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Importance: Understanding how socioeconomic factors are associated with cognitive aging is important for addressing health disparities in Alzheimer disease. Objective: To examine the association of neighborhood disadvantage with cognition among a multiethnic cohort of older adults. Design, Setting, and Participants: In this cross-sectional study, data were collected between September 1, 2017, and May 31, 2022. Participants were from the Health and Aging Brain Study-Health Disparities, which is a community-based single-center study in the Dallas/Fort Worth area of Texas. A total of 1614 Mexican American and non-Hispanic White adults 50 years and older were included. Exposure: Neighborhood disadvantage for participants' current residence was measured by the validated Area Deprivation Index (ADI); ADI Texas state deciles were converted to quintiles, with quintile 1 representing the least disadvantaged area and quintile 5 the most disadvantaged area. Covariates included age, sex, and educational level. Main Outcomes and Measures: Performance on cognitive tests assessing memory, language, attention, processing speed, and executive functioning; measures included the Spanish-English Verbal Learning Test (SEVLT) Learning and Delayed Recall subscales; Wechsler Memory Scale, third edition (WMS-III) Digit Span Forward, Digit Span Backward, and Logical Memory 1 and 2 subscales; Trail Making Test (TMT) parts A and B; Digit Symbol Substitution Test (DSST); Letter Fluency; and Animal Naming. Raw scores were used for analyses. Associations between neighborhood disadvantage and neuropsychological performance were examined via demographically adjusted linear regression models stratified by ethnic group. Results: Among 1614 older adults (mean [SD] age, 66.3 [8.7] years; 980 women [60.7%]), 853 were Mexican American (mean [SD] age, 63.9 [7.9] years; 566 women [66.4%]), and 761 were non-Hispanic White (mean [SD] age, 69.1 [8.7] years; 414 women [54.4%]). Older Mexican American adults were more likely to reside in the most disadvantaged areas (ADI quintiles 3-5), with 280 individuals (32.8%) living in ADI quintile 5, whereas a large proportion of older non-Hispanic White adults resided in ADI quintile 1 (296 individuals [38.9%]). Mexican American individuals living in more disadvantaged areas had worse performance than those living in ADI quintile 1 on 7 of 11 cognitive tests, including SEVLT Learning (ADI quintile 5: ß = -2.50; 95% CI, -4.46 to -0.54), SEVLT Delayed Recall (eg, ADI quintile 3: ß = -1.11; 95% CI, -1.97 to -0.24), WMS-III Digit Span Forward (eg, ADI quintile 4: ß = -1.14; 95% CI, -1.60 to -0.67), TMT part A (ADI quintile 5: ß = 7.85; 95% CI, 1.28-14.42), TMT part B (eg, ADI quintile 5: ß = 31.5; 95% CI, 12.16-51.35), Letter Fluency (ADI quintile 4: ß = -2.91; 95% CI, -5.39 to -0.43), and DSST (eg, ADI quintile 5: ß = -4.45; 95% CI, -6.77 to -2.14). In contrast, only non-Hispanic White individuals living in ADI quintile 4 had worse performance than those living in ADI quintile 1 on 4 of 11 cognitive tests, including SEVLT Learning (ß = -2.35; 95% CI, -4.40 to -0.30), SEVLT Delayed Recall (ß = -0.95; 95% CI, -1.73 to -0.17), TMT part B (ß = 15.95; 95% CI, 2.47-29.44), and DSST (ß = -3.96; 95% CI, -6.49 to -1.43). Conclusions and Relevance: In this cross-sectional study, aging in a disadvantaged area was associated with worse cognitive functioning, particularly for older Mexican American adults. Future studies examining the implications of exposure to neighborhood disadvantage across the life span will be important for improving cognitive outcomes in diverse populations.

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BACKGROUND: Despite tremendous advancements in the field, our understanding of mild cognitive impairment (MCI) and Alzheimer's disease (AD) among Mexican Americans remains limited. OBJECTIVE: The aim of this study was to characterize MCI and dementia among Mexican Americans and non-Hispanic whites. METHODS: Baseline data were analyzed from n = 1,705 (n = 890 Mexican American; n = 815 non-Hispanic white) participants enrolled in the Health and Aging Brain Study-Health Disparities (HABS-HD). RESULTS: Among Mexican Americans, age (OR = 1.07), depression (OR = 1.09), and MRI-based neurodegeneration (OR = 0.01) were associated with dementia, but none of these factors were associated with MCI. Among non-Hispanic whites, male gender (OR = 0.33), neighborhood deprivation (OR = 1.34), depression (OR = 1.09), and MRI-based neurodegeneration (OR = 0.03) were associated with MCI, while depression (OR = 1.09) and APOEɛ4 genotype (OR = 4.38) were associated with dementia. CONCLUSION: Findings from this study revealed that the demographic, clinical, sociocultural and biomarker characteristics of MCI and dementia are different among Mexican Americans as compared to non-Hispanic whites.

