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Objectives: Many sleep-wake behaviors have been associated with cognition. We examined a panel of sleep-wake/activity characteristics to determine which are most robustly related to having low cognitive performance in midlife. Secondarily, we evaluate the predictive utility of sleep-wake measures to screen for low cognitive performance., Methods: The outcome was low cognitive performance defined as being >1 standard deviation below average age/sex/education internally normalized composite cognitive performance levels assessed in the Hispanic Community Health Study/Study of Latinos. Analyses included 1006 individuals who had sufficient sleep-wake measurements about 2years later (mean age=54.9, standard deviation= 5.1; 68.82% female). We evaluated associations of 31 sleep-wake variables with low cognitive performance using separate logistic regressions., Results: In individual models, the strongest sleep-wake correlates of low cognitive performance were measures of weaker and unstable 24-hour rhythms; greater 24-hour fragmentation; longer time-in-bed; and lower rhythm amplitude. One standard deviation worse on these sleep-wake factors was associated with ∼20%-30% greater odds of having low cognitive performance. In an internally cross-validated prediction model, the independent correlates of low cognitive performance were: lower Sleep Regularity Index scores; lower pseudo-F statistics (modellability of 24-hour rhythms); lower activity rhythm amplitude; and greater time in bed. Area under the curve was low/moderate (64%) indicating poor predictive utility., Conclusion: The strongest sleep-wake behavioral correlates of low cognitive performance were measures of longer time-in-bed and irregular/weak rhythms. These sleep-wake assessments were not useful to identify previous low cognitive performance. Given their potential modifiability, experimental trials could test if targeting midlife time-in-bed and/or irregular rhythms influences cognition., (Copyright © 2024 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Hispanic/Latino individuals in the U.S. have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanic/Latino individuals of diverse heritages., Research Design and Methods: Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is a Hispanic Community Health Study/Study of Latinos (HCHS/SOL) ancillary study. HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability sampled prospective cohort study. SOL-INCA enrolled 6,377 diverse Hispanic/Latino individuals aged 50 years and older (2016-2018). The primary outcomes were cognitive function, 7-year cognitive decline, and mild cognitive impairment (MCI). The primary glycemia exposure variables were measured from fasting blood samples collected at HCHS/SOL visit 1 (2008-2011)., Results: Visit 1 mean age was 56.5 years ± 8.2 SD, and the average glycosylated hemoglobin A1C (HbA1c) was 6.12% (43.5 ± 14.6 mmol/mol). After covariate adjustment, higher HbA1c was associated with accelerated 7-year global (b = -0.045; 95% CI -0.070; -0.021; in z score units) and executive cognitive decline and a higher prevalence of MCI (odds ratio 1.20; 95% CI 1.11; 1.29)., Conclusions: Elevated HbA1c levels were associated with 7-year executive cognitive decline and increased MCI risk among diverse middle-aged and older Hispanic/Latino individuals. Our findings indicate that poor glycemic control in midlife may pose significant risks for cognitive decline and MCI later in life among Hispanic/Latino individuals of diverse heritages., (© 2024 by the American Diabetes Association.)

Background: US-based Latinos have lower education and income combined with higher health risks than non-Latino whites, but often 'paradoxically' evidence better health-related outcomes. Less work has investigated this paradox for cognitive-related outcomes despite nativity diversity., Objective: We evaluated cognitive aging within older Latinos of diverse nativity currently living in the US and participating in Rush Alzheimer's Disease Center studies., Methods: Participants without baseline dementia, who completed annual neuropsychological assessments (in English or Spanish) were grouped by US-born (n = 117), Mexico-born (n = 173), and born in other Latin American regions (LAr-born = 128). Separate regression models examined associations between nativity and levels of (N = 418) or change in (n = 371; maximum follow-up ∼16 years) global and domain-specific cognition., Results: Demographically-adjusted linear regression models indicated that foreign-born nativity was associated with lower levels of global cognition and select cognitive domains compared to US-born Latinos. No associations of nativity with cognitive decline emerged from demographically-adjusted mixed-effects models; however, Mexico-born nativity appeared associated with slower declines in working memory compared to other nativity groups (p-values ≥ 0.051). Mexico-born Latinos had relatively higher vascular burden and lower education levels than other nativity groups; however, this did not alter results., Conclusions: Nativity differences in baseline cognition may be due, in part, to accumulated stressors related to immigration and acculturation experienced by foreign-born Latinos which may hasten meeting criteria for dementia later in life. In contrast, Mexico-born participants' slower working memory declines, taken in the context of other participant characteristics including vascular burden, suggests the Hispanic Paradox may relate to factors with the potential to affect cognition.

Background: Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited., Objective: To examine associations of AL with level of cognition, performance in cognition 7 years later, and change in cognition over 7 years among middle-aged and older US-based Hispanic/Latino adults., Methods: We used data (n = 5,799, 45-74 years at baseline) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation of Neurocognitive Aging (SOL-INCA). The AL score comprised 16 biomarkers representing cardiometabolic, glucose, cardiopulmonary, parasympathetic, and inflammatory systems (higher scores = greater dysregulation). Cognitive outcomes included GC and individual tests of verbal learning and memory, world fluency (WF), Digit Symbol Substitution (DSS), and Trail Making (Parts A & B). Survey-linear regressions assessed associations of AL with performance in cognition at baseline, 7 years later, and via 7-year cognitive change scores adjusting for sociodemographic characteristics, lifestyle factors, and depressive symptoms., Results: Higher AL was associated with lower baseline performance in GC and WF; and lower 7-year follow-up performance in these same measures plus DSS and Trail Making Parts A & B. Higher AL was associated with more pronounced 7-year change (reduction) in GC and on WF and DSS tests., Conclusions: Findings extend previous evidence in predominantly older non-Hispanic white cohorts to show that AL is related to level of and change in GC (as well as WF and DSS) among middle-aged and older US-based Hispanic/Latino adults.

