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4
Ethnic Differences in Dementia and Alzheimer’s Disease

Jennifer J. Manly and Richard Mayeux


The proportion of ethnic minorities among the elderly in the United States is increasing. The U.S. Census Bureau estimates that the proportion of elders who are white and non-Hispanic will decline from 87 percent in 1990 to 67 percent in 2050. As compared to the 1990 Census, the population of Hispanic elders is expected to double in 2010, and will be 11 times greater by 2050. Of the 80.1 million elderly projected for 2050, 8.4 million (10.4 percent) will be black, as compared to 8 percent of elders in 1990. With these changes, ethnic minority populations will bear an increased share of the economic and social burden associated with diseases that predominantly affect the elderly, such as Alzheimer’s disease (AD). This presents the potential for a major public health issue because ethnic minorities may be at higher risk for AD and dementia than non-Hispanic whites.

Investigations of ethnic populations that have migrated across several cultures offer the opportunity to study groups for which genetic factors essentially remain the same but environmental and cultural forces undergo dramatic change. At the same time, comparison of different racial groups residing in the same environment with similar socioeconomic status and equal exposure to risk factors may help to uncover genetic factors responsible for AD (Osuntokun et al., 1992).

The studies reviewed in this chapter examine ethnic differences in rates of broad categories such as “cognitive impairment” or “dementia” as well as specific neurodegenerative diseases such as Alzheimer’s disease and vascular dementia. Cognitive impairment, a necessary prerequisite for diagnosis of any dementia, is determined using either screening tests, such as the



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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life 4 Ethnic Differences in Dementia and Alzheimer’s Disease Jennifer J. Manly and Richard Mayeux The proportion of ethnic minorities among the elderly in the United States is increasing. The U.S. Census Bureau estimates that the proportion of elders who are white and non-Hispanic will decline from 87 percent in 1990 to 67 percent in 2050. As compared to the 1990 Census, the population of Hispanic elders is expected to double in 2010, and will be 11 times greater by 2050. Of the 80.1 million elderly projected for 2050, 8.4 million (10.4 percent) will be black, as compared to 8 percent of elders in 1990. With these changes, ethnic minority populations will bear an increased share of the economic and social burden associated with diseases that predominantly affect the elderly, such as Alzheimer’s disease (AD). This presents the potential for a major public health issue because ethnic minorities may be at higher risk for AD and dementia than non-Hispanic whites. Investigations of ethnic populations that have migrated across several cultures offer the opportunity to study groups for which genetic factors essentially remain the same but environmental and cultural forces undergo dramatic change. At the same time, comparison of different racial groups residing in the same environment with similar socioeconomic status and equal exposure to risk factors may help to uncover genetic factors responsible for AD (Osuntokun et al., 1992). The studies reviewed in this chapter examine ethnic differences in rates of broad categories such as “cognitive impairment” or “dementia” as well as specific neurodegenerative diseases such as Alzheimer’s disease and vascular dementia. Cognitive impairment, a necessary prerequisite for diagnosis of any dementia, is determined using either screening tests, such as the

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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life Mini-Mental State Exam (MMSE), or more sensitive and extensive neuropsychological test batteries incorporating individual measures such as Logical Memory from the Weschler Memory Scale. To meet clinical criteria for dementia, cognitive impairment must be of sufficient severity to interfere with activities of daily living. Cross-cultural research on dementia must contend with the fact that assessments of both cognitive impairment and daily functioning are susceptible to culturally dependent definitions and are quantified by measures that are sensitive to cultural and educational background. There are many possible etiologies of progressive dementia, but the most frequent causes are Alzheimer’s pathology and cerebrovascular disease. Although the exact etiology cannot be definitively determined before an autopsy, there are research criteria for AD and vascular dementia that have been shown to predict the specific pathological determination upon autopsy with up to 90 percent accuracy. However, the supporting research has involved almost exclusively white subjects. Few autopsy studies have been performed to confirm the accuracy of these diagnoses among ethnically diverse groups. This chapter will first review the findings of epidemiological studies of dementia and AD among different ethnic groups within the United States and other countries. This review is not intended to be a comprehensive survey of AD epidemiology, which is available elsewhere (Chang, Miller, and Lin, 1993; Hendrie, 1998; Jorm, 1990; Larson and Imai, 1996; Yeo, Gallagher-Thompson, and Lieberman, 1996); rather, it is intended to highlight specific studies that emphasize the issues in research of ethnicity and AD. We will then explore some potential explanations for ethnic differences in rates of AD and dementia: (1) statistical limitations, (2) bias in measurement of cognitive functioning, (3) genetic factors, (4) nongenetic medical risk factors, and (5) social factors. EPIDEMIOLOGY OF AD: CROSS-CULTURAL COMPARISONS Ethnic Comparisons Within the United States A number of studies have compared the rates of dementia and AD between ethnic groups residing in the United States. Despite differences in sampling methods and definitions of dementia as well as in definitions of race/ethnicity, the most frequent findings in reviewing this literature are that African Americans and Hispanics have higher prevalence and incidence of dementia and AD than whites. Native Americans appeared to have lower rates of AD in comparison to whites. Asian Americans had rates of dementia comparable to whites; however, whether there is the same proportion of AD compared to vascular dementia among Asian Americans and

