Hideo Sasaki

The Cognitive Abilities Screening Instrument (CASI): A Practical Test for Cross-Cultural Epidemiological Studies of Dementia

The Cognitive Abilities Screening Instrument (CASI) has a score range of 0 to 100 and provides quantitative assessment on attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, list-generating fluency, abstraction, and judgment. Scores of the Mini-Mental State Examination, the Modified Mini-Mental State Test, and the Hasegawa Dementia Screening Scale can also be estimated from subsets of the CASI items. Pilot testing conducted in Japan and in the United States has demonstrated its cross-cultural applicability and its usefulness in screening for dementia, in monitoring disease progression, and in providing profiles of cognitive impairment. Typical administration time is 15 to 20 minutes. Record form, manual, videotape of test administration, and quizzes to qualify potential users on the administration and scoring of the CASI are available upon request.

Prevalence and risks of dementia in the Japanese population : RERF's adult health study Hiroshima subjects

OBJECTIVES: 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 Alzheimers disease or vascular dementia.

Noncancer disease incidence in the atomic bomb survivors : 1958-1986

Using the longitudinal data of the Adult Health Study (AHS) cohort collected during 1958-1986, we examined for the first time the relationship between exposure to ionizing radiation and the incidence of 19 nonmalignant disorders in the A-bomb survivors. Affected individuals were ascertained through the three-digit codes of the International Classification of Diseases which are encoded in the AHS database subsequent to diagnoses made on the basis of general laboratory tests, physical examinations, and history-taking conducted during biennial AHS examinations. The disease onset time was estimated using the mid-point between the AHS examination data when the disease was initially reported and the previously attended disease-free examination date. Dosimetry System 86 organ doses judged to be most appropriate were used. Tests of dose effects were performed assuming a linear relative risk model with stratified background incidence. For the entire study period, significant excess risk was detected for uterine myoma (P < 0.001), chronic liver disease and cirrhosis (P = 0.006), and thyroid disease (P < 0.0001), defined broadly as the presence of one or more of certain noncancerous thyroid conditions. The incidence of myocardial infarction was shown to be increased (P = 0.03) in later years (1968-1986) among the younger heavily exposed AHS subjects, confirming the results of the recent Life Span Study (LSS) noncancer mortality report on coronary heart disease. The findings for uterine myoma may serve as additional evidence indicating benign tumor growth as a possible consequence of radiation exposure. Our results indicating the involvement of radiation in the development of liver diseases are consistent with the report of increased mortality from liver cirrhosis with radiation dose in the LSS cohort. An effect of age at exposure was detected for nonmalignant thyroid disease (P = 0.02), with an increased risk for those exposed who were under 20 years of age, but not for older survivors. Thus the AHS data suggest that thyroid glands in the young are more radiosensitive not only to the development of malignancies, but also to the development of nonmalignant disorders as well. The findings hold independently of the dose effects observed for thyroid cancer. This study also shows that for the period 1958-1986 new occurrences of lens opacity are not increased with radiation dose (P = 0.39) in the AHS subjects.

Effects of Radiation on the Longitudinal Trends of Total Serum Cholesterol Levels in the Atomic Bomb Survivors

The effects of radiation on the long-term trends of the total serum cholesterol levels of the Hiroshima and Nagasaki atomic bomb survivors were examined using data collected in the Adult Health Study over a 28-year period (1958-1986). The growth-curve method was used to model the longitudinal age-dependent changes in cholesterol levels. For each sex, temporal trends of cholesterol levels were characterized with respect to age, body mass index, city and birth year. We then examined whether the temporal trends differed by radiation dose. We showed that the mean growth curve of cholesterol levels for the irradiated subjects were significantly higher than that for the unirradiated subjects, and that the increase was greater for women than for men. No difference in dose response was detected between Hiroshima and Nagasaki. An increased mean level of cholesterol was evident for irradiated women in general, but a notable increase was apparent in males only for the youngest birth cohort of 1935-1945. The difference in the mean cholesterol levels between the irradiated and unirradiated subjects diminished past 70 years of age. It is not known whether this is due to natural progression or is an artifact of nonrandom variation in the rate of participation in the examinations. The maximum predicted increase at 1 Gy for women occurred at age 52 years for the 1930 cohort: 2.5 mg/dl (95% CI 1.6-3.3 mg/dl) for Hiroshima and 2.3 mg/dl (95% CI 1.5-3.1 mg/dl) for Nagasaki. The corresponding increase for men occurred at age 29 years for the 1940 cohort: 1.6 mg/dl (95% CI 0.4-2.8) for Hiroshima and 1.4 mg/dl (95% CI 0.3-2.6) for Nagasaki. Controlling for cigarette smoking did not alter the dose-response relationship. Although the difference in the mean growth curves of the irradiated and unirradiated groups was statistically significant, there was a considerable overlap in the individual growth curves of the two groups. The significant sex difference and the greater magnitude of radiation effects in women suggest that hormonal changes resulting from radiation exposure, such as accelerated menopause, is an area worth investigating to delineate the mechanisms underlying the increased cholesterol levels of the irradiated female subjects. This increase may also partially explain the increased rate of coronary heart disease seen in the atomic bomb survivors.

