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Introduction: Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. Methods: We 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. Results: A 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- ϵ 2 and APOE- ϵ 4 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- ϵ 4 and APOE- ϵ 2 alleles were not associated with MCI. Discussion: A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE- ϵ 4 and APOE- ϵ 2 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. • Paradoxical effect for cumulative life stress on information processing speed • Interaction occurred in Hispanics/Latinos with highest resting heart rate variability. • Data supports ultra-short HRV as transdiagnostic marker of resilience to stress. • Greater Spanish-English word fluency with HRV supports marker of prefrontal lobe function. [ABSTRACT FROM AUTHOR]

Background: The 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]). Methods: This 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. Results: Among 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. Conclusions: Hispanic/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. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sleep disordered breathing (SDB) is a risk factor of stroke and Alzheimer disease and related dementias (ADRDs). Hispanic/Latino adults have higher risk of SDB and ADRDs, which emphasizes the need to better understand the association between SDB and brain health. Furthermore, results on SDB and brain aging are mixed, and there are limited data for Hispanic/Latino adults. The main goal of this study is to assess the association between SDB and brain MRI measures in a diverse Hispanic/Latino population., Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a community-based prospective cohort multisite (Bronx, Chicago, Miami, San Diego) study of diverse Hispanic/Latino adults in the United States. Participants underwent 1 night of unsupervised home testing with a sleep apnea test device at baseline. The SOL-Investigation of Neurocognitive Aging MRI, an ancillary study, recruited 2,667 HCHS/SOL participants (35-85 years) who underwent neuroimaging approximately 10 years after baseline sleep assessment. The main exposure was the respiratory event index (REI, 3% desaturation). Secondary exposures encompassed measures of oxygen saturation. Main outcomes included total brain, gray matter, white matter hyperintensity (WMH), and hippocampal volumes. Survey linear regression models were used to determine associations between SDB and brain MRI measures., Results: The mean age was 67.6 years, with a body mass index of 29.7, and 58.3% were female. We found that increased REI was associated with larger hippocampal volumes ( b hippocampus = 0.006 [0.001-0.012]). These results were consistent with oxygen levels (minimum SpO 2 %) during sleep ( b hippocampus = -0.013 [-0.021 to -0.004]). Lower oxygen levels (mean SpO 2 ) during sleep were associated with enlarged WMH volumes ( b WMH = -0.095 [-0.164 to -0.025])., Discussion: We found that SDB and worse oxygenation during sleep were linked to larger hippocampal volumes. These results underscore the complex relationships between sleep health and brain aging and warrant longitudinal follow-up, starting in middle age or earlier.

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.)

Introduction: We conducted a study within the Hispanic Community Health Study/Study of Latinos- Investigation of Neurocognitive Aging (HCHS/SOL-INCA) cohort to examine the association between gut microbiome and cognitive function., Methods: We analyzed the fecal metagenomes of 2,471 HCHS/SOL-INCA participants to, cross-sectionally, identify microbial taxonomic and functional features associated with global cognitive function. Omnibus (PERMANOVA) and feature-wise analyses (MaAsLin2) were conducted to identify microbiome-cognition associations, and specific microbial species and pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG modules) associated with cognition., Results: Eubacterium species( E. siraeum and E. eligens ), were associated with better cognition. Several KEGG modules, most strongly Ornithine, Serine biosynthesis and Urea Cycle, were associated with worse cognition., Discussion: In a large Hispanic/Latino cohort, we identified several microbial taxa and KEGG pathways associated with cognition.

