A functional polymorphism within the mu-opioid receptor gene and risk for abuse of alcohol and other substances.

Genetic association studies investigating the role of the +118A allele of the human mu-opioid receptor gene in risk for alcohol dependency have produced inconsistent findings, possibly because of the failure to recognize sampling methodology difficulties inherent in association studies of polygenic disorders. We examined the frequency of the AA genotype and A allele in several groups of substance-dependent cases, unrestricted controls, and super controls screened for the use of alcohol and cigarettes. Our findings and analyses suggest that the OPRM1 +118 polymorphism is a general risk gene for substance dependence, but is not specific to a particular substance. The nature of the conferred risk is likely to be in use of multiple substances, but it is not yet determined if the risk could be expressed in severity of use of any particular substance. The contribution of the gene to risk for substance dependence is small, and is detected most easily in studies that use control samples that are screened for all forms of substance dependence.

Alcohol, aging, and cognitive performance in a cohort of Japanese Americans aged 65 and older: the Kame project.

OBJECTIVE: To investigate the effects of light to moderate alcohol consumption on cognitive performance. DESIGN AND SETTING: A cross-sectional analysis including older Japanese Americans in King County, WA, enrolled in the Kame Project, a population-based study of cognition, dementia, and aging. PARTICIPANTS: 1,836 cognitively intact participants aged 65 and older who participated in the baseline (1992-1994) examination. MEASUREMENT: Cognitive performance was measured using the Cognitive Abilities Screening Instrument, reaction time (simple and choice), and a measure of vocabulary (North American Adult Reading Test). RESULTS: Multivariate analyses were used to examine the relationship between cognitive performance and alcohol consumption at baseline with men and women together and then separately controlling for age, education, smoking, history of stroke, angina, hypertension, diabetes, and coronary heart disease. Findings showed lower cognitive test scores were observed for men who were either abstainers or in the heavy drinking group. For women, a linear relationship between alcohol consumption and cognitive performance was seen on two of the four measures of cognitive functioning. No significant difference in the association of drinking and cognitive function was identified within the different Japanese American subgroups. CONCLUSION: RESULTS suggest a possible positive relationship between light to moderate drinking and cognitive performance in an aging Japanese American population. Additional long-term prospective and cross-cultural studies are needed to determine the generalizability of these findings to other aging cohorts.

Ethnicity and cognitive performance among older African Americans, Japanese Americans, and Caucasians: the role of education.

This cross-sectional analysis evaluated the association between ethnicity and cognitive performance and determined whether education modifies this association for nondemented older people (103 African Americans, 1,388 Japanese Americans, 2,306 Caucasians) in a study of dementia incidence. African Americans scored lower (median 89 out of 100) than Japanese Americans (93) and Caucasians (94) on the Cognitive Abilities Screening Instrument (CASI). Education affected CA

Dietary soy isoflavone intake in older Japanese American women.

OBJECTIVE: In a sample of older Japanese American women, we aimed to: (1) describe the most commonly consumed soy foods, (2) estimate dietary soy isoflavone intake, (3) describe characteristics associated with dietary soy isoflavone intake, and (4) compare our estimates with previously published estimates in other Japanese samples. DESIGN: A 14-item soy food-frequency questionnaire was administered to older Japanese American women and responses were converted to quantitative estimates of soy isoflavones (genistein plus daidzein). Multiple regression was used to examine characteristics associated with dietary soy isoflavone intake, including self-reported lifestyle and cultural factors and dietary intake of various foods ascertained from a semi-quantitative food-frequency questionnaire. To compare our estimates with other samples, a review of the literature was conducted. SETTING/SUBJECTS: Data are from 274 women aged 65+ years, recruited from a longitudinal cohort study of Japanese Americans in King County, Washington State. RESULTS: The soy foods most commonly consumed were tofu (soybean curd), miso (fermented soybean paste) and aburaage (fried thin soybean curd). The mean intake of dietary soy isoflavones was 10.2 (standard deviation (SD), 12.4) mg day(-1), approximately a quarter to a half that of previously published estimates in Japanese samples. Dietary soy isoflavone intake was positively associated with speaking Japanese, the consumption of traditional Japanese dishes (kamaboko, manju and mochi), low-fat/non-fat milk and yellow/red vegetables, vitamin E supplement use, and walking several blocks each day. Dietary soy isoflavone intake was negatively associated with the consumption of butter. CONCLUSIONS: The estimated dietary soy isoflavone intake in Japanese American women living in King County, Washington State was about a quarter to a half that of women living in Japan. Dietary soy isoflavone intake was associated with speaking Japanese and healthy lifestyle and dietary habits.

