Racial/ethnic differences in neuropsychological test performance in frontotemporal degeneration

Abstract

BACKGROUND

Racial and/or ethnic differences in neuropsychological test performance are understudied in frontotemporal degeneration (FTD) but their identification is critical to identifying ways to improve care of representative FTD populations.

METHODS

Differences in cognitive scores between Black (n = 56) and Hispanic (n = 76) relative to White (n = 2281) participants and the likelihood of impairment status in cognitive test performance were evaluated.

RESULTS

Minoritized individuals had lower scores and/or greater likelihood of impairment on measures of lexical retrieval, processing speed, cognitive flexibility, and working memory but not global cognition, verbal recall, attention, and category fluency. Addition of severity, age (M = 65.18), sex (40% female), education (M = 15.62), and vascular comorbidities attenuated group differences.

DISCUSSION

Racial/ethnic differences on neuropsychological tests used in diagnosis and monitoring of FTD were substantially attenuated when accounting for potential contributing factors. To address these differences in FTD, future efforts must increase representative research participation of patients and understand social determinants of health.

Highlights

• Racially/ethnically minoritized individuals with frontotemporal dementia are severely underrepresented in the National Alzheimer's Coordinating Center dataset

• Racially/ethnically minoritized individuals with frontotemporal dementia obtained lower scores and greater likelihood of impairment on common neuropsychological tests

• The effect of racial/ethnic group on neuropsychological test scores was substantially attenuated when adjusting for disease severity, education level, sex, and age

1. INTRODUCTION

Frontotemporal degeneration (FTD) is a common cause of young‐onset dementia. The most common clinical phenotypes of FTD are behavioral variant FTD (bvFTD) and primary progressive aphasia (PPA). ¹ Both bvFTD and PPA are characterized by progressive deterioration in executive functioning, language, and social comportment. Limited research has examined the epidemiology of FTD across minoritized groups but population‐based studies from across the globe indicate that individuals of all races and ethnicities are affected by FTD. ² Although limited information on the prevalence of FTD across racial/ethnic groups exists, all‐cause dementia including Alzheimer's disease (AD) are more common in minoritized groups. ³ The greater prevalence of dementia in minoritized groups may be due, in part, to cultural bias within neuropsychological tests that can result in worse performance or misclassification, thus reducing diagnostic accuracy. ⁴ , ⁵ We previously demonstrated differences in the clinical presentation of Asian and Black groups compared to White individuals diagnosed with FTD (bvFTD or PPA). ⁶ In particular, Black, compared to White, individuals, exhibited greater functional impairment and distinct neuropsychiatric symptom profiles at initial National Alzheimer's Coordinating Center (NACC) visits. However, cognitive performance differences between racial/ethnic groups have not been examined in individuals with FTD. Due to our focus on cognitive performance, we restricted analysis to phenotypes of FTD that present with predominant cognitive dysfunction (i.e., bvFTD and PPA) and not other phenotypes, such as corticobasal syndrome and progressive supranuclear palsy which can be confounded by motor dysfunction. ¹

Extant research has compared neuropsychological test performance of Black and Hispanic individuals to White individuals, but this has been largely reported in nonclinical/community samples of older adults, ⁷ , ⁸ all‐cause dementia ⁹ , ¹⁰ or AD. ¹¹ , ¹² , ¹³ On average, minoritized individuals score lower on traditional neuropsychological tests than White individuals in both dementia and cognitively normal samples and across the lifespan. ⁷ , ¹⁴ Several clinical and demographic factors could contribute to observed differences in neuropsychological performance. In addition to evidence that traditional neuropsychological tests are sensitive to cultural bias, ¹⁵ other factors like differences in quality and attainment of education ¹⁶ are thought to contribute to observed differences in neuropsychological test performance. ¹⁷ , ¹⁸ , ¹⁹ Beyond years of education, ¹² , ¹⁴ age and sex are known to contribute independently to neuropsychological test performance. ⁸ , ²⁰ Clinically, vascular disease is often comorbid with neurodegenerative disease and contributes independently to cognitive deficits. ²¹ Moreover, some studies find that vascular risk factors including hypertension, diabetes, and stroke are more prevalent in Black and Hispanic, compared to White participant groups in studies of dementia ⁹ and older adults. ²² Thus, demographic and clinical factors are important to consider for accurate ascertainment of cognitive function of all individuals with FTD.

