Race and Ethnicity in Lewy Body Dementia: A Narrative Review

Race and ethnicity in dementia

Prevalence of dementia and AD is often reported to be higher in underrepresented racial and ethnic groups compared to people identifying as White [16]. These differences are largely explained by variations in health conditions (e.g., diabetes, cardiovascular disease), socioeconomic risk factors, health-related behaviors, and life experiences [16, 17]. Socioeconomic risk factors commonly relate to disparities resulting from structural racism, including higher rates of poverty, less access to quality education, increased exposure to environmental hazards, and greater exposure to discrimination and adversity in minoritized populations [16]. Cumulative burden of chronic stress and life events is associated with cognitive decline and contributes to racial disparities [18, 19]. Other factors include cultural norms and attitudes regarding aging and dementia, lack of trust in healthcare, health literacy, and implicit and explicit bias [20, 21].

Individuals in the US with AD and dementia identifying as Asian, Black, or Hispanic are more likely to live in urban areas and areas with higher poverty and less access to education, timely care, mental health care, and dementia specialists. They also have more difficulty communicating with their healthcare professionals than people identifying as White [22–24]. People identifying as Black or Hispanic with dementia are less likely to receive and more likely to discontinue antidementia drugs, have higher hospital mortality rates, and are less likely to have advanced care planning, more likely to reside in nursing homes with lower quality of care, less likely to enroll in hospice, and have markedly higher end-of-life inpatient expenditures compared to people identifying as White with dementia [25].

So far, anxiety, depression, stroke, hypertension, diabetes, and hyperlipidemia have been associated with a higher risk of LB dementia (Table 1) [26–31]. Prevalence of these medical conditions, health care access, and outcomes for these conditions seem to differ across ethnoracial groups [32]. Within AD, clinical profile, progression rate, risk factors, and prevalence of biomarkers differ across ethnoracial groups [33, 34]. Whether such differences exist in LB dementia needs investigation. For example, research is needed on the degree to which educational attainment, vascular comorbidities, and mood disorders may contribute to potential differences in LB presentations between groups [24, 35]. Environmental factors likely also contribute to the risk and manifestation of LB dementia [26, 36] and may be different between ethnoracial groups. Geography (rather than race) may be a driver; people identifying as Black or African-American in the US had a higher prevalence of Parkinson’s disease than people identifying as Black or African in sub-Saharan Africa [37, 38]. This likely relates to various considerations including diagnostic rates and life expectancy. However, Parkinson’s disease prevalence can differ across regions within a single country or rural and urban areas within a single region [39, 40], which may interact with race and ethnicity [24]. The effect of urban or rural living has not been studied extensively in LB dementia and should be considered when assessing ethnoracial differences for prevalence.

Education is suggested to be a protective factor against PDD and cardiovascular diseases, which are associated with higher LB dementia risk [28, 41]. Compared to people identifying as White, people identifying as Black or Hispanic can have lower educational attainment and lower quality of education [42]. A recent review showed that disparities between people identifying as Black and White with dementia can be reduced by about half by equalizing the education quality [43]. This supports that potential ethnoracial disparities for LB dementia can be overcome if determined and addressed.

Race and ethnicity terminology

When investigating ways to improve diagnosis and treatment in LB dementia, considering race and ethnicity can reveal important disparities in care and inform generalizability of findings to all affected people. Race, ethnicity, and ancestry are often used synonymously, although they have different meanings. Race is defined as “a group of people connected by common descent or origin”, and ethnicity is defined as “membership of a group regarded as ultimately of common descent or having a common national or cultural tradition” [44, 45]. They are social constructs without biological meanings. The terms ancestry (referencing a person’s lineage or region of origin) or genetic admixture (describing a person’s genetic background from different ancestries) likely better reflect disease risk than race and ethnicity, but race and ethnicity still have important social meanings and implications for health research [26]. Recent publications highlight the importance of precise terminology for race and ethnicity in healthcare research [26]. Use and classification of race and ethnicity should be consistent and self-reported rather than assigned by an observer [46]. Categories should not be viewed as absolute as people may identify with more than one race or ethnicity. The Inclusive Language section of the AMA Manual of Style can be used for guidance and clarification about the correct up to date terminology [26].