Hispanic/Latino adults are a growing segment of the older U.S. population yet are underrepresented in brain aging research. We aimed to characterize brain aging among diverse Hispanic/Latino individuals. Hispanic/Latino individuals (unweighted n = 2273 ages 35-85 years; 56% female) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) population-based study underwent magnetic resonance imaging (MRI) as part of the SOL- Investigation of Neurocognitive Aging MRI (SOL-INCA-MRI) ancillary study (2018-2022). We performed linear regressions to calculate age associations with brain volumes for each outcome (total (global) brain, hippocampal, lateral ventricle, total white matter hyperintensity (WMH), individual cortical lobar, and total cortical gray matter) and tested modification by sex. Older age was associated with smaller gray matter volumes and larger lateral ventricle and WMH volumes. Age-related differences in global brain volumes and gray matter volumes in specific regions (i.e., the hippocampus and temporal and occipital lobes) were less pronounced among women. Our findings warrant further investigation into sex-specific mechanisms of brain aging using longitudinal studies., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background We previously outlined the importance of considering acculturation within the context of older Latino adults' lived experience (ie, acculturation in context) to better capture contributors to cognitive aging. We now examine this conceptual framework as related to level of and change in cardiovascular health, and whether cardiovascular health modifies previously documented associations of acculturation in context with cognition. Methods and Results Acculturation in context data from 192 Latino participants without dementia at baseline (age ~70 years) were compiled into 3 separate composite scores: acculturation-related (nativity, language-, and social-based preferences), contextually related socioenvironmental (experiences of discrimination, social isolation, social networks), and familism-related (Latino-centric family ethos). A modified American Heart Association's Life's Simple 7 (mLS7; ie, smoking, physical activity, body mass index, blood pressure, total cholesterol, blood glucose) was used to measure cardiovascular health. Mixed effects regressions simultaneously tested the association of all 3 composite scores with total mLS7 adjusting for confounders. Separate models tested whether mLS7 modified associations of the 3 composite scores and cognition. The contextually related socioenvironmental composite score reflecting higher discrimination, higher social isolation, and smaller social networks (estimate=0.22, SE=0.10, P =0.02) and the familism score (estimate=0.16, SE=0.07, P =0.02) both significantly associated with change in total mLS7. The acculturation-related composite was not significantly associated with change in mLS7. No composite was significantly associated with level of mLS7. Total mLS7, however, significantly modified associations between the acculturation-related composite and change in working memory (estimate=-0.02, SE=0.01, P =0.043). Conclusions Acculturation within the context of older Latino adults' lived experience is important for maintaining cardiovascular health, relationships that also affect domain-specific cognitive decline.

Introduction: Studies suggest bilingualism may delay behavioral manifestations of adverse cognitive aging including Alzheimer's dementia., Methods: Three thousand nine hundred sixty-three participants (unweighted mean population age ≈56 years) at Hispanic Community Health Study/Study of Latinos baseline (2008-2011) self-reported their and their parents' birth outside the United States, Spanish as their first language, and used Spanish for baseline and comparable cognitive testing 7 years later (2015-2018). Spanish/English language proficiency and patterns of use were self-rated from 1 = only Spanish to 4 = English > Spanish. Cognitive testing included test-specific and global composite score(s) of verbal learning, memory, word fluency, and Digit Symbol Substitution (DSS). Survey linear regression models examined associations between baseline bilingualism scores and cognition., Results: Higher second-language (English) proficiency and use were associated with higher global cognition, fluency, and DSS at follow-up and better than predicted change in fluency., Discussion: The bilingual experience was more consistently related to 7-year level versus change in cognition for Hispanics/Latinos., (© 2022 the Alzheimer's Association.)

Background: Studies of cumulative anticholinergic drug burden on cognitive function and impairment are emerging, yet few for Hispanics/Latinos., Objective: To examine associations between anticholinergic use and neurocognitive performance outcomes among diverse Hispanics/Latinos., Methods: This prospective cohort study included diverse Hispanic/Latino participants, enrolled in the Study of Latinos-Investigation of Neurocognitive, from New York, Chicago, Miami, and San Diego (n = 6,249). Survey linear regression examined associations between anticholinergic use (measured during baseline [Visit 1] and average 7-year follow up [Visit 2]) with global cognition, episodic learning, memory, phonemic fluency, processing speed, executive functioning, and average 7-year change., Results: Anticholinergic use was associated with lower cognitive global cognition (β= -0.21; 95% CI [-0.36; -0.05]), learning (β= -0.27; 95% CI [-0.47; -0.07]), memory (β= -0.22; 95% CI [-0.41; -0.03]), and executive functioning (β= -0.22; 95% CI [-0.40; -0.03]) scores, particularly among those who took anticholinergics at both visits. Anticholinergic use was associated with faster decline in global cognition, learning, and verbal fluency (β: -0.28 [95% CI: -0.55, -0.01]; β: -0.28 [95% CI: -0.55, -0.01]; β: -0.25, [95% CI -0.47, -0.04], respectively). Sex modified associations between anticholinergic use with global cognition, learning, and executive functioning (F3 = 3.59, F3 = 2.84, F3 = 3.88, respectively)., Conclusion: Anticholinergic use was associated with lower neurocognitive performance, especially among those who used anticholinergics at both visits, among a study population of diverse Hispanics/Latinos. Findings will support evidence-based decisions regarding anticholinergic prescriptions and efforts to minimize cognitive impact.

