Prior endogenous and exogenous estrogen and incident dementia in the 10th decade of life: The 90+ Study.

Objective: This study aimed to investigate the association of endogenous and exogenous estrogen exposure with risk of incident dementia in the oldest-old (age 90+ years).Methods: Participants were part of The 90+ Study, a longitudinal study begun in 2003 of aging and dementia among people aged 90+ years. Menstrual, reproductive, and menopausal data were collected in the 1980s as part of the population-based Leisure World Cohort Study. Cognitive status at baseline was determined from an in-person neurological evaluation with biannual follow-up through June 2019. Hazard ratios (HRs) of dementia associated with estrogen-related variables were estimated using Cox regression analysis. No adjustment was made for multiple comparisons.Results: A total of 424 women without dementia at baseline had at least one follow-up evaluation. The mean age was 68.5 years at enrollment in the Leisure World Cohort Study, 93.2 years at enrollment in The 90+ Study, and 96.5 years at last follow-up. During follow-up (mean 3.4 years) dementia was diagnosed in 209 (49%) participants. No individual menstrual, reproductive, menopausal, or estrogen replacement variable was associated with risk of incident dementia after age 90 years. However, women with a high endogenous estrogen exposure index (summarizing exposure from menarche to menopause) had a non-significant 25% lower risk (HR = 0.75, 95% confidence interval 0.53-1.06).Conclusions: Prior exposure to estrogen, endogenous or exogenous, had little effect on risk of dementia in the 10th decade of life.

Immune responses of healthy humans 83-104 years of age.

The immune responses of 19 healthy people 83-104 years of age were compared to those of younger healthy persons. A decline in mitogen response to concanavalin A and pokeweed mitogen, but not to phytohemagglutinin, was observed. Positive skin test to two recall antigens occurred in only 5 of the 19 aged people; 4 of these 5 reported a history of blood transfusion. Antibody titers were elevated for persistent DNA viruses but not for RNA viruses. An excess of ABO blood type B was found, but no human leukocyte antigen (HLA)-A or HLA-B type was found in elevated proportion.

Vitamin A, beta-carotene, and the risk of cancer: a prospective study.

A cohort of 10,473 residents of Leisure World, Laguna Hills, CA, who were initially free of cancer were followed from 1981 to 1986. A health survey questionnaire completed by all cohort members included usual frequencies of consumption of certain food items, including vegetables, fruits, dairy products, liver, and cereal, as well as specific information on brand and formulation of vitamin supplements containing vitamins A, C, or E. Pathologic diagnosis of incident cancer was confirmed in 643 persons (56 lung, 110 colon, 59 bladder, 93 prostate, 123 female breast, and 202 cancers of other sites). Our study found little indication that increased intake of vitamin A or beta-carotene from the diet or supplements protects against the development of cancer overall. Dietary vitamin A intake was highly associated with smoking status; 25% of current smokers were in the highest third of dietary vitamin A consumption versus 32% of past smokers and 36% of never-smokers. In males who never smoked there was some indication that cancer rates decreased with increasing vitamin A intake, but the results were not statistically significant.

A genetic epidemiologic investigation of breast cancer in families with bilateral breast cancer. I. Segregation analysis.

A complex segregation analysis was conducted of breast cancer in 200 families with bilateral breast cancer. Results for two analyses are presented. The first analysis considered only premenopausal cases of breast cancer as affected. The results indicate that mendelian transmission of a single locus is not sufficient to explain the distribution of premenopausal breast cancer seen. A mixed model, i.e., a major locus plus other transmission (genetic and/or cultural), is necessary to explain the distribution. The second analysis added postmenopausal cases of breast cancer to the premenopausal ones, thus considering all breast cancer cases to be affected with the same disorder. The all-cases analysis is unable to reject a mixed model with no generation differences in heritability when tested against the general model, which allows for generation differences (i.e., the likelihoods for the two models were not significantly different). Approaches to studying etiologic heterogeneity in segregation analysis and results of other segregation analyses of breast cancer are presented.

Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin.