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Introduction: Despite tremendous advancements in the research of Alzheimer's disease (AD), Mexican Americans, who reflect 65% of the US Hispanic community, remain severely underrepresented in research. Our data demonstrate that risk factors for, and biomarkers of, AD are different among Mexican Americans as compared with non-Hispanic whites. Here, we examined the impact of depressive symptoms on cognitive and AD-relevant biomarker outcomes among the Mexican Americans. Methods: Data were examined from 1,633 (852 Mexican Americans and 781 non-Hispanic whites) of the Health and Aging Brain Study-Health Disparities (HABS-HD). Depression was assessed using the Geriatric Depression Scale while cognition was measured using detailed neuropsychological testing. Plasma biomarkers of Aß40, Aß42, total tau, and NfL were examined in addition to MRI-based neurodegeneration. PET amyloid data were available in a subset of participants. Results: Depressive symptoms were significantly associated with cognitive testing results among both Mexican Americans and non-Hispanic whites. However, depression was only significantly associated with cognitive outcomes and plasma biomarkers among the Mexican American APOEε4 non-carriers. Discussion: Depressive symptoms are more commonly endorsed by Mexican Americans and these symptoms are more strongly associated with cognitive and AD-biomarker outcomes among this ethnic group. However, depression scores were only related to AD outcomes among APOEε4 non-carriers within the Mexican American group. These findings can aid in the development of a population-informed precision medicine for treating and preventing cognitive loss among the Mexican Americans.

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Introduction: Despite the fact that Hispanics are expected to experience the greatest increase in Alzheimer's disease (AD) and related dementias (ADRDs) by 2060, very little data is available regarding the fundamental biomarkers of AD among Mexican Americans who reflect the majority of Hispanics in the U.S. Here we sought to examine the link between APOEε4 genotype and brain amyloid among Mexican Americans as compared to non-Hispanic white participants from the Health & Aging Brain Study - Health Disparities (HABS-HD) cohort. Methods: PET amyloid (florbetaben) data were analyzed from 105 Mexican American and 150 non-Hispanic white participants. Results: Among Mexican Americans, APOEε4 genotype presence was associated with Global SUVR (p = 0.003) as well as amyloid burden in the frontal (p < 0.001), lateral parietal (p = 0.003), lateral temporal (p = 0.008) and anterior-posterior cingulate (p = 0.005) regions of interest (ROIs). Among non-Hispanic white participants, APOEε4 genotype presence was associated with Global SUVR (p < 0.001) as well as amyloid burden in the frontal (p < 0.001), lateral parietal (p < 0.001), lateral temporal (p < 0.001) and anterior-posterior cingulate (p < 0.001) regions of interest (ROIs). The association between APOEε4 genotype and cerebral amyloid was strongest among non-Hispanic white participants. Discussion/Conclusion: Despite the fact that the APOEε4 genotype is significantly less frequent among Mexican Americans, its presence remains to be a significant risk factor among this group for AD pathological burden across all regions. Additional work is needed to understand the presence, progression, and clinical impact of brain amyloid among Mexican Americans.

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BACKGROUND: Despite the tremendous amount of research on Alzheimer's disease (AD) biomarkers, very little data is available regarding the fundamental biomarkers of AD among Mexican Americans. OBJECTIVE: Here we sought to examine the link between metabolic markers and brain amyloid among Mexican Americans as compared to non-Hispanic whites from the Health & Aging Brain Study -Health Disparities (HABS-HD) cohort. METHODS: PET amyloid (florbetaben) data was analyzed from 34 Mexican American and 22 non-Hispanic white participants. RESULTS: Glucagon (t = 3.84, p < 0.001) and insulin (t = -2.56, p = 0.02) were both significantly related to global SUVR levels among Mexican Americans. Glucagon and insulin were both related to most ROIs. No metabolic markers were significantly related to brain amyloid levels among non-Hispanic whites. CONCLUSION: Metabolic markers are related to brain amyloid burden among Mexican Americans. Given the increased risk for diabetes, additional research is needed to determine the impact of diabetes on core AD biomarkers among this underserved population.

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BACKGROUND: Hispanics are expected to experience the largest increase in Alzheimer's disease (AD) and AD related dementias over the next several decades. However, few studies have examined biomarkers of AD among Mexican Americans, the largest segment of the U.S. Hispanic population. OBJECTIVE: We sought to examine proteomic profiles of an MRI-based marker of neurodegeneration from the AT(N) framework among a multi-ethnic, community-dwelling cohort. METHODS: Community-dwelling Mexican Americans and non-Hispanic white adults and elders were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T MRI of the brain. A neurodegeneration MRI meta-ROI biomarker for the AT(N) framework was calculated. RESULTS: Data was examined from n = 1,291 participants. Proteomic profiles were highly accurate for detecting neurodegeneration (i.e., N+) among both Mexican Americans (AUC = 1.0) and non-Hispanic whites (AUC = 0.98). The proteomic profile of N + was different between ethnic groups. Further analyses revealed that the proteomic profiles of N + varied by diagnostic status (control, MCI, dementia) and ethnicity (Mexican American versus non-Hispanic whites) though diagnostic accuracy was high for all classifications. CONCLUSION: A proteomic profile of neurodegeneration has tremendous value and point towards novel diagnostic and intervention opportunities. The current findings demonstrate that the underlying biological factors associated with neurodegeneration are different between Mexican Americans versus non-Hispanic whites as well as at different levels of disease progression.