Background and Purpose: There is limited literature on the prevalence of incidental brain MRI findings in the Hispanic/Latino population, despite their increased prevalence of vascular disease and undertreatment of chronic conditions. The purpose of our study was to determine the prevalence of clinically relevant incidental findings on brain MRI examinations obtained as a part of the Study of Latinos-Investigation of NeuroCognitive Aging MRI (SOL-INCA-MRI) study., Methods: Brain MRI examinations were obtained on 1389 participants in the SOL-INCA-MRI study, a cross-sectional ancillary study of the Hispanic Community Health Study, Study of Latinos, which is a longitudinal, community-based study. Study design of SOL-INCA-MRI involves imaging cognitively normal and participants with mild cognitive impairment. Brain MRI findings were categorized as Level 1 (normal), Level 1.5 (findings of unclear medical significance), Level 2 (potential medical concern), or Level 3 (medically urgent). This article focuses on Level 2 and Level 3 findings., Results: The average age of the sample was 60.8 years (+/- 10.3 years), 66.1% were females. Level 2 and 3 findings were identified in 117 participants, (8.4%), of which 109 (7.8%) were recommended for medical follow-up (Level 2), and 8 (0.6%) were recommended for immediate medical attention (Level 3). Brain MRI findings consisted of chronic infarction in 33 (2.4%), vascular abnormality in 27 (1.9%), intracranial mass in 20 (1.4%), other intracranial findings in 28 (2.0%), and skull base/extracranial findings in 26 (1.9%) patients., Conclusion: Incidental findings of clinical relevance were common among SOL-INCA-MRI participants, but rarely required urgent medical intervention., (© 2021 American Society of Neuroimaging.)

Objective: Neuropsychological 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., Method: To 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., Results: One 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., Conclusions: We 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).

Introduction: Apolipoprotein E (APOE) alleles are associated with cognitive decline, mild cognitive impairment (MCI), and Alzheimer's disease in Whites, but have weaker and inconsistent effects reported in Latinos. We hypothesized that this heterogeneity is due to ancestry-specific genetic effects., Methods: We investigated the associations of the APOE alleles with significant cognitive decline and MCI in 4183 Latinos, stratified by six Latino backgrounds, and explored whether the proportion of continental genetic ancestry (European, African, and Amerindian) modifies these associations., Results: APOE ε4 was associated with an increased risk of significant cognitive decline (odds ratio [OR] = 1.15, P-value = 0.03), with the strongest association in Cubans (OR = 1.46, P-value = 0.007). APOE-ε2 was associated with decreased risk of MCI (OR = 0.37, P-value = 0.04) in Puerto Ricans. Amerindian genetic ancestry was found to protect from the risk conferred by APOE ε4 on significant cognitive decline., Discussion: Results suggest that APOE alleles' effects on cognitive outcomes differ across six Latino backgrounds and are modified by continental genetic ancestry., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Evidence suggests that psychosocial factors are associated with cognitive health in older adults; however, associations of psychosocial factors with cognition remain largely unexamined in middle-aged and older Hispanics/Latinos., Objective: To examine the cross-sectional associations of psychosocial factors with cognitive function among middle-aged and older Hispanics/Latinos living in the US., Methods: Baseline (2008-2011) data from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study (n = 2,818; ages 45-74) were used to examine the associations of each psychosocial factor with global cognition (GC), verbal learning, verbal memory, verbal fluency, and processing speed independent of age, sex, education, Hispanic/Latino background, income, language, and depressive symptoms. Psychosocial variables included: intrapersonal factors (ethnic identity, optimism, and purpose in life), interpersonal factors (family cohesion, familism, social network embeddedness, and social support), and social stressors (perceived ethnic discrimination, loneliness, and subjective social status)., Results: In fully-adjusted models, purpose in life and social support were each positively associated with all five cognitive variables. Loneliness was negatively associated with GC, verbal learning, memory, and processing speed. Ethnic identity was positively and familism negatively associated with GC, verbal fluency, and processing speed. Family cohesion was positively associated with verbal learning., Conclusion: These findings extend previous evidence from older, largely non-Hispanic White cohorts to show that higher purpose in life and social support are also strongly associated with cognitive health among middle-aged and older Hispanics/Latinos. We also highlight that intrapersonal factors, interpersonal factors, and social stressors have differential relationships with individual cognitive tests.