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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life Asian immigrants remains uncertain. Opinion differs on whether correction for education accounted for the different rates of dementia and AD found among these cultural groups. Most U.S.-based studies have focused on comparing rates of dementia or AD among African Americans and Hispanics to rates among whites. These studies found higher rates of cognitive impairment, dementia, and AD among ethnic minorities than among whites (Folstein, Bassett, Anthony, Romanoski, and Nestadt, 1991; George, Landerman, Blazer, and Anthony, 1991; Gurland et al., 1998; Haerer, Anderson, and Schoenberg, 1987; Perkins et al., 1997; Prineas et al., 1995; Schoenberg, Anderson, and Haerer, 1985; Still, Jackson, Brandes, Abramson, and Macera, 1990; Teresi, Albert, Holmes, and Mayeux, 1999). One of the largest projects, a population-based, longitudinal study of 2,126 elderly residents of New York City, examined the incidence of AD among three ethnic/racial groups, self-defined according to U.S. Census criteria: Non-Hispanic whites, non-Hispanic blacks, and Hispanics (mostly Caribbean) (Tang et al., 2001). These individuals were identified as Medicare recipients residing in selected Census tracts of the neighborhoods of Washington Heights and Inwood. Using National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Associations (NINCDS-ADRDA) criteria, neurological examination, and results from an extensive neuropsychological test, the standardized incidence rate for non-Hispanic black elders (4.2 percent per person-year) and Caribbean Hispanics (3.8 percent per person-year) was significantly higher than that of the referent group, non-Hispanic whites, even after correcting for differences in years of education. Another large study, the Duke Established Populations for Epidemiological Studies of the Elderly project, found no differences in frequency of dementia between African Americans and whites. This study described a sample of 4,136 participants (Fillenbaum et al., 1998), 55 percent of whom were African American. The sample was defined using multistage probability sampling with unequal probabilities of selection to sample community-dwelling residents age 65 and older within five adjacent counties, one urban and four rural. However, the way in which the racial groups were defined is unclear. The authors used the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Neuropsychological Test battery to assess cognitive functioning, and norms correcting for years of education (Unverzagt, Hall, Torke, and Rediger, 1996) were used for the determination of significant cognitive deficit and dementia. The prevalence of dementia among elders above age 67, as determined by clinical consensus, was 7 percent for African Americans and 7.2 percent for whites. There were also no differences in the 3-year incidence of dementia for African Americans (5.8 percent) versus whites (6.2 percent). The authors did not report inci-

