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IntroductionReproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women.MethodsParticipants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence).ResultsYounger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence.DiscussionSeveral aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

Background and objectivesTo investigate the associations between self-reported visual functioning (VF) and hearing functioning with cognition in the Hispanic/Latino population.Research design and methodsWe utilized data from the Miami Ocular Study of Latinos ancillary study to Hispanic Community Health Study/Study of Latinos with 1,056 participants aged 45 and older. The outcomes were cognitive performances assessed by the Digit Symbol Substitution Test (DSST), Word Fluency, Brief-Spanish English Verbal Learning Test-recall (B-SEVLT recall), words recalled over 3 trials, and the Six-Item Screener. VF was measured by National Eye Institute Visual Function Questionnaire (NEI-VFQ), and hearing function was measured by Hearing Handicap Inventory Screening Questionnaire for Adults and Elderly (HHIA/E-S). Multiple regressions were performed for each cognitive outcome while controlling for covariates and complex sampling design.ResultsNEI-VFQ was associated with 3 of the 5 cognitive outcomes. A 4-point NEI-VFQ score difference was associated with a 0.56-point difference in DSST (standard error [SE] = 0.27, p

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.

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.

IntroductionCoronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term.MethodsThis article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions.ResultsSuccessful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe.DiscussionThe Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection.Key pointsThe following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.

IntroductionBlood metabolomics-based biomarkers may be useful to predict measures of neurocognitive aging.MethodsWe tested the association between 707 blood metabolites measured in 1451 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), with mild cognitive impairment (MCI) and global cognitive change assessed 7 years later. We further used Lasso penalized regression to construct a metabolomics risk score (MRS) that predicts MCI, potentially identifying a different set of metabolites than those discovered in individual-metabolite analysis.ResultsWe identified 20 metabolites predicting prevalent MCI and/or global cognitive change. Six of them were novel and 14 were previously reported as associated with neurocognitive aging outcomes. The MCI MRS comprised 61 metabolites and improved prediction accuracy from 84% (minimally adjusted model) to 89% in the entire dataset and from 75% to 87% among apolipoprotein E ε4 carriers.DiscussionBlood metabolites may serve as biomarkers identifying individuals at risk for MCI among US Hispanics/Latinos.

IntroductionWe aimed to determine whether obesity or metabolic syndrome (MetS) modify associations between sleep-disordered breathing (SDB), self-reported sleep duration (SD), and phenotypes of combined SDB/SD with 7-year neurocognitive decline (ND) in a community based-cohort of U.S. Hispanic/Latinos (N = 5500) in different age and sex groups.MethodsThe exposures were baseline SDB (respiratory event index ≥ 15), sleepiness (Epworth Sleepiness Scale ≥ 10), SD (

Background and purposeThere 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.MethodsBrain 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.ResultsThe 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.ConclusionIncidental findings of clinical relevance were common among SOL-INCA-MRI participants, but rarely required urgent medical intervention.

Chronic stress has a deleterious effect on prefrontal lobe functioning. Empirical evidence suggests elevated vagal tone, indexed by elevated heart rate variability (HRV), mitigates the effect of mental stress on frontal lobe function. Here, the mitigating effect of HRV on stress-related decrements in cognitive performance is assessed based on information processing speed (DSST), word fluency and verbal learning task performance. Artifact free electrocardiogram (ECG) data was analyzed from 1420 Hispanic/Latino adults from the Sociocultural Ancillary of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). A 12-lead ECG was used to collect short-term recordings of the root mean square of successive differences in all normal R-peak to R-peak intervals (RMSSD) and the change between adjacent beats and the standard deviation of those intervals (SDNN) as indices of total HRV. As predicted, an interaction emerged for HRV and stress on the task presumed to require the greatest prefrontal lobe involvement, i.e., the DSST. After accounting for sociodemographic factors, chronic stress was associated with better DSST performance amongst individuals at higher quartile of SDNN, but not RMSSD. The paradoxical effect for greater stress exposure on DSST performance may in part be explained by increased speed of information processing and decision making often reported in high-stress cohorts. The nature of this interaction highlights the importance of examining the relationship between stress and cognition across a spectrum of vagal tone.

IntroductionTo determine if sleep-disordered breathing (SDB), daytime sleepiness, insomnia, and sleep duration predict seven-year neurocognitive decline in US Hispanics/Latinos (N = 5247).MethodsThe exposures were baseline SDB, daytime sleepiness, insomnia, and sleep duration. The outcomes were change in episodic learning and memory (B-SEVLT-Sum and SEVLT-Recall), language (word fluency [WF]), processing speed (Digit Symbol Substitution), and a cognitive impairment screener (Six-item Screener [SIS]).ResultsMean age was 63 ± 8 years, with 55% of the population being female with 7.0% Central American, 24.5% Cuban, 9.3% Dominican, 35.9% Mexican, 14.4% Puerto Rican, and 5.1% South American background. Long sleep (>9 hours), but not short sleep (

