Glycemic Control, Cognitive Aging, and Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging (Hispanic Community Health Study/Study of Latinos).

OBJECTIVE: Hispanics/Latinos in the United States 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 Hispanics/Latinos 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 Hispanics/Latinos age 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 covariates 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 Hispanics/Latinos. Our findings indicate that poor glycemic control in midlife may pose significant risks for cognitive decline and MCI later in life among Hispanics/Latinos of diverse heritages.

Hypertension, Cognitive Decline, and Mild Cognitive Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging Results (SOL-INCA).

BACKGROUND: Hypertension can have deleterious effects on cognitive function; however, few studies have examined its effects on cognition among Hispanics/Latinos. OBJECTIVE: To assess associations between hypertension status with 1) change in cognitive performance, and 2) having mild cognitive impairment (MCI) among diverse Hispanics/Latinos. METHODS: This population-based, prospective cohort, multisite study included Hispanic/Latino adults aged 45 to 72 years in enrolled in the Hispanic Community Health Study/Study of Latinos at Visit 1 (2008-2011; mean age of 63.40±8.24 years), and the Study of Latinos-Investigation of Neurocognitive Aging at Visit 2 (2016-2018), with a mean follow-up duration of 7 years (n = 6,173). Hypertension status was assessed at both visits: normotension (no hypertension), incident hypertension (only at Visit 2), and persistent hypertension (at both visits). We examined change in cognitive performance and having MCI (only assessed at Visit 2) relative to hypertension status and adjusted for demographics and cardiovascular disease risk factors. RESULTS: Compared to normotension, persistent hypertension was associated with significantly increased decline in verbal fluency (ß= -0.08; CI = [-0.16;-0.01]; p < 0.05), and processing speed (ß= -0.11; CI = [-0.20;-0.02]; p < 0.05). Incident hypertension was not associated with significant change in cognitive performance. Both incident (OR = 1.70; CI = [1.16;2.50]; p < 0.01) and persistent hypertension (OR = 2.13; CI = [1.57;2.88]; p < 0.001) were associated with significantly higher odds ratios of having MCI. CONCLUSIONS: These findings indicate that persistent hypertension is associated with clinical impairment and domain-specific cognitive decline in middle-aged and older Hispanics/Latinos. It underscores the importance of monitoring blood pressure in routine healthcare visits beginning at midlife in this population to reduce the burden of cognitive decline.

Sleep duration and brain MRI measures: Results from the SOL-INCA MRI study.

INTRODUCTION: Sleep duration has been associated with dementia and stroke. Few studies have evaluated sleep pattern-related outcomes of brain disease in diverse Hispanics/Latinos. METHODS: The SOL-INCA (Study of Latinos-Investigation of Neurocognitive Aging) magnetic resonance imaging (MRI) study recruited diverse Hispanics/Latinos (35-85 years) who underwent neuroimaging. The main exposure was self-reported sleep duration. Our main outcomes were total and regional brain volumes. RESULTS: The final analytic sample included n = 2334 participants. Increased sleep was associated with smaller brain volume (ßtotal_brain  = -0.05, p < 0.01) and consistently so in the 50+ subpopulation even after adjusting for mild cognitive impairment status. Sleeping >9 hours was associated with smaller gray (ßcombined_gray  = -0.17, p < 0.05) and occipital matter volumes (ßoccipital_gray  = -0.18, p < 0.05). DISCUSSION: We found that longer sleep duration was associated with lower total brain and gray matter volume among diverse Hispanics/Latinos across sex and background. These results reinforce the importance of sleep on brain aging in this understudied population. HIGHLIGHTS: Longer sleep was linked to smaller total brain and gray matter volumes. Longer sleep duration was linked to larger white matter hyperintensities (WMHs) and smaller hippocampal volume in an obstructive sleep apnea (OSA) risk group. These associations were consistent across sex and Hispanic/Latino heritage groups.

Characterizing age- and sex-related differences in brain structure among middle-aged and older Hispanic/Latino adults in the study of Latinos- investigation of neurocognitive aging magnetic resonance imaging (SOL-INCA MRI).

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.