BACKGROUND: Hormone replacement therapy (HRT) given as unopposed estrogen replacement therapy (ERT) gained widespread popularity in the United States in the 1960s and 1970s. Recent prescribing practices have favored combination HRT (CHRT), i.e., adding a progestin to estrogen for the entire monthly cycle (continuous combined replacement therapy [CCRT]) or a part of the cycle (sequential estrogen plus progestin therapy [SEPRT]). Few data exist on the association between CHRT and breast cancer risk. We determined the effects of CHRT on a woman's risk of developing breast cancer in a population-based, case-control study. METHODS: Case subjects included those with incident breast cancers diagnosed over 4(1/2) years in Los Angeles County, CA, in the late 1980s and 1990s. Control subjects were neighborhood residents who were individually matched to case subjects on age and race. Case subjects and control subjects were interviewed in person to collect information on known breast cancer risk factors as well as on HRT use. Information on 1897 postmenopausal case subjects and on 1637 postmenopausal control subjects aged 55-72 years who had not undergone a simple hysterectomy was analyzed. Breast cancer risks associated with the various types of HRT were estimated as odds ratios (ORs) after adjusting simultaneously for the different forms of HRT and for known risk factors of breast cancer. All P values are two-sided. RESULTS: HRT was associated with a 10% higher breast cancer risk for each 5 years of use (OR(5) = 1.10; 95% confidence interval [CI] = 1.02-1.18). Risk was substantially higher for CHRT use (OR(5) = 1.24; 95% CI = 1.07-1.45) than for ERT use (OR(5) = 1. 06; 95% CI = 0.97-1.15). Risk estimates were higher for SEPRT (OR(5) = 1.38; 95% CI = 1.13-1.68) than for CCRT (OR(5) = 1.09; 95% CI = 0. 88-1.35), but this difference was not statistically significant. CONCLUSIONS: This study provides strong evidence that the addition of a progestin to HRT enhances markedly the risk of breast cancer relative to estrogen use alone. These findings have important implications for the risk-benefit equation for HRT in women using CHRT.

Case-control study of intracranial meningiomas in women in Los Angeles County, California.

A case-control study was conducted among women in Los Angeles County to investigate possible causes of intracranial meningiomas. Questionnaires sought information from patients and from a neighbor of each one on characteristics and past experiences that might be associated with the development of this disease. Information was obtained on 188 matched patient-neighbor pairs. Three primary factors appeared to be associated with meningioma occurrence: 1) a history of head trauma (odds ratio = 2.0, P = 0.01), 2) consumption of certain cured meats (odds ratio = 2.8, P less than 0.01), and 3) exposure to medical and dental diagnostic X-rays to the head. For diagnostic X-rays, the strongest association was with early exposure (less than 20 yr old) to full-mouth dental X-ray series (odds ratio = 4.0, P less than 0.01).

Case-control studies of prostate cancer in blacks and whites in southern California.

To identify risk factors for prostate cancer and to try to explain the high risk of blacks relative to whites, case-control interview studies of prostate cancer were conducted in both populations in southern California. Both studies included 142 pairs of cases and population controls matched on age. Cases in blacks were identified by the population-based tumor registry of Los Angeles County and cases in whites were identified by a population-based tumor registry of a southern California retirement community. A past history of venereal disease was associated with a high risk of prostate cancer in both populations [relative risk (RR) = 2.3 in whites; RR = 1.7 in blacks]. The result in blacks was statistically significant (P = .03). Black cases tended to have more frequent sexual intercourse than black controls at all ages; the difference became statistically significant for intercourse late in life. Data from controls suggested that, overall, blacks have earlier and more frequent sexual activity than whites, but the two populations were dissimilar in social class characteristics. Fat intake was a risk factor for prostate cancer in both populations, but vitamin A consumption and protein intake were inconsistently related or unrelated to prostate cancer risk. While beta-carotene was not consistently related to risk, there was some indication that in persons with low fat intake, low beta-carotene intake may be associated with high risk. Circumcision was negatively associated with risk in both populations (RR = 0.5 in whites; RR = 0.6 in blacks). These results are discussed in the context of major etiologic hypotheses for prostate cancer.

Urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio and risk of breast cancer in postmenopausal women.