Association of ethnicity and race with overall health and disease states is due to complex relationships between ancestry, heritage, demographic, socioeconomic, cultural, structural, institutional, and other factors [47–50]. Therefore, race and ethnicity should not be reported in isolation but instead accompanied by sociodemographic factors and social determinants of health. Although definitions and categories can change over time, place, and context, lack of information on race and ethnicity can lead to neglection of social stratification, injustices, inequities, and health [47, 48]. As social factors play an important role in cognitive decline and dementia [51], inclusion of diverse populations and a closer look at underrepresented ethnoracial groups in dementia research can help advance diagnostic and therapeutic efforts.

Approach to the narrative review

The majority of the studies in LB dementia come from Japan, the United Kingdom, and the US; 79% of the authors for the most recent DLB diagnostic criteria were working in these countries [15]. This challenges the applicability of current literature across different populations. As the European population is expected to shrink and the sub-Saharan African population is expected to double in the coming decades [52], generalizability of the available data on dementia will decrease even further.

In this review, we aimed to underscore the current knowledge and gaps to raise awareness and outlined recommendations for future research in LB dementia to advance efforts for diversity, equity, and inclusivity. We present and discuss the available findings for differences across ethnoracial groups in LB dementia, stratifying for DLB and PDD when possible, with a focus on risk, prevalence, progression, clinical and neuropathological features, treatment options, and clinical trials. In the US, the National Institutes of Health (NIH) standard for classification of race includes the options of “American Indian or Alaska Native”, “Asian”, “Black or African American”, “Native Hawaiian or Other Pacific Islander”, “White”, “More than one race”, or “Unknown”. Classification of ethnicity includes the options of “Hispanic or Latino”, “Not Hispanic or Latino”, or “Unknown” [53]. Recent studies from US tend to follow these standards. However, these categories reflect US-based populations and not ethnic and racial groups globally. Therefore, we outline the racial and ethnic groups as reported in the included studies or report the country of origin when such data are not disclosed.

International

There are several systematic reviews focusing on the prevalence of DLB and PDD [2, 55]. Studies from broad geographic areas, including North and South America, Europe, and Asia, are represented in these systematic reviews; however, data across studies were averaged to overall prevalence rates of   5% for DLB and  3.5% for PDD of all dementia cases. Differences across ethnoracial groups within included countries were not evaluated in these studies. In a separate study, higher age-standardized Parkinson’s disease prevalence rates were reported in North America with lower rates in Africa [56]. Although there are currently no studies investigating ethnoracial differences for LB dementia prevalence on a global scale, there are efforts to combine LB dementia cohorts from different regions [15]. Such initiatives will enable future efforts to compare prevalence and incidence of LB dementia based on ancestry, ethnicity, and race.

Geographical differences can be important for LB dementia and contribute to potential ethnoracial differences. Prevalence and clinical correlates of genetic factors (e.g., GBA, LRRK2), social determinants of health (e.g., education), medical conditions (e.g., cardiovascular disease), and exposure to environmental factors (e.g., smoking) are associated with different risk for LB dementia and these can differ across regions [26–28, 57].

Immigration status represents another social determinant of health that can interact with ethnicity and race [58]. A study in Belgium compared DLB prevalence across their clinical cohort including people born in Belgium and first-generation immigrants (including people born in North Africa, Sub-Saharan Africa, Europe, and Latin America) [59]. DLB prevalence was significantly higher in people born in North Africa (6.3% out of all born in North Africa, total n = 205) and Latin America (19.0% out of all born in Latin America, total n = 21) compared to people born in Belgium (5.2% out of all born in Belgium, total n = 2,011). However, the number of first-generation immigrants was much smaller than people born in Belgium.

US-based

For the general demographics of the US population 65 years and older (total estimate = 52,888,621), American Community Survey 5-year estimates from 2021 note 0.5% of people identify as American Indian and Alaska Native, 4.8% as Asian, 9.2% as Black, 0.1% as Native Hawaiian and Other Pacific Islander, 79.8% as White, 3.0% as two or more races; 8.6% Hispanic and 75.7% as non-Hispanic White [60].

