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Critical Perspectives on Racial and Ethnic Differences in Health in Late Life (2004)

Chapter: 4 Ethnic Differences in Dementia and Alzheimer’s Disease

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Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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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

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

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

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

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-

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

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).

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

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

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

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

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

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-

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

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.

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

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

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

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

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

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.

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

A number of basic socioeconomic variables are known to influence measures of cognitive and functional ability and to be associated with the risk of AD. Studies comparing ethnic groups within the United States, as well as comparing groups residing in different countries, face a challenge in proving that different rates of AD are due to racial or ethnic background and not simply a function of the vast disparities in socioeconomic factors that are almost always found between such groups.

The most common research strategy has been to attempt to correct for differences in socioeconomic status (SES) by using matching procedures, covariance, or other methods of statistical control. Several of the studies reviewed in the previous sections found that after correcting for years of education, there were “persisting” ethnic group differences in prevalence or incidence of AD. However, these methods depend on the assumption that there is no significant error in the measurement of SES indicators. This assumption is questionable in the extreme; large measurement error of SES variables such as educational attainment, occupation, and income is common because of their high vulnerability to differential unresponse, underreporting, and volatility over time (Elo, Preston, Rosenwaike, Hill, and Cheney, 1996). To conclude that biological or genetic factors drive differences in risk of AD between ethnic or cultural groups, researchers must deal with this problem of residual confounding.

Kaufman and colleagues have provided an excellent analysis of issues surrounding residual confounds in health outcome research (Kaufman and Cooper, 1995; Kaufman, Cooper, and McGee, 1997) that can also be directly applied to research on AD among ethnic and cultural groups. Sources of residual confounding include errors in categorization of the SES variable. Statistics such as income or education are often dichotomized, which introduces an assumption that individuals from each ethnic group within each category have equivalent social positions, or an equal distribution above and below the cutpoints. For example, if educational level is cut at 9 years, residual confounding will occur if the mean for African Americans below the cutpoint is 6 years and the mean for whites below the cutpoint is 8 years.

The use of aggregated SES measures can also inflate group effects; one simulation demonstrated that when SES was estimated for each ethnicity by using average income for that group, the effect of race as a predictor of outcome was inflated 38 percent as compared to a model where SES was estimated using individual values (Geronimus, Bound, and Neidert, 1996).

The final and most salient cause of residual confounding is incommensurability of SES variables. We use SES variables to “stand in” for unmeasured aspects of the cultural and social experience of ethnically diverse individuals. However, if the relationship between these unmeasured aspects

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

and the SES variable differs systematically between ethnic or cultural groups, the variable is not commensurate. One example is years of education, in which the difference in payoff for any given level of educational attainment is vastly different between ethnic groups. In other words, matching on quantity of formal education does not necessarily mean that the quality of education received by each ethnic group is comparable, nor does it mean that the occupational or economic opportunities associated with that education are the same (Baker, Johnson, Velli, and Wiley, 1996; Loewenstein, Arguelles, Arguelles, and Linn-Fuentes, 1994).

Not only does the educational system of the United States differ from that of many other countries, but the quality of education within the United States is also variable. African Americans educated in the South before the Supreme Court’s 1954 Brown v. Board of Education decision attended segregated schools, which were more poorly funded than white Southern schools and most integrated Northern schools (Anderson, 1988). Several researchers have demonstrated that school characteristics such as pupil expenditures, teacher quality, pupil-to-teacher ratios, presence of special facilities such as science laboratories, length of school year, and peer characteristics accounted for much of the difference in achievement and other outcomes (e.g., wage earnings) between African Americans and whites (Hanushek, 1989; Hedges, Laine, and Greenwald, 1994; Margo, 1985; O’Neill, 1990; Smith, 1984; Smith and Welch, 1977; Welch, 1966, 1973). African-American children were often employed or used as labor during the harvest, which reduced attendance during the year. This gap in “days attended” also contributes to differences in quality of education and literacy levels per “year” in school (Margo, 1990).

Despite this evidence that the number of years of education is an inconsistent estimate of educational experience when compared across ethnic groups, educational attainment remains the variable most commonly used by AD researchers to correct for differences in SES. The alternatives of income variables and occupational level are vulnerable to problems of incommensurability as well. Income level does not reflect standard value; that is, income is not equivalent to wealth because a certain level of income does not translate into the same resources, such as higher quality housing and health insurance, in minority communities.

Because of any one of these statistical factors, in a sufficiently large study race effects will always persist after adjustment, even if there is no true difference between groups. The problem is that effects that are actually from covariant factors are instead being attributed to race. When the concept of race is deconstructed into more meaningful variables (Kaufman and Cooper, 2001; Manly and Jacobs, 2001), the underlying reasons for racial or ethnic differences in rates of AD may be determined more definitively.

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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COGNITIVE TEST PERFORMANCE

Ethnic Differences and Cognitive Testing

The most commonly accepted research criteria for probable or possible AD (McKhann et al., 1984) require the diagnosis to be confirmed by neuropsychological tests demonstrating impairments of performance in memory and two other cognitive domains. However, few cognitive ability measures have been properly validated for use among ethnic minorities in the United States. Lack of such validation may account for the fact that, based on neuropsychological test performance, ethnic minorities are judged to be cognitively impaired more often than non-Hispanic whites. This section will review studies within and outside the United States that have compared the cognitive test performance of different ethnic groups, and describe constructs that might allow for more sophisticated investigations of ethnic differences in the future.

Use of the standard cutoff of 23 on the MMSE leads to overdiagnosis of dementia among African Americans, even after controlling for years of education (Bohnstedt, Fox, and Kohatsu, 1994). Racial, ethnic, and cultural differences have been found on MMSE performance and other screening measures before (Mast, Fitzgerald, Steinberg, MacNeill, and Lichtenberg, 2001; Unverzagt et al., 1996) and after adjusting for education (Escobar et al., 1986; Fillenbaum, Heyman, Williams, Prosnitz, and Burchett, 1990; Fillenbaum, Hughes, Heyman, George, and Blazer, 1988; Kuller et al., 1998; Salmon et al., 1989; Teresi, Albert, Holmes, and Mayeux, 1999; Welsh et al., 1995).

Difficulties in interpreting cognitive scores among ethnic minority elders are not limited to brief screening instruments; several studies have indicated that ethnic or cultural factors have a substantial effect on neuropsychological batteries (Adams, Boake, and Crain, 1982; Overall and Levin, 1978). Even when ethnic groups are matched on socioeconomic variables, discrepancies in neuropsychological test performance have remained (Jacobs et al., 1997; Kaufman, McLean, and Reynolds, 1988; Manly et al., 1998b; Reynolds, Chastain, Kaufman, and McLean, 1987). Roberts and Hamsher (1984) found that neurologically intact whites obtained significantly higher scores on a measure of visual naming ability than did neurologically intact African Americans, even after correcting for education level. Several other studies also reported ethnic differences in performance on tests of visual confrontation naming (Carlson, Brandt, Carson, and Kawas, 1998b; Lichtenberg, Ross, and Christensen, 1994; Ross, Lichtenberg, and Christensen, 1995; Welsh et al., 1995).