Neuropsychological test performance in a cognitively intact sample of older Japanese American adults.

The purpose of this paper was to present population-based data showing the effects of age on cognitive test performance in a sample of older Japanese American adults. In addition, the relative effects of education, gender, and primary spoken language were compared to effects that have been reported in the literature for majority culture older adults. Subjects included 201 non-demented Japanese American adults age 70 and older currently enrolled in the Kame Project, a prospective study of aging and dementia in King County, WA. Cognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological assessment battery, WAIS-R Digit Span and Digit Symbol subtests, Trail Making Test, Purdue Pegboard, and Finger Tapping. Older age was associated with significantly (p<0.05) lower scores on all tests; less than high school education was associated with lower scores on all tests except Digit Span, Finger Tapping, and the Purdue Pegboard. Women and English-speaking participants scored higher than men and Japanese speakers on various tests of memory, attention, and visuomotor ability. These data reinforce the importance of using appropriately corrected norms when interpreting results of cognitive screening tests with minority culture older adults.

Postmenopausal estrogen and estrogen-progestin use and 2-year rate of cognitive change in a cohort of older Japanese American women: The Kame Project.

BACKGROUND: The relation between estrogen and cognition among postmenopausal women remains controversial. Also uncertain is whether the proposed association varies between women taking unopposed estrogen and those taking estrogen combined with progestin. OBJECTIVE: To determine whether unopposed estrogen and combined estrogen-progestin use were associated with the rate of cognitive change in a cohort of older, Japanese American, postmenopausal women. METHODS: A prospective observational study in a population-based cohort of older Japanese Americans (aged > or =65 years) living in King County, Washington. Cognitive performance was measured in 837 women at baseline (1992-1994) and 2-year follow-up (1994-1997) examinations using the 100-point Cognitive Abilities Screening Instrument (CASI). Least squares means general linear models were used to estimate the 2-year rate of cognitive change according to categories of postmenopausal estrogen use. RESULTS: Approximately half of this cohort (n=455) had never used estrogen at any time since menopause, 186 were past users, 132 were current unopposed estrogen users, and 64 were current estrogen-progestin users. The majority of current estrogen users were taking conjugated estrogens, and all women receiving combined therapy were taking medroxyprogesterone acetate. After adjusting for age, education, language spoken at the interview, surgical menopause, and baseline CASI score, women who had never used postmenopausal estrogen improved slightly on the CASI scale (mean adjusted change, 0.79; SEM, 0.19). This change was significantly greater for current unopposed estrogen users (mean adjusted change, 1.68; SEM, 0.36; P=.04) and significantly worse for current estrogen-progestin users (mean adjusted change, -0.41; SEM, 0.50; P =.02) compared with never users. The improvement observed in past users (mean adjusted change, 1.12; SEM, 0.29) was intermediate between the changes for never users and current unopposed estrogen users and not significantly greater than that for never users (P=.35). CONCLUSIONS: Our findings support a modest beneficial association between current unopposed estrogen use and the rate of cognitive change. We also observed a modest detrimental association between current estrogen-progestin use and the rate of cognitive change. The clinical significance of these modest differences, however, is uncertain. Data from large, long-term randomized trials are required before applying this information to the clinical setting.