Despite the fact that most LB dementia studies reflect primarily non-Hispanic White populations, the frequency of DLB-related diagnosis codes was similar across ethnoracial groups amongst Medicare fee-for-service beneficiaries over the age of 68 as of December 31, 2013 in the US (total n = 21,624,228) [61]. Among all beneficiaries with a claim for dementia (n = 3,110,654), 4.0% of people identifying as non-Hispanic Black, 4.4% of people identifying as American Indian or Alaska Native, 5.4% of people identifying as Asian or Pacific Islander, 5.5% of people identifying as non-Hispanic White and 6.1% of people identifying as Hispanic were diagnosed with DLB [61]. DLB prevalence was lower in people living in rural (4.5%) compared to urban areas (5.2–5.5%). Although rural living has been associated with increased Parkinson’s disease risk, potentially as a result of agricultural pesticide or other environmental factors [62], higher Parkinson’s disease prevalence in urban areas is also reported [40]. Higher DLB prevalence in urban areas may reflect bias of more diagnoses made among populations living closer to academic/specialized care centers or areas with higher density of clinicians trained in diagnosing these disorders.

Racial, ethnic, and ancestral considerations in LB dementia clinical care

Clinical diagnosis of LB dementia is challenging regardless of the person’s background. Medicare and NACC data in this review were mixed on whether race and ethnicity affect identification of LB dementia [61, 77]. Risk of LB dementia misdiagnosis can be higher in a primary care setting than a tertiary care facility [63, 88]. In the US, access to timely care and specialists is significantly lower for people identifying as Asian, Black, or Hispanic in comparison to people identifying as White [24]. Different or delayed diagnosis is common in LB dementia, and leads to uncertainty, fear, worry and concern about the future for both people with LB dementia and their families [10, 89]. Mis- or delayed diagnosis interferes with timely support and treatment, which are top research priorities for people with LB dementia and caregivers [90]. Misdiagnosis can also to inappropriate treatments, such as risky antipsychotic use [91].

Minoritized populations with dementia may be at a higher risk for receiving delayed or insufficient healthcare with less access to new treatment options [92, 93]. Disparities in healthcare access and obtaining accurate diagnoses expand to disparities in access to appropriate treatments, as suggested by different rates of medication use across people with LB dementia or MCI identifying as Black, Hispanic, or White [67].

Racial and ethnic considerations in LB dementia research

While a few studies suggest potential ethnoracial differences in LB pathology and co-pathology, this research is severely limited given small numbers of individuals from minoritized groups, likely reflecting a combination of under-diagnosis and concerns regarding research participation and brain donation [94]. More representation is needed across LB studies, including neuropathological studies but also observational studies and clinical trials. Of clinical trials reporting detailed ethnicity and race data, over 90% of participants with identified as White and non-Hispanic. This likely reflects a complex interplay of barriers to accessing healthcare and historically rooted distrust of clinical research [33, 95]. Although many of these studies are conducted in the US and Europe, the ratio of research participants identifying as White continues to be higher than the ratio of people identifying as White in thepopulation.

Increasing participation of underrepresented groups in clinical trials requires efforts from individuals, institutions and funding agencies involved with research. Research suggests that minoritized people are interested in participating in trials [96] and are more likely to be recruited from internal sources such as referrals by healthcare providers, community outreach and local research registries [34, 97]. However, healthcare professionals may assume lack of interest or other barriers and not provide information [96]. This can significantly limit the participation of diverse populations in trials. Diversifying the research team and including professionals that can speak the native language of the targeted populations will allow people to feel more comfortable and overcome potential mistrust.

In addition to recruitment challenges, trial inclusion and exclusion criteria may affect enrollment of racial and ethnic minorities. The fact that individuals from underrepresented groups may have more co-morbidities and are more likely to be single (and thus potentially lack convenient study partners) may influence the likelihood of fulfilling trial eligibility criteria [67]. Trials may also use cognitive tools developed and validated in cohorts mostly including people identifying as White to determine eligibility. For instance, people identifying as Black without cognitive impairment may have scores below average or low-average, whereas people identifying as White may have high-average or superior scores, leading to misdiagnosis of cognitive impairment in these groups [98]. Applying ethnically and culturally appropriate tests or test norms can help interpret the level of impairment more reliably to determine eligibility. Additionally, views regarding dementia may vary by culture [99] and this may affect study partner responses to commonly used tools such as the Clinical Dementia Rating Scale [34].

Additional suggested strategies for improving recruitment of individuals from minoritized communities can include providing resources to cover costs associated with participation, expanding research sites to community settings, and incentives from funding agencies to the research teams to encourage recruitment of underrepresented groups [97, 101].

There are established consortia and emerging collaborative initiatives to diversify and expand LB dementia cohorts [15, 102]. Supporting these efforts to reach more diverse populations and harmonization of data across different consortia studies can allow analysis of geographic, social, and other factors driving the ethnoracial differences more reliably. More global research is still needed to incorporate both additional countries and representation of different groups within formal borders.