Ethnicity-related differences have been reported on measures of nonverbal abilities as well (Bernard, 1989; Brown et al., 1991; Campbell et al., 1996; Heverly, Ixaac, and Hynd, 1986; Miller, Bing, Selnes, Wesch, and Becker, 1993). Jacobs et al. (1997) found that Spanish-speaking elders

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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scored significantly lower than age- and education-matched English-speaking elders on a measure of nonverbal abstraction (i.e., the Identities and Oddities subtest from the Mattis Dementia Rating Scale); multiple-choice matching and recognition formats of the Benton Visual Retention Test; and measures of category fluency and comprehension. In another study, healthy Spanish-speaking Mexicans and Mexican Americans who lived near a U.S.-Mexico border (n = 200) were compared with residents of Madrid, Spain (n = 218). After accounting for education, borderland residents obtained significantly lower scores on measures of recognition discriminability for stories and figures, learned fewer details from a story over five trials, and made more perseverative responses on the Wisconsin Card Sorting Task (Artiola i Fortuny, Heaton, and Hermosillo, 1998). There were some interactions between years of education and place of birth, suggesting that among those with high levels of education, borderland and Spanish participants performed similarly on several measures.

Unverzagt et al. (1996) gave the CERAD neuropsychological test battery to 83 normal, nondemented African-American elders who volunteered from the local community. Their study found significant effects of years of education on several test scores. Its African-American sample was older and less well educated, and scored significantly lower on every measure than a previously collected sample of primarily white elders (Morris et al., 1989). This study also found that well-established cutoffs for dementia (i.e., MMSE below 24 and standard CERAD cutoffs) (Welsh, Butters, Hughes, Mohs, and Heyman, 1992) would misclassify a large percentage of these normal African Americans as demented.

In another study using the CERAD, the performance of elderly African-American and white representative community residents in North Carolina was compared with that of African Americans in Indianapolis and with whites in the Monongahela Valley, Pennsylvania (Fillenbaum, Heyman, Huber, Ganguli, and Unverzagt, 2001). Although on average African Americans performed more poorly than whites after controlling for demographic characteristics, no significant racial differences were found in the North Carolina sample. Both African-American and white participants in North Carolina performed more poorly than their racial counterparts in the other two studies.

A study in rural Virginia (Marcopulos, McLain, and Giuliano, 1997) compared neuropsychological test performance between 69 African-American and 64 non-Hispanic white nondemented, community-dwelling elders, all of whom had less than 10 years of formal education. Although education accounted for a significant amount of variance in nearly every measure that was administered, race was an independent predictor of performance on WAIS-R Vocabulary and Block Design subtests, as well as Wechsler Memory Scale-Revised (WMS-R) Logical Memory Delay.

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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Manly et al. (1998a) found that after matching neurologically normal African-American and white groups on age and years of education, there were significant ethnic group differences on measures of figure memory, verbal abstraction, category fluency, and visuospatial skill. These discrepancies in test performance of education-matched African Americans and whites could not be accounted for by occupational attainment or history of medical conditions such as hypertension and diabetes.

In contrast, a number of studies have failed to find discrepancies in test performance among racial, ethnic, or cultural groups after participants were matched on years of education (Ford, Haley, Thrower, West, and Harrell, 1996; Marcopulos et al., 1997), after statistically adjusting for education (Loewenstein, Ardila, Rosselli, and Hayden, 1992; Marcopulos et al., 1997; Mungas, Marshall, Weldon, Haan, and Reed, 1996), or after cutscores were adjusted for those with low education (Murden, McRae, Kaner, and Bucknam, 1991). However, the statistical power to detect a significant difference in some of these studies was severely limited by their small sample sizes of nonwhite participants. For example, there were no significant ethnic differences among a small number of African Americans (n = 11) and whites (n = 32) with AD on measures of naming, picture vocabulary, verbal abstraction, verbal list learning, and pragmatic language use after controlling for MMSE score and years of education (Ripich, Carpenter, and Ziol, 1997). Another study found that among 18 black and 114 white participants who met NINCDS-ADRDA criteria for AD, there were no significant differences by race on decline in MMSE score over an average 2.5-year period, whereas left-handedness, more years of education, and family history of dementia were associated with more rapid decline (Rasmusson, Carson, Brookmeyer, Kawas, and Brandt, 1996).

A meta-analysis of studies published between 1973 and 1994, which conducted cross-cultural comparisons of cognitive test scores, revealed that cross-cultural differences were, as expected, greater in cross-national comparisons than intranational cross-ethnic comparisons. Cross-cultural differences in test performance increased with age and were most pronounced when the discrepancies in affluence between the groups were greatest. Differences in performance were also larger on tests developed in the West as compared to tests developed in non-Western areas. Differences were present across many cognitive domains, and were not limited to tasks that purported to assess abstract abilities (van de Vijver, 1997).

Taken together, most previous studies of ethnic group differences in performance on the MMSE and neuropsychological tests have shown that discrepancies between scores of different ethnic groups persist, despite equating groups on other demographics such as age, education, gender, and socioeconomic background. These discrepancies cause attenuated specificity of verbal and nonverbal neuropsychological tests, such that

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

cognitively normal ethnic minorities are more likely to be misdiagnosed as impaired as compared to whites (Ford-Booker et al., 1993; Klusman, Moulton, Hornbostle, Picano, and Beattie, 1991; Manly et al., 1998b; Stern et al., 1992; Welsh et al., 1995). These findings indicate that not all tasks are functionally equivalent (Helms, 1992; Ratcliff et al., 1998). Although establishing test norms for each ethnic group may help with misdiagnosis (Miller, Heaton, Kirson, and Grant, 1997), there is variability of educational and cultural experiences within ethnicity that may decrease the accuracy of these norms. In the following sections, we will review research that has focused on the effects of within-group factors on cognitive test performance.

Years of Education/Quality of Education/Literacy

Extreme differences in educational level are often found between ethnic minorities and whites or between residents of developed and undeveloped countries. Illiteracy rates in the United States are highest among people aged 65 and over, but are especially elevated among ethnic minority elders (Kirsch, Jungeblut, Jenkins, and Kolstad, 1993). Cross-cultural researchers are therefore challenged to find measures that are sensitive to cognitive impairment across these broad educational backgrounds (Ratcliff et al., 1998). Although it is common for investigators to use covariance, matching procedures, or education-corrected norms in order to “equate” ethnic groups on years of education before interpreting neuropsychological test performance, as discussed earlier, these techniques ignore ethnic discrepancies in quality of education. Therefore, disparate school experiences could explain why many ethnic minorities obtain lower scores on cognitive measures even after controlling for years of education.