Background: Cognitively-defined subgroups are well-documented within neurodegeneration., Objective: We examined such profiles in diverse non-demented older adults and considered how resulting subgroups relate to modifiable factors associated with neurodegeneration., Methods: 121 non-demented (MMSE = 28.62) diverse (46%non-Latino Black, 40%non-Latino White, 15%Latino) community-dwelling adults (age = 67.7 years) completed cognitive, cardiovascular, physical activity, and diet evaluations. Latent profile analyses (LPA) employed six cognitive scores (letter fluency, letter-number sequencing, confrontational naming, 'animal' fluency, list-learning delayed recall, and recognition discriminability) to characterize cognitively-defined subgroups. Differences between resulting subgroups on cardiovascular (composite scores of overall health; specific health components including fasting blood levels) and lifestyle (sedentary behavior; moderate-to-vigorous physical activity; Mediterranean diet consumption) factors were examined using ANCOVAs adjusting for relevant confounders., Results: Based on sample means across cognitive scores, LPA resulted in the following cognitive subgroups: 1) high-average cognition, 55%non-Latino White and 64%female participants; 2) average cognition, 58%non-Latino Black and 68%male participants; 3) lower memory, 58%non-Latino Black participants; and 4) lower executive functioning, 70%Latinos. The high-average subgroup reported significantly higher Mediterranean diet consumption than the average subgroup (p = 0.001). The lower executive functioning group had higher fasting glucose and hemoglobin A1c than all other subgroups (p-values<0.001)., Conclusion: LPA revealed two average subgroups reflecting level differences in cognition previously reported between non-Latino White and Black adults, and two lower cognition subgroups in domains similar to those documented in neurodegeneration. These subgroups, and their differences, suggest the importance of considering social determinants of health in cognitive aging and modifiable risk.

Purpose: To examine cross-sectional associations between perceived neighborhood environment and cognitive function among middle-aged and older Hispanic/Latino women and men., Methods: Data from the Hispanic Community Health Study/Study of Latinos (2008-2011) and its Sociocultural Ancillary Study (2009-2010) were used. Participants were Hispanic/Latino women (n = 1812) and men (n = 1034) aged 45-74 years. Survey-weighted linear regression models were used to examine associations between self-reported perceived neighborhood environment (i.e., neighborhood social cohesion and problems categorized as quintiles, and neighborhood safety from crime categorized as low, medium, or high) with cognitive function (i.e., global cognition, verbal learning, memory, verbal fluency, and processing speed scores) in women and men. Final model adjusted for age, Hispanic/Latino background, language, field site, household income, education, years lived in neighborhood, and depressive symptoms., Results: Women in the lowest quintile of perceived neighborhood problems (vs. highest quintile) had higher global cognition (β 0.48, 95% CI 0.03, 0.94, p trend 0.229) and memory scores (0.60, 95% CI 0.11, 1.09, p trend: 0.060). Women in the highest quintile of perceived neighborhood social cohesion (vs. lowest quintile) had lower global cognition (β - 0.56, 95% CI - 1.02, - 0.09, p trend 0.004), verbal learning (B - 1.01, 95% CI - 2.00, - 0.03, p trend 0.015), verbal fluency (B - 2.00, 95% CI - 3.83, - 0.16, p trend 0.006), and processing speed (B - 2.11, 95% CI - 3.87, - 0.36, p trend 0.009). There was no association between perceived neighborhood safety from crime and cognition among women, or between any perceived neighborhood environment measure and cognition among men., Conclusions: Middle-aged and older Hispanic/Latina women living in neighborhoods with the lowest perceived problems had higher global cognition and memory. Women living in neighborhoods with the highest perceived social cohesion had lower global cognition, verbal learning, verbal fluency, and processing speed.

Background: Diet quality may be an important area of focus for promoting cognitive health; however, the association between diet quality and cognitive function among Hispanics/Latinos remains largely unexamined. We hypothesized that a healthier diet quality will be associated with better cognitive function in middle-aged and older Hispanics/Latinos., Objective: The objective of this study was to examine associations between the Alternate Healthy Eating Index (AHEI-2010), a measure of diet quality, and cognitive function in middle-aged and older Hispanics/Latinos., Methods: Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visit 1 (2008-2011) were used (n = 8461; ages 45-74 y). Cognitive function was assessed with tests of verbal learning and memory, verbal fluency, and processing speed; a global cognition score was derived by summing the z scores of individual tests. Dietary intake was assessed via two 24-h recalls. Total AHEI-2010 score was categorized into quintiles (higher quintiles indicating healthier diet). Linear regression models were used to examine associations between AHEI-2010 quintiles and cognitive function adjusting for sociodemographic characteristics, daily energy intake, type 2 diabetes, smoking, and depressive symptoms., Results: Compared with the lowest quintile, in the second to fourth AHEI-2010 quintiles, global cognition scores were significantly higher by 0.28, 0.52, and 0.48 units (P-trend = 0.042). In the second to fifth AHEI-2010 quintiles, verbal learning scores were significantly higher by 0.60, 0.62, 0.92, and 0.88 units, and verbal memory scores were higher by 0.33, 0.40, 0.52, and 0.46 units (P-trend = 0.020 and 0.007, respectively). No associations were observed between the AHEI-2010 and verbal fluency or processing speed (P-trend = 0.49 and 0.84, respectively). Among AHEI-2010 components, adequate consumption of vegetables, alcohol, and whole fruits were each associated with better cognitive function., Conclusions: An overall healthier diet quality was associated with better global cognition, verbal learning, and verbal memory in middle-aged and older Hispanics/Latinos., (Copyright © The Author(s) 2020.)

