Adult Health Study Cohort Research Articles

Radiation effects on atherosclerosis in atomic bomb survivors: a cross\u2010sectional study using structural equation modeling

Past reports indicated that total-body irradiation at low to moderate doses could be responsible for cardiovascular disease risks, but the mechanism remains unclear. The purpose of this study was to investigate the association between radiation exposure and atherosclerosis, an underlying pathology of cardiovascular diseases, in the Japanese atomic bomb survivors. We performed a cross-sectional study measuring 14 clinical-physiological atherosclerosis indicators during clinical exams from 2010 to 2014 in 3274 participants of the Adult Health Study cohort. Multivariable analyses were performed by using a structural equation model with latent factors representing underlying atherosclerotic pathologies: (1) arterial stiffness, (2) calcification, and (3) plaque as measured with indicators chosen a priori on the basis of clinical-physiological knowledge. Radiation was linearly associated with calcification (standardized coefficient per Gy 0.15, 95 % confidence interval: CI [0.070, 0.23]) and plaque (0.11, 95 % CI [0.029, 0.20]), small associations that were comparable to about 2 years of aging per Gy of radiation exposure, but not with arterial stiffness (0.036, 95 % CI [− 0.025, 0.095]). The model fitted better and had narrower confidence intervals than separate ordinary regression models explaining individual indicators independently. The associations were less evident when the dose range was restricted to a maximum of 2 or 1 Gy. By combining individual clinical-physiological indicators that are correlated because of common, underlying atherosclerotic pathologies, we found a small, but significant association of radiation with atherosclerosis.

Causal mediation analysis in nested case-control studies using conditional logistic regression.

The paper proposes an approach to causal mediation analysis in nested case-control study designs, often incorporated with countermatching schemes using conditional likelihood, and we compare the method's performance to that of mediation analysis using the Cox model for the full cohort with a continuous or dichotomous mediator. Simulation studies are conducted to assess our proposed method and investigate the efficiency relative to the cohort. We illustrate the method using actual data from two studies of potential mediation of radiation risk conducted within the Adult Health Study cohort of atomic-bomb survivors. The performance becomes comparable to that based on the full cohort, illustrating the potential for valid mediation analysis based on the reduced data obtained through the nested case-controldesign.

Reaction Time as a Predictor of Mortality

We investigated the association between reaction time (RT) and mortality in middle-aged and older atomic bomb survivors and their unexposed controls over a period of 30 years. During 1970-72, 4912 participants of the Adult Health Study cohort in Hiroshima, Japan, underwent biologic tests including RT. Mortality was followed to the end of 2003. In a multivariate-adjusted model, the hazard ratio (HR) for 1-standard deviation increments of RT was 1.08 (95% confidence interval [CI]=1.03-1.13) for men, 1.22 (95% CI=1.16-1.28) for women, and 1.13 (95% CI=1.09-1.16) for all. When the analysis was performed by sex, age, and follow-up period, a consistent increase of mortality with increments of RT was observed. The HR for mortality for the highest RT quintile was higher than that of the lowest quintile in all sex-age groups. A significant positive association between mortality risk and RT was observed even after 20 years of follow-up (p=.03 in men, p<.001 in women). RT and radiation dose were risk factors for mortality independent of conventional risk factors such as smoking, high blood pressure, and diabetes mellitus. Interaction between RT and radiation dose had no significant effect on mortality in men. Although increased radiation dose reduced the HR for mortality per RT increment in women, RT and radiation dose were still significant predictors of mortality. RT is a consistently strong predictor of mortality. Although mortality risk increased with radiation dose, radiation did not accelerate the relationship between RT and mortality.