Presence of poor literacy skills among elders is a particularly relevant issue for neuropsychologists attempting to accurately detect dementia using cognitive measures. Reading level, as measured by a bilingual measure of reading comprehension, was found to be more related to MMSE score than were years of education, age, or ethnicity (Weiss, Reed, Kligman, and Abyad, 1995). These results suggest that interpretation of cognitive test performance is more dependent on knowledge of literacy or reading skills than years of education. Nevertheless, only a few studies have been conducted to identify ways to accurately assess literacy and reading level among elders that differ ethnically (Baker et al., 1996; Boekamp, Strauss, and Adams, 1995) and linguistically (Del Ser, Gonzalez-Montalvo, Martinez-Espinosa, Delgado-Villapalos, and Bermejo, 1997).

Our group recently reported a study that sought to determine if discrepancies in quality of education could explain differences in cognitive test scores between African-American and white elders matched on years of edu-

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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cation. A comprehensive neuropsychological battery was administered to a sample of nondemented African-American and non-Hispanic white participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. The Reading Recognition subtest from the Wide Range Achievement Test-Version 3 (WRAT-3) was used as an estimate of quality of education. African-American elders obtained significantly lower scores than whites on measures of word list learning and memory, figure memory, abstract reasoning, fluency, and visuospatial skill even though the groups were matched on years of education. However, after adjusting the scores for WRAT-3 reading score, the overall effect of race was greatly reduced and racial differences on all tests (except category fluency and a drawing measure) became nonsignificant. Reading score also attenuated the effect of race after accounting for an estimate of test-wiseness, or familiarity with the testing situation. This finding suggests that years of education is an inadequate measure of the educational experience among multicultural elders, and that adjusting for quality of education may improve the specificity of certain neuropsychological measures across racial groups.

Despite the clear improvement in specificity that is provided by adjusting cognitive test scores for differences in educational experience across ethnic groups, some researchers caution against controlling for educational variables in studies of dementia because low education may itself be a risk factor for disease. The logic behind this argument will be discussed in the section on the nongenetic risk factor of cognitive reserve.

Acculturation

Most previous research on ethnicity has classified participants on the basis of physical appearance or self-identified racial/ethnic classification, rather than measuring the cultural variables that accompany ethnic group membership. However, as suggested by Helms (1992), specification of experiential, attitudinal, or behavioral variables that distinguish those belonging to different ethnic groups, and that also vary among individuals within an ethnic group, may allow investigators to understand better the underlying reasons for the relationship between ethnic background and cognitive test performance.

Level of acculturation is one way in which social scientists have operationalized within-group cultural variability. Acculturation is defined as the level at which an individual participates in the values, language, and practices of his or her own ethnic community versus those of the dominant culture (Landrine and Klonoff, 1996; Padilla, 1980). Previous studies have identified ideologies, beliefs, expectations, and attitudes as important components of acculturation, as well as cognitive and behavioral characteristics

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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such as language and customs (Berry, 1976; Moyerman and Forman, 1992; Negy and Woods, 1992; Padilla, 1980).

Few studies have examined the relationship of cognitive test performance to within-group ethnic or cultural factors independent of those associated with SES. Arnold and colleagues (Arnold, Montgomery, Castenada, and Longoria, 1994) found a relationship between Hispanic acculturation and performance on selected tests of the Halstead-Reitan Battery among college students. Artiola i Fortuny et al. reported that among Mexican and Mexican-American residents of a U.S.-border region, percentage of life in which individuals lived in the United States was significantly and negatively related to number of words generated on a Spanish oral fluency measure, especially among those with fewer than 8 years of education. In addition, those who spent a larger percentage of their life in the United States made more perseverative errors on the Wisconsin Card Sorting Test, and bilingualism accounted for a significant amount of variance in performance on a Spanish Verbal Learning Test (Artiola i Fortuny et al., 1998).

Three studies have explored the relationship of African-American acculturation (as measured by the African American Acculturation Scale) (Landrine and Klonoff, 1994, 1995) to cognitive test performance. Manly et al. (1998c) found that among neurologically intact African Americans between the ages of 20 and 65, those who were less acculturated (more traditional) obtained lower scores on measures of general information and naming than more acculturated African Americans. Among elderly residents of Northern Manhattan (Manly et al., 1998b), acculturation accounted for a significant amount of variance in several neuropsychological measures assessing verbal and nonverbal abilities after accounting for age, education, and gender. Among elderly African Americans living in Jacksonville, Florida, acculturation accounted for a significant amount of variance in Verbal IQ (as measured by the Wechsler Adult Intelligence Scale), Boston Naming Test, and delayed recall of stories from the WMS-R (Lucas, 1998).

Taken together, investigations of acculturation level suggest that there are cultural differences within elders of the same ethnicity that relate to neuropsychological measures of verbal and nonverbal skills, and that accounting for acculturation may improve the accuracy of certain neuropsychological tests. Although previous research has focused on ethnic minority elders in the United States, it is likely that within-group cultural differences are also significant factors in the test performance of American elders who identify themselves as white or Caucasian, as well as ethnic groups outside the United States.

Racial Socialization

Level of comfort and confidence during the testing session may also vary among ethnic groups. The concept of stereotype threat has been described as

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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a factor that may attenuate the performance of racial minorities on cognitive tests. Stereotype threat describes the effect of attention diverting from the task at hand to the concern that one’s performance will confirm a negative stereotype about one’s group. Steele and colleagues (Steele, 1997; Steele and Aronson, 1995) demonstrated that when a test consisting of difficult verbal GRE exam items was described as measuring intellectual ability, black undergraduates at Stanford University performed worse than SAT score-matched whites. However, when the same test was described as a “laboratory problem-solving task” or a “challenging test” that was unrelated to intellectual ability, scores of African Americans matched those of white students. Researchers have also shown that when gender differences in math ability were invoked, stereotype threat undermined performance of women on math tests (Spencer, Steele, and Quinn, 1999) and among white males (when comparisons to Asians were invoked) (Aronson et al., 1999). The role of stereotype threat in neuropsychological test performance of African Americans and Hispanics has not been investigated to date. In addition, it is likely that the salience of negative stereotypes differs among racial minorities, and therefore, stereotype threat will likely affect some test takers more than others. Investigation of the experiential, social, and cultural variables that affect vulnerability to stereotype threat should be examined.

Linguistic Issues
Translation of English-Language Tests

Clinicians and researchers sometimes erroneously assume that instruments are equivalent across populations as long as the test is administered in the native language of the individual. However, literal translation may not produce items with comparable word frequency and/or salience in each culture, resulting in different difficulty levels (Sano et al., 1997; Teng, 1996). In addition, idiosyncrasies of different languages may introduce problems in equating certain tests. For example, when asked to name as many animals as possible in a minute, Hispanics produce fewer exemplars than do Vietnamese. This discrepancy can be explained by the fact that most animal names in Spanish are multisyllabic, while most animal names in Vietnamese are monosyllabic (Kempler, Teng, Dick, Taussig, and Davis, 1998).

