Using census data and birth certificates to reconstruct the early-life socioeconomic environment and the relation to the development of Alzheimer's disease.

The early-life environment and its effect on growth and maturation of children and adolescents are associated with several adult chronic diseases, including Alzheimer's disease. Because it is not feasible to collect information prospectively over the average life span, methods to reconstruct the early-life environment of the aged are necessary to evaluate these associations. In a community-based case-control study conducted in the United States, we collected U.S. census records and birth certificates to reconstruct the early-life socioeconomic environment of each elderly subject. Information was found on 82% of the available Alzheimer's disease cases (239 of 292) and 87% of the available controls (245 of 282). We investigated risk of Alzheimer's disease associated with father's occupation, parental age, household size, sibship size, and birth order. Subjects whose fathers were unskilled manual workers or laborers were at higher risk for Alzheimer's disease (odds ratio = 1.80, 95% confidence interval = 1.19--2.73). The risk of Alzheimer's disease was increased with increasing number of people in the household. We also evaluated whether subjects with the apolipoprotein epsilon 4 allele (APOE epsilon 4), a strong genetic risk factor that is not a necessary cause or a sufficient cause by itself for the development of Alzheimer's disease, were at higher risk than subjects who did not carry this allele. Among subjects with the APOE epsilon 4 allele whose fathers held lower-socioeconomic level occupations, the odds of developing Alzheimer's disease were higher (odds ratio = 2.35, 95% confidence interval = 1.07--5.16) compared with subjects without the allele (odds ratio = 1.40, 95% confidence interval = 0.78--2.52). Subjects carrying the APOE epsilon 4 allele alone have a threefold increased risk of Alzheimer's disease (odds ratio = 3.17, 95% confidence interval = 1.99--5.04). Compared with subjects with neither risk factor, subjects with both the genetic and the environmental risk factors (household size of seven or more and father's occupation being manual) had a relatively high risk of Alzheimer's disease (odds ratio = 14.8, 95% confidence interval = 4.9--46). The data suggest that APOE epsilon 4 may modify the associations between father's occupation, other early-life environmental factors, and development of Alzheimer's disease in late life.

Early-life risk factors and the development of Alzheimer's disease.

OBJECTIVE: To investigate the association of early-life factors with AD. BACKGROUND: The early-life environment and its effect on growth and maturation of children and adolescents are linked to many adult chronic diseases (heart disease, stroke, hypertension, and diabetes mellitus), and these effects are also linked to maternal reproduction. AD may have an early-life link. The areas of the brain that show the earliest signs of AD are the same areas of the brain that take the longest to mature during childhood and adolescence. A poor-quality childhood or adolescent environment could prevent the brain from reaching complete levels of maturation. Lower levels of brain maturation may put people at higher risk for AD. METHODS: In a community-based case-control study (393 cases, 377 controls), we investigated the association of early-life factors and AD. Early-life variables include mother's age at patient's birth, birth order, number of siblings, and area of residence before age 18 years. Patient education level and apolipoprotein E (APOE) genotypes were also included in the analysis. RESULTS: Area of residence before age 18 years and number of siblings are associated with subsequent development of AD. For each additional child in the family the risk of AD increases by 8% (OR = 1.08, 95% CI = 1.01 to 1.15). More controls compared with cases grew up in the suburbs (OR = 0.45, 95% CI = 0.25 to 0.82). APOE epsilon 4 and the patient's education level did not confound or modify the associations. CONCLUSIONS: The early-life childhood and adolescent environment is associated with the risk of AD.

Ten-year risk of false positive screening mammograms and clinical breast examinations.