Is APOE--epsilon4 a risk factor for cognitive impairment in normal aging?

OBJECTIVES: To examine the relationship between APOE genotype and cognitive functioning in normal aging, and to determine whether this relationship was moderated by age or the presence of a number of disease conditions, including cardiovascular disease and diabetes. METHODS: The sample was drawn from the Charlotte County Healthy Aging Study, a community-based, cross-sectional study of randomly selected older adults in Charlotte County, FL. A total of 413 older adults (mean age = 72.90 years) were examined in the current study. Participants completed tasks that indexed a variety of dimensions of cognitive functioning, including episodic memory, implicit memory, psychomotor speed, and attention. In addition, participants provided self-reported and objective indices of health status and were genotyped for APOE. RESULTS: Mean-level results indicated that groups with and without the APOE-epsilon4 allele performed similarly on all domains of cognitive functioning. Significant age group differences were observed in episodic memory, psychomotor speed, and attention but not implicit memory. Significant gender differences were present for episodic memory and the Stroop test. Analyses also indicated that participants' age did not exert an impact on the relationship between APOE-epsilon4 and cognitive functioning. Further, the presence of cardiovascular disease or diabetes did little to moderate the relationship between APOE-epsilon4 and cognition. CONCLUSIONS: The authors found no evidence for a relationship between presence of the APOE-epsilon4 allele and cognitive functioning. Further, age or the presence of a number of chronic conditions did not significantly moderate the effect of APOE genotype on cognitive performance. These results indicate that the presence of the epsilon4 allele is not a risk factor for cognitive impairment in normal aging.

Elderly norms for the Hopkins Verbal Learning Test-Revised.

The present study evaluates the effects of age, education, and gender in a representative sample of older adults and provides normative data for community-dwelling elderly. Age and gender had significant effects on HVLT-R performance. We provide age- and gender-adjusted normative data. Surprisingly, education level did not affect HVLT-R performance, indicating that education-adjusted norms are not necessary for this measure within this age range. We evaluated a subsample of subjects census-matched on age, education, and gender. These subjects did not differ in overall performance from our entire sample. Therefore, the normative data provided in this paper can be considered to be census-comparable for age, education, and gender.

Impaired olfaction as a marker for cognitive decline: interaction with apolipoprotein E epsilon4 status.

OBJECTIVE: To determine whether olfactory status predicts cognitive decline (CD) over a 2-year follow-up period. METHODS: The authors enrolled individuals in a community-based longitudinal study of memory and aging in the Japanese-American community in King County, WA, between 1992 and 1994. At baseline they screened 1,985 persons using the Cognitive Abilities Screening Instrument (CASI) and the 12-item Cross-Cultural Smell Identification Test (CC-SIT). Of these 1,985 people, 1,836 were found not to be demented. Two years later the authors rescreened 1,604 participants with the CASI. They defined CD as a 2-year loss of > or =5.15 points/100 on the CASI. They genotyped 69% of the 1,604 people completing both examinations for apolipoprotein E (apoE). RESULTS: After adjusting for age, CASI score at baseline, education, smoking, sex, and follow-up time, the authors determined an odds ratio (OR) for CD of 0.90 (95% CI, 0.84 to 0.97) for an increase in each correct point on the CC-SIT (range, 0 to 12). Compared with normosmics, the OR for persons with impaired olfaction (microsmics) was 1.25 (95% CI, 0.83 to 1.89) and for anosmics the OR was 1.92 (95% CI, 1.06 to 3.47). Persons who were anosmic at baseline and who had at least one APOE-epsilon4 allele had 4.9 times the risk of CD (95% CI, 1.6 to 14.9) compared with normosmics without the epsilon4 allele. The estimated relative risk among women was 9.7 (95% CI, 1.3 to 70.4), and for men the risk was 3.2 (95% CI, 0.8 to 12.6). Receiver operating characteristic (ROC) curves showed that although the area under the curve (AUC) for baseline CASI was only 0.51, the AUC for CC-SIT alone was 0.62. Adding CC-SIT to the ROC model with CASI improved the AUC curve from 0.51 to 0.62. CONCLUSIONS: Unexplained olfactory dysfunction in the presence of one or more APOE-epsilon4 alleles is associated with a high risk of cognitive decline. Cross-Cultural Smell Identification Test classifies people with cognitive decline correctly to a greater degree than a global cognitive test.

