The population at risk for Alzheimer's disease (AD) and AD-related dementia (ADRD) in the United States and worldwide is becoming increasingly racially and ethnically diverse. The majority of AD/ADRD research, however, remains focused primarily on white populations in Europe and North America. The literature has documented many of the challenges investigators face enrolling diverse populations in dementia research and clinical trials (Alzheimer's Association, 2016; Gilmore-Bykovskyi et al., Reference Gilmore-Bykovskyi2019); however, the impact of this underrepresentation on knowledge of disease mechanisms, drug efficacy, and safety warrants continued and concerted efforts in this regard. As prevention and treatment studies strive to identify individuals early in the course or in preclinical stages of AD/ADRD, the risk of leaving behind racial and ethnic minorities is heightened. Mild cognitive impairment (MCI) is considered a risk condition for AD/ADRD; however, much remains to be understood regarding the precise risks and predictive value of MCI diagnosis for specific dementia syndromes (Petersen et al., Reference Petersen, Caracciolo, Brayne, Gauthier, Jelic and Fratiglioni2014). Improved knowledge of MCI among racial and ethnic minorities will therefore be crucial in facilitating diverse representation in prevention and treatment studies.
In this issue, Perales-Puchalt et al. (Reference Perales-Puchalt2020) compare the risk of developing MCI among several ethnic and racial groups in the United States. This article is extremely thoughtful in describing its methodology and theoretical approach to categorizing individuals by race and ethnicity. The ability to specify subgroups within Hispanic/Latino samples provides new insights into important differences among these groups that have previously been underappreciated.
The authors highlight the ways in which the results are consistent with other findings that Mexican American individuals have a similar risk profile to whites in the United States but that other Latino groups, particularly Caribbean Latinos, have a higher risk of MCI than whites. The potential explanation for these differential risks is unclear. The authors suggest possible protective factors for Mexican American individuals including different levels of discrimination, acculturation, social support, or genetic factors. Unfortunately, this study does not provide further insights into the reasons for this difference in MCI risk among different Latino groups.
An important component that is overlooked in this study is the factor of immigrant status with relation to Hispanic/Latino populations. A 2018 study showed that Hispanic immigrants had a higher risk of dementia compared to US born Hispanics (Moon et al., Reference Moon, Badana, Hwang, Sears and Haley2019). It may be the case with the Perales-Puchalt et al. (Reference Perales-Puchalt2020) study that Mexican Latinos were more likely to be US born vs other Latino groups, which could account for the differences in dementia risk. Individuals who were raised outside of the US and later moved to the United States are likely to be subject to a variety of socioeconomic and demographic factors that cannot be accounted for solely by a racial/ethnic designation. In an examination of worldwide risk of dementia, Latin America was shown to have the highest risk, with a prevalence of 8.5% of those over age 60 (Prince et al., Reference Prince, Bryce, Albanese, Wimo, Ribeiro and Ferri2013). It is unknown whether immigrant status could have been a factor that contributed to the differences in MCI risk among US Latino populations that are observed in this study.
In addition to immigrant status, this study does not address factors related to bilingualism or primarily Spanish-speaking individuals that may have impacted the findings regarding Latinos. This study does not provide information about primary language spoken by each participant and whether Latino participants were tested in Spanish or English. Research has indicated potential cognitive advantages and disadvantages of bilingualism. A recent meta-analysis indicated that bilingual individuals have a later age of onset of dementia and MCI, but not necessarily a lower rate of developing dementia (Brini et al., Reference Brini2020). Bilingualism, ESL, and level of acculturation have been associated with lower performance on neuropsychological tests (Boone et al., Reference Boone, Victor, Wen, Razani and Ponton2007; Razani et al., Reference Razani, Murcia, Tabares and Wong2007). The National Alzheimer's Coordinating Center (NACC) utilizes the Uniform Data Set (UDS), which consists of a standardized clinical and neuropsychological assessments, with the Spanish version of the UDS implemented in 2007 (Acevedo et al., Reference Acevedo2009). Having standardized measures for Spanish-speaking patients is an important step forward; however, there is much less normative data available for Spanish-speaking populations compared to English speakers, making it more challenging to accurately discern MCI in this population (Benson et al., Reference Benson, De Felipe, Xiaodong and Sano2014).
