were individually matched by age (+/-1 y) to control women free of dementia from the same population (controls, n=264). ET exposure (>/=6 mo after menopause) was ascertained by abstracting the complete medical records archived in the records-linkage system of the Rochester Epidemiology Project. The frequency of ET use was similar in cases (11.4%) and controls [10.6%; odds ratio=1.10; 95% confidence interval (CI)=0.63-1.93]. However, cases who used ET had a suggestive trend for an earlier age at start of ET compared with controls (median, 49.0 vs. 50.5 y; P=0.06). Although smoking (ever vs. never) was not associated with AD overall, we observed an interaction between smoking and ET. The odds ratio of AD in ET users was 4.55 (95% CI=1.33-15.53) among smokers, but was 0.68 (95% CI=0.35-1.32) among never-smokers (P for interaction=0.01). Our findings do not confirm a significant association between ET and AD overall; however, the possible interaction with smoking deserves further study.     

Hormone replacement therapy in postmenopausal women with schizophrenia: positive effect on negative symptoms?

BACKGROUND: Some studies of premenopausal women suggest that the severity of psychopathology associated with schizophrenia may be related to levels of estrogen. METHODS: We examined psychopathology in community-dwelling postmenopausal women with schizophrenia who had received (n = 24) versus had never received (n = 28) hormone replacement therapy. RESULTS: Users of hormone replacement therapy and nonusers did not differ significantly with respect to age, ethnicity, education, age of onset, duration of schizophrenia, global cognitive functioning, or neuroleptic-induced movement disorders. The hormone replacement therapy users received lower average daily doses of antipsychotic medication; they had similar levels of positive symptoms but significantly less severe negative symptoms compared with hormone replacement therapy nonusers, independent of differences in antipsychotic dosage. CONCLUSIONS: Our results suggest that the use of hormone replacement therapy in conjunction with antipsychotic medication in postmenopausal women with schizophrenia may help reduce negative, but not positive, symptoms.     

Endogenous estrogen levels and Alzheimer's disease among postmenopausal women

BACKGROUND: Although several studies have suggested that hormone replacement therapy lowers the risk of AD among postmenopausal women, few studies have evaluated the relationship of endogenous estrogen levels and AD. The current study investigated whether serum estrone and estradiol levels were related to the presence of AD among postmenopausal women not currently taking hormone replacement therapy. METHODS: Using a case-control design, we examined an ethnically diverse sample of postmenopausal women who met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 50) and nondemented controls (n = 93). All women were participants in a study of aging and dementia and were seen consecutively between August 1997 and October 1998. RESULTS: Patients with AD had lower estradiol (F[1,141] = 8.3, p = 0.005) levels than did normal controls. Patients also had lower estrone levels; however, this comparison did not quite meet significance criteria (F[1,141] = 3.6, p = 0.06). Compared to estradiol levels >20 pg/mL, women with AD were four to six times more likely to have levels <20 pg/mL after adjusting for age, years of education, presence of an APOE-epsilon4 allele, ethnicity, and body mass index. There were no significant differences in frequency of AD among women within different quartiles of estrone after adjusting for potential confounds. CONCLUSIONS: The results of this preliminary case-control study suggest that estradiol levels may decline significantly in women in whom AD develops.     

Postmenopausal estrogen use affects risk for Parkinson disease

BACKGROUND: Although estrogen therapy has been associated with improved cognitive functioning, a reduced risk of dementia in women with Parkinson disease (PD), and a decreased risk of Alzheimer disease, estrogen therapy has not affected the risk of PD per se. OBJECTIVE: To determine whether postmenopausal women with PD differed from control subjects with regard to estrogen exposure.Design, Setting, and Patients A case-control design was used, abstracting questionnaire data obtained via interview from 133 female PD cases and 128 female controls during routine outpatient clinic visits in 1999 at a mid-Atlantic tertiary care referral center. There were 140 subjects (68 PD cases and 72 controls) who met the inclusion criteria.Main Outcome Measure Use of postmenopausal estrogen therapy. RESULTS: More women in the control group than in the PD group took postmenopausal estrogen (36 [50%] of 72 women vs 17 [25%] of 68 women; P<.003), and women who had taken postmenopausal estrogen were less likely to develop PD than those who had not (odds ratio, 0.40 [95% confidence interval, 0.19-0.84]; P<.02). Among PD cases only, postmenopausal estrogen use was not associated with age of onset. CONCLUSION: Postmenopausal estrogen therapy may be associated with a reduced risk of PD in women.     