Occupational exposure to electromagnetic fields and Alzheimer disease.

The association between occupational exposure to electromagnetic fields (EMF) and Alzheimer disease (AD) was examined. Subjects were identified from a large health maintenance organization in Seattle, Washington, and matched by age, sex, and proxy type. A complete occupational history was obtained from proxies and controls. Following the interview, two industrial hygienists (IHs) rated exposures to EMF for each job blinded to case-control status. Exposures to EMF were rated as probable intermittent exposure or probable exposure for extended periods to levels above threshold. Conditional logistic regression was used to calculate the risk of AD given EMF exposure stratified by IH. The odds ratios for ever having been exposed to EMF were 0.74 [95% confidence interval (CI) 0.29-1.92] and 0.95 (95% CI 0.27-2.43) for each IH, adjusting for age and education. No dose-response effect was noted. Agreement between the two IHs for ever having been exposed to EMF was good (kappa = 0.57, p < 0.0001). This study was unable to support an association between EMF and AD.

Estimation and sample design in prevalence surveys of dementia.

Population prevalence rates of dementia using stratified sampling have previously been estimated using two methods: standard weighted estimates and a logistic model-based approach. An earlier study described this application of the model-based approach and reported a small computer simulation comparing the performance of this estimator to the standard weighted estimator. In this article we use large-scale computer simulations based on data from the recently completed Kame survey of prevalent dementia in the Japanese-American residents of King County, Washington, to describe the performance of these estimators. We found that the standard weighted estimator was unbiased. This estimator performed well for a sample design with proportional allocation, but performed poorly for a sample design that included large strata that were lightly sampled. The logistic model-based estimator performed consistently well for all sample designs considered in terms of the extent of variability in estimation, although some modest bias was observed.

Cognitive decline and Japanese culture in a cohort of older Japanese Americans in King County, WA: the Kame Project.

OBJECTIVES: The prevalence of Alzheimer's disease in studies of Japanese show generally lower rates when compared with those of Caucasians. We hypothesized that among a cohort of Japanese Americans lifestyle differences would act to modify progression of the Alzheimer pathologic process over many years, resulting in a slower cognitive decline among persons whose lifestyle is more characteristically Japanese. METHODS: One thousand, eight hundred and thirty-six nondemented persons were screened with the Cognitive Abilities Screening Instrument (CASI) at baseline, and 1,604 were rescreened 2 years later. Baseline questions included migration status, exposure to Japanese culture in early life and maintenance of such culture in adulthood, and other risk factors. Cognitive decline was defined as a 2-year loss of > or = 5.15 points/100 on CASI. RESULTS: In multivariable logistic regression, variables relating to reading, writing, and speaking Japanese, being born or having lived in Japan in early life, and having friends who are only/mostly Japanese were inversely associated with cognitive decline (odds ratios ranged between 0.28 and 0.64, with p < .05). Two factors emerged in a factor analysis of these variables. The strongest explained 49% of the variance for acculturation and loaded heavily on knowledge of the Japanese language and having spent one's early years in Japan. When this factor was dichotomized into the top 20th percentile, it predicted cognitive decline with an odds ratio of 0.12 (95% CI 0.03-0.49). DISCUSSION: These results show that a Japanese lifestyle may decrease the risk of expressing cognitive decline over a 2-year follow-up period. Lower cardiovascular disease rates among Japanese may also predispose them to lower rates of cognitive decline. The greater social support characteristic of Japanese culture as well as the role that Japanese language and culture may play in neural connectivity during brain development and/or in mental stimulation in adult life may also explain our findings.