Association of Mitochondrial DNA Copy Number With Brain MRI Markers and Cognitive Function: A Meta-analysis of Community-Based Cohorts.

BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults. METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear DNA. Brain MRI markers included total brain, hippocampal, and white matter hyperintensity volumes. General cognitive function was derived from distinct cognitive domains. We performed cohort-specific association analyses of mtDNA CN with AD/ADRD endophenotypes assessed within ±5 years (i.e., cross-sectional analyses) or 5-20 years after blood draw (i.e., prospective analyses) adjusting for potential confounders. We further explored associations stratified by sex and age (<60 vs ≥60 years). Fixed-effects or sample size-weighted meta-analyses were performed to combine results. Finally, we performed mendelian randomization (MR) analyses to assess causality. RESULTS: We included up to 19,152 participants (mean age 59 years, 57% women). Higher mtDNA CN was cross-sectionally associated with better general cognitive function (ß = 0.04; 95% CI 0.02-0.06) independent of age, sex, batch effects, race/ethnicity, time between blood draw and cognitive evaluation, cohort-specific variables, and education. Additional adjustment for blood cell counts or cardiometabolic traits led to slightly attenuated results. We observed similar significant associations with cognition in prospective analyses, although of reduced magnitude. We found no significant associations between mtDNA CN and brain MRI measures in meta-analyses. MR analyses did not reveal a causal relation between mtDNA CN in blood and cognition. DISCUSSION: Higher mtDNA CN in blood is associated with better current and future general cognitive function in large and diverse communities across the United States. Although MR analyses did not support a causal role, additional research is needed to assess causality. Circulating mtDNA CN could serve nevertheless as a biomarker of current and future cognitive function in the community.

Serum Cystatin-C is linked to increased prevalence of diabetes and higher risk of mortality in diverse middle-aged and older adults.

OBJECTIVE: Type 2 Diabetes Mellitus (henceforth diabetes) affects roughly 35 million individuals in the US and is a major risk factor for cardiovascular and kidney disease. Serum Cystatin-C is used to monitor renal function and detect kidney damage. Recent research has focused on linking Cystatin-C to cardiovascular risk and disease, but most findings focus on small sample sizes and generalize poorly to diverse populations, thus limiting epidemiological inferences. The aim of this manuscript is to study the association between Cystatin-C, diabetes, and mortality and test for possible sex or racial/ethnic background modifications in these relationships. METHODS: We analyzed 8-years of biennial panel data from Health and Retirement Study participants 50-years and older who self-identified as White (unweighted N (uN) = 5,595), Black (uN = 867), or Latino (uN = 565) for a total of uN = 7,027 individuals. We modeled diabetes and death over 8-years as function of baseline Cystatin-C (log transformed) adjusting for covariates and tested modifications in associations by race/ethnic background and sex. RESULTS: Mean log Cystatin-C at visit 1 was 0.03±0.32 standard deviation. A 10% increase in Cystatin-C levels was associated with 13% increased relative risk of diabetes at baseline (11% and 9% by years 4 and 8). A 10% increase in Cystatin-C was highly associated with increased relative risk of death (28% and 31% by years 4 and 8). These associations were present even after adjusting for possible confounders and were not modified by sex or racial/ethnic background. CONCLUSION: Despite differential risks for diabetes and mortality by racial/ethnic groups, Cystatin-C was equally predictive of these outcomes across groups. Cystatin-C dysregulations could be used as a risk indicator for diabetes and as a warning sign for accelerated risk of mortality.

Anticholinergic Drug Burden and Neurocognitive Performance in the Study of Latinos-Investigation of Neurocognitive Aging.

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 (ß= -0.21; 95% CI [-0.36; -0.05]), learning (ß= -0.27; 95% CI [-0.47; -0.07]), memory (ß= -0.22; 95% CI [-0.41; -0.03]), and executive functioning (ß= -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 (ß: -0.28 [95% CI: -0.55, -0.01]; ß: -0.28 [95% CI: -0.55, -0.01]; ß: -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.