Effect of estrogen on cerebral glucose metabolism in postmenopausal women

PET was used to evaluate the effect of estrogen use on regional cerebral glucose metabolism in postmenopausal women. Women receiving estrogen replacement therapy (ERT+), women not receiving estrogen (ERT-), and women with AD were studied. The ERT- group showed metabolic ratios that were intermediate to the ERT+ and AD groups, although they did not show any signs of cognitive impairment. These findings show an effect of estrogen depletion on brain metabolic activity.     

Postmenopausal hormone therapy and Alzheimer's disease risk: interaction with age

We examined the relation between oestrogen containing hormone therapy (HT) used for more than 6 months and Alzheimer's disease (AD) risk in 971 postmenopausal women (426 AD patients, 545 relatives without dementia). There was a significant interaction between age and HT use on AD risk (p = 0.03). In stratified analyses, a significant protective association was seen only in the youngest age tertile (50-63 years; odds ratio = 0.35, 95% confidence interval = 0.19 to 0.66). Results must be considered cautiously in light of recent clinical trial evidence that oestrogen plus progestin increases dementia incidence in older postmenopausal women. However, our observational findings are consistent with the view that HT may protect younger women from AD or reduce the risk of early onset forms of AD, or that HT used during the early postmenopause may reduce AD risk.     

Effects of long-term estrogen replacement therapy on growth hormone response to pyridostigmine in healthy postmenopausal women

OBJECTIVE: There is growing evidence that estrogen may protect against age-related cognitive decline and reduce the risk of developing Alzheimer's disease (AD) in healthy, postmenopausal women. The underlying biological basis for this is not known but may include preservation of cholinergic systems. Cholinergic dysfunction has been implicated in the aetiology of age-related memory impairment and AD. We studied the effect of prolonged use of estrogen replacement therapy (ERT) on central cholinergic tone in healthy postmenopausal women. METHOD: Growth hormone (GH) responses to oral pyridostigmine (120 mg) were measured over a 3 h period in thirty healthy postmenopausal women, 15 on long-term ERT and 15 ERT na?ve. RESULTS: GH release following pyridostigmine was significantly larger in ERT treated women than in ERT na?ve women. In addition within the ERT treated group there was a significant positive correlation between duration of estrogen treatment and GH response. CONCLUSIONS: Long-term ERT can enhance cholinergic function in postmenopausal women and this may be related to duration of estrogen treatment. Modulation of central cholinergic function may be one mechanism by which long-term ERT could preserve cognitive function in healthy, postmenopausal women.     

Onset of dementia is associated with age at menopause in women with Down's syndrome

Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community-based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system. Information from cognitive assessments, medical record review, neurological evaluation, and caregiver interviews was used to establish ages for onset of menopause and dementia. We used survival and multivariate regression analyses to determine the relation of age at menopause to age at onset of Alzheimer's disease, adjusting for age, level of mental retardation, body mass index, and history of hypothyroidism or depression. Women with early onset of menopause (46 years or younger) had earlier onset and increased risk of Alzheimer's disease (AD) compared with women with onset of menopause after 46 years (rate ratio, 2.7; 95% confidence interval [CI], 1.2-5.9). Demented women had higher mean serum sex hormone binding globulin levels than nondemented women (86.4 vs 56.6 nmol/L, p = 0.02), but similar levels of total estradiol, suggesting that bioavailable estradiol, rather than total estradiol, is associated with dementia. Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD.     

Can estrogen play a significant role in the prevention of Alzheimer's disease?

In women the abrupt decline estrogen levels at menopause may be associated with cognitive deficits and increased risk for Alzheimer's disease (AD); estrogen replacement therapy may reduce this risk. Animal studies indicate that estrogen modulates neurotransmitter systems, regulates synaptogenesis, and is neuroprotective. These beneficial effects occur in brain areas critical to cognitive function and involved in AD. Reduced estrogen levels can compromise neuronal function and survival. Estrogen replacement therapy can reverse cognitive deficits associated with low estrogen levels and may reduce the risk of AD. However, clinical trials for estrogen replacement in the treatment of AD have produced ambiguous results. Initial, small, open-label and double blind clinical trials indicated improved cognitive function in women with AD. Recent large trials failed to show a beneficial effect for long-term estrogen replacement for women with AD. There are several variables that could affect these results, such as genetic factors, time between estrogen loss and replacement, extent and types of AD pathology, and other environmental and health factors. Presently large prospective studies are being conducted as the National Institutes of Health in the Women's Health Initiative and the Preventing Postmenopausal Memory Loss and Alzheimer's with Replacement Estrogens studies to provide a better assessment of the role of estrogen for age related health issues, including dementia.     