Occupational exposures to solvents and aluminium and estimated risk of Alzheimer's disease.

OBJECTIVES: To study the role of occupational exposures to solvents and aluminium in the aetiology of Alzheimer's disease (AD). An industrial hygienist rated exposure. METHODS: 89 subjects diagnosed with probable AD were matched by age, sex, and type of informant to 89 controls. Subjects were identified from a large health maintenance organisation in Seattle, WA. A complete occupational history was obtained from spouses of cases and controls as well as from controls themselves. After the interview an industrial hygienist, blinded to case-control status, rated exposures. RESULTS: Non-significant associations were found between AD and ever having been occupationally exposed to solvents (odds ratio (OR) 1.77, 95% confidence interval (95% CI) 0.81 to 3.90) and aluminium (OR 1.46, 95% CI 0.62 to 3.42). Although an increasing risk was found with increasing number of years of exposure to solvents, there was an inverse association between exposure intensity and AD, and measures of cumulative exposure taking into account both intensity and duration of exposure were not significant. Analysis of the age at which half the cumulative exposure to solvents was achieved showed that an older age incurred a greater risk of AD than a younger age. However, the total amount of exposure carried no risk. CONCLUSIONS: The results suggest that lifetime occupational exposure to solvents and aluminium are not likely to be important risk factors for Alzheimer's disease.

Standardization of the clinical diagnosis of the dementia syndrome and its subtypes in a cross-national study: the Ni-Hon-Sea experience.

BACKGROUND: Clinical investigators from Seattle, Honolulu, Tokyo, and Hiroshima participated in two standardization exercises in which data were collected on independent assessments. Exercises were conducted to evaluate the interobserver agreement on clinical diagnoses of dementia and dementia subtypes in a cross-national study of dementia prevalence and incidence rates in the United States and Japan. METHOD: Fifteen clinicians from four participating sites assessed the diagnosis of 85 patients based on standardized summaries of clinical and diagnostic test data on each patient. Diagnostic guidelines and conventions were adopted on the basis of group consensus during standardization exercises. RESULTS: Using DSM-III-R criteria, generally good levels of agreement for all dementia diagnostic categories occurred in both years. For most measures of diagnostic agreement, improvements were observed between the 1995 and 1996 standardization sessions. Interrater agreement was highest for discrimination between dementia and nondementia (1996 overall kappa, K = .90). The kappa values for dementia subtypes in 1996 ranged from .5 to .85, and for all sites combined the value was .67. For dementia subtypes, percent agreement was highest for vascular dementia and Alzheimer's disease, but was less reliable for other types of dementia. CONCLUSIONS: Clinicians from different cultures and medical traditions can reliably use the DSM-III-R criteria to classify dementia cases in cross-national research. The interrater agreement on dementia and its subtypes improved after clear-cut guidelines for interpretation of diagnostic criteria were developed and followed.

Estrogen replacement therapy and cognitive function in postmenopausal women without dementia.

The epidemiologic evidence for an association between estrogen and cognitive function among healthy postmenopausal women remains controversial. Equivocal findings may be explained, in part, by differences in the methodologic approaches of these studies. Overall, the evidence for a positive relationship comes primarily from randomized clinical trials. These trials suggest an acute effect on specific tests of recent verbal memory and tasks incorporating concept formation and reasoning. The potential long-term effects of estrogen in slowing or delaying the age-related decline in cognitive function require further study. More data are needed to determine the effects of estrogen replacement therapy on cognitive function, independent of changes in mood and depressive symptoms. In addition, evidence suggests that progesterone may mitigate the beneficial effects of estrogen on mood. Research should be undertaken to determine the interactive effects of estrogen and progesterone on cognitive function. Lastly, there should be continued investigation by both epidemiologic and basic neuroscientific studies to further elucidate the specific cognitive domains that may respond to estrogen.