Translators of cognitive measures must use extreme caution and proper methods to adapt measures into another language. Artiola i Fortuny and Mullaney (1997) describe several examples of Spanish versions of tests that include syntactic, lexical, and spelling errors. These authors also suggest that investigators consult only those who possess native fluency and indepth knowledge of the culture before attempting to translate a measure. The accuracy of translated and adapted instruments should be checked

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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following established guidelines (Ardila, Rosselli, and Puente, 1994; Artiola i Fortuny and Mullaney, 1997; Brislin, 1970, 1980; Dick, Teng, Kempler, Davis, and Taussig, 2002; Fuld, Muramoto, Blau, Westbrook, and Katzman, 1988; Hall et al., 1996; LaCalle, 1987; Mungas, 1996; Ponton et al., 1996; Ritchie and Hallerman, 1989; Salmon, Jin, Zhang, Grant, and Yu, 1995; Teng et al., 1994; van de Vijver and Hambleton, 1996). Researchers and clinicians must also develop standards to determine in which language bilinguals should be assessed (Ponton et al., 1996).

Translation of measures is not simply a linguistic issue; measures must be culturally equivalent as well. That is, it must be determined whether the use of a particular test format to assess the cognitive skill of interest is equally valid within every culture in which the test will be administered (Teng, 1996; Teng et al., 1994).

Norms

Investigators must be aware that the published norms for tests administered in English are not necessarily valid when the tests are administered in another language. Furthermore, they should not assume that test norms can be applied to distinct populations simply because they share a language. For example, there is evidence that several instruments developed in Spanish-speaking countries may not be functionally or linguistically equivalent when used among Spanish speakers in the United States (Artiola i Fortuny et al., 1998). Similarly, tests and norms developed among a particular group of immigrants to the United States (e.g., Cuban Americans) may not be valid among other groups in the United States who share a language (e.g., Dominicans or Puerto Ricans) (Loewenstein et al., 1994).

Use of Interpreters

Misinterpretation is a serious threat to the reliability and validity of testing. Family members are often used as translators, but are not likely to be objective. Even translators who are reasonably fluent in both languages may not be familiar with many of the terms used in neuropsychological testing (Ardila et al., 1994; LaCalle, 1987). Increasing the linguistic diversity of testers and improving the availability of objective translators are thus worthwhile goals for investigators; when this is not feasible, the possibility of misinterpretation must be considered when interpreting results.

Development of Cross-Cultural Cognitive Tests

A number of measures have been adapted for use in different cultures and for multiple languages, and proven to be useful in distinguishing de-

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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mented and nondemented elders in cross-cultural studies. The multiple sources of difficulty in linguistic and cultural test adaptation will often make it preferable to use a preexisting measure that has been validated; unfortunately, much work remains to be done in this area.

Fuld et al. (1988) compared a small number of [Japanese and white American] elders on the Fuld Object-Memory Test, a measure of memory for common objects. The Japanese and American groups were of similar educational and occupational attainment and were diagnosed as nondemented based on mental status exams. There were no differences in total recall between the two groups among elders aged 70 to 79. However, the 80- to 89-year-old Japanese group obtained slightly but significantly higher scores than both Americans (of all ages) and Japanese aged 70 to 79. The authors suggested that the manner in which participants were selected in Japan and the United States might have contributed to these findings; however, the results indicated that, for at least some groups, the Fuld Object Memory Test measured comparable cognitive functions in both cultures.

The Cognitive Abilities Screening Instrument (CASI) (Teng, 1996; Teng et al., 1994) was described as a family of similar tests designed for easy adaptability for cross-cultural research. The CASI has been adapted for use among elderly speakers of English, Japanese, Chinese, Vietnamese, and Spanish residing within a number of cultural and socioeconomic environments. The majority of the items were taken from the MMSE and the Hasegawa Dementia Screening Scale, and the measure has been shown to have acceptable sensitivity and specificity as a dementia screening instrument.

The Cross-Cultural Neuropsychological Battery (Dick et al., 2002) includes the CASI and 10 neuropsychological tests assessing memory for common objects, language, visuospatial skill, attention, reasoning, and psychomotor speed. Norms for the battery have been generated using 336 normal elders who identify as African American, white, Chinese, Hispanic, or Vietnamese. The authors found that years of education and ethnicity accounted for a significant amount of variance in performance on every measure except the learning, delayed recall, and recognition on the Common Objects Memory Test. These measures may be suitable for direct comparison between cultures, while for the rest of the battery, the use of norms may allow groups to be compared. However, further research is needed to determine the sensitivity and specificity of the Cross-Cultural Neuropsychological Battery to detect subtle cognitive impairment and early AD among ethnically diverse elders.

Salmon et al. (1995) reported the successful translation and adaptation of several neuropsychological measures (including the Fuld Object Memory Test, Boston Naming Tests, Category Fluency Tests, Wechsler Adult Intel-

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

ligence Scale Vocabulary, Digit Span, and Digit Symbol subtests, Wechsler Intelligence Scale for Children-Revised Block Design subtest, Clock Drawing Tests, and Trail Making Test) for detection of dementia among Chinese elders participating in the Shanghai Dementia Survey. However, some items, especially tasks that required elders to draw, were influenced by both educational and cultural factors. Another cognitive screening instrument (the CSID) was developed and validated in a study comparing Cree Indians in Manitoba to European Manitobans (Hall et al., 1996), and was applied to a sample of African Americans in Indiana and Yorubans in Ibadan, Nigeria. Although there were significant ethnic group differences in individual items of the instrument and total score, these differences resolved after accounting for years of education. Ritchie and Hallerman (1989) found that among 78 elderly Israelis of diverse ethnic background (i.e., Russian, Moroccan, Polish, Argentine, and Iraqi), raw scores from the Iowa Screening Battery had acceptable sensitivity and specificity (82.2 percent and 80.6 percent, respectively) measured against the diagnosis of dementia based on a neurologist’s and neuropsychologist’s clinical examination.

Sano et al. (1997) used established translation and adaptation methods to test the validity of a number of global severity measures among 94 Spanish speakers and 306 English speakers. The MMSE, Clinical Dementia Rating Scale, Global Deterioration Scale, and Functional Assessment Staging proved able to discriminate participants with AD from controls and were all equally sensitive to disease severity. Mungas and colleagues also report the successful development of a neuropsychological test battery for English and Spanish speakers (Gonzalez, Mungas, Reed, Marshall, and Haan, 2001; Mungas, 1996; Mungas et al., 1996; Mungas, Reed, Marshall, and Gonzalez, 2000).