Estrogen modulates cognitive and cholinergic processes in surgically menopausal monkeys

Estrogen deficiency in postmenopausal women is associated with changes in physiological processes. The extent to which estrogen loss is associated with cognitive changes noted by postmenopausal women has been more difficult to determine for a variety of reasons. Primate models of menopause are now being used to determine the effects of estrogen loss and replacement on cognitive abilities and to investigate the neural mechanisms by which estrogen may influence cognitive function. The present report presents data from cognitive and neurobiological studies in surgically menopausal monkeys that have examined how estrogen loss and replacement may be affecting cognitive abilities and the cholinergic system; a neural system that is known to influence memory and attention function. These studies are indicating that visuospatial attention function is especially sensitive to estrogen states in young monkeys, but that multiple cognitive domains are sensitive to estrogen states in middle-aged monkeys. In addition, anatomical and functional imaging studies indicate that the primate cholinergic system is modulated by estrogen, and pharmacological studies demonstrate that estrogen uses cholinergic muscarinic receptors to influence visuospatial attention. These studies demonstrate that estrogen influences cognitive abilities in monkey models of menopause and the cholinergic system may be one of the mechanisms by which estrogen modulates cognitive function. Given the current unknowns and concerns regarding the use of hormone replacement therapy in postmenopausal women, continued studies in monkey models of menopause are especially needed to further elucidate the effects of estrogen on cognitive and neurobiological processes, with particular emphasis on studies in middle-aged monkeys, determining the optimal aspects of ERT regimens, and identifying the relationships between estrogen effects on cognitive and neurobiological function.     

Association of circulating cellular adhesion molecules with menopausal status and hormone replacement therapy. Time-dependent change in transdermal, but not oral estrogen users

The incidence of coronary heart disease is lower in premenopausal than in postmenopausal women, and estrogen use may be cardioprotective among postmenopausal women. Cellular adhesion molecules (CAM) are involved in the early stage of atherosclerosis, and short-term administration of oral estrogen decreased plasma concentrations of their soluble forms in postmenopausal women. However, data evaluating transdermal estrogen are sparse and long-term effect of hormone replacement therapy (HRT) on CAM is unknown. Therefore, we have investigated the association of circulating CAM (cCAM) with menopausal status and long-term HRT. Plasma levels of intercellular adhesion molecule-1 (cICAM-1), vascular cell adhesion molecule-1 (cVCAM-1), P-selectin, E-selectin, C-reactive protein (CRP), and fibrinogen were measured in 74 premenopausal women, 60 postmenopausal women not using HRT, 30 postmenopausal women using opposed oral estrogen therapy, and 30 postmenopausal women using opposed transdermal estrogen therapy. All women were apparently healthy and aged between 45 and 54 years. Duration of HRT ranged from 3 to 96 months. Postmenopausal women not receiving HRT had 24% higher mean levels of cICAM-1 than premenopausal women (318 vs. 255 ng/ml, P < .001). In postmenopausal women, users of oral estrogen had 16% lower, and users of transdermal estrogen had 17% lower mean levels of cICAM-1 than non-users (268 and 264 vs. 318 ng/ml, P = .001 for both comparisons). Furthermore, in users of transdermal route, the lowering effect of estrogen on cICAM-1 was dependent on treatment duration, while no time-dependent effect was seen in oral estrogen users. Users of transdermal estrogen had lower cVCAM-1 and P-selectin levels than postmenopausal non-users (327 vs. 364 ng/ml (P = .05) and 18 vs. 23 ng/ml (P = .05). There was no difference in CRP and E-selectin levels between the groups. Adjustment for age and body mass index (BMI) made no substantial change in the results. These data suggest that oral and transdermal estrogen may play a long-term cardioprotective role through favourable changes in endothelial function.     