BACKGROUND: The cumulative risk of a false positive result from a breast-cancer screening test is unknown. METHODS: We performed a 10-year retrospective cohort study of breast-cancer screening and diagnostic evaluations among 2400 women who were 40 to 69 years old at study entry. Mammograms or clinical breast examinations that were interpreted as indeterminate, aroused a suspicion of cancer, or prompted recommendations for additional workup in women in whom breast cancer was not diagnosed within the next year were considered to be false positive tests. RESULTS: A total of 9762 screening mammograms and 10,905 screening clinical breast examinations were performed, for a median of 4 mammograms and 5 clinical breast examinations per woman over the 10-year period. Of the women who were screened, 23.8 percent had at least one false positive mammogram, 13.4 percent had at least one false positive breast examination, and 31.7 percent had at least one false positive result for either test. The estimated cumulative risk of a false positive result was 49.1 percent (95 percent confidence interval, 40.3 to 64.1 percent) after 10 mammograms and 22.3 percent (95 percent confidence interval, 19.2 to 27.5 percent) after 10 clinical breast examinations. The false positive tests led to 870 outpatient appointments, 539 diagnostic mammograms, 186 ultrasound examinations, 188 biopsies, and 1 hospitalization. We estimate that among women who do not have breast cancer, 18.6 percent (95 percent confidence interval, 9.8 to 41.2 percent) will undergo a biopsy after 10 mammograms, and 6.2 percent (95 percent confidence interval, 3.7 to 11.2 percent) after 10 clinical breast examinations. For every 100 dollars spent for screening, an additional 33 dollars was spent to evaluate the false positive results. CONCLUSIONS: Over 10 years, one third of women screened had an abnormal test result that required additional evaluation, even though no breast cancer was present. Techniques are needed to decrease false positive results while maintaining high sensitivity. Physicians should educate women about the risk of a false positive result from a screening test for breast cancer.

Breast carcinoma tumor characteristics in black and white women.

BACKGROUND: A significant disparity in mortality rates exists between black and white patients with breast carcinoma. This study was designed to compare breast carcinoma tumor characteristics by race and to examine the possible reasons for these differences. METHODS: Female patients with an initial diagnosis of breast carcinoma between January 1, 1985 and December 31, 1993 were selected from the Yale-New Haven Hospital Tumor Registry for this retrospective cohort study. All black patients were eligible and white patients were selected randomly and matched to each black patient by year of diagnosis. Data were gathered from multiple sources including the hospital, the Connecticut Tumor Registry, and the U. S. Census. All pathology specimens were reviewed at Yale-New Haven Hospital. RESULTS: The final cohort had 100 black and 300 white patients. The black patients tended to be younger than white patients at the time of diagnosis (mean age 55 years vs. 60 years; P = 0.001). A significant racial difference was noted in eight tumor characteristics: stage, size of the tumor, lymph node status, presence of necrosis, vascular/lymphatic invasion, ductal carcinoma in situ, perineural invasion, and progesterone receptor status. Although income, medical insurance coverage, and method of tumor detection explained some pathology differences, black patients still were more likely to have necrosis and a larger tumor size, even after adjustment. CONCLUSIONS: Black patients with breast carcinoma tend to be diagnosed at a younger age and in a few important respects have different tumor characteristics compared with white patients, even after controlling for income, medical insurance coverage, and method of tumor detection after screening mammography. These differences may have etiologic and clinical implications.

Abnormal body fat distribution detected by computed tomography in diabetic men.

Previous studies of body fat using tape measurement of body circumference and hand-held caliper skinfold measurements have suggested abnormal fat distribution in patients with diabetes mellitus. These methods, however, have high interobserver variability and cannot assess intra-abdominal fat independent of subcutaneous fat. We used computed tomography to evaluate body fat distribution in a group of 53 Japanese-American men of similar age and body mass index (weight divided by height squared). As determined by a 75-g oral glucose tolerance test, 29 subjects had type II diabetes and 24 were normal. Computed tomography cuts were obtained at three body levels to measure thorax, abdomen, and thigh subcutaneous fat area as well as intra-abdominal fat area. We found greater intra-abdominal fat in men with diabetes than in those without (123.74 vs. 95.54 cm2, P = 0.034) and a greater ratio of thorax to thigh subcutaneous fat (2.55 vs. 1.88, P = 0.016). These findings support the hypothesis that fat in different areas of the body differs metabolically. Computed tomography can be a useful tool for investigating whether abnormal body fat distribution is associated with the pathogenesis of abnormal glucose tolerance.