RESEARCH IN CONTEXT

1. Systematic review: The authors reviewed the literature using traditional (e.g., PubMed) sources and meeting abstracts and presentations. Although differences in neuropsychological test performance by racial/ethnic group are not yet as widely studied in frontotemporal degeneration (FTD), there have been several publications describing this in Alzheimer's disease (AD) or all‐cause dementia. These relevant citations are appropriately cited.

2. Interpretation: Our findings led to a call‐to‐action for efforts to increase research participation in underrepresented populations with FTD as well as an improved understanding of the contribution of social and structural determinants of health to disparities in cognitive outcomes in FTD.

3. Future directions: We identify specific gaps that should be addressed in the future, including measurement and assessment of specific social and structural determinants of health factors in relation to neuropsychological test performance.

Previous research demonstrates poorer neuropsychological test performance among minoritized individuals diagnosed with dementia, particularly AD, relative to White individuals, ⁹ , ¹⁰ , ¹³ and differences in the functional and neuropsychiatric symptoms of FTD in Black compared to White individuals. ⁶ However, performance differences on neuropsychological testing between racial/ethnic groups with an FTD diagnosis have not been reported. Thus, we sought to identify potential contributors to differences in cognitive performance across racial/ethnic groups of individuals with an FTD diagnosis from a large national cohort, NACC. Our first aim was to evaluate racial/ethnic differences on cognitive tests currently used in the diagnosis and assessment of FTD. We hypothesized that total differences in cognitive test performance by racial/ethnic group, where we expected Black and Hispanic individuals to obtain worse scores, relative to White individuals, would be attenuated with the addition of typical demographic covariates (age, sex, and education) and medical comorbidities that contribute to vascular disease. Our second aim was to determine whether observed differences in cognitive test scores are reflected in increased rates of classification of impairment among Black and Hispanic, relative to White, individuals.

2. METHODS

Data were obtained from NACC, a public dataset established by the National Institute on Aging that collects standardized clinical and neuropathological data. ²³ Data used in this study is from the December 2023 data freeze which included data collected from 2005 to 2023, across Uniform Data Set (UDS) versions 1‐3 and 40 ADRCs. Sample selection is detailed in Figure S1 and the Supplement. Briefly, bvFTD and PPA participants with complete demographic data and at least one neuropsychological test completed in their primary language were included.

We used propensity matching to ensure that the composition of the White group was similar to that of the Black and Hispanic groups. Consistent with previous work ⁶ each member of the minoritized groups was matched to 1 or more White individuals (see Supplement). Because participants were included even if they did not complete all tests, different subsets of Black (n = 27–47), Hispanic (n = 32–56), and White (n = 1212–1716) participants were included in analyses for specific neuropsychological tests. See Table 1 for the 10 cognitive measures examined (details in Supporting Information) and their corresponding sample sizes.

TABLE 1.

Sample characteristics.

