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APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two. We identified such variants in the APOE region with a predicted moderate impact based on the SnpEff tool. We tested their interaction with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) population and African Americans from the Atherosclerosis Risk In Communities (ARIC) study. We identified 5 Amerindian and 14 African enriched variants with an expected moderate effect. A suggestive significant interaction (p-value = 0.01) was found for one African-enriched variant, rs8112679, located in the ZNF222 gene fourth exon. Our results suggest there are no ancestry-enriched variants with large effect sizes of interaction effects with APOE-ɛ4 on MCI in the APOE region in the Hispanic/Latino population. Further studies are needed in larger datasets to identify potential interactions with smaller effect sizes.

ObjectivesIdentifying sociocultural correlates of neurocognitive dysfunction among Hispanics/Latinos, and their underlying biological pathways, is crucial for understanding disparities in Alzheimer's disease and related dementias. We examined cross-sectional associations between stress and neurocognition, and the role that metabolic syndrome (MetS) and systemic inflammation might play in these associations.MethodParticipants included 3,045 adults aged 45-75 (56% female, education 0-20+ years, 86% Spanish-speaking, 23% U.S.-born), enrolled in the Hispanic Community Health Study/Study of Latinos and its Sociocultural Ancillary Study. Global neurocognition was the primary outcome and operationalized as the average of the z scores of measures of learning and memory, word fluency, and processing speed. Stress measures included self-report assessments of stress appraisal (perceived and acculturative stress) and exposure to chronic and traumatic stressors. MetS was defined via established criteria including waist circumference, high blood pressure, elevated triglycerides, fasting plasma glucose, and high levels of high-density lipoprotein cholesterol. Systemic inflammation was represented by high-sensitivity C-reactive protein (hs-CRP).ResultsSeparate survey multivariable linear regression models adjusting for covariates showed that higher perceived (b = -0.004, SE = 0.002, p < .05) and acculturative stress (b = -0.004, SE = 0.001, p < .0001) were significantly associated with worse global neurocognition, while lifetime exposure to traumatic stressors was associated with better global neurocognition (b = 0.034, SE = 0.009, p < .001). Neither MetS nor hs-CRP were notable pathways in the association between stress and neurocognition; rather, they were both independently associated with worse neurocognition in models including stress measures (ps < .05).DiscussionThese cross-sectional analyses suggest that stress appraisal, MetS, and systemic inflammation may be targets to reduce neurocognitive dysfunction among Hispanics/Latinos.

IntroductionDespite increased risk of cognitive decline in Hispanics/Latinos, research on early risk markers of Alzheimer's disease in this group is lacking. Subjective cognitive decline (SCD) may be an early risk marker of pathological aging. We investigated associations of SCD with objective cognition among a diverse sample of Hispanics/Latinos living in the United States.MethodsSCD was measured with the Everyday Cognition Short Form (ECog-12) and cognitive performance with a standardized battery in 6125 adults aged ≥ 50 years without mild cognitive impairment or dementia (x̄age  = 63.2 years, 54.5% women). Regression models interrogated associations of SCD with objective global, memory, and executive function scores.ResultsHigher SCD was associated with lower objective global (B = -0.16, SE = 0.01), memory (B = -0.13, SE = 0.02), and executive (B = -0.13, SE = 0.02, p's

ObjectiveNeuropsychological instruments are often developed in English and translated to other languages to facilitate the clinical evaluation of diverse populations or to utilize in research environments. However, the psychometric equivalence of these assessments across language must be demonstrated before populations can validly be compared.MethodTo test this equivalence, we applied measurement invariance procedures to a subsample (N = 1,708) of the Hispanic Community Health Survey/Study of Latinos (HCHS/SOL) across English and Spanish versions of a neurocognitive battery. Using cardinality matching, 854 English-speaking and 854 Spanish-speaking subsamples were matched on age, education, sex, immigration status (U.S. born, including territories, or foreign-born), and Hispanic/Latino heritage background. Neurocognitive measures included the Six-Item Screener (SIS), Brief-Spanish English Verbal Learning Test (B-SEVLT), Word Fluency (WF), and Digit Symbol Substitution (DSS). Confirmatory factor analysis was utilized to test item-level invariance of the SIS, B-SEVLT, and WF, as well as factor-level invariance of a higher-order neurocognitive functioning latent variable.ResultsOne item of both the SIS and WF were more difficult in Spanish than English, as was the DSS test. After accounting for partial invariance, Spanish-speakers performed worse on each of the subtests and the second-order neurocognitive functioning latent variable.ConclusionsWe found some evidence of bias at both item and factor levels, contributing to the poorer neurocognitive performance of Spanish test-takers. While these results explain the underperformance of Spanish-speakers to some extent, more work is needed to determine whether such bias is reflective of true cognitive differences or additional variables unaccounted for in this study. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