BACKGROUND: It has been suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16alpha-hydroxylation pathway may be at elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxylation pathway. However, the supporting epidemiologic data are scant. Consequently, we compared the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alphahydroxyestrone (16alpha-OHE1) in postmenopausal women with breast cancer and in healthy control subjects. METHODS: Estrogen metabolites were measured in urine samples obtained from white women who had participated in a previous population-based, breast cancer case-control study at our institution. All P values are from two-sided tests. RESULTS: All of the urinary estrogens measured, with the exception of estriol, were higher in the 66 case patients than in the 76 control subjects. The mean value of urinary 2-OHE1 in case patients was 13.8% (P = .20) higher than that in control subjects, 16alpha-OHE1 was 12.1% (P = .23) higher, estrone was 20.9% higher (P = .14), and 17beta-estradiol was 12.0% higher (P = .36). The ratio of 2-OHE1 to 16alpha-OHE1 was 1.1% higher in the patients (P = .84), contrary to the hypothesis. Compared with women in the lowest third of the values for the ratio of urinary 2-OHE1 to 16alpha-OHE1, women in the highest third were at a nonstatistically significantly increased risk of breast cancer (odds ratio = 1.13; 95% confidence interval = 0.46-2.78), again contrary to the hypothesis. CONCLUSION: This study does not support the hypothesis that the ratio of the two hydroxylated metabolites (2-OHE1/16alpha-OHE1) is an important risk factor for breast cancer.

Analgesics, cigarette smoking, and other risk factors for cancer of the renal pelvis and ureter.

Results from a population-based case-control study of cancer of the renal pelvis and ureter are reported. Telephone interviews were conducted with 187 residents of Los Angeles County diagnosed with cancer of the renal pelvis and ureter over a 4-year period ending December 31, 1982, and with individually sex-, age- and race-matched neighborhood controls. The major risk factor identified for cancer of the renal pelvis and ureter was cigarette smoking. Subjects who smoked more than 25 years had a relative risk of 4.5 of developing these tumors, compared to nonsmokers (P less than 0.0001). Heavy use of over-the-counter analgesics was also associated with a significant increase in risk; it appears that an elevated risk was conveyed by all the major active constituents of those compounds currently marketed in the United States, aspirin, caffeine, and acetaminophen. Persons who had used these drugs for 30 consecutive days at any time in their life preceding diagnosis had twice the risk of developing cancer of the renal pelvis or ureter compared to persons not reporting such use (P less than 0.01). Heavy coffee drinkers (greater than or equal to 7 cups/day) had a 1.8-fold increase in risk compared to nondrinkers. Although risk tended to increase with increasing consumption, this result was not statistically significant. The risk associated with heavy coffee consumption was reduced to 1.3 after adjusting for smoking. Nine cases compared to no controls reported a first degree relative with kidney cancer. A history of kidney stones was associated with an increased risk of cancer of the ureter (relative risk = 2.5) that was not, however, statistically significant.

Linkage analysis of DRD2, a marker linked to the ataxia-telangiectasia gene, in 64 families with premenopausal bilateral breast cancer.

Recent reports suggest that subjects who are heterozygous for the ataxia-telangiectasia gene are at increased risk of breast cancer. We conducted linkage analyses of 64 families with premenopausal bilateral breast cancer using DRD2, a marker linked to the ataxia-telangiectasia locus at 11q22-23. We assumed a model with dominant transmission of breast cancer. Lod scores summed over all families provided strong evidence against tight linkage (e.g., a lod score of -6.08 at theta = 0.00001), although a single family provides suggestive evidence of tight linkage to DRD2. Evidence against linkage to 11q was strongest among families that may involve the BRCA1 breast cancer susceptibility gene on 17q21. However, we did not observe evidence of linkage to 11q among the remaining subgroup with neither a family history of ovarian cancer nor the appearance of linkage to 17q21.

Effects of reserpine on prolactin levels and incidence of breast cancer in postmenopausal women.

Epidemiological studies of reserpine use and breast cancer have generally found only small increases in breast cancer risk, even after long-term use. Prolactin levels in short-term reserpine users have been reported to be in the range of those of lactating women, levels which rodent experiments suggest should greatly increase breast cancer incidence. We measured prolactin levels in 15 women who had been taking reserpine-containing drugs for at least 5 years and compared them to levels in 15 women taking non-reserpine-containing antihypertensives and 15 women taking no antihypertensive medicines. Although reserpine users had significantly elevated levels of prolactin, their mean level was only approximately 50% greater than the mean level of the combined results from the two control groups. Based on a statistical model of breast cancer incidence, we calculate that such increases in prolactin in the postmenopausal period would be likely to cause only small increases in breast cancer risk, as have been observed in epidemiological studies.