Another consideration with regard to diverse populations is the limitations surrounding the use of educational level in AD/ADRD research. Studies in this area frequently control for educational attainment based on years of education reported. However, a simple report of years of education may not accurately reflect educational experience, especially for diverse populations. The role of racial segregation in the quality of education in the United States is a significant consideration for African-American individuals. Similarly, the educational systems available to individuals living outside of the United States are quite variable. It has been suggested that literacy level should be considered as a better marker of overall educational attainment and cognitive reserve rather than years of education (Manly et al., Reference Manly, Schupf, Tang and Stern
2005). This current study includes adjustments for total self-reported years of education; however, different results might be expected if literacy level was examined as a nonmodifiable risk factor.
Although this study represents important findings regarding the comparative risks of MCI among different ethnic and racial groups in the United States, it remains unclear how this relates to the disparate findings regarding risks associated with AD or other types of dementia. For example, while African Americans did not show higher rates of MCI in this study, many other studies have shown higher rates of dementia for African Americans vs whites (Moon et al., Reference Moon, Badana, Hwang, Sears and Haley2019). The explanation for this discrepancy is unclear. It may be that MCI is not as clear a risk factor for the development of dementia later in life for African Americans. This could in part be related to higher risk of vascular dementia in African Americans due to increased cardiovascular risks. One recent study showed that the increased rate of dementia among African Americans began to diminish between 2000 and 2012, while continuing to rise for Hispanics (Chen and Zissimopoulos, Reference Chen and Zissimopoulos2018). It was suggested that these effects were likely mediated by treatment of cardiovascular risks factors such as hypertension.
The use of biomarkers may also be helpful in the understanding of differential risk of progression from MCI to AD based on race/ethnicity. As biomarkers move into the mainstream of clinical evaluation for dementia and MCI, attention must be paid to potential racial differences with biomarkers. A recent study showed African Americans have lower CSF total tau and phosphorylated tau181 than whites; however, this racial difference was seen only for APOE ɛ4-positive participants (Morris et al., Reference Morris2019). This study indicates complex, racially mediated differences in biomarkers of AD.
The cultural considerations in AD/ADRD are highly complex and require inclusion of multiple sociodemographic factors including ethnicity, language, country of origin, immigration status, acculturation, and healthcare disparities. As was noted by the authors, future studies should explore factors that may explain the differential MCI risk among ethnically diverse racial groups. These studies also should include additional subtypes of MCI (amnestic vs nonamnestic) to help further delineate those types of MCI most likely to progress to either AD or other types of dementia such as Lewy body or vascular dementia. This may provide additional insights into the racial and ethnic differences seen in both MCI and various dementia syndromes.
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The population at risk for Alzheimer's disease (AD) and AD-related dementia (ADRD) in the United States and worldwide is becoming increasingly racially and ethnically diverse. The majority of AD/ADRD research, however, remains focused primarily on white populations in Europe and North America. The literature has documented many of the challenges investigators face enrolling diverse populations in dementia research and clinical trials (Alzheimer's Association, 2016; Gilmore-Bykovskyi et al., Reference Gilmore-Bykovskyi2019); however, the impact of this underrepresentation on knowledge of disease mechanisms, drug efficacy, and safety warrants continued and concerted efforts in this regard. As prevention and treatment studies strive to identify individuals early in the course or in preclinical stages of AD/ADRD, the risk of leaving behind racial and ethnic minorities is heightened. Mild cognitive impairment (MCI) is considered a risk condition for AD/ADRD; however, much remains to be understood regarding the precise risks and predictive value of MCI diagnosis for specific dementia syndromes (Petersen et al., Reference Petersen, Caracciolo, Brayne, Gauthier, Jelic and Fratiglioni2014). Improved knowledge of MCI among racial and ethnic minorities will therefore be crucial in facilitating diverse representation in prevention and treatment studies.
In this issue, Perales-Puchalt et al. (Reference Perales-Puchalt2020) compare the risk of developing MCI among several ethnic and racial groups in the United States. This article is extremely thoughtful in describing its methodology and theoretical approach to categorizing individuals by race and ethnicity. The ability to specify subgroups within Hispanic/Latino samples provides new insights into important differences among these groups that have previously been underappreciated.
The authors highlight the ways in which the results are consistent with other findings that Mexican American individuals have a similar risk profile to whites in the United States but that other Latino groups, particularly Caribbean Latinos, have a higher risk of MCI than whites. The potential explanation for these differential risks is unclear. The authors suggest possible protective factors for Mexican American individuals including different levels of discrimination, acculturation, social support, or genetic factors. Unfortunately, this study does not provide further insights into the reasons for this difference in MCI risk among different Latino groups.