Objective: Hispanics/Latinos are the largest ethnic/racial group in the U.S., have the highest prevalence of diabetes, and are at increased risk for neurodegenerative disorders. Currently, little is known about the relationship between diabetes and cognitive decline and disorders among diverse Hispanics/Latinos. The purpose of this study is to clarify these relationships in diverse middle-aged and older Hispanics/Latinos., Research Design and Methods: The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability-sampled (i.e., representative of targeted populations), and prospective cohort study. Between 2016 and 2018, SOL-INCA enrolled diverse Hispanics/Latinos aged ≥50 years ( n = 6,377). Global cognitive decline and mild cognitive impairment (MCI) were the primary outcomes., Results: Prevalent diabetes at visit 1, but not incident diabetes at visit 2, was associated with significantly steeper global cognitive decline (β GC = -0.16 [95% CI -0.25; -0.07]; P < 0.001), domain-specific cognitive decline, and higher odds of MCI (odds ratio 1.74 [95% CI 1.34; 2.26]; P < 0.001) compared with no diabetes in age- and sex-adjusted models., Conclusions: Diabetes was associated with cognitive decline and increased MCI prevalence among diverse Hispanics/Latinos, primarily among those with prevalent diabetes at visit 1. Our findings suggest that significant cognitive decline and MCI may be considered additional disease complications of diabetes among diverse middle-aged and older Hispanics/Latinos., (© 2020 by the American Diabetes Association.)

Objective: Hispanics/Latinos in the United States are less aware of their cholesterol levels and have a higher burden of associated adverse cardiovascular and cerebrovascular outcomes than non-Latino whites. Investigations of the associations between cholesterol levels and cognition in this population have often occurred within the context of metabolic syndrome and are limited to select lipids despite the fact that triglycerides (TGs) may be more relevant to the health of Hispanics/Latinos., Methods: Baseline data from the Hispanic Community Health Study/Study of Latinos, collected from 2008 to 2011, was used to investigate the associations of lipid levels (i.e., TG, total cholesterol, TC; low-density and high-density lipoprotein cholesterol, LDL-C and HDL-C) with cognition (i.e., learning, memory, verbal fluency, and digit symbol substitution, DSS), adjusting for relevant confounders., Results: In 7413 participants ages 45 to 74 years from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds, separate, fully adjusted linear regression models revealed that TG levels were inversely associated with DSS performance; however, this relationship was no longer significant once additional cardiovascular disease risk factors were added to the model (p = .06). TC and LDL-C levels (separately) were positively associated with learning and verbal fluency regardless of adjustments (p-values < .05). Separate analyses investigating the effect modification by background and sex revealed a particularly robust association between TC levels and DSS performance for Puerto Ricans and Central Americans (albeit in opposite directions) and an inverse relationship between TG levels and DSS performance for women (p-values < .02)., Conclusions: It is important to consider individual lipid levels and demographic characteristics when investigating associations between cholesterol levels and cognition in Hispanics/Latinos.

Background: Cardiovascular disease is linked to cognitive decline and disorders (e.g., dementia). The evidence is based largely on older non-Latino White cohorts., Objective: Examine the association between global vascular risk and cognitive function among Hispanics/Latinos in the United States., Methods: We 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., Results: Higher 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., Discussion: CVR 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.

The Rush Alzheimer's Disease Center (RADC) conducts 5 harmonized prospective clinical-pathologic cohort studies of aging - with 1 study, the Latino Core, focused exclusively on Latinxs, 2 studies consisting of mostly non-Latinx whites, and 2 studies of mostly non-Latinx blacks. This paper contextualizes the Latino Core within the other 4 harmonized RADC cohort studies. The overall aim of the paper is to provide information from the RADC, so that researchers can learn from our participants and procedures to better advance the science of Alzheimer's disease and related dementias in Latinxs. We describe an annual clinical evaluation that assesses risk factors for Alzheimer's dementia among older adults without known dementia at enrollment. As all RADC cohort studies offer brain donation as a part of research participation, we discuss our approach to brain donation and subsequent participant decision-making among older Latinxs. We also summarize baseline characteristics of older Latinxs across the 5 RADC cohort studies in relation to the baseline characteristics of non-Latinx blacks and non-Latinx whites. Finally, we outline challenges and considerations as well as potential next steps in cognitive aging research with older Latinxs., (© 2020 S. Karger AG, Basel.)

Introduction: We estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos., Methods: Middle-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., Results: The 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., Discussion: MCI 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., (Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Objective: Hispanics/Latinos have some of the highest prevalence rates for cardiovascular disease risk factors, but stark differences exist by self-reported background. Cardiovascular disease risk factors negatively impact cognition in Hispanics/Latinos; less is known about these relationships by Hispanic/Latino backgrounds. We investigated cognitive associations with cardiovascular disease risk factor burden in a diverse cohort, the Hispanic Community Health Study/Study of Latinos., Methods: Baseline data from this observational study of cardiovascular disease and its antecedents was collected from 2008-2011. We included 7,121 participants 45-74 years old from Central American, Cuban, Dominican, Mexican, Puerto Rican, or South American backgrounds. Dichotomous indicators for hypertension, diabetes, hypercholesterolemia, obesity, and smoking were evaluated and totaled, with participants grouped by lowest (0-2), middle (3) or highest (4-5) burden. Cognitive testing included the Brief Spanish English Verbal Learning Test, letter fluency, and digit symbol substitution., Results: In separate fully-adjusted linear regression models, lower fluency and digit symbol substitution performance were restricted to the highest compared to the lowest burden group; whereas the middle burden group displayed impaired memory performance compared to the lowest burden group (p-values≤0.05). Background interacted with burden for learning and memory performance. That is, the association of burden level (i.e., lowest, middle, or highest) with cognitive performance was modified by background (e.g., Mexicans vs Cuban)., Conclusions: Hispanics/Latinos with higher levels of cardiovascular disease risk factor burden displayed lower levels of cognitive performance, with learning and memory performance modified by background., Competing Interests: The authors have declared that no competing interests exist.