A linkage analysis of D17S74 (CMM86) in thirty-five families with premenopausal bilateral breast cancer.

We report here results of a linkage analysis of a marker in 35 families in which the proband had premenopausal bilateral breast cancer. This group is of particular interest given their high family risk and the question of etiological heterogeneity. Probands were ascertained from cancer registries in Los Angeles County and Connecticut and major hospitals in Montréal and Québec. Assuming no residual heterogeneity and summing lod scores over all families, we obtained strong evidence against tight linkage (e.g., lod score at theta = 0.000001 is -3.39). To address the issue of heterogeneity, we performed admixture and predivided sample analyses. Using an admixture model we were able to reject the hypothesis of no linkage versus that of linkage with homogeneity (P = 0.045). However, we were unable to reject the hypothesis of no linkage versus linkage with heterogeneity (P = 0.119) or to distinguish between linkage with homogeneity and linkage with heterogeneity (P = 0.500). Predivided sample analyses based upon age of onset, pathological characteristics, time between diagnoses of the breast cancers in each bilateral proband, and the span of ages at diagnoses within a family did not discriminate between apparently linked and unlinked families.

The benefits of estrogen replacement therapy on oral health. The Leisure World cohort.

BACKGROUND: Several studies have demonstrated a relationship between tooth loss and alveolar residual ridge resorption and systemic osteoporosis. The recognized benefit of estrogen replacement therapy (ERT) in postmenopausal osteoporosis prompted review of the Leisure World Cohort Study regarding the effects of ERT on tooth loss and the need for dentures in older women. METHODS: The Leisure World Cohort, established in 1981, comprises 13,979 residents (8877 women) of a retirement community. Of the 5935 cohort women alive in 1992, 3921 returned a dental survey with sufficient information to analyze relationships with ERT as reported on the original baseline questionnaire. RESULTS: After adjusting for age, tooth loss and rates of edentia were significantly lower in estrogen users than in nonusers (relative risk for edentia, 0.64; 95% confidence interval, 0.51 to 0.79). The proportion of women with edentia decreased with increasing duration of ERT. Denture wearing was also less common in estrogen users than in nonusers (relative risk, 0.81; 95% confidence interval, 0.71 to 0.93) and decreased with increasing duration of ERT. CONCLUSION: Estrogen replacement therapy may be beneficial in preventing tooth loss and the need for dentures in older women.

Estrogen replacement therapy and risk of Alzheimer disease.

BACKGROUND: With Alzheimer disease emerging as a major public health problem, the identification of factors that might prevent this disease are important. Estrogen loss associated with menopause may contribute to the development of Alzheimer disease. OBJECTIVE: To evaluate the effects of different estrogen preparations, varying dosages of estrogen, and duration of estrogen replacement therapy on the risk of Alzheimer disease in postmenopausal women. STUDY DESIGN AND METHODS: A case-control study nested within a prospective cohort study of residents of Leisure World Laguna Hills, a retirement community in Southern California. The cohort comprised 8877 women who were first mailed a health survey in 1981. Of the 3760 female cohort members who died between 1981 and 1995, 248 women with Alzheimer disease or other dementia diagnoses likely to represent Alzheimer disease (senile dementia, dementia, or senility) mentioned on the death certificate were identified. Five controls were individually matched to each case according to year of death and year of birth (+/- 1 year). RESULTS: The risk of Alzheimer disease and related dementia was significantly reduced in estrogen users compared with nonusers (odds ratio, 0.65; 95% confidence interval, 0.49-0.88). The risk was reduced for both oral and nonoral (i.e., injections and/or creams) routes of administration. The risk decreased significantly with both increasing dosages (P = .01) and increasing duration (P = .01) of oral therapy with conjugated equine estrogen, the most commonly used estrogen preparation. Within each dose category, the risk decreased with increasing duration of therapy, with the lowest observed risk in long-term users who received high doses (odds ratio, 0.48; 95% confidence interval, 0.19-1.17). CONCLUSION: This study suggests that estrogen replacement therapy may be useful for preventing or delaying the onset of Alzheimer disease in postmenopausal women.

Decreased mortality in users of estrogen replacement therapy.

