The Association of Neighborhood Socioeconomic Status with Executive Function and Processing Speed in Cognitively Normal Mexican American Elders from the Health and Aging Brains Study: Health Disparities Cohort.

INTRODUCTION: Neighborhood socioeconomic status (NSES) has been linked with overall health, and this study will evaluate whether NSES is cross-sectionally associated with cognition in non-Hispanic whites (NHWs) and Mexican Americans (MAs) from the Health and Aging Brain: Health Disparities Study (HABS-HD). METHODS: The HABS-HD is a longitudinal study conducted at the University of North Texas Health Science Center. The final sample analyzed (n = 1,312) were 50 years or older, with unimpaired cognition, and underwent an interview, neuropsychological examination, imaging, and blood draw. NSES was measured using the national area deprivation index (ADI) percentile ranking, which considered socioeconomic variables. Executive function and processing speed were assessed by the trail making tests (A and B) and the digit-symbol substitution test, respectively. Linear regression was used to assess the association of ADI and cognitive measures. RESULTS: MAs were younger, more likely to be female, less educated, had higher ADI scores, performed worse on trails B (all p < 0.05), and had lower prevalence of APOE4 + when compared to NHWs (p < 0.0001). A higher percentage of MAs lived in the most deprived neighborhoods than NHWs. For NHWs, ADI did not predict trails B or DSS scores, after adjusting for demographic variables and APOE4. For MAs, ADI predicted trails A, trails B, and DSS after adjusting for demographic covariates and APOE4 status. CONCLUSION: Our study revealed that living in an area of higher deprivation was associated with lower cognitive function in MAs but not in NHWs, which is important to consider in future interventions to slow cognitive decline.

Evaluation of Neighborhood-Level Disadvantage and Cognition in Mexican American and Non-Hispanic White Adults 50 Years and Older in the US.

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.

Vascular risk profile and white matter hyperintensity volume among Mexican Americans and non-Hispanic Whites: The HABLE study.

INTRODUCTION: Among vascular risk factors we hypothesized that an increased prevalence of diabetes in Hispanics would be associated with greater white matter hyperintensity (WMH) volume, which may contribute to cognitive decline. METHODS: A total of 1318 participants (60% female; 49% Hispanic, 51% non-Hispanic White; age 66.2 ± 8.9 years) underwent clinical evaluation and brain magnetic resonance imaging (MRI). WMH volume associations were assessed with age, sex, and ethnicity and then with vascular risk factors in a selective regression model. RESULTS: WMH volume was greater with older age (P < .0001), Hispanic ethnicity (P = .02), and female sex (P = .049). WMH volume was best predicted by age, diastolic blood pressure, hypertension history, hemoglobin A1c (HbA1c), white blood cell count, and hematocrit (P < .01 for all). Elevated HbA1c was associated with greater WMH volume among Hispanics (parameter estimate 0.08 ± 0.02, P < .0001) but not non-Hispanic Whites (parameter estimate 0.02 ± 0.04, P = .5). DISCUSSION: WMH volume was greater in Hispanics, which may be partly explained by increased WMH volume related to elevated HbA1c among Hispanics but not non-Hispanic Whites.

Proteomic Profiles of Neurodegeneration Among Mexican Americans and Non-Hispanic Whites in the HABS-HD Study.

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.

The Link between APOE4 Presence and Neuropsychological Test Performance among Mexican Americans and Non-Hispanic Whites of the Multiethnic Health & Aging Brain Study - Health Disparities Cohort.

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.

A blood screening tool for detecting mild cognitive impairment and Alzheimer's disease among community-dwelling Mexican Americans and non-Hispanic Whites: A method for increasing representation of diverse populations in clinical research.

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.

Using Fractional Anisotropy Imaging to Detect Mild Cognitive Impairment and Alzheimer's Disease among Mexican Americans and Non-Hispanic Whites: A HABLE Study.

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.

Relationship of Neurofilament Light (NfL) and Cognitive Performance in a Sample of Mexican Americans with Normal Cognition, Mild Cognitive Impairment and Dementia.

INTRODUCTION: This study characterized the relationship between plasma NfL and cognition in a community-based sample of older Mexican Americans. METHODS: 544 participants completed a battery of neuropsychological tests and were diagnosed using clinical criteria. NfL was assayed using Simoa. NfL levels across groups and tests were analyzed. RESULTS: Difference in NfL was found between normal and impaired groups and was related to global cognition, processing speed, executive functions and a list of learning tasks with a significant negative effect for all diagnostic groups. NfL had a negative impact on processing speed, attention, executive functions and delayed and recognition memory for both normal and MCI groups. CONCLUSION: The research supports plasma NfL as a marker of cognitive impairment related to neurodegenerative processes in Mexican Americans and may be a marker of early changes in cognition in those with normal cognition and at risk for developing MCI.