Body iron stores and breast cancer risk in female atomic bomb survivors

Iron can be a potent pro-oxidant and, on this basis, elevated body iron may increase the risk of cancer. Although epidemiological evidence is mixed, there is overall support for this possibility. In addition, because of this same oxidative capacity, body iron levels may alter radiation sensitivity. In the present study, a nested case-control study of breast cancer was conducted in Japanese atomic bomb survivors. Stored serum samples from the Adult Health Study cohort were assayed for ferritin levels and joint statistical analyses were conducted of ferritin and radiation dose on the risk of breast cancer. Serum ferritin is the best feasible indicator of body iron levels in otherwise healthy people. A total of 107 cases and 212 controls were available for analysis. The relative risk (RR) of breast cancer for a 1 log unit increase in ferritin was 1.4 (95% confidence interval 1.1-1.8). This translates to an RR of 1.64 comparing high and low values of the interquartile range among controls (58 and 13.2 ng/mL, respectively). The results support the hypothesis that elevated body iron stores increase the risk of breast cancer. However, the study was inconclusive regarding the question of whether body iron alters radiation-induced breast cancer risk.

Incidence of dementia among atomic-bomb survivors — Radiation Effects Research Foundation Adult Health Study

Radiotherapy has been reported to cause neuropsychological dysfunction. Here we examined whether exposure to atomic bomb radiation affected the incidence of dementia among 2286 atomic bomb survivors and controls — all members of the Adult Health Study cohort. Study subjects were non-demented and aged ≥ 60 years at baseline examination and had been exposed in 1945 at ≥ 13 years of age to a relatively low dose (≤ 4 Gy), compared with total dose from radiotherapy. Dementia diagnoses were made during biennial health examinations with a two-phase procedure. DSM IV criteria were used for diagnosing dementia, NINCDS-ADRDA for Alzheimer disease, and NINDS-AIREN for vascular disease. To estimate the effect of radiation on the dementia incidence rate, we applied Poisson regression analysis. Incidence per 1000 person–years was 16.3 in the < 5 mGy group, 17.0 in the 5–499 mGy group, and 15.2 in the ≥ 500 mGy group. Alzheimer disease was the predominant type of dementia in each dose category. After adjustment for potential risk factors, radiation exposure did not affect the incidence rate of either all dementia or any of its subtypes. No case of dementia had a history of therapeutic cranial irradiation. Although we found no relationship between radiation exposure and the development of dementia among atomic bomb survivors exposed at ≥ 13 years old in this longitudinal study, effects on increased risk of early death among atomic bomb survivors will be considered.

Validation of a food frequency questionnaire in the Hiroshima/Nagasaki Life Span Study.

We evaluated the performance of a 22-item food frequency questionnaire (FFQ) administered in 1980-81 to 3,005 members of the Adult Health Study cohort, part of the Life Span Study. The questionnaire was compared with the records of a 24-hour dietary survey that was performed in 1984-85. From the dietary records, food and nutrient intakes were estimated. The association between the two measures of dietary intake was assessed using Mantel-Haenszel chi-square test and the Spearman's rank correlation coefficient. The frequency of food intake as measured by the FFQ was linearly associated with food intake as measured by the 24-hour diary, with the exception of dry fish. The highest correlations were observed for beverages, including coffee (0.51), milk (0.32) and black tea (0.26). Foods such as fruit (0.27), confectionery (0.23), rice (0.34) and bread (0.28) were also moderately correlated. These results show that, with the exception of dry fish, the FFQ is moderately correlated with the 24-hour diary and can be used to assess diet intake in this cohort.

Prevalence and risks of dementia in the Japanese population: RERF's adult health study Hiroshima subjects. Radiation Effects Research Foundation.