In a prospective study of 8881 postmenopausal female residents of a retirement community in southern California, we evaluated in detail the relationship between estrogen use and overall mortality. After 7 1/2 years of follow-up, there had been 1447 deaths. Women with a history of estrogen use had 20% lower age-adjusted, all-cause mortality than lifetime nonusers (95% confidence interval, 0.70 to 0.87). Mortality decreased with increasing duration of use and was lower among current users than among women who used estrogens only in the distant past. Current users with more than 15 years of estrogen use had a 40% reduction in their overall mortality. Among oral estrogen users, relative risks of death could not be distinguished by specific dosages of the oral estrogen taken for the longest time. Women who had used estrogen replacement therapy had a reduced mortality from all categories of acute and chronic arteriosclerotic disease and cerebrovascular disease. This group of women had a reduced mortality from cancer, although this reduction was not statistically significant. The mortality from all remaining causes combined was the same in estrogen users and lifetime nonusers.

Association of male circumcision with risk of prostate cancer: a meta-analysis.

BACKGROUND: Although early reports have suggested an association between circumcision and prostate cancer (PCa) development, results of subsequent epidemiological studies have been conflicting. Here we examine published articles that explore this association. METHODS: We searched MEDLINE through PubMed and Embase for articles reporting on the association between PCa and circumcision, and performed a meta-analysis of qualifying studies. RESULTS: On the basis of seven reports of case-control studies published from 1971 to 2014, overall findings showed nonsignificant reduced risk (odds ratio (OR) 0.88, P=0.19) of PCa in circumcised men compared with uncircumcised men, obtained under heterogeneous conditions (I(2)=65%). Heterogeneity and nonsignificance were erased when the overall effect was subjected to outlier treatment and three studies omitted (OR 0.90, P=0.04, I(2)=0%). Furthermore, subgroup analysis showed significantly reduced risks in the following subgroups: (i) post-PSA testing publications (OR 0.88, P=0.01), (ii) population-based studies (OR 0.84, P=0.05), (iii) studies that collected data by personal interview (OR 0.83, P=0.03) and (iv) studies in black race (OR 0.59, P=0.02). The strengths of these summary effects lie in the robustness revealed by sensitivity analysis. CONCLUSIONS: Stability of the reduced risks observed in key subgroups suggests that the protective feature of circumcision status against PCa is best seen in the context of the post-PSA testing and population-based studies as well as in the black race subgroup.

Infection and risk of ischemic stroke: differences among stroke subtypes.

BACKGROUND AND PURPOSE: Although prior studies have demonstrated that 25% to 35% of stroke patients have had a recent infection, the role of infection as a risk factor remains unclear. Our aim was to characterize the effect of infectious/inflammatory syndromes on stroke risk. METHODS: Case-control and crossover analyses of 233 cases and 363 controls aged 21 to 89 years were performed. Cases were patients hospitalized with a first ischemic stroke at a Los Angeles, California, medical center. Controls were outpatients in the hypertension, diabetes, and general medical clinics. All subjects were administered a neurological examination, an infection/inflammation (I/I) examination, and an interview to elicit recent I/I history at baseline (within several days of stroke onset) and again approximately 2 months later. Three physicians classified subjects by the presence or absence of I/I within 1 month of the index dates, based on findings of the I/I examination, the interview report, and laboratory results. RESULTS: Infections, either total or specific, were not found more frequently in cases than controls. However, patients with a recent respiratory tract infection suffered more often from large-vessel atherothromboembolic or cardioembolic stroke than did patients without infection (48% vs 24%, P=0.07). The age- and sex-adjusted relative risk estimate for these subtypes was 1.75 (95% CI, 0.86 to 3.55). The risk was notably high for those without stroke risk factors: 4.15 (95% CI, 1.22 to 14.1) for normotensives, 2.71 (95% CI, 1.04 to 7.06) for nondiabetics, and 1.74 (95% CI, 0.74 to 4.07) for nonsmokers. Patients with a recent respiratory infection also had a more severe neurological deficit on admission than those without infection (P=0.05). CONCLUSIONS: Our results suggest that respiratory tract infection may act as a trigger and increase the risk of large-vessel and/or cardioembolic ischemic stroke, especially in those without vascular risk factors.

Total and free estrogens and androgens in postmenopausal women with hip fractures.