Subjective cognitive decline and objective cognition among diverse U.S. Hispanics/Latinos: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

INTRODUCTION: Despite increased risk of cognitive decline in Hispanics/Latinos, research on early risk markers of Alzheimer's disease in this group is lacking. Subjective cognitive decline (SCD) may be an early risk marker of pathological aging. We investigated associations of SCD with objective cognition among a diverse sample of Hispanics/Latinos living in the United States. METHODS: SCD was measured with the Everyday Cognition Short Form (ECog-12) and cognitive performance with a standardized battery in 6125 adults aged ≥ 50 years without mild cognitive impairment or dementia (x̄age  = 63.2 years, 54.5% women). Regression models interrogated associations of SCD with objective global, memory, and executive function scores. RESULTS: Higher SCD was associated with lower objective global (B = -0.16, SE = 0.01), memory (B = -0.13, SE = 0.02), and executive (B = -0.13, SE = 0.02, p's < .001) function composite scores in fully adjusted models. DISCUSSION: Self-reported SCD, using the ECog-12, may be an indicator of concurrent objective cognition in diverse middle-aged and older community-dwelling Hispanics/Latinos.

Normative data for the Brief Spanish-English Verbal Learning Test for representative and diverse Hispanics/Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

INTRODUCTION: Episodic learning and memory performance are crucial components of cognitive assessment. To meet the needs of a diverse Hispanic/Latino population, we aimed to provide normative data on the Brief Spanish-English Verbal Learning Test (B-SEVLT). METHODS: The target population for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) included individuals 45+ years old from Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American backgrounds. Average age was 56.5 years ± 9.92, 54.5% were female, and mean education was 11.0 years ± 5.6 (unweighted n = 9309). Participants were administered the B-SEVLT in their preferred language (Spanish or English). Hispanic/Latino background adjusted B-SEVLT scores and percentile cut-points were created using survey-adjusted regression models. RESULTS: Higher educational attainment, younger age, and being female were associated with higher learning and memory performance. Hispanic/Latino background groups differed in B-SEVLT performance. DISCUSSION: Representative learning and memory norms for Hispanic/Latinos of diverse backgrounds will improve cognitive assessment and accuracy of neurocognitive disorder diagnosis.

Cognitive and Neuroimaging Correlates of the Insomnia Severity Index in Obstructive Sleep Apnea: A Pilot-Study.

We aim to determine the sleep correlates of age-related brain loss in a sample of middle-aged to older males with obstructive sleep apnea (OSA). We recruited consecutive treatment naïve male patients with moderate to severe OSA from January to November of 2019. We excluded participants if they had dementia, stroke or heart disease. We collected demographic variables and vascular risk factors. We also obtained the insomnia severity index, the Epworth sleepiness scale and the Pittsburgh sleep quality index. We also obtained computerized neurocognitive testing with the go-no-go response inhibition test, Stroop interference test, catch game test, staged information processing speed test, verbal memory test and non-verbal memory test. We derived age and education adjusted domain-specific Z-scores for global cognition, memory, attention, processing speed and executive function. We used brain MRI T1-weighted images to derive total hippocampal and gray matter volumes. Partial correlations evaluated associations between variables from sleep questionnaires (e.g., insomnia severity index score), and polysomnographic variables (the apnea-hypopnea index, average oxygen levels during sleep) with cognitive domains and brain volumes. We examined 16 participants with an age range of 40-76 years, 73% Hispanic/Latino. The mean apnea-hypopnea index was 48.9 ± 25.5 and average oxygen saturation during sleep was 91.4% ± 6.9%. Hypertension was seen in 66% and diabetes mellitus in 27%. We found that the insomnia severity index score and average oxygen levels during sleep had the strongest correlations with brain volumes and cognition. These preliminary findings may aid in developing future strategies to improve age-related brain loss in patients with OSA.

Phenotypes of obstructive sleep apnea in the Hispanic Community Health Study/Study of Latinos.