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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life dence of dementia subtypes; therefore, it is possible that although the overall rates of dementia were similar among African Americans and whites, the frequencies of AD and vascular dementia may differ within the groups. The rate of dementia on admission to nursing homes is higher among black residents than among white residents (Weintraub et al., 2000); however, findings from studies of long-term outcomes for African-American elders with dementia are not consistent. Mortality associated with dementia was found to be higher among blacks than non-Hispanic whites, especially among black males (Lanska, 1998). However, there were no statistically significant differences in survival from time of entry into the CERAD study of whites and African Americans after accounting for the effects of age, gender, and severity of dementia (Heyman, Peterson, Fillenbaum, and Pieper, 1996). However, for each of these studies, the exact way in which racial groups were defined was not stated. The role of immigration and changes in environmental risk factors was examined in several epidemiological studies of elders with Japanese ancestry. The age-standardized prevalence of dementia (using Diagnostic and Statistical Manual of Mental Disorders—Third Edition [DSM-III] criteria) among Japanese-American men aged 71 to 93 living in Hawaii (White et al., 1996) was 7.6 percent. This rate was higher than Japanese men living in Japan (4 percent to 6 percent), and similar to prevalence rates in European populations. The age-standardized prevalence of AD (using NINCDS-ADRDA criteria) in this Japanese-American population was 4.7 percent. The authors suggested that environmental or cultural exposures associated with migration from Japan to Hawaii influenced the development of AD in these Japanese Americans. Similar results were reported in a study of 1,985 Japanese-American participants in the Kame project in King County, Washington (Graves et al., 1996). A cross-sectional study of dementia prevalence using the California Alzheimer’s Disease and Diagnostic Treatment Centers found that, as compared to whites, Asian Americans had a greater proportion of vascular dementia and lower proportion of AD (Still et al., 1990), similar to studies of Asians in Asia (to be discussed). Native Americans appear to have a lower rate of AD than whites, but equivalent rates of overall cognitive impairment or dementia. Hendrie et al. (1993) examined 192 Cree, aged 65 and older, living on two reserves in Manitoba, Canada, and an age-stratified sample of 241 English-speaking whites living in Winnipeg. Using the Community Screening Interview for Dementia (CSID) to screen for cognitive impairment, the authors found a significant difference between the age-adjusted prevalence of AD among the Cree Indians (0.5 percent) as compared to whites (3.5 percent), despite the two groups having an equivalent age-adjusted prevalence of dementia (4.2 percent in each population).

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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life A study of Cherokee Indians living in northeastern Oklahoma (Rosenberg et al., 1996) used NINCDS-ADRDA criteria to identify 26 people aged 65 and older with AD, and then assessed an equal number of normal controls. The investigators found that as the genetic degree of Cherokee ancestry increased, the frequency of AD decreased. That is, after taking into account whether the ε4 allele of the apolipoprotein E (APOE) gene is present, elders with more than 50 percent genetic Cherokee ancestry were less likely to be in the AD group than the control group. Genetic degree of ancestry for each participant was calculated using genealogical records provided by the Cherokee Nation Tribal Registration Department. A limitation of this study is its case-control design; however, this study represents a unique method of examining the relationship of race/ethnicity to disease because the degree of ethnic ancestry was assessed (albeit not through formal genetic analysis), as opposed to classifying individuals into racial groups based on self-report or investigator observation. South America The racial, ethnic, cultural, and socioeconomic diversity found within South America provides an excellent opportunity to evaluate biological and environmental risk factors for cognitive impairment and Alzheimer’s among elders; however, more work must be carried out in this area to equal the epidemiological information available in other regions. A study of dementia in Chile (Quiroga et al., 1999) found a prevalence of 5.98 percent for elders 65 years and older, with the majority of these cases meeting criteria for AD (60 percent). Dementia rates in Brazil appear to be equivalent to those found in Europe and among white Americans, and rates are highest among illiterates (Nitrini et al., 1995). Rates of dementia and cognitive impairment in other South American countries appear to be comparable to Europe and the United States (Mangone and Arizaga, 1999). Africa A number of studies lead Osuntokun and his colleagues to state that “No authentic case of AD has been reported in an indigenous black African” (Osuntokun, Ogunniyi, Lekwauwa, and Oyediran, 1991; Osuntokun et al., 1992). In a door-to-door survey of 1,122 individuals above the age of 40 (32 percent above the age of 65) in Ibadan, Nigeria, these investigators reported finding no cases of severe dementia. They found that 3.6 percent of the sample had cognitive impairment, but their functional activities were intact. The same research group found that in an autopsy series of 198 brains, none were found with AD-like pathological changes. Among elderly