Hip fracture constitutes the most serious complication of postmenopausal osteoporosis. To examine the possible role of circulating estrogen or androgen levels in the development of this type of fracture, 25 patients with hip fractures after minimal trauma were compared to an equal number of controls, matched for age and years since menopause. All were from a retirement community, had intact ovaries, and had not taken estrogen replacement for longer than 3 months during their entire lifetime. Hip fracture patients were found to have a significantly lower (P = 0.031) mean (+/-SE) percent ideal weight (89.4 +/- 2.9%) than controls (100.0 +/- 2.5%). Sex hormone-binding globulin levels were significantly higher (P = 0.004) in patients (6.7 +/- 0.4 X 10-8 M) than in controls (4.9 +/- 0.3 X 10-8 M), resulting in lower concentrations of biologically available estradiol and testosterone. In a subgroup of 12 patients and controls matched for percent ideal weight, differences in sex hormone binding globulin and free testosterone and estradiol levels were no longer statistically significant; however, the difference in the percentage of free testosterone persisted. These data suggest that endogenous sex steroids in their unbound form may play a role in the pathogenesis of postmenopausal hip fractures. The differences in free hormone levels appeared to be influenced by the differences in mean body size of the 2 groups. This factor is known to have an important negative effect on the concentration of sex hormone-binding globulin.

Dietary intake and nutrient supplement use in a Southern California retirement community.

Dietary histories and information concerning the use of nutritional supplements were obtained from 51 randomly selected residents of an Orange County, CA, retirement community. The nutrients for which dietary intakes were most apt to fall below 100% of the 1980 Recommended Dietary Allowance were: calcium, in both sexes; energy, in males; and iron, thiamin, riboflavin, and niacin in females. With the exception of calcium, few subjects had intakes below two-thirds of the Recommended Dietary Allowances. These findings are similar to those reported in previous dietary surveys of the elderly. Vitamin and mineral supplements were consumed by 72% of the subjects; such consumption was unrelated to dietary intake. Supplemental vitamin C was consumed by 67% of the subjects in amounts ranging from 30 to 5200 mg daily; supplemental vitamin E was taken by 51%, with amounts ranging from 8 to 1000 IU daily. Supplement use by this population is one of the highest reported among the elderly, an effect that may result from the affluence of the community, its geographic location, and from a high level of nutritional consciousness among its residents.

Estrogen replacement therapy in older women. Comparisons between Alzheimer's disease cases and nondemented control subjects.

OBJECTIVES: We hypothesized that oral estrogen replacement therapy would be less common among elderly women meeting criteria for Alzheimer's disease (AD) than among nondemented elderly women. For women with AD, we hypothesized that estrogen users would perform better on a cognitive task than would nonusers. DESIGN: A case-control study of estrogen replacement therapy, in which hierarchical procedures were used to control for potentially confounding effects of age and education. When cognitive performances were compared between estrogen users and nonusers with AD, the duration of dementia symptoms was an additional control variable. SETTING: Alzheimer's Disease Research Center at the University of Southern California, Los Angeles. SUBJECTS: Subjects were a volunteer sample of consecutively enrolled elderly women, recruited primarily from the community, who met clinical criteria for probable AD (n = 143) or met criteria for nondemented control status (n = 92). Seventy case patients who have subsequently died met histopathologic criteria for AD; one other demented woman who did not meet the autopsy criteria for AD was excluded from all analyses. MAIN OUTCOME MEASURES: Current use of estrogen replacement at the time of enrollment as reported by control subjects or by the primary caregivers of AD case patients. Among cases, performances on a brief cognitive screening instrument were compared between estrogen users (n = 10) and nonusers (n = 128) for whom this information was available. RESULTS: Alzheimer's disease case patients were significantly less likely than control subjects to use estrogen replacement (7% vs 18%), but groups did not differ with regard to the total number of prescription medications or to the most frequently prescribed class of drug (thyroid medication). Demented case patients using estrogen did not differ significantly from those not using estrogen in terms of age, education, or symptom duration, but their mean performance on a cognitive screening instrument was significantly better (Mini-Mental State examination scores of 14.9 vs 6.5). CONCLUSIONS: Findings are consistent with contentions that postmenopausal estrogen replacement therapy may be associated with a decreased risk of AD and that estrogen replacement may improve cognitive performance of women with this illness.