Although these findings are encouraging, more work is needed to be certain that the proposed cross-cultural measures are truly free of bias; many of these studies had a relatively limited number of subjects in each ethnic group studied, so it remains possible that the researchers were simply unable to detect the cultural biases that existed in their measures.

GENETICS

The APOE ε4 Story

Differences in genetic background could contribute to the disparate rates of dementia and AD among ethnic groups. Because of the identification of the APOE ε4 allele as a major risk factor for the development of AD (reviewed in Farrer et al., 1997; Kamboh, 1995; Roses, 1996), and an apparent protective effect of the ε2 allele among whites, several investigations (Corder et al., 1995) have focused on the role of APOE polymor-

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

phisms in the development of AD among other ethnic groups. Racial (Gerdes, Klausen, Sihm, and Faergeman, 1992; Kamboh, Sepehrnia, and Ferrell, 1989) and geographic (Lucotte, Loirat, and Hazout, 1997; Zekraoui et al., 1997) differences in the frequency of the APOE ε4 allele create opportunities to investigate the independent effects of genetics and environment on development of AD. It has also been suggested that racial differences affect the linkage between the ε4 allele and the density of SPs and number of NFTs found in the brain (Itoh and Yamada, 1996). Investigations of the risk associated with the APOE ε4 allele in different ethnic or cultural groups are currently taking place throughout the world.

Studies in the United States

A series of case-control studies (Maestre et al., 1995; Mayeux et al., 1993; Tang et al., 1996) comparing ethnic groups in the Washington Heights-Inwood Columbia Aging Project’s (WHICAP’s) community-based random sample found different degrees of association between AD risk and presence of the APOE ε4 allele. Among African Americans the association of the APOE ε4 allele to AD was weak or absent, but it was significant among white study participants. The ε4-associated risk among Hispanics in this project was intermediate to that of African Americans and whites.

The relationship between APOE genotype and ethnicity was investigated among elders with late-onset AD in Florida (Duara, Barker, Lopez-Alberola, and Loewenstein, 1996). Participants were classified into four ethnic groups: Ashkenazi Jewish (n = 100), Hispanic (n = 46), non-Hispanic white (n = 30), and African American (n = 19). Diagnosis of probable or possible AD was made using NINCDS-ADRDA criteria. The investigators found that age of onset was later in Ashkenazi Jewish elders than among African-American, Hispanic, and non-Hispanic non-Jewish whites. The ε4 allele frequency was 29 percent for the entire sample, which is significantly different from the 13.7 percent frequency reported among normal subjects aged 45 and over. These investigators found no ethnic differences in frequency of the ε4 allele (Ashkenazi Jewish = 30 percent; African American = 29 percent; Hispanic = 28 percent; and non-Hispanic non-Jewish white = 33 percent) or the ε2 allele. A later case-control study by the same group found that although the ε4 allele is a risk factor for AD among white non-Hispanics (392 AD patients, 202 normal subjects) and white Hispanics (188 AD patients, 84 normal controls) (Harwood et al., 1999), other risk factors such as low education and hypertension appear to be important only for white non-Hispanics.

A meta-analysis (Farrer et al., 1997) of raw data provided by 40 research teams, comprising 5,930 elders with AD and 8,607 normal controls, examined the association between APOE genotype and AD within four

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

ethnic groups (whites, African Americans, Hispanics, and Japanese). Although there was an elevated frequency of APOE ε4 allele among elders with AD from every ethnic group, the ε4 allele’s association with AD among whites was weaker than that of Japanese, but stronger than that of African Americans. The investigators found that among Hispanics, the ε3/ε4 genotype was associated with a significant risk for AD, but the ε4/ε4 genotype did not confer an increased risk, which they attributed to the small number of Hispanics who were homozygous for the ε4 allele.

All the studies described computed the risk associated with possession of an ε4 allele by using the ε3/ε3 genotype as a reference group. An incidence study by Tang et al. (1998) used a different approach by comparing participants in a longitudinal, random community cohort in Northern Manhattan (WHICAP) with and without the ε4 allele. African Americans and Hispanics with one or more ε4 allele were as likely to develop probable or possible AD as were whites; however, African Americans and Hispanics without an ε4 allele were two to four times more likely than whites to develop AD by age 90. Years of education did not account for these ethnic differences in AD incidence, and reclassifying elders who developed only mild disease (Clinical Dementia Rating Scale of 0.5) as normal did not alter the findings.

Indianapolis-Ibadan Study

In a pilot study, Hendrie and his colleagues (1995a) examined the APOE genotypes of the first 85 African-American participants in the Indianapolis study who were either normal (n = 54) or diagnosed with AD (n = 31) using NINCDS-ADRDA criteria. The frequency of the ε4 allele was 13.9 percent among normal African-American elders and 40.3 percent among African-American elders with AD. The investigators found that 22.6 percent of those with AD were homozygous for the ε4 allele, while only 3.7 percent of the normal controls were homozygous. The odds ratio (OR) associated with one copy of the ε4 allele was 4.14, while the OR associated with two copies of the ε4 allele was 17.16. This estimate of risk was at least as high as that found among white populations. The authors suggested that the overall frequency of the ε4 allele in their sample (13.9) was smaller than the reported frequency for the African-American population (26 percent) because of the general decrease in frequency of the ε4 allele with age (differential mortality). The risk associated with having an ε4 allele appeared to be independent of ethnic background.

At about the same time, these researchers reported an association between the presence of an ε4 allele and AD among Nigerians living in Ibadan (Osuntokun et al., 1995). Using NINCDS-ADRDA criteria, 12 elders with AD and 39 normal controls were identified from the community survey. There

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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were no significant differences in the frequency of the ε4 allele between controls (20.5 percent) and elders with AD (16.7 percent). The authors noted that the frequency of the ε4 allele was higher among the Nigerian controls than among the African-American participants in Indianapolis, and concluded that differences in the expression of APOE ε4 allele or its receptors may explain its lack of association with AD. They also suggested the possibility that the presence of other genetic or environmental factors could intensify the effects of ε4 in those populations for which this genotype was a risk factor for AD.

In a follow-up to their pilot study (Sahota et al., 1997), the Indianapolis-Ibadan group examined a larger sample of 288 African-American participants, 60 of whom were diagnosed with AD using NINCDS-ADRDA criteria. They found that the OR was 4.83 for AD with the ε4/ε4 genotype, but did not reach significance for the ε3/ε4 genotype. The frequency of the ε4 allele among those with AD was significantly higher than it was among controls (34.17 percent versus 21.76 percent, respectively). It was also found that the ε2 allele was less frequent in the AD group than in the control group (4.17 percent versus 10.65 percent, respectively). These results did not change after the removal of elders who had cognitive impairment, but were not demented, from the control group. The investigators noted that their original findings were likely due to sampling bias, and concluded that the association between the APOE allele and AD among African Americans was weaker than that found among whites. Together with the Nigerian data, they suggested that other genetic or environmental factors reduced the ε4-associated risk for AD in populations of African origin.