Recommendations for future research in LB dementia

Improving representation in LB dementia research starts with improving recognition and diagnosis in underrepresented groups (Table 4). This has critical implications for accurate prevalence estimates and for connecting individuals with LB dementia to both clinical care and research. Research into barriers affecting diagnosis and access to dementia care is critical. Diagnosis of LB dementia relies heavily on informant report for core clinical features including symptoms of dementia, REM sleep behavior disorder, visual hallucinations, and cognitive fluctuations [6]. Research outside LB dementia suggests that informant reporting may vary by background in terms of cognitive symptoms [103, 104] and level of functioning [105, 106]. Additionally, the type of caregiver available (e.g., spouse versus child) and whether that caregiver lives with the older adult may vary among racial-ethnic groups [107], which has implications for assessing functionality and symptoms like dream enactment [106]. Whether LB dementia diagnostic criteria perform well across different people groups also requires furtherstudy.

Studies should use culturally sensitive batteries and neuropsychological tests adapted and validated across populations and languages. Prior US-based research, for example, has found that neuropsychological tests were less specific and had higher false-positive error rates for people identifying as Black or Hispanic [108]. Implications relating to primary language and social determinants of health/disparities need to be incorporated into assessments of impairment based on neuropsychological testing, in addition to classically assessed factors such as age, gender, and education [109].

Longitudinal studies should assess whether risk factors (e.g., environmental exposures, comorbid vascular conditions) vary between different people groups and how this might affect both diagnosis and progression. Consistent and systematic collection of data for structural and social determinants of health is also critical, ideally using approaches that will allow harmonization of data and findings from different cohorts [110]. Research in AD is mixed regarding whether biomarkers (e.g., cerebrospinal fluid, plasma biomarkers) perform differently based on participant background and medical comorbidities [111–113], suggesting that biomarkers should be validated across diverse LB dementia populations.

There is a critical need to assess whether there are any pathologic differences by background, which will necessitate greater diversity in studies including pathology. Religious beliefs and cultural attitudes, which may vary along with race, ethnicity, and ancestry, play an important role in the decision of brain donation [114]. In one US-based study, however, people identifying as Black were as likely as people identifying as White to be willing to donate their brains once approached by healthcare professionals [115]. From a global standpoint, each country’s own legislation and the attitudes of the ethnic, racial, or religious group in the majority can impact the approach towards brain donation [116, 117]. Barriers to brain donation include lack of knowledge and the approach of healthcare teams when providing education [116–118].

As demonstrated in this review, increased diversity in LB dementia clinical trials is a critical unmet need. Diverse populations are necessary to provide generalizable findings in clinical trials as pharmacokinetics and pharmacodynamics can differ across ethnoracial groups, with implications for both safety and efficacy [119–121]. Barriers to diverse clinical trial participation include LB dementia-specific considerations, such as under-diagnosis, and systemic barriers such as mistrust. A comprehensive review of approaches to improve clinical trial diversity is outside of the scope of this review, but such approaches include engaging diverse research staff (in terms of background and language), study team training regarding communication with diverse communities, designing culturally- and linguistically-appropriate documents using accessible literacy levels, using study materials available in multiple languages, choosing inclusion/exclusion criteria that allow for a broad range of backgrounds (e.g., in terms of language, education, study partner requirements), and sponsor requirements for enrollment of diverse populations [96, 122].

Strengths and limitations of review

This is the first known review focusing on ethnicity and race in LB dementia and it identifies numerous gaps in the existing literature. Limitations include the fact that this is a non-systematic review. Narrative reviews are prone to selection bias compared to systematic reviews. A systematic review with a clearly defined hypothesis, search method using different search engines, predefined selection criteria, data extraction and analysis based on the hypothesis can provide a better summary of existing data than a narrative review [123, 124]. A narrative review, on the other hand, can provide a broad overview of the studies with more emphasis on interpretation and critique [123, 124]. As our primary focus was to discuss current knowledge in order to outline future directions to advance the LB dementia field, we used a narrative review approach. Many of the identified studies are US-based and the majority use NACC, which is not population-based and which has an under-representation of racial and ethnic minorities. It is also uncertain whether the NACC battery is ideally suited to assess individuals from different racial-ethnic and linguistic backgrounds. Furthermore, available US-based studies are limited to groups identifying as Black, Hispanic, or White, with almost no data for other groups including Asian, Pacific Islander, and Native/Indigenous populations.