Characteristic	Overall N = 1819 a	White N = 1716 a	Black N = 47 a	Hispanic N = 56 a	p‐value b
Age (years)	65.18 (9.31)	65.16 (9.30)	65.87 (9.43)	65.04 (9.43)	0.8
Sex					0.015
Male	1085 (60%)	1036 (60%)	19 (40%)	30 (54%)
Female	734 (40%)	680 (40%)	28 (60%)	26 (46%)
Education (years)	15.62 (2.74)	15.69 (2.71)	14.70 (2.89)	14.34 (3.24)	<0.001
Disease duration (years)	4.70 (2.93)	4.70 (2.93)	4.60 (2.86)	4.57 (3.04)	>0.9
Global CDR					0.026
Very mild	851 (47%)	814 (47%)	20 (43%)	17 (30%)
Mild	674 (37%)	636 (37%)	15 (32%)	23 (41%)
Moderate	220 (12%)	200 (12%)	8 (17%)	12 (21%)
Severe	74 (4.1%)	66 (3.8%)	4 (8.5%)	4 (7.1%)
NACC visit number	1.33 (1.00)	1.34 (1.02)	1.30 (0.62)	1.23 (0.85)	0.2
Stroke	21 (1.2%)	19 (1.1%)	2 (4.3%)	0 (0%)	0.2
Diabetes	166 (9.1%)	149 (8.7%)	7 (15%)	10 (18%)	0.027
Hypertension	700 (38%)	641 (37%)	27 (57%)	32 (57%)	<0.001
Clinical phenotype					0.6
bvFTD	981 (54%)	922 (54%)	25 (53%)	34 (61%)
PPA	838 (46%)	794 (46%)	22 (47%)	22 (39%)
UDS version					0.4
1	407 (22%)	383 (22%)	14 (30%)	10 (18%)
2	858 (47%)	816 (48%)	18 (38%)	24 (43%)
3	554 (30%)	517 (30%)	15 (32%)	22 (39%)
Global cognition: MMSE/MoCA	1,817 (99.9%)	1,715 (99.9%)	47 (100%)	55 (98%)	0.1
Immediate recall: Logical memory/Craft story 21	1676 (92%)	1590 (93%)	37 (79%)	49 (88%)	<0.001
Delayed recall: Logical memory/Craft story 21	1671 (92%)	1587 (92%)	37 (79%)	47 (84%)	<0.001
Attention: Digit/Number span forward	1699 (93%)	1609 (94%)	39 (83%)	51 (91%)	0.015
Working memory: Digit/Number span backward	1695 (93%)	1606 (94%)	39 (83%)	50 (89%)	0.017
Category fluency: Animals	1709 (94%)	1618 (94%)	39 (83%)	52 (93%)	0.009
Category fluency: Vegetables	1681 (92%)	1594 (93%)	38 (81%)	49 (88%)	0.008
Processing speed: TMT A	1589 (87%)	1509 (88%)	36 (77%)	44 (79%)	0.013
Cognitive flexibility: TMT B	1271 (70%)	1212 (71%)	27 (57%)	32 (57%)	0.017
Lexical retrieval: Naming (BNT/MINT)	1670 (92%)	1585 (92%)	37 (79%)	48 (86%)	0.001

Abbreviations: BNT, Boston Naming Test; bvFTD, behavioral variant frontotemporal dementia; MINT, Multilingual Naming Test; MMSE, Mini‐Mental State Examination; MoCA, Montreal Cognitive Assessment; PPA, primary progressive aphasia; TMT, Trail‐Making Test; UDS, Uniform Data Set.

^a Mean (SD); n (%).

^b Kruskal–Wallis rank sum test; Pearson's chi‐squared test; Fisher's exact test.

Analyses were performed with R Studio version 4.3.2 (R Foundation). Continuous demographic variables are summarized with mean and SD and categorical variables are summarized with frequencies. Kruskal–Wallis rank sum tests, Pearson's chi‐squared tests, and Fisher's exact test were used as appropriate to assess group differences.

To examine differences in cognitive performance by racial/ethnic group, a cross‐walk study ²⁴ was used to compute Version 3 scores that equate to Versions 1 and 2 (see Table 2). We first assessed the relationship of cognitive scores with racial/ethnic group alone to examine the total racial/ethnic difference in performance using linear regression. We then added Clinical Dementia Rating (CDR) Global as a measure of disease severity (reference = 0.5 [very mild]), demographic variables – age, sex (reference = male) and years of education – given that these variables can independently affect cognitive test performance and are typically adjusted for in similar analyses, ⁸ , ¹² , ²⁰ , ²³ and vascular comorbidities (definitions detailed in Supporting Information) including recent stroke, presence of diabetes, and the presence of hypertension, as vascular comorbidities influence cognition ²¹ and are disproportionately present in minoritized groups. ⁹ , ²² In an additional step, we add a complete data indicator of whether any of the 10 cognitive tests were missing (reference = complete data) as we observed that missingness was associated with poorer neuropsychological test performance and wanted to evaluate the unique contribution of missing data after accounting for factors with a known contribution to cognition. For all categorical variables, the reference group was the largest group for that variable, and thus, the White group was used as the reference group. Detail regression results are reported in Tables S1–10.