BackgroundCardiovascular disease is linked to cognitive decline and disorders (e.g., dementia). The evidence is based largely on older non-Latino White cohorts.ObjectiveExamine the association between global vascular risk and cognitive function among Hispanics/Latinos in the United States.MethodsWe used data from a large sample of stroke- and cardiovascular disease-free, middle-aged and older Hispanics/Latinos with diverse backgrounds (n=7,650) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We compared associations between two measures of cardiovascular risk (CVR), the Framingham Cardiovascular Risk Score (FCRS) and the multiethnic Global Vascular Risk Score (GVRS), and cognitive performance using measures of global and domain specific cognitive function, and tested for modification by sex and age.ResultsHigher FCRS and GVRS were associated with lower global cognition and higher probability of low mental status, after covariates adjustment. Both CVR indices were associated with lower performances in learning and memory, verbal fluency, and psychomotor speed. Higher GVRS presented stronger associations with lower cognitive function compared to the FCRS. Women and younger age (45-64 years) exhibited more pronounced associations between higher CVR and worse cognition, particularly so with the GVRS.DiscussionCVR is also a risk for compromised cognitive function and evident in middle-age among Hispanics/Latinos. The multiethnic GVRS, tailored to specific risks based on racial/ethnic background, is feasible to use in primary care settings and can provide important insight on cognitive risk. Even modest shifts in population toward cardiovascular health in the high-risk Hispanic/Latino population can have important positive impacts on healthy cognitive aging.

BackgroundAmong older adults, poorer cognitive functioning has been associated with impairments in instrumental activities of daily living (IADLs). However, IADL impairments among older Hispanics/Latinos is poorly understood.ObjectiveTo characterize the relationships between cognition and risk for IADL impairment among diverse Hispanics/Latinos.MethodsParticipants included 6,292 community-dwelling adults from the Study of Latinos - Investigation of Neurocognitive Aging, an ancillary study of 45+ year-olds in the Hispanic Community Health Study/Study of Latinos. Cognitive data (learning, memory, executive functioning, processing speed, and a Global cognitive composite) were collected at Visit 1. IADL functioning was self-reported 7 years later, and treated as a categorical (i.e., risk) and continuous (i.e., degree) measures of impairment. Survey two-part models (mixture of logit and generalized linear model with Gaussian distribution) and ordered logistic regression tested the associations of cognitive performance (individual tests and composite z-score) with IADL impairment. Additionally, we investigated the moderating role of age, sex, and Hispanic/Latino background on the association between cognition and IADL impairment.ResultsAcross all cognitive measures, poorer performance was associated with higher odds of IADL impairment 7 years later. Associations were generally stronger for the oldest group (70+ years) relative to the youngest group (50-59 years). Sex and Hispanic/Latino background did not modify the associations. Across the full sample, lower scores on learning, memory, and the Global cognitive composite were also associated with higher degree of IADL impairment.ConclusionAcross diverse Hispanics/Latinos, cognitive health is an important predictor of everyday functioning 7 years later, especially in older adulthood.

IntroductionWe estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos.MethodsMiddle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50-86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging-Alzheimer's Association diagnostic criteria.ResultsThe overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI.DiscussionMCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos.

IntroductionHigher cognitive stimulation (CS) is associated with improved cognition. Sources of CS among Hispanics/Latinos are understudied.MethodsIn the Hispanic Community Health Study/Study of Latinos 2008 to 2011 (n = 9438), we used finite mixture models to generate latent CS profiles, and multivariate linear regressions to examine associations with cognition in Hispanic/Latino adults (45-74 years). CS included education, occupation, social network, and acculturation. Cognitive measures included the Six-Item Screener, Brief-Spanish English Verbal Learning Test Sum and Recall, Controlled Oral Word Association Test, Digit Symbol Substitution, and Global Cognition.ResultsTwo CS profiles emerged, and were labeled "typical" and "enhanced." The enhanced CS profile (22%) had more family connections, bicultural engagements, skilled/professional occupations, education, and higher cognitive scores.DiscussionAn enhanced CS profile emerged from contextual and culturally relevant factors, and was associated with higher cognitive scores across all measures. This provides initial evidence on how factors coalesce to shape cognitive protection in Hispanics/Latinos.

The apoE4 isoform is associated with increased cholesterol, cardiovascular risk, and Alzheimer's Disease risk, however, its distribution is not well-understood among US Latinos. Latinos living in the US are highly Amerindian, European and African admixed, which varies by region and country of origin. However, Latino genetic diversity is understudied and consequently poorly understood, which has significant implications for understanding disease risk in nearly one-fifth of the US population. In this report we describe apoE distributions in a large and representative sample of diverse, genetically determined US Latinos.