To study the prevalence rate of dementia and its subtypes in Japan and to investigate the relationship of risk factors, such as demographic features and disease history, to the prevalence of Alzheimer's disease or vascular dementia. A prevalence study within a longitudinal cohort study. The original Adult Health Study (AHS) cohort consisted of atomic-bomb survivors and their controls selected from residents in Hiroshima and Nagasaki using the 1950 national census supplementary schedules and the Atomic Bomb Survivors Survey. Since 1958, the AHS subjects have been followed through biennial medical examinations. Subjects were 637 men and 1585 women aged 60 years or older in the AHS cohort. Forty-eight subjects resided in hospitals and institutions. In addition to the biennial medical examinations ongoing since 1958, a screening test for cognitive impairment (CASI) was conducted by trained nurses between September 1992 and September 1996. The prevalence of dementia and its subtypes was assessed in 343 subjects suspected to have dementia and in 272 subjects with high CASI scores who were selected randomly. The prevalence of dementia based on DSM III/R criteria, using neurological examination, the IQCODE, and CDR > or = 1, was 7.2%. The prevalence of Alzheimer's disease was 2.0% in men and 3.8% in women, and the prevalence of vascular dementia was 2.0% in men and 1.8% in women. The relationship of risk factors to Alzheimer's disease or vascular dementia was investigated by the multivariate logistic linear regression analysis. Odds ratios of Alzheimer's disease for age (in 10-year increments), attained education (in 3-year increments), history of head trauma, and history of cancer are 6.3, 0.6, 7.4, and 0.3, respectively. Odds ratios of vascular dementia for age, history of stroke, and history of hypertension are 2.0, 35.7, and 4.0, respectively. Neither type of dementia showed any significant effect of sex or radiation exposure. This study is the first study of Japanese dementia rates carried out with a protocol similar enough to that of a US study to allow meaningful comparisons. The prevalence rates demonstrated are more similar to US rates than were found in many previous reports in Japan.

28 Vascular dementia: Is there a link to Alzheimer's disease? Pathoanatomical considerations

Radiotherapy has been reported to cause neuropsychological dysfunction. Here we examined whether exposure to atomic bomb radiation affected the incidence of dementia among 2286 atomic bomb survivors and controls — all members of the Adult Health Study cohort. Study subjects were non-demented and aged ≥ 60 years at baseline examination and had been exposed in 1945 at ≥ 13 years of age to a relatively low dose (≤ 4 Gy), compared with total dose from radiotherapy. Dementia diagnoses were made during biennial health examinations with a two-phase procedure. DSM IV criteria were used for diagnosing dementia, NINCDS-ADRDA for Alzheimer disease, and NINDS-AIREN for vascular disease. To estimate the effect of radiation on the dementia incidence rate, we applied Poisson regression analysis. Incidence per 1000 person–years was 16.3 in the < 5 mGy group, 17.0 in the 5–499 mGy group, and 15.2 in the ≥ 500 mGy group. Alzheimer disease was the predominant type of dementia in each dose category. After adjustment for potential risk factors, radiation exposure did not affect the incidence rate of either all dementia or any of its subtypes. No case of dementia had a history of therapeutic cranial irradiation. Although we found no relationship between radiation exposure and the development of dementia among atomic bomb survivors exposed at ≥ 13 years old in this longitudinal study, effects on increased risk of early death among atomic bomb survivors will be considered.

Osteoporosis and Associated Bone Fractures in a Japanese Population

Along with the lengthening life span, maintaining good quality of life in the elderly is an important goal. We determined frequency and risk factors for osteoporosis and associated fractures among a Japanese cohort in Hiroshima and Nagasaki, known as the Adult Health Study (AHS). We found lower bone mass and a higher vertebral fracture prevalence among Japanese women, compared to women of Japanese descent living in Hawaii and American Caucasians. However, the incidence of vertebral fracture has decreased progressively among successive younger Japanese birth cohorts. These findings suggested that environmental factors probably play an important role on occurrence of osteoporosis and vertebral fracture. Age, sex, weight, menstrual history, and calcium intake were associated with bone mass and vertebral fracture prevalence. From the AHS cohort study, age, body mass index, age at menarche, and number of children, milk intake, alcohol intake, and prevalent vertebral fracture were related to the risk of hip fracture. Risk factors for falls, such as alcohol consumption, may be responsible for occurrence of hip fracture in addition to the risk factors related to bone mass. Elucidating risk factors related to bone mass, bone quality, and falls may lead to new strategies for preventing osteoporosis and associated fractures. J Epidemiol, 1996 ; 6 : S225-S229.