Indo-U.S. Study

International differences in the APOE genotype risk of AD were also examined in the Indo-U.S. case-control study, which sampled individuals from two rural communities: Elders aged 55 or older in Ballabgarh, India (n = 4,450), and elders aged 70 or older in the Monongahela Valley region of Southwestern Pennsylvania (n = 886). Although frequency of APOE ε4 was significantly lower in Ballabgarh as compared to the Monongahela Valley, the association of the APOE ε4 allele with AD was the same across Indian and U.S. groups.

Cherokee Indians and AD

A small study performed among Cherokee Indians found no relationship between APOE genotype and AD diagnosis. However, there was a relationship of Cherokee ancestry with risk for AD: AD patients with a greater than 50 percent genetic degree of Cherokee ancestry constituted only 35 percent of the group with AD. In contrast, 17 (65 percent) of the

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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control subjects were more than 50 percent Cherokee. Unfortunately, this remains the only research assessing the relationship between APOE genotype and AD risk among Native Americans.

Dominican Republic and the Caribbean

In contrast to sporadic AD, late-onset familial AD among Caribbean Hispanics is strongly associated with APOE ε4. A study of 203 Caribbean Hispanic families residing in the greater New York City area, the Dominican Republic, and Puerto Rico found that the presence of the APOE ε4 allele was strongly associated with AD. In addition, 8 of the 19 families with at least 1 family member with onset of dementia before age 55 showed an association with a previously unreported presenilin mutation. The same group found modest evidence of linkage to loci on chromosome 12p among 79 Caribbean Hispanic families with AD, which varied by age at onset of AD and by the presence or absence of the APOE-ε4 allele.

Summary

Taken together, the finding of ethnic variability in the association between AD and APOE ε4 could mean the following:

  • The ε4 allele is in linkage disequilibrium with an AD susceptibility locus, rather than a direct cause of the disease. However, this possibility is unlikely because the APOE-AD association has been confirmed worldwide.

  • African Americans and Hispanics may have genes modifying the expression of APOE. This is possible because regulatory sequences in enhancer/promoter regions of APOE are associated with modification in disease risk.

  • Factors such as head injury or coronary artery disease may modify the biological effect of the ε4 allele.

Cross-national studies offer great promise in resolving these possibilities because they permit environmental risk factors for AD to be distinguished from genetic causes. However, they all suffer from the difficulty of accurately identifying parental populations for genetic studies that use admixed groups to map disease genes (Parra et al., 1998).

In addition, our ability to draw conclusions from these studies is hampered by many of the same issues that confound interpretation of studies of prevalence and incidence, such as small sample sizes and differences in identification of cases and controls; sampling strategies; definitions of race and ethnicity; and methods for measuring the risk associated with the possession

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

of a particular APOE genotype (i.e., differences in reference group). When studies do not sufficiently address these problems, the generalizability of their results, as well as our ability to resolve discordant findings, is limited.

NONGENETIC RISK FACTORS

Stroke

Compared to non-Hispanic whites, African Americans have a 2.4-fold and Hispanics a twofold increase in stroke incidence (Sacco et al., 1998). Among patients with dementia, a higher proportion of African Americans and Asian/Pacific Islanders were found to have vascular dementia than whites and Hispanics (Gorelick et al., 1994). Therefore, cerebrovascular disease could partially explain higher rates of dementia among African Americans when all subtypes are considered together. It is also possible that vascular disease could help to explain higher incidence of AD among African Americans and Hispanics; among elders who meet the neuropathologic criteria for AD, those with concomitant lacunar infarcts are more likely to clinically express dementia (Snowdon et al., 1997). If this is the case, African Americans, who are at higher risk for stroke, may be at higher risk to develop the clinical signs of dementia even though they may be just as likely as whites to have AD pathology. One possible mechanism may be that silent infarcts decrease cognitive reserve and thus the brain’s ability to compensate for AD pathology (Moroney et al., 1997).

Hypertension

The high prevalence of hypertension among African Americans is well known, and the frequency of hypertension is further increased among African Americans with Alzheimer’s disease (Gorelick et al., 1994; Hargrave, Stoeklin, Haan, and Reed, 1998; Yeo et al., 1996). Hypertension places African Americans at higher risk for neurovascular pathology that is often found among people diagnosed with AD such as cerebral amyloid angiopathy, white-matter lesions, and vascular endothelial damage (Shadlen et al., 2000). However, the role this neurovascular pathology plays in AD and its significance remains uncertain.

Diabetes

Prevalence of diabetes is higher in African Americans and Hispanics; therefore, it is possible that this disorder, or the cardiovascular problems that go along with it, can help explain elevated rates of AD in these ethnic groups as compared to whites. The mechanisms underlying a possible

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

association between diabetes and AD are unclear, but include the possibility that the production of glycation end products increase Alzheimer’s pathology (Sasaki et al., 1998; Smith, Sayre, and Perry, 1996). However, elevated plasma levels of glucose and insulin are associated with reductions in plasma amyloid precursor protein (Boyt et al., 2000), and insulin decreases β-amyloid neurotoxicity in vitro (Takadera, Sakura, Mohri, and Hashimoto, 1993). A more tenable explanation is that the presence of diabetes increases the possibility that an individual will have a stroke or small-vessel disease, both of which increase the risk of AD and dementia diagnosis.

Studies of the relationship between diabetes mellitus and AD have produced conflicting results. Three longitudinal studies have reported an increased risk of dementia, including AD, among persons with diabetes (Brayne et al., 1998; Leibson et al., 1997; Ott et al., 1996, 1999). These studies had a limited ability to detect vascular dementia. If cases of stroke-associated dementia are misclassified as cases of AD, risk factors for stroke-associated dementia can appear to predict AD. One study found a relation of diabetes with vascular dementia (defined by criteria established by the California State Alzheimer’s Disease Diagnostic and Treatment Centers) but not with AD (defined by NINCDS-ADRDA criteria; McKhann et al., 1984). A recent study (Luchsinger, Tang, Stern, Shea, and Mayeux, 2001) followed 1,262 ethnically diverse elders who were not demented at baseline for approximately 4.3 years. The adjusted relative risk for the composite outcome of Alzheimer’s disease and cognitive impairment without dementia (or stroke) in subjects with diabetes was significant, at 1.6, whereas the adjusted relative risk of stroke-associated dementia in persons with diabetes was 3.4. Among blacks and Hispanics, one-third of the risk of stroke-associated dementia was attributable to diabetes as compared with 17 percent among whites. The risk for diabetes in relation to stroke-associated dementia varied by ethnic group; it was approximately twice as great in Hispanics and blacks as in whites.