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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life clinical patients in this area, a high frequency of vascular dementia was encountered. Soon after these reports, Hendrie and his colleagues from the Indiana University School of Medicine and the University of Ibadan, Nigeria began investigating the epidemiology of dementia among community-dwelling African Americans living in Indianapolis and Yoruba living in Ibadan. This study hoped to take advantage of the fact that African Americans are predominantly of the lineage of West African blacks but reside in quite different environments than Nigerians, and are therefore likely to have different exposures to possible environmental risk factors. A total of 2,212 African-American elders and 2,494 Nigerians were assessed (Hendrie et al., 1995b). Door-to-door screening was performed in each population, but the exact way in which the American sample was defined as “African American” is unclear. Diagnoses were made under World Health Organization guidelines, using DSM-II-R and ICD-10 criteria for dementia and NINCDS-ADRDA criteria for AD. Age-adjusted prevalence rates for dementia (2.29 percent) and AD (1.41 percent) among community-dwelling Yoruba elders in Ibadan were significantly lower than rates of dementia (8.24 percent) and AD (6.24 percent) among African Americans. Age-standardized annual incidence rates of dementia (1.35 percent) and AD (1.15 percent) were significantly lower in Ibadan than rates of dementia (3.24 percent) and AD (2.52 percent) among African Americans in Indiana (Hendrie et al., 2001). Investigators in the Indianapolis-Ibadan study suggested several possible explanations for reduced rates among Nigerian elders, including differential mortality (those who would eventually develop AD may die at a younger age in Nigeria); the relatively younger age structure of the population; absence of environmental factors that might increase risk of AD; and disparate diagnostic criteria for functional decline. The authors also suggested that the Nigerians may have a lower rate of amyloid deposition as compared to African Americans; a recent study suggests that this is not the case among East Africans (Kalaria et al., 1997). Asia In general, it has been noted that although the overall rates of dementia are similar among Asian and European elders, the distribution of subtypes of dementia are different. Specifically, early studies indicate that Asian populations appear to have a larger proportion of vascular dementia (VAD), whereas in most European studies the relative proportion of AD is larger (Jorm, 1991; Yeo et al., 1996). The Japanese were initially believed to have substantially lower prevalence of AD and higher prevalence of VAD (reviewed in Shadlen, Larson, and Yukawa, 2000). However, more recent studies have shown decreases

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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life in prevalence of VAD and increases in AD (Yamada et al., 1999). This changing pattern of dementia diagnosis could reflect changes in diagnostic accuracy, a decrease in VAD prevalence due to better control over cardiovascular risk factors, or an increase in AD prevalence due to Westernization of risk factors such as a diet rich in fat and cholesterol. One interesting study estimated the prevalence of dementia among Japanese who immigrated to Brazil before World War II. The prevalence of dementia on the mainland of Japan was previously found to be approximately 8 percent (Ishii et al., 1999). Diagnosis of dementia was made using the DSM-IV criteria, and cognitive ability was assessed using the Cognitive Abilities Screening Instrument. Japanese immigrants were not found to differ from the mainland Japanese population or native Brazilians in the overall prevalence of dementia (7.8 percent) or distribution of dementia types (half of the cases were AD and half were VAD). This study argues against an effect of environmental factors (at least later in life) on dementia prevalence or subtype. Zhang et al. (1990) found that among 5,055 older residents of Shanghai, China, the prevalence rate of dementia among those 65 years and older was 4.6 percent, with 65 percent of these individuals having clinical diagnosis of AD. Approximately 47 percent of the sample had no formal education, and another 29 percent had less than 7 years of education. Participants were screened with a Chinese version of the MMSE using specific cutoffs by educational level. Those below cutoffs were further administered Chinese versions of the Fuld Object Memory Test, a Verbal Fluency Test, and Digit Span and Block Design subtests from the Wechsler Adult Intelligence Scale-Revised (WAIS-R). The authors found that lack of education was a significant and independent risk factor for the prevalence of dementia. Europe Rocca et al. (1991) combined data from 23 population-based prevalence studies from several European countries (collected by the EURODEM Prevalence Research Group), all of which used DSM-III or similar criteria to diagnose dementia and NINCDS-ADRDA criteria for AD. Age-specific prevalence rates ranged from 0.3 percent in the 60 to 69 age group to 10.8 percent in the 80 to 89 age group. Another study of nondemented residents of Gothenburg, Sweden between the ages of 85 and 88 revealed an incidence of 36.3 per 1,000 per year for AD (Aevarsson and Skoog, 1997). The prevalence and incidence of vascular dementia (based on National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria) among Swedish el-