TABLE 2.

Neuropsychological tests by UDS versions.

Version 1 and 2	Version 3
Mini ‐Mental State Examination (MMSE)	Montreal Cognitive Assessment (MoCA)
Boston Naming Test (BNT)	Multilingual Naming Test (MINT)
Logical memory (immediate and delayed)	Craft Story 21 recall (immediate and delayed)
Digit span (forward [DSF], backward [DSB])	Number span (forward, backward)

Abbreviation: UDS, uniform data set.

To examine differences in impairment rates on cognitive tests by racial/ethnic group, we applied age, sex, and education adjusted norms derived for UDS Versions 1 and 2, ²³ , ²⁵ and for UDS Version 3 ²⁰ to the corresponding raw data. We implemented binary logistic regression to examine group differences in the proportion of participants classified as impaired on a given test covarying for CDR Global, using the threshold of ≤ −1.5 standard deviations below the normative sample mean, consistent with prior studies. ²⁰ , ²³ For all analyses the CDR, rather than the frontotemporal lobe dementia (FTLD) CDR, was used as a measure of disease severity as the FTLD‐CDR was not available for UDS Versions 1 and 2 (70% of participants).

2.1. Supplementary analyses

In Tables S11‐12 we report results of analyses stratified by clinical phenotype (bvFTD, PPA). In Table S13 and Figure S2 we report results of analyses among all individuals, regardless of primary language, including Black, Hispanic, White, and Asian participants.

3. RESULTS

3.1. Participant characteristics

The final sample included 47 (2.58%) Black, 56 (3.08%) Hispanic, and 1,716 (94.34%) White individuals. Hispanic individuals were also provided the opportunity to report their origin: 46.4% Mexican, Chicano, or Mexican‐American, 10.7% Puerto Rican, 1.8% Dominican, 5.4% Central American, 16.1% South American, 5.4% reported an alternative origin (Latino, Spain, USA), and 5.4% did not report an origin. Participant characteristics by group are reported in Table 1.

3.2. Differences in cognitive test performance between minoritized and White groups

Regressing raw neuropsychological test scores on race/ethnicity gives the total difference between Black and Hispanic, relative to White, participants in scaled units. We identified differences in global cognition, processing speed and lexical retrieval for both Black and Hispanic participants, working memory and cognitive flexibility for Black participants, and immediate and delayed recall for Hispanic participants. We identified no group differences for attention and category fluency. Note that for all tests except the Trail‐Making Tests, a higher raw score is indicative of better performance. Results of models for each neuropsychological test are illustrated in Figure 1 and reported in Tables S1–10.

FIGURE 1.

Estimated racial/ethnic disparities by linear regression models for each neuropsychological test examined. Coefficient terms for the difference adjusting for predictors listed on the y‐axis and 95% confidence intervals are displayed. Coefficients and confidence intervals were multiplied by −1 for processing speed and cognitive flexibility so that the direction of effect (higher score reflects better cognition) is the same across all tests. Imm. = immediate, Del. = delayed.

Global Cognition (Figure 1, top row; Table S1): The total (i.e., unadjusted) racial/ethnic difference in global cognition is ‐0.43 (p < 0.05) for Black and −0.33 (p < 0.05) for Hispanic participants. Addition of covariates reduced racial/ethnic differences in global cognition to −0.14 (n.s.) for Black and −0.07 (n.s.) for Hispanic participants.

Lexical Retrieval (Figure 1, top row; Table S2): The total racial/ethnic difference in lexical retrieval, as measured by the BNT or MINT, is −0.51 (p < 0.05) for Black and −0.43 (p < 0.05) for Hispanic participants. Accounting for all covariates reduced the total racial/ethnic difference for Black (β = −0.51 to −0.44) and Hispanic (β = −0.43 to −0.38) participants but differences remained significant (ps < 0.05).