Introduction: Reproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women., Methods: Participants 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)., Results: Younger 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., Discussion: Several aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background and Objectives: To investigate the associations between self-reported visual functioning (VF) and hearing functioning with cognition in the Hispanic/Latino population., Research Design and Methods: We 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., Results: NEI-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  < .001), 0.17 in Word fluency ( SE  = 0.16, p  < .01), and 0.08 in B-SEVLT-recall ( SE  = 0.07, p  < .01). HHIA/E-S was not associated with any of the cognitive measures examined., Discussion and Implications: These data suggest that impaired VF is associated with worse cognition in the Hispanic/Latino population. Although previous work in this cohort indicated hearing loss assessed by pure tone audiometry was associated with worse cognition, we found self-perceived hearing function was not associated with cognition, suggesting the potential limitation of self-reported hearing function as a proxy for hearing loss in epidemiological research in Hispanic/Latino populations. Results also imply impaired VF and hearing function may be linked to cognition differently in the Hispanic population, and more research is needed to better understand the underlying linking mechanisms. Visual and hearing impairments are common and treatable and represent important modifiable risk factors that can be treated to preserve cognitive function in Hispanics/Latinos., Competing Interests: None., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Introduction: Coronavirus 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., Methods: This 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., Results: Successful 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., Discussion: The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection., Key Points: The 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., Competing Interests: All authors state that they have no relationships/activities/interests to disclose related to the content of this submission. Author disclosures are available in the supporting information., (© 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Blood metabolomics-based biomarkers may be useful to predict measures of neurocognitive aging., Methods: We 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., Results: We 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., Discussion: Blood metabolites may serve as biomarkers identifying individuals at risk for MCI among US Hispanics/Latinos., Competing Interests: Jan Bressler reports receiving the following financial support, with all payments made to her institution: NIH/NHLBI HHSN268201700001I (University of North Carolina at Chapel Hill; this is support for the present manuscript), NIH/NHLBI HHSN268201700001I (University of North Carolina at Chapel Hill), NIH/NIA 1R01AG058921 01A1 (Wake Forest School of Medicine), NIH/NHLBI R01HL141292 (University of Michigan), NIH/NHLBI R01HL141291‐02 NIH/NIAMS R01AR073178‐03 (University of Mississippi Medical Center), NIH/NIA 1R03 AG065420‐02 NIH/NHLBI 2U01HL096812‐09 (Johns Hopkins University), NIH/OD 1OT2OD00275 (Baylor College of Medicine), NIH/NIDDK R01DK552556‐01 (Johns Hopkins University), NIH/NIEHS 5R01ES022165 NIH/NINDS R01NS087541 NIH/NCI 2P01CA138338 (University of Minnesota), NIH/NIDDK U01DK078616 (Massachusetts General Hospital), NIH/NHGRI UM1HG006542 (Johns Hopkins University). Tianyi Huang reports receiving grant support from NHLBI, to himself. Sylvia Wassertheil‐Smoller reports receiving an NIH grant, and support from the Fred Hutchinson Cancer Center, with payment made to her. She reports royalties for her textbook Biostatistics and Epidemiology from Springer Publishing and consulting fees from RxScholar for review of STEP 1 testing materials for medical students. Melissa Lamar reports receiving funding support from the NIH, with payments made to the institution; support from the International Neuropsychological Society, with payments made to her. She is a member of the Rush University Medical Center's Data Safety and Monitoring Board or Advisory Board, with no payment to her or her institute and receives a reimbursement in the form of an honorarium (later donated to student fellowship fund of INS) from the International Neuropsychological Society travel reimbursement, with payment made to her. Martha Daviglus reports receiving multiple NIH grants, with payments made to the University of Illinois at Chicago. Maria J. Marquine reports receiving support through multiple NIH grants: R01MD013502 and 3R01MD013502‐03S1 (as a PI, with payments made to her institution), as well as support from the Federal Defenders of San Diego, from the American Academy of Neuropsychology Annual Meeting, and the International Neuropsychological Society, with payments made to her. Jianwen Cai reports funding support from the NIH, 75N92019D00010, with payments made to her institution. She reports being a Chair of American