An important component that is overlooked in this study is the factor of immigrant status with relation to Hispanic/Latino populations. A 2018 study showed that Hispanic immigrants had a higher risk of dementia compared to US born Hispanics (Moon et al., Reference Moon, Badana, Hwang, Sears and Haley2019). It may be the case with the Perales-Puchalt et al. (Reference Perales-Puchalt2020) study that Mexican Latinos were more likely to be US born vs other Latino groups, which could account for the differences in dementia risk. Individuals who were raised outside of the US and later moved to the United States are likely to be subject to a variety of socioeconomic and demographic factors that cannot be accounted for solely by a racial/ethnic designation. In an examination of worldwide risk of dementia, Latin America was shown to have the highest risk, with a prevalence of 8.5% of those over age 60 (Prince et al., Reference Prince, Bryce, Albanese, Wimo, Ribeiro and Ferri2013). It is unknown whether immigrant status could have been a factor that contributed to the differences in MCI risk among US Latino populations that are observed in this study.
In addition to immigrant status, this study does not address factors related to bilingualism or primarily Spanish-speaking individuals that may have impacted the findings regarding Latinos. This study does not provide information about primary language spoken by each participant and whether Latino participants were tested in Spanish or English. Research has indicated potential cognitive advantages and disadvantages of bilingualism. A recent meta-analysis indicated that bilingual individuals have a later age of onset of dementia and MCI, but not necessarily a lower rate of developing dementia (Brini et al., Reference Brini2020). Bilingualism, ESL, and level of acculturation have been associated with lower performance on neuropsychological tests (Boone et al., Reference Boone, Victor, Wen, Razani and Ponton2007; Razani et al., Reference Razani, Murcia, Tabares and Wong2007). The National Alzheimer's Coordinating Center (NACC) utilizes the Uniform Data Set (UDS), which consists of a standardized clinical and neuropsychological assessments, with the Spanish version of the UDS implemented in 2007 (Acevedo et al., Reference Acevedo2009). Having standardized measures for Spanish-speaking patients is an important step forward; however, there is much less normative data available for Spanish-speaking populations compared to English speakers, making it more challenging to accurately discern MCI in this population (Benson et al., Reference Benson, De Felipe, Xiaodong and Sano2014).
Another consideration with regard to diverse populations is the limitations surrounding the use of educational level in AD/ADRD research. Studies in this area frequently control for educational attainment based on years of education reported. However, a simple report of years of education may not accurately reflect educational experience, especially for diverse populations. The role of racial segregation in the quality of education in the United States is a significant consideration for African-American individuals. Similarly, the educational systems available to individuals living outside of the United States are quite variable. It has been suggested that literacy level should be considered as a better marker of overall educational attainment and cognitive reserve rather than years of education (Manly et al., Reference Manly, Schupf, Tang and Stern 2005). This current study includes adjustments for total self-reported years of education; however, different results might be expected if literacy level was examined as a nonmodifiable risk factor.
Although this study represents important findings regarding the comparative risks of MCI among different ethnic and racial groups in the United States, it remains unclear how this relates to the disparate findings regarding risks associated with AD or other types of dementia. For example, while African Americans did not show higher rates of MCI in this study, many other studies have shown higher rates of dementia for African Americans vs whites (Moon et al., Reference Moon, Badana, Hwang, Sears and Haley2019). The explanation for this discrepancy is unclear. It may be that MCI is not as clear a risk factor for the development of dementia later in life for African Americans. This could in part be related to higher risk of vascular dementia in African Americans due to increased cardiovascular risks. One recent study showed that the increased rate of dementia among African Americans began to diminish between 2000 and 2012, while continuing to rise for Hispanics (Chen and Zissimopoulos, Reference Chen and Zissimopoulos2018). It was suggested that these effects were likely mediated by treatment of cardiovascular risks factors such as hypertension.
The use of biomarkers may also be helpful in the understanding of differential risk of progression from MCI to AD based on race/ethnicity. As biomarkers move into the mainstream of clinical evaluation for dementia and MCI, attention must be paid to potential racial differences with biomarkers. A recent study showed African Americans have lower CSF total tau and phosphorylated tau181 than whites; however, this racial difference was seen only for APOE ɛ4-positive participants (Morris et al., Reference Morris2019). This study indicates complex, racially mediated differences in biomarkers of AD.
The cultural considerations in AD/ADRD are highly complex and require inclusion of multiple sociodemographic factors including ethnicity, language, country of origin, immigration status, acculturation, and healthcare disparities. As was noted by the authors, future studies should explore factors that may explain the differential MCI risk among ethnically diverse racial groups. These studies also should include additional subtypes of MCI (amnestic vs nonamnestic) to help further delineate those types of MCI most likely to progress to either AD or other types of dementia such as Lewy body or vascular dementia. This may provide additional insights into the racial and ethnic differences seen in both MCI and various dementia syndromes.