Aims: Insulin resistance (IR) adversely impacts memory and executive functioning in non-Hispanic whites without diabetes. Less is known in Hispanics/Latinos, despite the fact that Hispanics/Latinos have higher rates of insulin resistance than non-Hispanic whites. We investigated the association between IR and cognition and its variation by age., Methods: Data from 5987 participants 45-74 years old without diabetes from the Hispanic Community Health Study/Study of Latinos. IR was considered continuously using homeostasis model assessment for insulin resistance (HOMA-IR) and also dichotomized based on clinically relevant thresholds for hyperinsulinemia (fasting insulin > 84.73 pmol/L or HOMA-IR > 2.6) and sample-based norms (75th percentile of fasting insulin or HOMA-IR). Cognitive testing included the Brief Spanish English Verbal Learning Test (B-SEVLT), Verbal Fluency, and Digit Symbol Substitution., Results: There was 90% overlap in participant categorization comparing clinically relevant and sample-based thresholds. In separate fully-adjusted linear regression models, age modified the association between HOMA-IR and Digit Symbol Substitution (p = 0.02); advancing age combined with higher HOMA-IR levels resulted in higher scores. Age also modified the association between clinically relevant hyperinsulinemia and B-SEVLT recall (p = 0.03); with increasing age came worse performance for individuals with hyperinsulinemia., Conclusion: The relationship of IR with cognition in Hispanics/Latinos without diabetes may reflect an age- and test-dependent state., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Sixty percent of Hispanics/Latinos are bilingual which research suggests may confer certain cognitive advantages. Female sex confers cognitive advantages in verbal learning and memory compared to male sex, regardless of race or ethnicity. Understanding the independent and interactive associations of bilingualism and sex with cognition may aid in predicting cognitive aging in Hispanics/Latinos. We examined baseline (2008-2011) data from the Hispanic Community Health Study/Study of Latinos, a multicenter, prospective community-based study. Our analyses included 6,110 males and females ≥45 years old who self-reported birth and parents' origin outside of the continental US, Spanish as their first language, and were evaluated in Spanish. Bilingualism was assessed along a Likert scale (1 = only Spanish to 4 = English>Spanish) for language proficiency (reading/spoken) and patterns of use (thinking/socializing). Cognitive testing included verbal learning, memory, fluency, and Digit Symbol Substitution (DSS). Linear regression models adjusted for relevant confounders, the complex survey design, and sampling weights. Participants' self-reported language proficiency was Spanish better than English, while patterns of use suggested more Spanish than English. Higher language proficiency was associated with higher performance on all cognitive indices while higher patterns of use associated with higher fluency and DSS scores (p-values < 0.01). Female sex was associated with higher performance on all cognitive indices (p-values < 0.05). There were no significant interactions with bilingualism (regardless of metric) by sex on cognition. For Hispanics/Latinos residing in the continental US and reporting birth and parents' origin elsewhere, bilingualism and female sex have independent cognitive benefits that are important to consider when evaluating cognitive performance.

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.