Statistical Association Lifetime Data Science Section Chair of American Statistical Association Fellow Committee. Thomas Mosley reports receiving NIH grants, with payments made to the institution. He reports serving on the CARDIA Observational studies monitoring board with remuneration paid to him for time spent on meeting (<$200). Robert Kaplan reports receiving NIH grants and receiving consulting fees from the University of Texas. Eric Boerwinkle reports receiving multiple grants: ARIC Contract (support for the present manuscript), payments made to his institution; UM1HG008898 NIH/Baylor College of Medicine, R01HL131136 NIH/NHLBI, R01HL131136‐S1 NIH/NHLBI, HHSN268201700001I NIH/NHLBI/UNC at Chapel Hill, 1R01HL141824 NIH/NHLBI, 1OT2OD00275 NIH/Baylor College of Medicine, 1R01MD013349 NIH/UNC at Chapel Hill, 1U01AG058589‐01 NIH/Boston University, HHSN268201800002I NHLBI/U. of Michigan, R01AG059727 NIH/Boston University, R01AG061022 NIH/University of California‐San Diego, 1R01HL148050‐01 NIH/Baylor College of Medicine, U01 HL096812 NIH/Johns Hopkins University, HHS000866600001 Texas Department of State Health Services TOPMed Centralized Omics Resource (CORE) BCM/NIH/NHLBI, R01 HL148218 NIH/Brigham and Women's Hospital. He also reports participating in the PRIDE Programs to Increase Diversity‐Lecture at Washington University in St. Louis‐annual lecture, and payments were made to him and donated to the institution. He reports receiving reimbursement for travel expenses out of pocket for several NIH meetings. He reports serving as a member in numerous NIH Special Emphasis Panels (mostly NHLBI and NHGRI). Eric Boerwinkle further reports serving as a co‐cChair of the Alzheimer's Disease Sequencing Project Steering Committee; as a member of the Alzheimer's Disease Sequencing Project Executive Committee; a member of the NHLBI TOPMed Program Steering Committee; a member of the NHLBI TOPMed Program Executive Committee; a member of the All of Us Steering Committee; a member of the All of Us Science Committee; a member of the All of Us Reassessment Committee; and a member of the anchoring committee for the Greater Houston Coalition for the Social Determinants of Health. This group is working to bring together organizations and service providers to help those in need navigate available services and coordinate across service providers to reduce duplication and increase efficiency. He also reports serving as a chair of the Greater Houston Health Connect Research Committee, a group working to build health services research in the State's largest health information exchange (HIE), and as a board member for the Hackett Center for Mental Health Consulting member of the TMC CEO COVID‐19 Task Force Consulting member of the LHA (Local Health Authorities). Myriam Fornage reports receiving NIH grants. Charles DeCarli reports receiving NIH ADRC support with money paid to the institution. He reports receiving consulting fees from Novartis Novo Nordisk, and honoraria for teaching a Harvard Dementia Course. Bruce Kristal reports royalties from Metabolon, through Weill Medical of Cornell University, and consulting fees from Pfizer and Metabolon (both completed). He also reports holding Metabolon stock—both directly owned and through rights paid to Weill Medical College of Cornell University. He also reports an informatics patent‐pending, unrelated to the current study. His interests were reviewed by the Brigham and Women's Hospital and Mass General Brigham following their institutional policy. Accordingly, upon review, the institution determined that Kristal's financial interest in Metabolon does not create a significant financial conflict of interest with this research. Hector M. Gonzalez reports receiving NIA funding with payments made to his institution, and honoraria from USC and UTHSCSA, with payments made to him. Tamar Sofer reports funding through contracts from Brown University, the Broad Institute of MIT and Harvard, the Veterans Administration‐Boston, the University of California Davis, and the University of California San Diego, with payments made to the institution. She also reports funding from NHLBI, with payments made to the institution. She reports receiving honoraria after a presentation at the University of California San Diego, with payment made to her., (© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: We 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., Methods: The exposures were baseline SDB (respiratory event index ≥ 15), sleepiness (Epworth Sleepiness Scale ≥ 10), SD (< 6 hours, 6-9 hours, ≥ 9 hours). The outcome was 7-year ND., Results: Mean age was 56.0 years, 54.8% were females. Obesity modified the association between SDB/SD and ND in memory (F = 21.49, P < 0.001) and global cognition (F = 9.14, P < 0.001) in the oldest age group. Women without MetS with combined long sleep/SDB exhibited most pronounced decline in global cognition (F = 3.07, P = 0.010)., Discussion: The association between combined SDB/long sleep and declines in memory and global cognition was most pronounced in obese older adults. Among women, MetS status modified the association between long sleep/SDB and decline in global cognition., (© 2021 the Alzheimer's Association.)