STUDY OBJECTIVES: Recent work on US Whites from clinical samples used obstructive sleep apnea (OSA) symptoms to generate phenotypes for individuals with moderate-severe OSA which suggested 3 to 5 symptom classes. However, it is unknown whether similar classes generalize to diverse Hispanics/Latino adults. Therefore, we sought to fill this gap by empirically deriving sleep phenotypes among a large sample of diverse Hispanics/Latinos. METHODS: We used data from The Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008-2011), a prospective cohort study designed using a multisite multistage probability sample of adults 18-74 years old. The subpopulation of interest included participants with moderate-severe OSA symptoms (≥15 respiratory event index (REI) events per hour; n = 1,605). We performed latent class analysis for complex survey data using 15 common OSA symptoms (e.g. Epworth Sleepiness Scale) and 4 comorbidities to identify phenotype classes. RESULTS: Average age was 52.4 ± 13.9 years and 34.0% were female. Mean REI was 33.8 ± 22.5 events per hour. Fit statistics and clinical significance suggested that a three-class solution provided the best fit to the data. The three phenotypes were: (1) Minimally Symptomatic (47.7%), (2) Excessive sleepiness (37.1%), and (3) Disturbed Sleep (15.2%). Sensitivity models were consistent with the main proposed solution. CONCLUSIONS: Derived sleep phenotypes among diverse Hispanic/Latinos were consistent with recent findings from the Sleep Apnea Global Interdisciplinary Consortium, but we found notable differences in class prevalence relative to Whites. Further research is needed to link derived sleep phenotypes to health comorbidities in diverse populations.

Central Obesity, Cardiometabolic Risk, and Cognitive Change in the Study of Latinos - Investigation of Neurocognitive Aging.

BACKGROUND: The relationships between obesity and cognitive decline in aging are mixed and understudied among Hispanics/Latinos. OBJECTIVE: To understand associations between central obesity, cognitive aging, and the role of concomitant cardiometabolic abnormalities among Hispanics/Latinos. METHODS: Participants included 6,377 diverse Hispanics/Latinos enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation for Neurocognitive Aging (SOL-INCA). Participants were 45 years and older at the first cognitive testing session (Visit 1). Cognitive outcomes (z-score units) included global composite and domain specific (learning, memory, executive functioning, processing speed) measures at a second visit (SOL-INCA, on average, 7 years later), and 7-year change. We used survey linear regression to examine associations between central obesity (waist circumference≥88 cm and≥102 cm for women and men, respectively) and cognition. We also tested whether the relationships between obesity and cognition differed by cardiometabolic status (indication of/treatment for 2 + of the following: high triglycerides, hypertension, hyperglycemia, low high-density lipoprotein cholesterol). RESULTS: Central obesity was largely unassociated with cognitive outcomes, adjusting for covariates. However, among individuals with central obesity, cardiometabolic abnormality was linked to poorer cognitive function at SOL-INCA (ΔGlobalCognition =-0.165, p < 0.001) and to more pronounced cognitive declines over the average 7 years (ΔGlobalCognition = -0.109, p < 0.05); this was consistent across cognitive domains. CONCLUSION: Central obesity alone was not associated with cognitive function. However, presence of both central obesity and cardiometabolic abnormalities was robustly predictive of cognition and 7-year cognitive declines, suggesting that in combination these factors may alter the cognitive trajectories of middle-aged and older Hispanics/Latinos.

Modifying pathways by age and sex for the association between combined sleep disordered breathing and long sleep duration with neurocognitive decline in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

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.

Diabetes, Cognitive Decline, and Mild Cognitive Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging Results (HCHS/SOL).

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 (ßGC = -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.

A research framework for cognitive aging and Alzheimer's disease among diverse US Latinos: Design and implementation of the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Hispanics/Latinos are the largest ethnic/racial group in the United States and at high risk for Alzheimer's disease and related dementia (ADRD). Yet, ADRD among diverse Latinos is poorly understood and disparately understudied or unstudied compared to other ethnic/racial groups that leave the nation ill-prepared for major demographic shifts that lay ahead in coming decades. The primary purpose of this Perspectives article was to provide a new research framework for advancing Latino ADRD knowledge, encompassing the unique sociocultural, cardiometabolic, and genomic aspects of Latino health, aging, and ADRD. In addition, we describe some of the research challenges to progress in Latino ADRD research. Finally, we present the Study of Latinos - Investigation of Neurocognitive Aging (SOL-INCA) as an example of implementing this new framework for advancing Latino ADRD research.