Objective: The purpose of this study is to examine the association between verbal learning, fluency, and processing speed with anxious depression symptomatology (ADS) among diverse Hispanics. We hypothesized an inverse association of anxious depression with neurocognition among Hispanics of different heritage., Design: Data are from the Hispanic Community Health Study/Study of Latinos. The sample included 9,311participants aged 45-74 years (mean: 56.5 years). A latent class analysis of items from the Center for Epidemiological Studies for Depression scale and the Spielberger Trait Anxiety Inventory was used to derive an anxious depression construct. Neurocognitive measures included scores on the Brief Spanish English Verbal Learning Test (B-SEVLT, learning and recall trials), Word Fluency (WF), Digit Symbol Substitution (DSS) test, and a Global Cognitive Score (GCS). We fit survey linear regression models to test the associations between anxious depression symptomatology and cognitive function. We tested for effect modification by sex, Hispanic heritage, and age groups., Results: Among men, 71.6% reported low, 23.3% moderate, and 5.1% high ADS. Among women, 55.1% reported low, 33.2% moderate, and 11.8% high ADS. After controlling for age, sex, sociodemographic characteristics, cardiovascular risk factors and disease, and antidepressant use, we found significant inverse associations between moderate and high anxious depression (ref:low) with B-SEVLT learning and recall, DSS and GCS. Moderate, but not high, anxious depression was inversely associated with WF. Associations were not modified by sex, Hispanic heritage, or age., Conclusions: Increased anxious depression symptomatology is associated with decreased neurocognitive function among Hispanics. Longitudinal studies are needed to establish temporality and infer if negative emotional symptoms precede cognitive deficits., (Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Normative changes in cognitive function are expected with increasing age. Research on the relationship between normative cognitive decline and moderate-to-vigorous physical activity (MVPA) and sedentary behavior (SED) needs further investigation in Hispanic/Latinos adults. We assessed the cross-sectional association between accelerometer assessed MVPA and SED with cognitive function in 7,478 adults aged 45-74years from the Hispanic Community Health Study/Study of Latinos. At baseline, cognitive tests included two executive function tests (Digit Symbol Substitution Test (DSST), a test of language (Word Fluency), and a test of memory (Spanish English Verbal Learning Test). Multiple regression models were used to examine associations of time spent in MVPA and SED with cognitive function by age groups, adjusted for age, education, sex, acculturation, and field center. Mean time spent in sedentary behaviors was 12.3h/day in females and 11.9 h/day in males (75% and 77% of accelerometer wear time, respectively). Higher SED, but not MVPA, was associated with lower DSST raw scores (β -0.03 with each 10-min increment in SED; P<0.05), indicating lower performance in executive function in all age groups. No associations were observed for MVPA and SED with tests of language or memory tests. Our findings suggest a distinct association of SED but not MVPA on executive functioning in middle-aged and older Latino adults. Longitudinal studies are needed to more conclusively determine causal links., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Hypertension control in Hispanics/Latinos lag behind general US trends by 10-15%. Intensive systolic blood pressure (SBP) management <120 mm Hg may significantly reduce morbidity/mortality risk in adults with hypertension; less is known about cognition. We investigated cross-sectional associations of cognition with observed hypertension control at currently recommended (SBP < 140 mm Hg) and more intensive (SBP < 120 mm Hg) levels using baseline data from the Hispanic Community Health Study/Study of Latinos., Methods: From this multicenter cohort study, we focused on 1,735 Hispanic/Latino men and women ages 45-74 years with hypertension and verified antihypertensive use. Verbal fluency, information processing speed, learning, and memory were tested in Spanish or English., Results: Separate linear regressions revealed that being on 1 vs. >1 antihypertensive medication was not associated with cognition; however, individuals with SBP controlled to currently recommended levels outperformed individuals with uncontrolled SBP on verbal fluency [Beta = 1.44 (0.52), P < 0.01] and information processing speed [Beta = 3.01 (0.89), P < 0.001] in age-adjusted regression analyses; only information processing speed remained significant (P < 0.05) after additional adjustments including acculturation, health insurance, and other cardiovascular disease risk factors. When regrouping individuals based on more intensive SBP control, individuals with levels <120 mm Hg outperformed individuals with higher SBP on verbal fluency regardless of adjustments (P < 0.01). More intensive rather than currently recommended levels of control associated with higher verbal fluency performance regardless of adjustments (P < 0.05)., Conclusions: Individual cognitive test scores related to distinct SBP management with more intensive management appearing more robust against confounders. While cognitive associations with hypertension in Hispanics/Latinos may be multifactorial, different levels of SBP control should be considered in future prospective intervention studies., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Hispanics/Latinos are at increased risk for cardiovascular disease and cognitive decline and dementias. High blood pressure (BP) has been implicated in both stroke and dementias. Associations between BP and cognition among diverse Latinos are still unpublished., Objective: We examined associations between cognition and four BP based measures among diverse Hispanics/Latinos. We hypothesized that higher BP, particularly systolic pressure, and increased arterial stiffness (i.e., pulse pressure), would be associated with lower cognitive function., Methods: We used baseline (2008-2011) Hispanic Community Health Study/Study of Latinos (HCHS/SOL; n = 9,019; ages 45-74 years) data to examine cognition in relation to BP measures., Results: In age, sex, and education adjusted models, systolic, pulse, and mean arterial pressure were consistently negatively associated with executive function, psychomotor speed and sustained attention, verbal episodic learning and memory, speech fluency, and mental status measures. These associations were attenuated but remained statistically significant in fully adjusted models., Conclusion: Among middle-aged and older diverse Hispanics/Latinos, we found modest but consistent associations between indicators of arterial stiffness, and compromised blood flow and lower cognitive function. Clinical management and public health interventions to raise awareness and enhance BP management beginning in midlife could reduce disparities and improve population health by reducing cognitive decline burdens.

INTRODUCTION: Few studies have examined the associations of psychosocial factors with cognitive change in Hispanics/Latinos. METHODS: Data from the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL INCA) and Sociocultural studies were used (n = 2,155; ages ≥45 years). Psychosocial exposures included intrapersonal (ethnic identity, optimism, purpose in life), interpersonal (family cohesion, familism, social networks, social support), and social factors (ethnic discrimination, loneliness, subjective social status). Survey-linear regression models examined associations between psychosocial exposures and 7-year cognitive change (global cognition [GC], verbal learning, memory, word fluency [WF], and digit symbol substitution [DSS]). RESULTS: Familism predicted decline in GC, verbal learning, and memory; family cohesion predicted DSS decline; and loneliness predicted memory decline. Ethnic identity was protective against decline in GC and memory, optimism and social support were protective against decline in memory, and purpose in life was protective against WF decline. DISCUSSION: Psychosocial factors are differentially related to cognitive changes. Culturally relevant factors should be explored in Hispanic/Latino cognitive aging research. HIGHLIGHTS: Psychosocial factors are differentially related to cognitive changes in Latinos. Role of culturally relevant factors on cognition should be further explored. Familism predicted decline in global cognition, verbal learning, and memory. Ethnic identity predicted increase in global cognition and memory.

Hispanic/Latino adults are a growing segment of the older U.S. population yet are underrepresented in brain aging research. We aimed to characterize brain aging among diverse Hispanic/Latino individuals. Hispanic/Latino individuals (unweighted n = 2273 ages 35-85 years; 56% female) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) population-based study underwent magnetic resonance imaging (MRI) as part of the SOL- Investigation of Neurocognitive Aging MRI (SOL-INCA-MRI) ancillary study (2018-2022). We performed linear regressions to calculate age associations with brain volumes for each outcome (total (global) brain, hippocampal, lateral ventricle, total white matter hyperintensity (WMH), individual cortical lobar, and total cortical gray matter) and tested modification by sex. Older age was associated with smaller gray matter volumes and larger lateral ventricle and WMH volumes. Age-related differences in global brain volumes and gray matter volumes in specific regions (i.e., the hippocampus and temporal and occipital lobes) were less pronounced among women. Our findings warrant further investigation into sex-specific mechanisms of brain aging using longitudinal studies.