Prevalence of dementia and its subtypes in the Japanese American population of King County, Washington state. The Kame Project.

Studies of Asian populations generally have reported prevalence rates for dementia similar to those of predominantly Caucasian populations, but relative prevalence rates of Alzheimer's disease and vascular dementia have differed. Between May 1, 1992 and May 1, 1994, the prevalence rates of dementia, Alzheimer's disease, and vascular dementia were examined in the Japanese American population aged over 65 years in King County, Washington State. A total of 3,045 eligible individuals were identified in a census of persons who were of at least 50% Japanese heritage. Of 1,985 persons who participated in the baseline examination, 382 individuals of 450 sampled from all cognitive performance strata received a diagnostic evaluation. A total of 107 cases with a Clinical Dementia Rating (CDR) of > or = 1 met criteria for dementia according to the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-III-R); 58 of these cases were diagnosed with Alzheimer's disease and 24 with multi-infarct dementia. The estimated prevalence rate for all dementias was 6.3% (95% confidence interval 5.9-6.8). Prevalence rates for dementia increased continuously with age and were 30%, 50%, and 74% for participants aged 85-89, 90-94, and > or = 95 years, respectively; for Alzheimer's disease, prevalence rates were 14%, 36%, and 58% for these three age groups. Rates for Alzheimer's disease were generally higher among women; for multi-infarct dementia, rates for men and women were similar. In the institutional population, the prevalence rate was 66%, and in the community, 2.9%. Persons with lower education had higher overall rates of dementia than those with higher education, but this tendency became weak and inconsistent when rates were age-stratified. The prevalence of dementia in this geographically defined population of Japanese Americans was somewhat higher than prevalence rates reported from Japan, and the distribution of dementia subtypes more closely resembled that found in Caucasian populations in North America and Europe than previously reported in Asian populations.

Attitudes toward use of nursing homes and home care in older Japanese-Americans.

OBJECTIVE: A cohort of 1142 older Japanese Americans was identified to study preferences and attitudes regarding use of long-term care (nursing home or home care). DESIGN: Prospective cohort study. PARTICIPANTS AND SETTING: Older Japanese Americans in King County, Washington. RESULTS: Subjects were asked to consider hypothetical situations in which they were temporarily disabled by hip fracture or permanently disabled by dementing illness. If they fractured a hip, only 12% intended to use a nursing home; 29% intended to recover at home with the help of family or friends; another 54% intended to use paid home health care. If they became demented, the majority (53%) intended to use a nursing home; only 11% intended to rely on family or friends for care, and another 29% intended to use paid home health care. Similar responses were observed when subjects were asked what most members of their family or friends would wish them to do; however, they tended to value the perceived wishes of religious figures or the Japanese American community-at-large less than those of family or friends. Significant correlates with intention to enter nursing homes were lack of social support (unmarried, few or no close relatives or housemates), female gender, and high levels of acculturation into American society (never lived in Japan, English-speaking only). Other factors that were not significantly correlated were health perceptions, satisfaction and life control scales, and health care utilization (hospitalizations and MD visits). In multivariate logistic regression, marital status and level of acculturation were the most powerful independent predictors of intention to enter nursing homes. Age and female gender were predictors of intention to use home care. In the base population of subjects, the prevalence of nursing homes use (5%) was similar to that of the general US older population. CONCLUSIONS: We conclude that older Japanese Americans in the Pacific Northwest often intend to enter nursing homes if they became disabled by dementing illness. Actual use is similar to other older populations. This may be attributable largely to the existence of an ethically appropriate nursing home which is strongly supported by, and familiar to, this close-knit community. Intention to use long-term care services appears to be dependent primarily on the level of social supports and acculturation into American society.