Longitudinal trends in total serum cholesterol levels in a Japanese cohort, 1958–1986

The 28-year follow-up of a Japanese cohort, having collected vast amounts of data collected on total serum cholesterol (TC), provided an exceptional opportunity to examine TC temporal trends. The longitudinal statistical method of growth-curve analysis was used to elucidate the age-related changes in TC levels and to characterize these trends in relation to sex, birth cohort, time period, place of residence, and body mass index (BMI). Japanese TC levels at initial examination were remarkably lower than those in western countries. During the study period from 1958 to 1986, TC levels increased dramatically with age in both sexes. The slope of the cholesterol growth curve was steeper for women than for men, with the difference growing larger after age 40 years. Drastic changes in Japanese behavior and lifestyle, especially westernization of the diet, are thought to have affected the TC values as time-period effects. As a result of this temporal change, which affected different cohorts at different ages, TC values were higher in members of the younger cohort. The increase of the TC values as time-period effects were larger in earlier period than in later period. These time-period effects appeared to be almost similar in men and women. The TC growth curves also varied by city of residence. Subjects in urban areas had higher TC values than subjects in rural areas. Changes associated with BMI from 1958 to 1986 were only partially responsible for the increased steepness of the TC growth curve.

The incidence of thoracic vertebral fractures in a Japanese population, Hiroshima and Nagasaki, 1958–1986

The incidence of thoracic vertebral fractures (TVF) in a Japanese population of 14,607 individuals from Hiroshima and Nagasaki was determined by sex, age, birth cohort, and exposure to atomic bomb radiation. The diagnosis of TVF was based on lateral chest radiographs made from 1 July 1958 to 28 February 1986. The subjects, who were born between 1880 through 1939, were categorized by sex into 10-year birth cohorts. TVF incidence increased by a factor of 1.7 in all birth cohorts with each 10-year increase in age in females, but did not increase with age in males. The incidence was significantly lower in the younger birth cohorts in both sexes. The incidence declined by a factor of 0.5 in males and 0.6 in females for each 10-year decrease in the year of birth. TVF incidence did not differ between the cities, and no correlation with atomic bomb radiation exposure was demonstrated.

Levels of parathyroid hormone and calcitonin in serum among atomic bomb survivors

To examine the potential causes of increased levels of calcium in serum with increasing dose of atomic bomb radiation, which was obtained from the previous preliminary analysis, levels of parathyroid hormone (PTH) and calcitonin in serum were examined among 1459 subjects in Hiroshima and Nagasaki. A significant effect of radiation on levels of calcium, PTH and calcitonin in serum was found, even after patients with hyperparathyroidism were excluded. The level of calcium in serum increased with radiation dose; this can be explained partly by the increase in the level of PTH with radiation dose. However, the dose effect on calcium remained even after adjustment for PTH, calcitonin and confounding factors such as renal function, serum albumin level and medication. Parathyroid hormone increased initially by 6.8% per gray, but the dose response leveled off after about 1 Gy. The level of calcitonin increased with radiation dose, probably in part due to feedback mechanisms stimulated by the increase in calcium. However, after adjustment for the level of calcium, the increase in the level of calcitonin with dose was still found. Although the etiological mechanisms of the effect of radiation on serum levels of calcium, PTH and calcitonin are unclear, radiation exposure may affect secretion of PTH and calcitonin and regulation of calcium a long time after atomic bomb exposure.

Study of Cognitive Function among the Adult Health Study (AHS) Population in Hiroshima and Nagasaki

Abstract Yamada, M., Sasaki, H., Kasagi, F., Akahoshi, M., Mimori, Y., Kodama, K. and Fujiwara, S. Study of Cognitive Function among the Adult Health Study (AHS) Population in Hiroshima and Nagasaki. Radiat. Res. 158, 236–240 (2002). Although neuropsychological dysfunction is found among A-bomb survivors exposed in utero as it is among patients who receive central nervous system radiotherapy, neuropsychological examinations have not been conducted on the survivors. Its prevalence may be increased as a result of the increased rate of strokes reported among those exposed to a high radiation dose. In this study, we examined the effects of radiation exposure on cognitive function among adult survivors in the Adult Health Study (AHS). The study subjects were men and women born prior to September 1932 who had undergone biennial examinations during the period 1992–1996 in Hiroshima or 1993–1998 in Nagasaki. We evaluated cognitive performance for 3,113 subjects with the Cognitive Abilities Screening Instrument (CASI), and we examined the relationship between cognitive performance and potentially related factors (sex, age, city where the subjects were exposed, years of education, and radiation dose). In contrast to exposure to radiotherapy, exposure to atomic bomb radiation had no apparent effect on cognitive function. Factors that did affect cognitive function were age, sex, city and years of education. Further investigation, including examination of other neurological functions, is required before a final conclusion regarding radiation-induced neurological dysfunction can be reached.

Incidence and risks of dementia in Japanese women: Radiation Effects Research Foundation Adult Health Study.

BACKGROUND Although dementia has a great impact on public health, there are few reports on dementia incidence and risk factors for Asian populations. OBJECTIVES To determine incidence and risk factors of dementia, Alzheimer disease (AD), and vascular dementia (VaD) among Japanese women. METHODS Between 1992 and 1996, 1637 non-demented women aged > or =60 years were followed for an average of 5.9 years in RERFs Adult Health Study. Dementia diagnoses were made during biennial health examinations using a two-phase procedure. DSM IV criteria were used for diagnosing dementia, NINCDS-ADRDA for AD, and NINDS-AIREN for VaD. Potential risk factors were analyzed using Poisson regression analysis. RESULTS 161 cases of dementia (109 of AD and 56 of VaD, based on individual criteria) were newly diagnosed. Incidence increased dramatically with age, especially for AD. Probable AD decreased with increasing education level. Probable VaD was significantly associated with hypertension and stroke. Age at menopause did not show any effect on dementia. All dementia and probable AD were significantly associated with grip strength. CONCLUSIONS AD is predominant in dementia incidence among Japanese women. Modification of stroke risk factors and improvement of physical fitness may help prevent dementia.

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 >or=60 years at baseline examination and had been exposed in 1945 at >or=13 years of age to a relatively low dose (<or=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 >or=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 >or=13 years old in this longitudinal study, effects on increased risk of early death among atomic bomb survivors will be considered.