Myocardial Infarction/Coronary Artery Disease

Coronary artery disease mortality is higher among African Americans and Hispanics than among whites (Williams, Massing, Rosamond, Sorlie, and Tyroler, 1999), and there is higher prevalence of risk factors for myocardial infarction, such as higher rates of diabetes among black and Mexican-American women and higher rates of hypertension among black men and women (Sundquist, Winkleby, and Pudaric, 2001). Because history of myocardial infarction and coronary artery disease have been associated with higher rates of dementia and presence of diffuse plaques in the brain, this health disparity may also contribute to epidemiologic observations of

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

higher rates of AD among African Americans and Hispanics. It is possible that increased β-amyloid deposits in the neuropil and within neurons occur in the brains of nondemented individuals with heart disease (Aronson et al., 1990; Sparks et al., 1990). Individuals with two APOE ε4 alleles have higher plasma cholesterol, and are thus at higher risk for myocardial infarction (Sparks, Martin, Gross, and Hunsaker, 2000).

Head Injury

Head injury is a frequently reported risk factor for AD (reviewed in Kawas and Katzman, 1999). The most likely biological mechanism for an association between head injury and AD is that insult to the brain leads to increased production of β-amyloid containing diffuse plaques. One study found a 10-fold increase in the risk of AD with both an APOE ε4 allele and a history of traumatic head injury, but head injury in the absence of an APOE ε4 allele did not increase risk (Tang et al., 1996).

Given the evidence for this connection, the fact that an increased risk of traumatic brain injury has been reported among ethnic minority populations (Collins, 1990; Rosenthal and Ricker, 2000) might contribute to disparities in risk for AD. Supporting evidence comes from the finding that African-American patients with AD were more likely to have a history of head injury than African Americans with vascular dementia (Gorelick et al., 1994).

Exposure to Possible Protective Factors

Nonwhite and Hispanic women are less likely to receive counseling about estrogen replacement therapy from their physician and less aware of its health benefits (Gallagher, Geling, FitzGibbons, Aforismo, and Comite, 2000; Ganesan, Teklehaimanot, and Norris, 2000). Access to and utilization of health care is significantly lower among ethnic minorities than among whites in the United States. Therefore, there may be less exposure to possible protective factors for AD, including estrogen replacement therapy and antiinflammatory drugs. Ethnic differences in diet and vitamin intake may reduce exposure to antioxidants, which may also protect the brain from AD pathology.

Cognitive Reserve

Cognitive reserve is another possible explanation for ethnic differences in rates of dementia and AD. Studies of ethnically diverse samples indicate that lifetime experiences, reflected in years of education or occupational level, may be independent risk factors for incidence of dementia and cognitive impairment (Callahan et al., 1996; Stern, 2002; Stern et al., 1994). This

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
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has led to the proposal that educational and occupational experience provide a “cognitive reserve” against clinical manifestation of Alzheimer’s neuropathology. In a recent review, Yaakov Stern conceptualized reserve as comprising both active and passive models (Stern, 2002). In the first model, the brain actively copes with AD pathology through compensation or more efficient use of brain networks. The passive model holds that innate ability or life experience determines the threshold of brain damage necessary to produce cognitive deficit. Operationalization of cognitive reserve includes measures of SES, such as years of education, income, or occupational attainment; anatomic measures such as brain size or synaptic count; or cognitive measures such as IQ.

Ethnic groups often have different levels of SES, and these SES variables may reflect either lack of educational or occupational experiences that contribute to cognitive reserve, or risk factors such as poor nutrition, toxic exposures, or poor health care that may diminish cognitive reserve. For example, cognitive decline appears to be faster (Stern, Albert, Tang, and Tsai, 1999; Unverzagt, Hui, Farlow, Hall, and Hendrie, 1998;) and associated with increased risk of mortality (Stern, Tang, Denaro, and Mayeux, 1995) among highly educated ethnic minorities. The cognitive reserve theory would explain this finding by stating that enriched educational experience produced an increased reserve in these individuals, delaying the onset of mental deterioration and thus reducing the interval between the initiation of memory loss and severe disability from dementia. In another study, childhood residence (rural versus urban) and educational level was evaluated in a random sample of 223 African-American elders, 180 of whom were neurologically normal and 43 of whom had AD (Hall, Gao, Unverzagt, and Hendrie, 2000). Childhood rural residence, combined with fewer than 7 years of school, was associated with an increased risk of AD. The authors hypothesized that low education by itself is not a major risk factor, but is a marker for other deleterious socioeconomic or environmental influences in childhood.

Operationalization of cognitive reserve is especially challenging among ethnic minorities. Variables such as years of education are often used as a proxy for an individual’s degree of cognitive reserve. However, these variables may not necessarily represent native ability, especially among elders whose educational and occupational opportunities were limited because of institutionalized racism and poverty. When number of years of education is used to represent an experience that increased the brain’s resistance to pathology or provided the brain with reserve, we cannot be sure that the same quantity of education provided the same quality of experience across ethnic groups. In addition, investigators must avoid confounding measures of reserve with outcome indicators. For example, IQ measures may be used to represent brain reserve, but the disease process itself may also affect such

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

measures. Ideally, we would be able to use childhood measures of cognitive ability to predict development of dementia late in life. This was elegantly demonstrated in studies showing that low scores on measures of intelligence in childhood (Whalley et al., 2000) and low linguistic ability in the early 20s (Snowdon et al., 1997) were associated with low cognitive test scores and dementia late in life. This kind of research is limited among ethnic minorities, however, if the cognitive measure administered did not accurately reflect true cognitive ability due to cultural effects on test performance.

Discrepancies in quantity and quality of education, literacy, and the limitations placed on occupational attainment by institutionalized racism may help to explain the increased rates of dementia and AD among ethnic minorities and illiterate individuals. Nevertheless, a notable finding from the studies discussed earlier in this chapter is that the lowest incidence of dementia is found in rural India and West Africa, areas where elders have low levels of education and literacy. These disparate findings may be clarified in the future if longitudinal studies of cognitive reserve are conducted in both Western and non-Western countries.

CULTURAL BELIEFS ABOUT DEMENTIA AND COGNITIVE DECLINE

Social and cultural differences in the meaning of dementia and beliefs about cognitive decline among elders may play a part in the different rates of AD by ethnicity, and may also explain the lack of consensus on rates of AD across studies. Cultural values may include beliefs that dementia-related changes are part of the normal aging process rather than an abnormal process, such that in some groups and communities, cognitive decline may not elicit concern until symptoms are well beyond the early or mild stages (Hart, Gallagher-Thompson, Davies, Diminno, and Lessin, 1996). Differences in the meaning of cognitive decline highlight the need for community-based random samples and recruitment strategies that improve the rates of participation of ethnically diverse elders (Baker, 1996).