BackgroundThe American Heart Association's 2020 Impact Goals propose to improve cardiovascular health (CVH) and reduce deaths from cardiovascular diseases and stroke in the US. Targeted health promotion efforts in workplaces and communities are needed to achieve these population-level changes. The present study examined the sex-specific cross-sectional associations between employment status and ideal CVH among Hispanics/Latinos, and whether these associations were modified by age (i.e., younger adults [aged 18-44] compared to middle-aged and older adults [aged 45-74]).MethodsThis study included 4,797 males and 7,043 females (aged 18-74) from the Hispanic Community Health Study / Study of Latinos. Employment status was categorized as employed full-time (FT), employed part-time (PT), employed (FT or PT) and homemakers, homemakers only, and unemployed. CVH metrics, operationalized as 'ideal' versus 'less than ideal,' included health factors (i.e., blood pressure, cholesterol, and fasting glucose) and health behaviors (i.e., body mass index, smoking, physical activity [PA], and diet). A total CVH score was derived based on the seven CVH metrics, and dichotomized as ideal vs. less than ideal (score of 11-14 vs. 0-10). Survey-based generalized linear regression models with Gaussian binomial distribution were used to estimate adjusted prevalence differences (APDs) and their 95% confidence intervals (CIs) for the associations between employment status (with employed FT as referent) and ideal CVH (total score and each metric), adjusting for socio-demographic characteristics. Effect modification by age was examined.ResultsAmong males, compared to their employed FT counterparts, those who were employed PT had a higher prevalence of ideal CVH score (APD = 6.8, 95% CI = 1.7, 11.8), ideal BMI (APD = 8.5, 95% CI = 3.0, 14.0), and ideal PA (APD = 4.8, 95% CI = 0.9, 8.7). Age modified the associations of employment type with ideal CVH score and ideal BMI, i.e., younger males who were employed PT had a higher prevalence of ideal CVH score and ideal BMI. Among females, employment status was not associated with ideal CVH score. Compared to females employed FT, females who were homemakers had a lower prevalence of ideal (non-) smoking (APD = -4.7, 95% CI = -8.5, -1.0) and ideal PA (APD = -7.9, 95% CI = -12.7, -3.0), and females who were unemployed had a lower prevalence of ideal PA (APD = -10.4, 95% CI = -16.7, -4.1). Age modified the associations of employment type with ideal fasting glucose and ideal PA, i.e., middle-aged and older females who were homemakers or unemployed had a lower prevalence of ideal fasting glucose and ideal PA.ConclusionsHispanic/Latino males who were employed PT had the most favorable CVH profiles but these associations were mostly driven by better CVH (total score and metrics) among younger males. Hispanic/Latino females who were homemakers or unemployed had lower rates of ideal CVH metrics.

BackgroundThe American Heart Association's 2020 Impact Goals propose to improve cardiovascular health (CVH) and reduce deaths from cardiovascular diseases and stroke in the US. Targeted health promotion efforts in workplaces and communities are needed to achieve these population-level changes. The present study examined the sex-specific cross-sectional associations between employment status and ideal CVH among Hispanics/Latinos, and whether these associations were modified by age (i.e., younger adults [aged 18-44] compared to middle-aged and older adults [aged 45-74]).MethodsThis study included 4,797 males and 7,043 females (aged 18-74) from the Hispanic Community Health Study / Study of Latinos. Employment status was categorized as employed full-time (FT), employed part-time (PT), employed (FT or PT) and homemakers, homemakers only, and unemployed. CVH metrics, operationalized as 'ideal' versus 'less than ideal,' included health factors (i.e., blood pressure, cholesterol, and fasting glucose) and health behaviors (i.e., body mass index, smoking, physical activity [PA], and diet). A total CVH score was derived based on the seven CVH metrics, and dichotomized as ideal vs. less than ideal (score of 11-14 vs. 0-10). Survey-based generalized linear regression models with Gaussian binomial distribution were used to estimate adjusted prevalence differences (APDs) and their 95% confidence intervals (CIs) for the associations between employment status (with employed FT as referent) and ideal CVH (total score and each metric), adjusting for socio-demographic characteristics. Effect modification by age was examined.ResultsAmong males, compared to their employed FT counterparts, those who were employed PT had a higher prevalence of ideal CVH score (APD = 6.8, 95% CI = 1.7, 11.8), ideal BMI (APD = 8.5, 95% CI = 3.0, 14.0), and ideal PA (APD = 4.8, 95% CI = 0.9, 8.7). Age modified the associations of employment type with ideal CVH score and ideal BMI, i.e., younger males who were employed PT had a higher prevalence of ideal CVH score and ideal BMI. Among females, employment status was not associated with ideal CVH score. Compared to females employed FT, females who were homemakers had a lower prevalence of ideal (non-) smoking (APD = -4.7, 95% CI = -8.5, -1.0) and ideal PA (APD = -7.9, 95% CI = -12.7, -3.0), and females who were unemployed had a lower prevalence of ideal PA (APD = -10.4, 95% CI = -16.7, -4.1). Age modified the associations of employment type with ideal fasting glucose and ideal PA, i.e., middle-aged and older females who were homemakers or unemployed had a lower prevalence of ideal fasting glucose and ideal PA.ConclusionsHispanic/Latino males who were employed PT had the most favorable CVH profiles but these associations were mostly driven by better CVH (total score and metrics) among younger males. Hispanic/Latino females who were homemakers or unemployed had lower rates of ideal CVH metrics.