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INTRODUCTION: We sought to examine a magnetic resonance imaging (MRI)-based marker of neurodegeneration from the AT(N) (amyloid/tau/neurodegeneration) framework among a multi-ethnic, community-dwelling cohort. METHODS: Community-dwelling Mexican Americans and non-Hispanic White adults and elders were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing and 3T MRI of the brain. A neurodegeneration MRI meta-region of interest (ROI) biomarker for the AT(N) framework was calculated. RESULTS: Data were examined from n = 1305 participants. Mexican Americans experienced N at significantly younger ages. The N biomarker was significantly associated with cognitive outcomes. N was significantly impacted by cardiovascular factors (e.g., total cholesterol, low-density lipoprotein) among non-Hispanic Whites whereas diabetes (glucose, HbA1c, duration of diabetes) and sociocultural (household income, acculturation) factors were strongly associated with N among Mexican Americans. DISCUSSION: The prevalence, progression, timing, and sequence of the AT(N) biomarkers must be examined across diverse populations.

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INTRODUCTION: The APOEε4 allele is the single strongest genetic risk for late-onset Alzheimer's disease (AD). Prior work demonstrates that not only the APOEε4 allele varies by race/ethnicity but also the risk for AD and cognitive impairment conveyed by the APOEε4 allele varies by the racial/ethnic group as well as genetic ancestry. Here, we sought to examine the link between the APOEε4 and neuropsychological functioning among Mexican Americans (MAs). METHODS: Data were examined from 1,633 (852 MAs and 781 non-Hispanic Whites [NHWs]) participants of the Health & Aging Brain Study - Health Disparities (HABS-HD) and were enrolled with all requisite data to be included into the current analyses. RESULTS: The frequency of both ε4 and ε2 alleles was significantly lower among MAs as compared to NHWs. Among MAs, APOEε4 allele presence was associated specifically with poorer immediate and delayed memory (Wechsler Memory Scale - Third Edition [WMS-III] Logical Memory and Spanish-English Verbal Learning Test [SEVLT]). Among NHWs, APOEε4 allele presence was associated with poorer immediate and delayed memory as well as worse executive functioning (Trials B) and verbal fluency (Animal naming). DISCUSSION/CONCLUSION: The APOEε4 allele was associated with poorer cognition across multiple domains among NHWs; however, allele presence was specifically associated with poorer memory performance among MAs. When combined with prior work, the current findings demonstrate that the risk factors associated with cognitive dysfunction differ among MAs as compared to NHWs and require additional investigation.

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INTRODUCTION: Representation of Mexican Americans in Alzheimer's disease (AD) clinical research has been extremely poor. METHODS: Data were examined from the ongoing community-based, multi-ethnic Health & Aging Brain among Latino Elders (HABLE) study. Participants underwent functional exams, clinical labs, neuropsychological testing, and 3T magnetic resonance imaging of the brain. Fasting proteomic markers were examined for predicting mild cognitive impairment (MCI) and AD using support vector machine models. RESULTS: Data were examined from n = 1649 participants (Mexican American n = 866; non-Hispanic White n = 783). Proteomic profiles were highly accurate in detecting MCI (area under the curve [AUC] = 0.91) and dementia (AUC = 0.95). The proteomic profiles varied significantly between ethnic groups and disease state. Negative predictive value was excellent for ruling out MCI and dementia across ethnic groups. DISCUSSION: A blood-based screening tool can serve as a method for increasing access to state-of-the-art AD clinical research by bridging between community-based and clinic-based settings.

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INTRODUCTION: Alzheimer's disease (AD) is the most frequently occurring neurodegenerative disease; however, little work has been conducted examining biomarkers of AD among Mexican Americans. Here, we examined diffusion tensor MRI marker profiles for detecting mild cognitive impairment (MCI) and dementia in a multi-ethnic cohort. METHODS: 3T MRI measures of fractional anisotropy (FA) were examined among 1,636 participants of the ongoing community-based Health & Aging Brain among Latino Elders (HABLE) community-based study (Mexican American n = 851; non-Hispanic white n = 785). RESULTS: The FA profile was highly accurate in detecting both MCI (area under the receiver operating characteristic curve [AUC] = 0.99) and dementia (AUC = 0.98). However, the FA profile varied significantly not only between diagnostic groups but also between Mexican Americans and non-Hispanic whites. CONCLUSION: Findings suggest that diffusion tensor imaging markers may have a role in the neurodiagnostic process for detecting MCI and dementia among diverse populations.

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