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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life ders aged 85 and older appears to exceed that of AD (Aevarsson and Skoog, 1996, 1997; Skoog, Nilsson, Palmertz, Andreasson, and Svanborg, 1993). The Liverpool Health and Ethnicity Project (McCracken et al., 1997) reported that the prevalence of dementia among a sample of 418 English-speaking elders with African, Caribbean, Chinese, Asian, and Middle Eastern backgrounds was comparable to that found among whites (2 to 9 percent). However, in this same study, the authors found that the prevalence of dementia among people who had the same ethnic backgrounds but were not English speaking was elevated (21 to 27 percent). The authors suggested that these higher rates were due to bias in the orientation test items. People who did not speak English were less likely to know their exact birth date, their address, or the name of the Prime Minister than were English speakers, but they did not differ on any other test items. Israel Treves et al. (1986) reported on a nationwide epidemiologic study of the incidence of AD among those aged 40 to 60 in Israel. Through examination of the Israeli National Neurologic Disease Register and clinical records of hospital patients, the authors found that the age- and sex-adjusted incidence of AD was higher among those who were born in Europe or America (2.9 per 100,000 population) than those born in Africa or Asia (1.4 per 100,000); however, there were no ethnic differences in survival. A 5-point rating scale of cognitive and daily functioning and a short cognitive screening test that did not involve reading or writing were administered to 1,399 residents of Ashkelon, Israel, who were 75 and older (Korczyn, Kahana, and Galper, 1991). Half of the participants were born in Africa or Asia and half were born in Europe or America. Frequency of dementia increased with age, and rates were higher among those born in Africa or Asia, among women, and among those who could not read. The authors suggested that a low level of education was the likeliest explanation for these ethnic group and gender differences. The prevalence of AD among the entire population of 823 elders aged 60 and older was also examined in the Arab community of Wadi-Ara in northeast Israel (Bowirrat, Treves, Friedland, and Korczyn, 1998). The majority of the participants were illiterate (42 percent of males and 96 percent of females). All participants were examined by an Arabic-speaking neurologist who used DSM-IV criteria to identify dementia and NINCDS-ADRDA criteria for AD. In that population, 20.5 percent had a diagnosis of AD, with the frequency of dementia increasing from 6 percent among those 70 years and younger to 49 percent among those 80 and older.

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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life Similar to the Zhang et al. (1990) study, the authors found that illiteracy was a significant and independent risk factor for AD in this population. India The Indo-US Cross-National Dementia Epidemiology project has been established to compare rates of dementia among elderly residents of a rural area of northern India to elders living in Monongahela Valley in Pennsylvania (MoVIES project). The group initially reported an overall prevalence rate of 1.36 percent for all dementias and a prevalence rate of 1.07 percent for AD (meeting NINCDS-ADRDA criteria) among those aged 65 and older in a community survey of 5,126 residents of Ballabgarh, India (Chandra et al., 1998). A recent report (Chandra et al., 2001) found that AD incidence rates were among the lowest ever reported: 3.24 per 1,000 person-years for those aged 65 and older and 1.74 for those aged 55 and older. These rates were significantly lower than those among elders in the Monongahela Valley. As with the Indianapolis/Ibadan study, the authors suggested the possibility that lower life expectancy, short survival with AD, or short follow-up duration could help to explain low incidence rates. Notably, the group found that literacy level was not related to prevalence or incidence of dementia. Autopsy Confirmation of AD Pathology Neuropathological confirmation of the presence and severity of AD pathology among patients diagnosed with AD is the only way to confirm ethnic discrepancies in AD prevalence and incidence. However, African Americans and other ethnic minorities are less likely to consent to autopsy (Amaducci, Baldereschi, Doody, Chandra, and Gaines, 1997; Bonner, Darkwa, and Gorelick, 2000; Fillenbaum et al., 1996; Ganguli et al., 1991; Harrell, Callaway, and Powers, 1993). Therefore, there are few published studies comparing the rates of neuropathologically defined AD among different ethnic groups in the United States; most published neuropathological studies of AD have examined whites almost exclusively. The few studies with ethnically diverse samples have found, among those autopsied, no racial differences in frequency of AD pathology (de la Monte, Hutchins, and Moore, 1989), or that AD lesions are more prevalent among whites than among blacks (Miller, Hicks, D’Amato, and Landis, 1984). Small sample size is a problem for each of these studies, and because there is a much lower rate of consent for autopsy among African Americans, there may be a selection bias. One study avoided selection bias by performing a survey of all autopsies on individuals ages 40 to 70 in the Maryland Chief Medical Examiner’s