Levels of α-2 Macroglobulin in cognitively normal Mexican- Americans with Subjective Cognitive Decline: A HABLE Study.

BACKGROUND: The presence of Subjective Cognitive Decline (SCD) in the absence of objective change and the inflammatory biomarker Alpha 2 Macroglobulin (A2M) have both been implicated in preclinical Alzheimer's disease. Mexican Americans are population with high rates of cardiovascular and inflammatory disorders. OBJECTIVES: The current study investigated the levels of A2M in cognitively normal Mexican Americans with and without complaints of cognitive decline. METHOD: 293 (243 females, 50 males) community-based cognitively normal older Mexican Americans from the ongoing Health and Aging Brain among Latino Elders (HABLE) study were grouped based on subjective cognitive decline and blood samples were assayed by electrochemiluminescence to determine levels of A2M. RESULTS: Participants with SCD had significantly higher levels of A2M than those without SCD. Females with SCD had a significantly higher level of A2M. CONCLUSIONS: Results suggest that higher levels of A2M, a marker of neuronal injury, may be involved in subtle changes in cognitive functioning recognizable to persons reporting SCD but too subtle to be objectively measured. Longitudinal research is needed to assess the impact of SDC and A2M in progression to MCI and dementia in Mexican Americans.

Inflammatory Biomarkers, Depressive Symptoms and Falls Among the elderly in Panama.

BACKGROUND: Falls are common among elderly adults, and are predictors of hospitalization, institutionalization and mortality. OBJECTIVE: The objective of the present study was to examine the relationship between blood-based markers of inflammation and fall events in a sample of elderly Hispanic adults. METHOD: Data were collected from 190 participants enrolled in the Panama Aging Research Initiative study who completed baseline clinical and cognitive assessments. A non-fasting blood sample was obtained. Self-reported falls were classified as no falls, single falls or recurrent (two or more) falls reported in the 12 months prior to baseline evaluations. Serum levels of C Reactive Protein (CRP), T-lymphocyte secreting protein (I-309), interleukin 10 (IL-10), interleukin 6 (IL-6) and interleukin 7 (IL-7) were measured. Global cognition was assessed with the Mini Mental State Examination and depressive symptoms were assessed with the Geriatric Depression Scale (GDS-30). Multinomial logistic regression was used to assess the link between inflammation and fall events. RESULTS: Depressive symptoms, limitations in Instrumental Activities of Daily Living (IADL), IL-7 and I-309 were significantly related to fall events. Elevated levels of IL-7 increased the likelihood of single and recurrent falls, while increased levels of I-309 were associated only with recurrent falls. Greater IADL limitations and depressive symptoms were associated with an increased likelihood of recurrent falls. CONCLUSION: There is a lack of research investigating the relationship between inflammatory biomarkers and fall events. These results provide evidence of risk factors for falls in Hispanic older adults, and could serve to guide public health professionals to establish clinical guidelines to reduce fall risks.

The Link between Potassium and Mild Cognitive Impairment in Mexican-Americans.

BACKGROUND: Recent evidence suggests that increasing dietary intake of minerals reduces the risk of dementia. This study aimed to examine the relationship between potassium and diagnosis of mild cognitive impairment (MCI) in a sample of older Mexican-Americans from rural and urban populations. METHODS: The sample was formed of a total of 139 participants with MCI and 371 normal controls from two independent cohorts: a rural cohort (Facing Rural Obstacles to Healthcare Now through Intervention, Education and Research [Project FRONTIER]) and an urban cohort (the Health and Aging Brain among Latino Elders [HABLE] study). Serum electrolytes examined were sodium and potassium. Age and education were entered in the model as covariates. RESULTS: Across both cohorts, the Project FRONTIER (OR = 3.1; p = 0.01) and the HABLE Project (OR = 2.0; p = 0.04), the results indicated that serum potassium levels significantly increased the risk of diagnosis of MCI. CONCLUSION: Our finding suggested a link between serum potassium levels and a diagnosis of MCI in Mexican-Americans. The results of this study support a previous research which has suggested that the risk factors for MCI may vary by ethnicity.

Characteristics of Cognitively Normal Mexican-Americans with Cognitive Complaints.