Individuals within some cultures may be more likely to view cognitive decline as disgraceful and something that should be kept within the family. A dementing illness may be difficult to accept when the ethnic elder may be the historian, mediator, and provider of emotional and financial support for many generations of family members living in the same home (Baker, 1992). Richards et al. (1998) found that although African-Caribbean elders living in London reported a larger number of family members living nearby and were more likely to live with at least one other family member, they received no more help from their families with activities of daily living, yet were more likely to have difficulties in this area.

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

One study found that black participants with AD evaluated at California Department of Health Alzheimer’s Disease Diagnostic and Treatment Centers reported a shorter duration of illness at the time of initial diagnosis (Hargrave et al., 1998). However, after adjusting for years of education, blacks with AD had more advanced cognitive dysfunction (as assessed by the MMSE) and were more functionally impaired (as assessed by the Blessed Dementia Rating Scale) at the time of initial diagnosis. These findings may be due to reporting bias, testing bias, or both; it is also possible that cognitive decline is more rapid among African-American elders with AD.

Black elders evaluated at several dementia assessment centers were more likely than whites to be in poverty, living alone, and poorly educated (Cohen and Carlin, 1993). Blacks with dementia (both U.S.-born African Americans and African Caribbeans) were more likely to have psychotic symptoms, while whites were more likely to have depression (Cohen and Magai, 1999). The possible contribution of limited economic, educational, and health care resources throughout the lifespan must be considered when assessing all elders for dementia, but may be especially salient among ethnic minorities and immigrants. Access to basic resources may be restricted by institutionalized segregation or residence in poorly developed areas within or outside the United States, such that poor nutrition throughout the lifespan could be a risk factor for cognitive decline as an older adult (Artiola i Fortuny et al., 1998; Baker, 1992).

CONCLUSIONS AND FUTURE DIRECTIONS

We conclude that there are ethnic differences in the observed prevalence and incidence of cognitive impairment, dementia, and AD. Although studies conducted in the United States have differences in sampling methods, definitions of dementia, and definitions of race/ethnicity, it appears that African Americans and Hispanics have higher prevalence and incidence of dementia and AD than whites. These differences may be at least partially explained by discrepancies in the specificity of functional and neuropsychological instruments used to detect cognitive impairment across cultures. No research group has been able yet to overcome the strong influence of cultural and educational experience on cognitive test performance, the meaning of dementia, and the significance attributed to cognitive change in aging. However, even using the most accurate cognitive measures, cross-cultural differences in rates of cognitive impairment, dementia, and AD may still exist. These can be explained by differences in biological risk factors such as cerebrovascular disease, differential exposure to environmental risk factors, cognitive reserve, or genetic risk factors. Cross-national studies such as the Indianapolis-Ibadan study indicate that ethnic differences in rates of dementia may be a result of a complex gene-

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

environment interaction. It remains to be seen whether such intricately entwined biological and genetic risk factors can be separated from their sociocultural or environmental context.

Cross-cultural researchers must be aware that racial and ethnic classifications are historically defined categories that are not direct reflections of genetic populations. There is also tremendous heterogeneity in cultural, linguistic, educational, and environmental exposures within traditionally defined racial and ethnic groups. Therefore, we believe that the highest priority for future cross-cultural research is to operationalize the behavioral, experiential, and biological factors that are assumed to differ between ethnic or racial groups. Without explicit measurement of one or more of these factors, the possible interpretations of differences between ethnic or racial groups are too varied and complex. For example, investigators of the genetics of AD could create comparison groups based on degree of shared ancestry using population-specific alleles, as opposed to self-reported racial or ethnic classifications.

Another crucial priority for cross-cultural investigations of cognitive impairment, dementia, and AD is to increase rates of autopsy among random samples of ethnic minority elders whose cognitive ability has been well characterized during life. Without neuropathological confirmation, we will never overcome the suspicion that our diagnoses are culturally biased, and without samples free of selection bias we can never determine if rates of AD pathology differ between ethnic groups. Improved pathological verification of dementia diagnoses will require large-scale education of communities about brain donation, as well as improved training of medical personnel on culturally sensitive discussion of autopsy. Another approach would be to refine anatomical and functional imaging techniques that can be used to accurately discriminate pathological changes associated with AD or vascular disease during life, and to detect these changes early in the course of the disorder.

The next priority is to improve the accuracy of cognitive tests used to detect impairment. Cultural experience has been hypothesized to correlate with specific cognitive variables such as problem-solving styles, speed versus accuracy tradeoffs, and salience or familiarity with items. Focus on these variables might guide research on cross-cultural differences in cognitive test performance and assist in the development of tests usable across cultures. Differences in quality of educational attainment within and between ethnic groups could be assessed with measures of reading level, and used in research on cognitive reserve. If cognitive reserve is a major factor in explaining ethnic differences in rates of dementia and AD, researchers should be able to demonstrate this using anatomic indicators of reserve such as brain size or brain network activity.

Suggested Citation:"4 Ethnic Differences in Dementia and Alzheimer’s Disease." National Research Council. 2004. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, DC: The National Academies Press. doi: 10.17226/11086.
×

Despite the methodological difficulties cross-cultural dementia researchers must face, these investigations challenge our definitions of race and ethnicity, cognitive impairment, functional deficit, and the definition of dementia itself (Richards and Brayne, 1996). The ultimate validity check for constructs involving these concepts may be their ability to supersede cultural boundaries. The challenges are significant, but we expect that as we clarify the complex etiology of AD and move toward prevention, the struggle to deconstruct ethnicity, culture, and biology will inevitably enrich our understanding of the effect of culture on cognition, genetic and environmental influences on AD, as well as the normal aging process.

ACKNOWLEDGMENTS

Support was provided by federal grants AG07232, AG10963, AG08702, and RR00645, an Alzheimer’s Association Grant (IIRG-98-020), the Taub Foundation, the Charles S. Robertson Memorial Gift for Alzheimer’s Disease Research from the Banbury Fund, and the Blanchette Hooker Rockefeller Foundation. Tavis Allison provided editorial assistance for this chapter.

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Next: Section II--Two Key Conceptual and Methodological Challenges5 The Life-Course Contribution to Ethnic Disparities in Health »
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In their later years, Americans of different racial and ethnic backgrounds are not in equally good--or equally poor--health. There is wide variation, but on average older Whites are healthier than older Blacks and tend to outlive them. But Whites tend to be in poorer health than Hispanics and Asian Americans. This volume documents the differentials and considers possible explanations.

Selection processes play a role: selective migration, for instance, or selective survival to advanced ages. Health differentials originate early in life, possibly even before birth, and are affected by events and experiences throughout the life course. Differences in socioeconomic status, risk behavior, social relations, and health care all play a role. Separate chapters consider the contribution of such factors and the biopsychosocial mechanisms that link them to health. This volume provides the empirical evidence for the research agenda provided in the separate report of the Panel on Race, Ethnicity, and Health in Later Life.

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