Processing Speed (Figure 1, top row; Table S3): The total racial/ethnic difference in processing speed, as measured by TMT‐A is 0.39 (p < 0.05) for Black and 0.47 (p < 0.05) for Hispanic participants. Accounting for all covariates reduced the difference for Black (β = 0.27; n.s.), but not Hispanic (β = 0.30; p < 0.05), participants to nonsignificance.

Cognitive Flexibility (Figure 1, top row; Table S4): A significant total racial/ethnic difference in cognitive flexibility, as measured by TMT‐B, was identified only for Black participants (β = 0.60; p < 0.05). The racial difference in cognitive flexibility remained significant for Black participants, even after considering covariates. Although no significant difference was identified for Hispanic participants in cognitive flexibility, the total difference (β = 0.12) was attenuated with the addition of covariates to β = −0.02 (total magnitude of 0.14 scaled units).

Working Memory (Figure 1, second row; Table S5): The total racial/ethnic difference in DSB, a measure of working memory, was identified only for Black participants (β = −0.40; p < 0.05). Accounting for all covariates reduced the racial difference for Black participants to nonsignificance (β = −0.26; n.s.). Although no significant difference was identified for Hispanic participants on working memory, the total difference (β = −0.09) was attenuated with the addition of covariates to β = 0.09 (magnitude of 0.18 scaled units).

Immediate Memory (Figure 1, second row; Table S6): The difference in immediate verbal recall was identified only for Hispanic (β = −0.38; p < 0.05) participants. After adding covariates, the racial/ethnic difference for Hispanic participants was reduced to β = −0.24 (n.s.). Although no significant difference was identified for Black participants on immediate verbal recall, the total difference (β = −0.13) was attenuated with the addition of covariates to β = −0.06.

Delayed Memory (Figure 1, second row; Table S7): We also observed a difference in delayed verbal recall for Hispanic (β = −0.31; p < 0.05) but not Black (β = −0.02; n.s.) participants. Adjustment for covariates reduced the racial/ethnic difference for Hispanic participants to β = −0.15 (n.s.). Although no significant difference was identified for Black participants on delayed verbal recall, the total difference (β = −0.02) was attenuated with the addition of covariates to β = 0.06 (magnitude of 0.08 scaled units).

Digit Span Forward (Figure 1, second row; Table S8) & Category Fluency (Figure 1, bottom row; Tables S9‐10): We did not observe a significant total racial/ethnic difference for attention (DSF) and category fluency (Animals and Vegetables) for Black and Hispanic participants. Although a significant total difference was not identified for these tests, the addition of covariates further reduced the estimated total difference.

3.3. Differences in likelihood of impairment status in cognitive test performance

Minoritized individuals had a greater likelihood of performing below an established threshold for clinical impairment relative to their White counterparts even when controlling for disease severity (Figure 2) on processing speed (Black: β = 0.93, standard error [SE] = 0.37, p = 0.013, and odds ratio [OR] = 2.54), cognitive flexibility (Black: β = 1.16, SE = 0.47, p = 0.014, OR = 3.20), and lexical retrieval (Black: β = 0.84, SE = 0.39, p = 0.030, OR = 2.32; Hispanic: β = 1.07, SE = 0.38, p = 0.004, OR = 2.92). We did not find differences in likelihood of impairment on global cognition, working memory, immediate and delayed verbal recall, attention, and category fluency (animals and vegetables).

FIGURE 2.

On average minoritized individuals have a higher likelihood of impairment on cognitive measures based on National Alzheimer's Coordinating Center (NACC) norms adjusting for age, sex, and education.

3.4. Results summary

Overall, observed differences on raw scores of neuropsychological measures between Black and Hispanic, relative to White, participants converge with observed differences in impairment status. We observed both group differences in raw scores and impairment on measures of processing speed, cognitive flexibility, and lexical retrieval. However, for global cognition and working memory, we found raw score but not impairment differences between groups. This pattern of findings suggests that observed raw score differences were statistically but not clinically meaningful for global cognition and working memory.

We did not identify differences in raw scores or impairment on measures of immediate and delayed verbal recall, attention, and category fluency. Moreover, we did not identify any neuropsychological tests where White individuals performed significantly worse or had greater likelihood of being classified as impaired than minoritized individuals.