Head circumference as a measure of cognitive reserve. Association with severity of impairment in Alzheimer's disease.

BACKGROUND: Recent studies suggest that larger brain size may offer some protection against the clinical manifestations of Alzheimer's disease. However, this association has not been investigated in population-based studies. METHOD: The relationship between head circumference, a measure of premorbid brain size, and score on the Cognitive Abilities Screening Instrument (CASI) was studied in a population of 1985 Japanese-Americans aged 65+ living in King County, Washington, USA. RESULTS: After adjusting for age, sex and education, head circumference was positively associated with CASI score (b = 3.8, 95% Cl: 2.2, 5.4; P = 0.0000), but not with diagnosis of probable AD (odds ratio = 0.87, 95% Cl: 0.33, 1.87). When the data were stratified by AD status, no association was seen among controls (b = 1.6, 95% Cl: -1.7, 5.1; P = 0.4), whereas a strong effect was present among cases (b = 35.3, 95% Cl: 12.2, 68.4: P = 0.006). CONCLUSIONS: These results suggest that persons with AD with smaller head circumference either had the disease longer or progressed more rapidly than those with larger head circumference. Improvement in environmental factors in prenatal and early life that partially determine completed brain/head size may have consequences for the late-life expression of Alzheimer's disease in vulnerable individuals.

Interaction between genetic and environmental risk factors for Alzheimer's disease: a reanalysis of case-control studies.

To study the interaction among genetic and environmental risk factors, a reanalysis of case-control studies of Alzheimer's disease (AD) was conducted based on the original data of all studies carried out to January 1, 1990. Seven studies were included in the present analysis, comprising a total of 814 AD patients and 894 control subjects. When comparing those with a positive and negative family history of dementia, similar odds ratio were found for late maternal age [1.7; 95% confidence interval (0.6-4.8) vs. 2.0 (1.1-3.5)], head trauma [1.7 (0.7-4.2) vs. 1.9 (1.1-3.2)], and history of depression [2.0 (0.2-19.8) vs. 2.1 (0.8-1.7)]. This suggests a model in which these risk factors increase the risk for AD independent of family history of dementia. Among those with a positive family history of dementia, the odds ratios for family history of Down's syndrome [4.2 (0.9-20.0)] and of Parkinson's disease [3.3 (0.4-28.2)] tended to be higher than among those with a negative family history of dementia [2.6 (0.8-8.5) and 2.4 (0.8-7.0), respectively]. However, for both disorders the difference in odds ratio was not statistically significant. For history of cigarette smoking, there was no association to AD for those with no first degree relatives with dementia and an inverse relation with AD for those with a positive family history. Although in all analyses, family history of dementia remained significantly associated with AD in the absence of other factors, the odds ratio associated with family history of dementia tended to be lower for those with a positive smoking history, particularly for those with two or more affected relatives. These findings suggest that smoking may interact specifically with a genetically determined process.

Opportunities and challenges in international collaborative epidemiologic research of dementia and its subtypes: studies between Japan and the U.S.

Estimates of the prevalence rates for dementia vary significantly among countries. Such variation may be explained, at least in part, by methodologic differences in studies. The disparities in prevalence rates of dementia subtypes, particularly Alzheimer's disease and multi-infarct dementia, are especially apparent in studies conducted in Eastern and Western countries. In Japan and China, the prevalence of multi-infarct dementia exceeds that of Alzheimer's disease, whereas in the West, Alzheimer's disease predominates in the vast majority of studies. Clearly, cross-cultural studies of incidence using standard methods are needed to investigate whether a true difference in risk exists, and which risk factors differentially contribute to this variation. Migrant studies of genetically homogeneous populations offer a unique opportunity to answer these questions. This article explores the value of migrant studies, their application to etiologic questions of dementia and its subtypes, and recommendations concerning how to conduct such studies.