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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life office for an 8-year time period (Sandberg, Stewart, Smialek, and Troncoso, 2001). All died of “nonnatural” causes, mostly accidents and homicides. The researchers assessed the prevalence of senile plaques (SPs) and neurofibrillary tangles (NFTs) in three brain areas: the hippocampus, entorhinal cortex, and inferior temporal cortex. In their sample of 138 individuals, 42 percent were African American and 61 percent were younger than age 65. NFTs were most common after age 54 and were found mostly in the hippocampus and entorhinal cortex. SPs were less frequent overall, but were found mostly in people 75 years and older in the entorhinal cortex and inferior temporal cortex. Prevalence of neuritic plaques was consistently lower in African Americans than whites. Although the authors confirmed that prevalence of mixed SPs and NFTs was strongly correlated with age, there was no evidence that these pathological changes had any differences in frequency by race. Imaging Evidence Brain imaging studies, using both structural and functional methods, might provide an alternative line of evidence concerning AD pathology that could back up the epidemiological findings of ethnic discrepancies in AD. However, there are few studies of structural or functional brain imaging using diverse groups of elders. Studies of African-American elders with clinical diagnoses of AD have shown that magnetic resonance imaging (MRI)-determined measurements of hippocampal volume (Sencakova et al., 2001) and qualitative computerized tomography and MRI findings (Charletta, Gorelick, Dollear, Freels, and Harris, 1995) were similar to those reported in other imaging studies of primarily white patients. One study using MRI and Single Photon Emission Computed Tomography showed no major ethnic differences in degree of white-matter hyperintensities, ventricle-to-brain ratio, and uptake among 3,301 nondemented community-dwelling elders without a history of stroke or transient ischemic attack (Longstreth et al., 2000). Other research has found a higher prevalence of white-matter lesions among nondemented African-Americans elders, a predictable finding given that cardiovascular risk factors (e.g., hypertension, diabetes) are more common among African Americans (Lesser et al., 1996; Liao et al., 1997). Summary Within the United States, most studies found higher rates of dementia and AD among African Americans and Hispanics as compared to non-Hispanic whites; however, these findings have not yet been confirmed by autopsy or imaging studies. Native Americans appeared to have lower rates

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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life of dementia as compared to whites. The Indianapolis-Ibadan study showed that Nigerians had lower rates of AD as compared to African Americans; prevalence rates in Nigeria appeared to be significantly lower than those for whites and Hispanics in the United States as well. Studies of Japanese Americans indicated that they have lower rates of AD than American and European whites, higher than Japanese living in Japan. The prevalence of dementia and AD were also lower in China than in the United States and Europe. Within Israel, risk for dementia and AD appeared to be higher among those of African or Asian background than among those of American or European background. The prevalence of AD in rural India appeared to be very low, and comparable with the rates of dementia found in Ibadan, Nigeria. The Nigerian data cast doubt on the theory that there is something inherent in African ancestry that connotes higher risk of AD. Rates of AD among African-American, Caribbean Hispanic, and non-Hispanic white participants in the New York City study (Gurland et al., 1998; Tang et al., 2001) appear to be higher than other studies. There are several possible explanations for these observed differences in rates of dementia across ethnic groups; we will discuss some of these factors in the following sections. These include statistical limitations, discrepancies in cognitive test performance, differential genetic factors, differences in prevalence of nongenetic medical risk factors, and differences in the social meaning and reaction to cognitive decline. Certainly, differential exposure to environmental risk factors may also help to explain ethnic group differences in frequency of AD; however, little work has been published addressing ethnic differences in these exposures. STATISTICAL LIMITATIONS A major problem in the studies reviewed here is that the concepts of ethnicity, race, and culture are often blurred, which can result in inconsistent and scientifically meaningless classification of people into groups (Lewontin, Rose, and Kamin, 1984; Wilkinson and King, 1987; Zuckerman, 1990). Because racial classifications are socially determined, changing over time and between geographical locations, different studies of “Hispanics” may yield incomparable findings because of the different populations gathered under that label. Although cross-national studies may offer powerful analyses of environmental and biological risk factors for cognitive impairment, it is important to remember that the meta-grouping of nationality is simply a proxy for the actual variables of interest, such as genetic makeup, cultural experience, or environmental exposure, and the conclusions that can be drawn from studies that do not measure these underlying factors are regrettably limited.

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