4. DISCUSSION

We investigated whether racial and/or ethnic differences exist in neuropsychological test performance among individuals diagnosed with FTD in a large national cohort. Furthermore, we tested whether racial/ethnic differences in neuropsychological test performance persisted when adjusting for factors that are known to both contribute to neuropsychological test performance and differ by racial/ethnic group. Largely consistent with the AD ¹³ and all‐cause dementia ⁹ literatures, we identified racial/ethnic differences in global cognition, processing speed, and lexical retrieval for Black and Hispanic individuals, working memory and cognitive flexibility for Black individuals, and immediate and delayed verbal recall for Hispanic participants. Critically, lower scores on processing speed, cognitive flexibility, and lexical retrieval translated to differences in the likelihood that individuals are classified as impaired. Consistent with past work, ⁹ we did not observe unadjusted group differences for attention and category fluency for either Black or Hispanic individuals. Lastly, for most tests, racial/ethnic differences did not persist after adjusting models for disease severity, demographic variables (age, sex, and education), and vascular comorbidities.

To our knowledge, this is the first study that examines racial/ethnic differences in neuropsychological test performance among participants with FTD. A novel and important aspect of our study is that we quantify the contribution of disease severity, common covariates (i.e., age, sex, and education), and vascular comorbidities (i.e., stroke, diabetes, and hypertension) to differences in cognitive performance. All of these covariates have known effects on neuropsychological test performance. ⁸ , ⁹ , ¹² , ²¹ , ²⁶ Critically, we implemented extensive and stringent matching between groups to account for potential systematic differences in groups on factors related to cognition. Despite these efforts, we identified significant total racial/ethnic differences for seven of the ten tests examined. Controlling for demographic and clinical factors that could contribute to differences in cognitive testing substantially attenuated differences for all tests and resulted in persistent differences on only three tests. These findings suggest future directions for research and actions that would advance progress toward eliminating racial/ethnic differences in the tools used in clinical and research settings to diagnosis, stage, and track FTD.

For most neuropsychological tests with a total (i.e., unadjusted) difference between Hispanic and White individuals, adjusting for disease severity attenuates the difference to the point that scores, and likelihood of impairment, no longer exist. However, differences persisted for lexical retrieval and processing speed. Acculturation may account for these differences. ²⁷ After Flores and colleagues applied normative standards developed separately for English and Spanish speakers, differences were no longer observed on a processing speed test between English and Spanish speaking Hispanic individuals. ²⁷ Similarly, performance on our measure of lexical retrieval may be influenced by cultural bias, ¹⁴ as most participants completed the BNT, particularly impacting individuals with English as a second language. In the present sample, 29% of Hispanic individuals reported Spanish as their primary language. Moreover, in supplemental analyses controlling for participants’ primary language, Hispanic individuals do not perform worse than White individuals.

For Black individuals, we observed persistent differences on measures of lexical retrieval, processing speed, and cognitive flexibility. Differences in lexical retrieval and cognitive flexibility for Black, relative to White, participants are consistent with those of prior research conducted in an all‐cause dementia NACC sample. ⁹ This study, which included a small proportion of FTLD cases (<6.4% of Black and 14.3% of White participants), observed that Black participants, on average, performed worse than White participants on measures of lexical retrieval and processing speed, consistent with current findings. The overlap of our findings with that of Lennon and colleagues of racial differences in lexical retrieval and cognitive flexibility for Black participants, suggests that these differences may not be unique to FTD but due to factors that we did not capture in our analyses. Indeed, we found that adjusting models for complete data reduced group differences in performance on processing speed and working memory to nonsignificance. This finding indicates that participants with FTD and missing at least one neuropsychological measure are more likely to perform worse on other measures that they did complete, compared to those with complete data. Therefore, our complete data indicator captured variance not otherwise explained by other covariates or addressed through matching. Future work should investigate and test potential factors that may contribute to our observed discrepancy in data missingness.