BACKGROUND: Subjective cognitive complaints in cognitively normal adults have been linked to later cognitive decline and dementia. Research on the characteristics of this group has been conducted on a variety of clinical and community-based populations. The current study focuses on the rapidly expanding population of Mexican-American elders. OBJECTIVE: The objective of the study is the determination of characteristics of cognitively normal Mexican-Americans with cognitive complaints. METHODS: Data on 319 cognitively normal participants in a large-scale community-based study of elderly Mexican-Americans (HABLE) were analyzed comparing those with cognitive complaints with those without on clinical characteristics, affective status, neuropsychological functioning, and proteomic markers. RESULTS: Those expressing concern about cognitive decline scored lower on the MMSE, were more likely to have significantly more affective symptoms, higher levels of diabetic markers, poorer performance on attention and executive functioning, and a different pattern of inflammatory markers. CONCLUSION: Although longitudinal research is needed to determine the impact of these differences on later cognition, possible targets for early intervention with Mexican-Americans were identified.

Texas Mexican American adult normative studies: Normative data for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is an assessment of neuropsychological functioning commonly used in clinical and research settings. To our knowledge, normative data for the RBANS is not available for Hispanic, Mexican Americans, which the current study sought to establish. Data from 136 Hispanic, Mexican Americans from Project FRONTIER were analyzed. Approximately half of the sample was administered testing in Spanish. Normative tables were created for English and Spanish speaking Mexican Americans. Generated RBANS normative references are provided for unadjusted raw scores as well as output adjusted by education level.

Comorbid Depression and Diabetes as a Risk for Mild Cognitive Impairment and Alzheimer's Disease in Elderly Mexican Americans.

BACKGROUND: The links between diabetes, depression, and Alzheimer's disease (AD) has been established, but they are still poorly understood. However, little research has examined the effect that comorbidity of depression and diabetes has on cognitive impairment in an ethnically diverse sample. OBJECTIVE: The purpose of this study was to investigate the relationship between comorbid diabetes and depression on cognitive dysfunction; and examine the relationship in an ethnically diverse population. METHODS AND RESULTS: Analyses of data from 2,436 participants (914 men and 1,522 women) of three separate cohorts: HABLE, FRONTIER, and TARCC. In the HABLE cohort, comorbidity (odds ratio [OR] = 3.008; 95% CI = 1.358-6.667), age (OR = 1.138; 95% CI = 1.093-1.185), and education (OR = 0.915; 95% CI = 0.852-0.982) increased the risk of mild cognitive impairment (MCI) diagnosis among elderly Mexican American. In the TARCC cohort, results showed an increase risk of MCI in both non-Hispanic whites (OR = 18.795; 95% CI = 2.229-158.485) and Mexican Americans (OR = 8.417; 95% CI = 2.967-23.878). Finally, results in the FRONTIER cohort showed that in elderly Mexican Americans, comorbidity (OR = 2.754; 95% CI = 1.084-6.995) and age (OR = 1.069; 95% CI = 1.023-1.118) significantly increased risk of MCI. In non-Hispanic whites, comorbidity did not significantly increase risk of MCI. CONCLUSIONS: Among elderly Mexican Americans, comorbid depression and diabetes significantly increased risk for MCI and AD across cohorts. Effects of comorbid diabetes and depression on MCI were inconclusive. Our results support the link between comorbid diabetes and depression and risk for cognitive decline among Mexican Americans. This finding is of critical importance as the Hispanic population is at higher risk of developing AD.

Oxidative stress, testosterone, and cognition among Caucasian and Mexican-American men with and without Alzheimer's disease.

BACKGROUND: The use of testosterone among aging men has been increasing, but results from studies addressing the effectiveness of testosterone replacement therapy have been equivocal. OBJECTIVE: Given our prior pre-clinical studies that reported a major influence of oxidative stress on testosterone's neuroprotective effects, we investigated whether the negative effects of testosterone on brain function were predicted by oxidative load. METHODS: In order to test our hypothesis, we determined whether circulating total testosterone and luteinizing hormone correlated with cognition in a subset of the Texas Alzheimer's Research & Care Consortium (TARCC) cohort, consisting of Caucasian (n = 116) and Mexican-American (n = 117) men. We also assessed whether oxidative stress (as indexed by homocysteine levels) modified this relationship between sex hormones and cognition, and whether the levels of two antioxidants, superoxide dismutase-1 and glutathione S-transferase (GST), varied as a function of circulating testosterone. RESULTS: In a low oxidative stress environment, testosterone was positively associated with the level of the antioxidant, GST, while no deleterious effects on cognitive function were noted. In contrast, under conditions of high oxidative stress (homocysteine levels >12 µmol/L), testosterone and luteinizing hormone were associated with cognitive impairment, but only among Caucasians. The ethnic difference was attributed to significantly higher GST levels among Mexican-Americans. CONCLUSION: While testosterone may be beneficial under conditions of low oxidative stress, testosterone appears to have negative consequences under conditions of elevated oxidative stress, but only in Caucasians. Mexican-Americans, however, were protected from any deleterious effects of testosterone, potentially due to higher levels of endogenous antioxidant defenses such as GST.