BackgroundTransactive Response DNA Binding Protein 43 kDa (TDP-43) pathology is frequently found in cases with Alzheimer's disease (AD). TDP-43 pathology is associated with hippocampal atrophy and greater AD severity denoted by cognition and clinical representation. Current TDP-43 pathology studies are predominantly based on non-Hispanic White cohorts.ObjectiveWe sought to evaluate the presence of TDP-43 pathology across ethnoracial groups utilizing the National Alzheimer's Coordinating Center; a database containing data from over 29 institutions across the United States. Cases (N = 1135: Hispanics/Latinos = 29, African Americans/Black Americans = 51, Asians/Asian Americans = 10, American Indians/Alaskan Natives = 2, non-Hispanic White = 1043) with intermediate/high AD having data on TDP-43 pathology in the amygdala, hippocampus, entorhinal cortex, and neocortex were included.MethodsTDP-43 pathology frequency in each neuroanatomic region among ethnoracial groups were compared using generalized linear mixed effects models with center as a random effect adjusting for age at death, education, and gender.ResultsAlthough groups were imbalanced, there was no significant difference across ethnoracial groups based on TDP-43 pathology (p = 0.84). With respect to neuroanatomical regions evaluated, there were no significant differences across ethnoracial groups (p-values > 0.06). There were also no significant differences for age at death and gender ratios across ethnoracial groups based on TDP-43 pathology. Although not statistically significant, TDP-43 pathology was present less often in Hispanic/Latinos (34%) when compared to non-Hispanic Whites (46%).ConclusionWhile this is a preliminary evaluation, it highlights the need for diverse cohorts and on TDP-43 pathology research across ethnoracial groups. This is the first study to our knowledge having a focus on the neuroanatomical distribution of TDP-43 deposits in Hispanic/Latino decedents with AD.

IntroductionPolygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome.MethodsWe used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank.ResultsA simple sum of 5 PRSs ("PRSsum"), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-[Formula: see text] and APOE-[Formula: see text] alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-[Formula: see text] and APOE-[Formula: see text] alleles were not associated with MCI.DiscussionA sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-[Formula: see text] and APOE-[Formula: see text] alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults.

Cognitive function such as reasoning, attention, memory, and language is strongly correlated with brain aging. Compared to non-Hispanic whites, Hispanics/Latinos have a higher risk of cognitive impairment and dementia. The genetic determinants of cognitive function have not been widely explored in this diverse and admixed population. We conducted a genome-wide association analysis of cognitive function in up to 7600 middle aged and older Hispanics/Latinos (mean = 55 years) from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). Four cognitive measures were examined: the Brief Spanish English Verbal Learning Test (B-SEVLT), the Word Fluency Test (WFT), the Digit Symbol Substitution Test (DSST), the Six-Item Screener (SIS). Four novel loci were identified: one for B-SEVLT at 4p14, two for WFT at 3p14.1 and 6p21.32, and one for DSST at 10p13. These loci implicate genes highly expressed in brain and previously connected to neurological diseases (UBE2K, FRMD4B, the HLA gene complex). By applying tissue-specific gene expression prediction models to our genotype data, additional genes highly expressed in brain showed suggestive associations with cognitive measures possibly indicating novel biological mechanisms, including IFT122 in the hippocampus for SIS, SNX31 in the basal ganglia for B-SEVLT, RPS6KB2 in the frontal cortex for WFT, and CSPG5 in the hypothalamus for DSST. These findings provide new information about the genetic determinants of cognitive function in this unique population. In addition, we derived a measure of general cognitive function based on these cognitive tests and generated genome-wide association summary results, providing a resource to the research community for comparison, replication, and meta-analysis in future genetic studies in Hispanics/Latinos.

AimsInsulin resistance (IR) adversely impacts memory and executive functioning in non-Hispanic whites without diabetes. Less is known in Hispanics/Latinos, despite the fact that Hispanics/Latinos have higher rates of insulin resistance than non-Hispanic whites. We investigated the association between IR and cognition and its variation by age.MethodsData from 5987 participants 45-74 years old without diabetes from the Hispanic Community Health Study/Study of Latinos. IR was considered continuously using homeostasis model assessment for insulin resistance (HOMA-IR) and also dichotomized based on clinically relevant thresholds for hyperinsulinemia (fasting insulin > 84.73 pmol/L or HOMA-IR > 2.6) and sample-based norms (75th percentile of fasting insulin or HOMA-IR). Cognitive testing included the Brief Spanish English Verbal Learning Test (B-SEVLT), Verbal Fluency, and Digit Symbol Substitution.ResultsThere was 90% overlap in participant categorization comparing clinically relevant and sample-based thresholds. In separate fully-adjusted linear regression models, age modified the association between HOMA-IR and Digit Symbol Substitution (p = 0.02); advancing age combined with higher HOMA-IR levels resulted in higher scores. Age also modified the association between clinically relevant hyperinsulinemia and B-SEVLT recall (p = 0.03); with increasing age came worse performance for individuals with hyperinsulinemia.ConclusionThe relationship of IR with cognition in Hispanics/Latinos without diabetes may reflect an age- and test-dependent state.