Characterization and health risk assessment of postmenopausal women with epilepsy

Postmenopausal women with epilepsy represent an understudied patient population. The objectives of this cross-sectional study were to characterize the impact of menopause on seizure activity and to conduct a health risk assessment. We conducted telephone interviews of 40 postmenopausal women with epilepsy concerning the effect of menopause on seizure frequency. We surveyed use of hormone replacement therapy, postmenopausal bone fractures, use of vitamins, and frequency of exercise. The average age and mean seizure duration were 55.8 and 27.6 years, respectively. Twenty-six women had onset of seizure activity before menopause. Of these 26, 3 reported fewer seizures after menopause, 7 reported more seizures, 11 reported no change, and 5 were unsure whether menopause affected their seizures. Only 30% of the 40 women were currently taking hormone replacement therapy. The impact of menopause on seizure activity was variable. Osteoporotic and cardiovascular preventive measures are underutilized. Patient education on these protective measures should be part of the comprehensive treatment approach in this "at-risk" patient population.     

Bone mineral density and the risk of Alzheimer disease

BACKGROUND: Some, but not all, studies have suggested that estrogen replacement therapy has a beneficial effect on cognition in postmenopausal women. Bone mineral density (BMD) is a potential surrogate marker for cumulative estrogen exposure and has been associated with cognitive performance and risk of cognitive deterioration. OBJECTIVE: To examine whether low BMD in elderly individuals is associated with an increased risk of developing Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS: Community-based prospective cohort study of 987 subjects (610 women) who were cognitively intact and had baseline BMD measured at the femoral neck, the trochanter, and the radial shaft between 1988 and 1989. MAIN OUTCOME MEASURES: Incidence of AD and all-cause dementia during an 8-year follow-up period. RESULTS: Women in the lowest quartile of femoral neck BMD had more than twice the incidence of AD (hazard ratio, 2.04; 95% confidence interval, 1.11-3.75) and all-cause dementia (hazard ratio, 2.01; 95% confidence interval, 1.16-3.49) compared with those in higher quartiles after adjusting for age, sex, apolipoprotein E epsilon4, baseline homocysteine level, education, estrogen use, smoking, and stroke. A similar but statistically nonsignificant relationship was observed between BMD of the femoral trochanter and AD, while no such relationship was seen between radial BMD and AD or all-cause dementia. In men, there was a trend toward an inverse relationship between BMD and the risk of AD, but the relationship was not statistically significant at any of the 3 sites. CONCLUSIONS: Low femoral neck BMD was associated with approximately 2 times the risk of AD and all-cause dementia in women but not men, suggesting the possibility that cumulative estrogen exposure may influence the risk of developing AD. Additional studies are needed to confirm this correlation.     

Effect of reproductive factors and postmenopausal hormone use on the risk of amyotrophic lateral sclerosis

OBJECTIVE: To examine the associations of reproductive factors and postmenopausal hormone use with the risk of amyotrophic lateral sclerosis (ALS) among women. METHODS: This case-control study was conducted within the Kaiser Permanente Medical Care Program (KPMCP) of Northern California during the years 1996-2000. Among the 193 postmenopausal women, 62 were incident ALS cases and 131 were controls randomly selected from KPMCP members and frequency matched by age and respondent type (self versus proxy) to the cases. Statistical analyses were carried out using logistic regression. RESULTS: Reproductive factors such as age at menarche, age at final menstrual period, parity, oral contraceptive use, and type of menopause (natural vs. hysterectomy with or without oophorectomy) were not associated with risk of ALS. Postmenopausal hormone use was positively, but not significantly, associated with the risk of ALS (adjusted OR 1.9, 95% CI 0.9-3.8). CONCLUSIONS: Reproductive factors were not associated with ALS risk. There is no evidence that suggests a protective effect of postmenopausal hormone use against the development of ALS. However, due to insufficient power, we cannot rule out a possible increase in ALS risk associated with postmenopausal hormone use.     

Postmenopausal hormone use impact on emotion processing circuitry

Despite considerable evidence for potential effects of estrogen on emotional processing, several studies of postmenopausal women who began hormone therapy (HT) remote from menopause report no effects of HT on emotional measures. As early HT initiation may preserve brain mechanisms, we examined effects of HT on emotional processing in postmenopausal women who started HT early after menopause. We performed a cross-sectional comparison of 52 postmenopausal women 66 ± 5 years old, including 15 users of conjugated equine estrogen, 20 users of conjugated equine estrogen plus medroxyprogesterone acetate, and 17 who never used hormones (NT). All hormone users started therapy within two years of menopause, and received at least 10 years of continuous therapy. Outcomes were fMRI-detected brain activity and behavioral measures during an emotional processing picture rating task. During processing of positive pictures, NT women had greater activation than estrogen treated women in medial prefrontal cortex extending to the anterior cingulate, and more activation than estrogen plus progestin treated women in the insula. During processing of negative pictures, estrogen treated women had higher activation than NT women in the entorhinal cortex. Current compared to past HT users showed greater activation in the hippocampus and higher emotion recognition accuracy of neutral stimuli. Estrogen plus progestin treated women had slower response time than NT women when rating all pictures. In conclusion, hormone use was associated with differences in brain functional responses during emotional processing. These fMRI effects were more prominent than those observed for behavioral measures and involved brain regions implicated in cognitive-emotional integration.     