Thyroid Diseases Among Atomic Bomb Survivors in Nagasaki

To elucidate the current thyroid disease status for the Nagasaki Adult Health Study cohort of the Radiation Effects Research Foundation. Survey study. Nagasaki, Japan. Cohort members of the Nagasaki Adult Health Study who received biennial health examinations from October 1984 to April 1987 (n = 2856). A total of 2587 subjects remained after exclusion of persons exposed in Hiroshima or in utero and those who were not in Nagasaki at the time of the bombing. Thyroid radiation dose by the dosimetry system established in 1986 was available for 1978 of the 2587 subjects. Thyroid diseases were diagnosed using uniform procedures including ultrasonic scanning. The relationship of the prevalence of each thyroid disease with thyroid radiation dose, sex, and age was analyzed using logistic models. A significant dose-response relationship was observed for solid nodules, which include cancer, adenoma, adenomatous goiter, and nodules without histological diagnosis, and for antibody-positive spontaneous hypothyroidism (autoimmune hypothyroidism) but not for other diseases. The prevalence of solid nodules showed a monotonic dose-response relationship, yet that of autoimmune hypothyroidism displayed a concave dose-response relationship reaching a maximum (+/- SE) level of 0.7 +/- 0.2 Sv. The present study confirmed the results of previous studies by showing a significant increase in solid nodules with dose to the thyroid and demonstrated for the first time a significant increase in autoimmune disease among atomic bomb survivors. A concave dose-response relationship indicates the necessity for further studies on the effects of relatively low doses of radiation on thyroid disease.

Thyroid diseases among atomic bomb survivors in Nagasaki

<h3>Objective.</h3> —To elucidate the current thyroid disease status for the Nagasaki Adult Health Study cohort of the Radiation Effects Research Foundation. <h3>Design.</h3> —Survey study. <h3>Setting.</h3> —Nagasaki, Japan. <h3>Participants.</h3> —Cohort members of the Nagasaki Adult Health Study who received biennial health examinations from October 1984 to April 1987 (n=2856). A total of 2587 subjects remained after exclusion of persons exposed in Hiroshima or in utero and those who were not in Nagasaki at the time of the bombing. Thyroid radiation dose by the dosimetry system established in 1986 was available for 1978 of the 2587 subjects. <h3>Main Outcome Measures.</h3> —Thyroid diseases were diagnosed using uniform procedures including ultrasonic scanning. The relationship of the prevalence of each thyroid disease with thyroid radiation dose, sex, and age was analyzed using logistic models. <h3>Results.</h3> —A significant dose-response relationship was observed for solid nodules, which include cancer, adenoma, adenomatous goiter, and nodules without histological diagnosis, and for antibody-positive spontaneous hypothyroidism (autoimmune hypothyroidism) but not for other diseases. The prevalence of solid nodules showed a monotonic dose-response relationship, yet that of autoimmune hypothyroidism displayed a concave dose-response relationship reaching a maximum (±SE) level of 0.7±0.2 Sv. <h3>Conclusions.</h3> —The present study confirmed the results of previous studies by showing a significant increase in solid nodules with dose to the thyroid and demonstrated for the first time a significant increase in autoimmune disease among atomic bomb survivors. A concave dose-response relationship indicates the necessity for further studies on the effects of relatively low doses of radiation on thyroid disease. (<i>JAMA</i>. 1994;272:364-370)

Aneuploidy in somatic cells of in utero exposed A-bomb survivors in Hiroshima.

Cytogenetic data on cultured lymphocytes of the in utero exposed A-bomb survivors in the RERF Adult Health Study cohort have been analyzed using the G-banding technique to determine the frequency of aneuploid cells. The data consist of blood samples collected between 1985 and 1987 from 264 Hiroshima individuals for whom DS86 maternal uterine dose estimates are available: 124 proximally exposed (74 males and 50 females) with an estimated dose of 0.005 Sv or more, and 140 distally exposed (76 males and 64 females) with a dose estimate of 0 Sv, assuming the neutron relative biological effectiveness (RBE) of 10. A main feature of aneuploidy was that aneuploid frequency in autosomes depended generally on chromosome length; aneuploidies were significantly more frequent in shorter chromosomes than in longer chromosomes. The frequency of aneuploidies also depended on type, with chromosome loss approximately five times more frequent than chromosome gain. However, chromosome 21, as well as the sex chromosomes, were notable in that aneuploidy was much more frequent for these chromosomes than would be predicted from a simple relationship with length. X chromosome aneuploidies were significantly more frequent in females than in males. There was no dependence of aneuploid frequencies on dose when measured 40 years after the exposure.