Racial/ethnic differences in neuropsychological performance were attenuated by accounting for clinical and demographic factors and data missingness. However, differences persisted for some tests examined, suggesting that there are additional factors that may explain the remaining differences. In the NACC UDS, the education variable reflects quantity of education, measured in total years of education. However, there is clear evidence of the importance of education quality, not just quantity, in contributing to differences in neuropsychological test performance. ¹⁶ , ²⁸ Thus, we may expect that observed differences in cognitive scores would be further reduced when accounting for access to and experience of high‐quality education.

Social and structural determinants of health (SSDOH) ²⁹ , ³⁰ , ³¹ , ³² are additional factors that future work should examine as contributors to observed differences. It is critical to acknowledge that race, or minoritized group affiliation, is a social construct and proxy for a number of SSDOH factors. ²⁹ , ³⁰ Indeed, SSDOH explain racialized differences in cognitive outcomes among those with dementia over and above cardiovascular risk and health behaviors ³³ , ³⁴ : poorer cognitive function is associated with increased exposure to racism ³⁵ and air pollution ³⁶ ; and experience of poverty ³⁷ and incarceration. ³⁸ Additionally, access to resources that promote better health outcomes (e.g., nutrition, insurance) also contribute to performance on neuropsychological tests. ¹⁷ , ¹⁸ , ¹⁹ Although comprehensive SSDOH measures are currently not available in the NACC UDS, UDS version 4 will introduce SSDOH measures, and thus, enable future investigation of these important factors. Furthermore, the racial and ethnic groups examined in this study represent a broad range of individuals (e.g., our Hispanic group consisted of individuals originating from Mexico, Puerto Rico, Central America, and South America among other places) whose exposure to various SSDOH factors likely differ.

There are several limitations of currently available data to understand how and why these cognitive differences emerge. The primary limitation of the current study is the underrepresentation of individuals from minoritized groups. A recent perspective paper discusses these barriers to inclusion in FTD research for racially and ethnically minoritized populations at length. ³⁹ The NACC cohort diagnosed with FTD is comprised of only 2.6% Black individuals, 3.5% Hispanic individuals, and 3.7% other minoritized groups. Lack of longitudinal data for minoritized individuals, particularly prior to disease onset (CDR = 0) through the development of FTD (CDR > 0), hinders the ability to examine longitudinal change in cognitive domains. This lack of data also limits the ability of norms to be based on data that accurately reflects the diversity of the population. As of the December 2023 data freeze, only 175 individuals with FTD had neuropsychological data and self‐identified as a race/ethnicity other than non‐Hispanic White. Within this group, only 80 had complete neuropsychological data and only four participants had complete data before exhibiting dementia (CDR = 0). Norms for UDS version 3 that include race ⁴⁰ and ethnicity ⁴¹ do exist. However, as 70% of the data used in the current study was collected as part of UDS version 1 or 2, we did not use these norms. Future work should examine whether race‐ and ethnicity‐adjusted norms impact impairment rates. Lastly, data are aggregated across a number of different Alzheimer's Disease Research Centers (ADRCs), and thus, site may also contribute to observed differences.

5. CONCLUSION

Neuropsychological data in racially and ethnically minoritized populations is severely lacking in the NACC cohort diagnosed with FTD. For nearly all (7/10) neuropsychological tests examined, we observed significant total racial/ethnic differences in performance that were substantially attenuated, with 4/7 to nonsignificance, after adding disease severity, age, sex, education, vascular comorbidities, and data missingness to models. Importantly, differences in performance translated to the classification of a greater proportion of minoritized, compared to White, individuals as impaired. Future efforts must increase research participation in underrepresented populations with FTD, ideally early in disease, measure factors known to contribute to racial/ethnic differences, and employ nonbiased tools when available to better capture cognitive performance in all participants.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest. Author disclosures are available in the supporting information.

CONSENT STATEMENT

This study involved secondary analysis of de‐identified data available from naccdata.org and did not require informed consent for the present study. All participants or their caregivers provided written informed consent before data were collected at each individual ADRC, as approved by individual institutional review boards (IRBs) at each site.

Supporting information

Supporting information

Supporting information

Matyi MA, Rhodes E, Emrani S. et al. Racial/ethnic differences in neuropsychological test performance in frontotemporal degeneration. Alzheimer's Dement. 2025;17:e70190. 10.1002/dad2.70190