Cognitive and neuroendocrine response to transdermal estrogen in postmenopausal women with Alzheimer's disease: results of a placebo-controlled, double-blind, pilot study.

Preliminary evidence from clinical studies indicates that treatment with estrogen augments cognitive function for women with Alzheimer's disease (AD). The neurobiology of estrogen, particularly its neuromodulatory and neuroprotective actions, provide a viable basis to support such cognition-enhancing effects. We conducted a placebo-controlled, double-blind, parallel-group design pilot clinical study to evaluate the cognitive and neuroendocrine response to estrogen administration for postmenopausal women with AD. Twelve women with probably AD of mild-moderate severity completed the study. During an eight week treatment period, six women received 0.05 mg/day dosage of 17 beta-estradiol via a skin patch and the remaining six wore a placebo skin patch. Subjects were randomized to equal distribution, and evaluated at baseline, at weeks 1, 3, 5, and 8 on treatment, and at weeks 9, 10, 11, and 13 off treatment. On each day of evaluation, cognition was assessed using a battery of neuropsychological tests, and blood samples were collected to measure plasma concentrations of estradiol and estrone. In addition, several neuroendocrine markers were measured in plasma to evaluate the relationship between estrogen-induced cognitive effects and fluctuations in the catecholaminergic and insulin-like growth factor systems. Significant effects of estrogen treatment were observed on attention (i.e. Stroop: number of self-corrections in the Interference condition, F[1,8] = 8.22, P < 0.03) and verbal memory (i.e., Buschke: delayed cued recall, F[3,30] = 4.31, P < 0.02). The salutary effects of estrogen on cognition were observed after the first week of treatment, and started to diminish when treatment was terminated. For women treated with estrogen, enhancement in verbal memory was positively correlated with plasma levels of estradiol (r = 0.96, P < 0.02) and negatively correlated with concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) in plasma (r = -0.92, P < 0.03). Furthermore, a trend in the data was evident to suggest a negative relationship between plasma levels of insulin-like growth factor-1 (IGF-1) and verbal memory (r = -0.86, P = 0.06). Estrogen administration suppressed peripheral markers of the IGF system, as evidenced by a negative correlation between plasma concentration of estradiol and IGF-1 (r = -0.93, P < 0.03), and a trend for a similar relationship between plasma levels of estradiol and IGFBP-3 (r = -0.86, P = 0.06). With respect to the catecholamines assayed, norepinephrine was positively correlated with verbal memory (r = 0.95, P < 0.02) for women who were treated with estrogen. Furthermore, there was a trend to suggest a negative relationship between plasma epinephrine levels and the number of errors committed on a test of attention (r = -0.84, P = 0.07). In the placebo group, no significant effects of estrogen replacement were evident either on measures of cognition or on any of the neuroendocrine markers. The results of this study suggest that estrogen replacement may enhance cognition for postmenopausal women with AD. Furthermore, several markers of neuroendocrine activity may serve to index the magnitude of estrogen-induced facilitation on cognition. In addition, research findings from the present study will provide important information for the design of larger prospective clinical studies that are essential to definitively establish the therapeutic role of estrogen replacement for postmenopausal women with AD.     

Estrogen and performance in recognition memory for olfactory and visual stimuli in females diagnosed with Alzheimer's disease.

Patients with Alzheimer's disease (AD) exhibit a deficit in episodic recognition memory for odors. It is hypothesized that the higher rate of AD in women may be due to estrogen-deprivation in postmenopausal women. Research suggests that estrogen may help to minimize cognitive decline in AD as well as postmenopausal olfactory loss. The current study examined the effects of estrogen replacement therapy (ERT) on performance of a recognition memory task for olfactory and visual stimuli in women AD patients. Participants included 24 women AD patients who were ERT users and 77 women AD patients who never used ERT. Compared with the ERT non-users, the ERT users committed significantly less false-positive memory errors for olfactory stimuli, whereas performance for visual stimuli did not differentiate between ERT users and non-users. The results suggest benefits of ERT could help ameliorate the earliest symptoms of AD, olfactory dysfunction, and memory impairment.