Objectives: Immigrants to the USA have disparate access to health insurance coverage and healthcare services. We evaluate the effects of gaining insurance following the January 2014 Affordable Care Act's (ACA) key provisions implementation on health services use among foreign- (FB) and US-born (USB) adults., Methods: Longitudinal data from two panels (2013/2014 and 2014/2015) of the Medical Expenditure Panel Survey on FB and USB adults, ages 26-64 (unweighted n = 15,232), and difference-in-differences analysis using generalized estimating equations were used to estimate the effects of insurance gain. The primary outcomes were five measures of healthcare utilization including yearly routine care appointment, annual number of physician office visits, annual number of prescription medications filled or refilled, use of the emergency department (ED) during the year, and having an inpatient hospital stay during the year., Results: Immigrants were more likely to gain health insurance between 2013 and 2015 relative to USB adults (6.3% vs. 4.4%) but remained much more likely to be continuously uninsured by 2015 (20.8% vs. 6.4%). Controlling for sociodemographic and health characteristics, FB and USB adults who gained insurance increased their use of health services, including routine care (absolute change Δ FB  = 15.7%; p < 0.001 and Δ USB  = 11.7%; p < 0.001), office-based doctor visits (Δ FB  = 1.3; p < 0.001 and Δ USB  = 0.6; p < 0.001), prescribed medications (Δ FB  = 2.5; p < 0.001 and Δ USB  = 1.6; p = 0.016), and inpatient hospitalizations (Δ FB  = 3.6%; p = 0.017 and Δ USB  = 3%; p < 0.001). ED use increased only among the FB (Δ FB  = 4.8%; p < 0.001). Gaining insurance eliminated the differences in health services use for all considered outcomes among the FB relative to the continuously insured USB., Conclusions: US immigrants had notable gains in health insurance after the ACA provisions took full effect, but major disparities in coverage persist. If insurance continues to expand among immigrants, then the gains may reduce longstanding disparities in health services use and enhance primary and preventive healthcare.

Objective: Intradetrusor onabotulinumtoxinA is a third-line treatment for urgency urinary incontinence (UUI) which is customarily reserved for severe disease. We sought to determine if symptom severity predicts the proportional response to onabotulinumtoxinA and whether low-dose injection may be an appropriate treatment for mild-moderate symptoms., Study Design: This prospective cohort study compared patients with urgency urinary incontinence who were recruited from the Urogynecology Clinic with mild-moderate (2-9 episodes/3-day diary) and severe UUI (>9 episodes/3-day diary) symptoms. Twenty-eight subjects were treated (11 mild-moderate, 17 severe) with 50 units of intradetrusor onabotulinumtoxinA. Voiding diaries and validated questionnaires (UDI-6 and IIQ-7) were collected at baseline and one, six, and twelve months post-treatment. The primary outcome was the difference in percent reduction in UUI episodes per 3-day diary at one month. Secondary outcomes included differences in absolute reduction of UUI events, treatment success rate (defined as greater than 50% reduction in UUI episodes), changes in UDI-6 and IIQ-7 questionnaire scores, and rates of urinary retention, self-catheterization, and urinary tract infection. Normally distributed data are presented as means with standard deviations (SD) and groups were compared using the two sample t-test. Data that were not normally distributed are presented as medians with the interquartile range (IQR) and were compared using the Wilcoxon rank sum test., Results: The mild-moderate group showed median improvement; 100% (IQR: 100%, 100%) and severe group; 81% (IQR: 35%, 100%), p < 0.019. Both had significant improvement in UUI episodes; the mild-moderate group decreased by four and the severe group by 15. No differences were noted in percent reduction between groups. There was no association between baseline severity and percent reduction in UUI episodes (rs = 0.127, p = 0.544); however, absolute reduction was highly correlated (rs = -0.821, p < 0.001). Treatment success was 90% in mild-moderate and 73% in the severe group (p = 0.615). Complications included urinary tract infections (25%) and intermittent catheterization (3.6%)., Conclusions: Patients with both mild-moderate and severe symptoms showed a statistically significant improvement in UUI events from baseline to one month, but no difference between the groups in proportional improvement or treatment success., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)