Annlia Paganini-Hill

Estrogen for Alzheimer’s disease in women: Randomized, double-blind, placebo-controlled trial

Background: AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder. Methods: Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks. Results: Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer’s Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences. Conclusions: Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.

Menopausal Estrogen Therapy and Hip Fractures

Abstract The association between menopausal estrogen therapy and hip fracture was studied in a retirement community. Ninety-one hip fracture cases during a 5-year period in female residents under a...

Alcohol, physical activity and other risk factors for colorectal cancer: a prospective study

The aetiology of colorectal cancer was studied in a cohort of 11,888 residents of a retirement community. After four and one-half years of follow-up, 58 male and 68 female incident colorectal cancers were identified. Daily alcohol drinkers experienced nearly a two-fold increase in risk (2 sided P = 0.002). Colorectal cancer was also positively associated with Quetelets index and inversely associated with avocational physical activity. The results were consistent for both sexes but were statistically significant only for males. With the exception of dietary vitamin C, none of the nutrients under study (i.e., vitamins A and E, dietary fibre, calcium, and beta carotene) showed a significant association with colorectal cancer. An inverse relationship between colorectal cancer and dietary vitamin C was observed in females, but there was no association with either vitamin C from supplements or with total vitamin C intake. Males and females who had 3 or more children showed a significantly reduced risk of colorectal cancer (RR = 0.45, 95% CI = 0.2, 0.9), but those with no children did not show the highest risk.

Exercise and Other Factors in the Prevention of Hip Fracture: The Leisure World Study

As part of a prospective study begun in 1981, we evaluated 8,600 postmenopausal women and 5,049 men residing in a southern California retirement community for risk factors for hip fracture. Incidence rates were twice as high in women as in men, but in both sexes the rates nearly doubled every 5 years between 70 and 90 years. Active exercise was strongly and negatively associated with hip fracture risk in both sexes; the age-adjusted relative risk was 0.6 and 0.5 for females and males, respectively, for 1 or more hours of exercise per day compared with less than 1/2 hour of exercise. A high body mass index (upper tertile of weight divided by height squared) was associated with a strong reduction in hip fracture risk for females (RR = 0.5). Current cigarette smokers had a significantly increased risk (RR = 1.8 and RR = 2.2 for females and males, respectively) compared with never-smokers, but the risk for past smokers was not different from that of lifetime nonsmokers. Other factors related to reduced hip fracture risk in women were high parity, late age at menarche, and long menstrual cycle length. These age-adjusted relative risk estimates did not change materially in multivariate analysis when adjusted simultaneously for age, active exercise, body mass, smoking, and, for women, age at menarche and number of children. Among estrogen users, the lowest risk of hip fracture was observed for recent users (RR = 0.8), while users who had stopped estrogen use 15 or more years ago had a relative risk of 1.1, suggesting that the protective effect of estrogen dissipates after many years since cessation of estrogen therapy

Aspirin use and chronic diseases: a cohort study of the elderly.

OBJECTIVE--To evaluate the associations between the use of aspirin and the incidences of cardiovascular diseases, cancers, and other chronic diseases. DESIGN--Postal questionnaire survey to elicit details of aspirin use. SETTING--Californian retirement community. SUBJECTS--All 22,781 residents of the community (white, affluent, and well educated) were sent a questionnaire that included questions on medical history and the use of drugs such as analgesics, laxatives, and vitamin supplements. In all 61% responded (13,987, 8881 women and 5106 men; median age 73). They formed the cohort that was followed up for 6 1/2 years using discharge summaries from three hospitals serving the area and death certificates from the health department. Only 13 respondents were lost to follow up but seemed not to have died. MAIN OUTCOME MEASURES--Incidences of cardiovascular diseases, cancers, gastrointestinal bleeding, ulcers, and cataracts were compared in participants who did and did not take aspirin daily. RESULTS--Age adjusted incidences were computed with an internal standard and five age groups. By 1 January 1988 there had been 25 incident cases of kidney cancer among all participants; 341 incident cases of stroke, 253 of acute myocardial infarction, 220 of ischaemic heart disease, and 317 of other heart disease were reported among respondents without a reported history of angina, myocardial infarction, or stroke. The incidence of kidney cancer was raised among those who took aspirin daily compared with those who did not take it, although the increase was significant only in men (relative risks = 6.3, 95% confidence interval 2.2 to 17, for men and 2.1, 0.53 to 8.5, for women). Those who took aspirin daily showed no increased risk of any other cancer, except colon cancer for both sexes combined (relative risk = 1.5, 1.1 to 2.2). The risk of acute myocardial infarction was reduced slightly among regular users of aspirin in men but not women. The risk of ischaemic heart disease was almost doubled in those who took aspirin daily compared with non-users (relative risks = 1.9, 1.1 to 3.1, for men and 1.7, 1.1 to 2.7, for women). Small, non-significant increased risks of stroke were observed in both sexes. CONCLUSION--The daily use of aspirin increased the risk of kidney cancer and ischaemic heart disease.

Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study.

A cohort of 11,580 residents of a retirement community initially free from cancer were followed from 1981 to 1989. A total of 1,335 incident cancer cases were diagnosed during the period. Relative risks of cancer were calculated for baseline consumption of vegetables, fruits, beta-carotene, dietary vitamin C, and vitamin supplements. After adjustment for age and smoking, no evidence of a protective effect was found for any of the dietary variables in men. However, an inverse association was observed between vitamin C supplement use and bladder cancer risk. In women, reduced cancer risks of all sites combined and of the colon were noted for combined intake of all vegetables and fruits, fruit intake alone, and dietary vitamin C. Supplemental use of vitamins A and C showed a protective effect on colon cancer risk in women. There was some suggestion that beta-carotene intake and supplemental use of vitamin A, C, and E were associated with reduced risk of lung cancer in women, but none of these results were statistically significant. These inverse associations observed in women seem to warrant further investigation, although there was inconsistency in results between the sexes.

Postmenopausal oestrogen treatment and stroke: a prospective study.

STUDY OBJECTIVE--To determine whether post-menopausal oestrogen use affects the risk of dying from stroke. DESIGN--Postal questionnaire survey to elicit details of oestrogen replacement therapy and potential risk modifiers. SETTING--Californian retirement community. PARTICIPANTS--All 22,781 residents of community (white, affluent, well educated) contacted by mail and phone; 13,986 (61%, median age 73) responded, including 8882 women. These formed cohort for mortality follow up, using health department death certification. Only 13 lost to follow up, apparently not deceased, but 34 excluded because no information on oestrogen use. INTERVENTIONS--None. END POINT--Mortality rate from stroke compared in women who did and did not receive oestrogen replacement treatment. MEASUREMENTS AND MAIN RESULTS--Age adjusted mortality rates were computed using internal standard and four age groups. By January 1987 there had been 1019 deaths in the cohort. Twenty out of 4962 women who used oestrogen replacement treatment died from stroke compared with 43 out of 3845 women who did not use oestrogen replacement treatment: relative risk 0.53, 95% confidence interval 0.31 to 0.91. Protection was found in all age groups except the youngest and was unaffected by adjustment for possible confounding factors (hypertension, smoking, alcohol, body mass index, exercise). CONCLUSIONS--Oestrogen replacement treatment protects against death due to stroke.

MENOPAUSAL OESTROGEN THERAPY AND PROTECTION FROM DEATH FROM ISCHAEMIC HEART DISEASE

The medical records of a Los Angeles retirement community were examined to find out the association between oestrogen replacement therapy and death from ischaemic heart disease. Women dying from ischaemic heart disease over a five-year period were compared with living and deceased control groups; both controls were matched with cases for date of birth, date of entry into the community, race, and socioeconomic status. The deceased control was also matched for date of death. Compared with living controls cases using conjugated oestrogens had a risk ratio for death from ischaemic heart disease of 0.43 (95% confidence interval 0.24-0.75). Comparison with deceased controls gave a similar relative risk. This association was not due to identifiable confounding factors. Other risk factors for ischaemic heart disease, including hypertension, diabetes, stroke, angina pectoris, and heavy cigarette smoking, were confirmed by this study.

Estrogen replacement therapy and protection from acute myocardial infarction

As part of a longitudinal study of a southern California retirement community begun in June 1981, 8841 women 44 to 101 years old completed a health survey questionnaire. As of January 1, 1987, 1019 deaths had occurred among these women, who had contributed 40,919 years of follow-up. Women who had used estrogen replacement therapy had a relative risk of death due to all causes of 0.80 compared with women who had never used estrogens (p = 0.0005). Much of this reduced mortality rate was due to a marked reduction in the death rate of acute myocardial infarction among users of estrogen (55 deaths) compared with nonusers (94 deaths; relative risk = 0.59, p = 0.002). This lower acute myocardial infarction death rate was maintained even in the presence of other known risk factors for coronary artery disease. There was no substantial effect of dose or duration of estrogen use on risk, but the relatively small number of deaths limited our ability to estimate these effects accurately. Current users (those who were using estrogen at the time of the initial questionnaire) had a relative risk of 0.47 and past users had a risk of 0.62 compared with women who had never used estrogen (p = 0.003 for trend). A reduced hospitalization rate for acute myocardial infarction was similarly observed for estrogen users compared with nonusers (relative risk = 0.72, p = 0.03).

Dementia Incidence Continues to Increase with Age in the Oldest Old The 90+ Study

The oldest old are the fastest growing segment of the US population, and accurate estimates of dementia incidence in this group are crucial for healthcare planning. Although dementia incidence doubles every 5 years from ages 65 to 90 years, it is unknown if this exponential increase continues past age 90 years. Here, we estimate age‐ and sex‐specific incidence rates of all‐cause dementia in people aged 90 years and older, including estimates for centenarians.