Admixture mapping of cognitive function in diverse Hispanic and Latino adults: Results from the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: We conducted admixture mapping and fine-mapping analyses to identify ancestry-of-origin loci influencing cognitive abilities. METHODS: We estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts. RESULTS: We identified nine local ancestry-associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13. DISCUSSION: Our study identified multiple novel loci harboring genes implicated in cognitive functioning and dementia, and uncovered ancestry-relevant genetic variants. It adds to our understanding of the genetic architecture of cognitive function in Hispanic and Latino adults and demonstrates the power of admixture mapping to discover unique haplotypes influencing cognitive function, complementing genome-wide association studies. HIGHLIGHTS: We identified nine ancestry-of-origin chromosomal regions associated with five neurocognitive traits. In each associated region, we identified single nucleotide polymorphisms (SNPs) that explained, at least in part, the admixture signal and were tested for replication in independent samples of Black, non-Hispanic White, and Hispanic/Latino adults with the same or similar neurocognitive tests. Statistical evidence of independent replication of the prioritized SNPs was observed for three of the nine associations, at chr4q12, chr9p22.1, and chr13q12.13. At all loci, there was strong biological support for the observed associations to cognitive function and dementia, prioritizing genes such as KIT, implicated in autophagic clearance of neurotoxic proteins and on mast cell and microglial-mediated inflammation; SLC24A2, implicated in synaptic plasticity associated with learning and memory; and MTMR6, implicated in phosphoinositide lipids metabolism.

Intracranial Volume Is Driven by Both Genetics and Early Life Exposures: The SOL-INCA-MRI Study.

Intracranial volume (ICV) reflects maximal brain development and is associated with later-life cognitive abilities. We quantified ICV among first- and second-generation Hispanic and Latino adults from the Study of Latinos-Investigation of Cognitive Aging - MRI (SOL-INCA-MRI), estimated ICV heritability, and tested its associations with previously reported genetic variants, both individually and as a genetic risk score (GRS). We also estimated the association of ICV with early life environmental measures: nativity or age of immigration and parental education. The estimated heritability of ICV was 19% (95% CI, 0.1%-56%) in n=1781 unrelated SOL-INCA-MRI individuals. Four of 10 tested genetic variants were associated with ICV and an increase of 1 SD of the ICV-GRS was associated with an increase of 10.37 cm3 in the ICV (95% CI, 5.29-15.45). Compared to being born in the continental United States, immigrating to the United States at age 11 years or older was associated with 24 cm3 smaller ICV (95% CI, -39.97 to -8.06). Compared to both parents having less than high-school education, at least 1 parent completing high-school education was associated with 15.4 cm3 greater ICV (95% CI, 4.46-26.39). These data confirm the importance of early life health on brain development.

Sleep-wake behaviors associated with cognitive performance in middle-aged participants of the Hispanic Community Health Study/Study of Latinos.

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.

Cardiovascular disease risk exacerbates brain aging among Hispanic/Latino adults in the SOL-INCA-MRI Study.

Background: Cardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals. Methods: Participants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (<10%), medium (10- < 20%), and high (≥20%)). MR infarcts were determined as present or absent. Outcomes included total brain, cerebral and lobar cortical gray matter, hippocampal, lateral ventricle, and total white matter hyperintensity (WMH) volumes. Linear regression models tested associations between CVD risk and infarct with MRI outcomes and for modifications by age and sex. Results: Sixty percent of participants were at medium or high CVD risk. Medium and high CVD risk were associated with lower total brain and frontal gray matter and higher WMH volumes compared to those with low CVD risk. High CVD risk was additionally associated with lower total cortical gray matter and parietal volumes and larger lateral ventricle volumes. Men tended to have greater CVDRF-related differences in total brain volumes than women. The association of CVD risk factors on total brain volumes increased with age, equal to an approximate 7-year increase in total brain aging among the high-CVD-risk group compared to the low-risk group. The presence of infarct(s) was associated with lower total brain volumes, which was equal to an approximate 5-year increase in brain aging compared to individuals without infarcts. Infarcts were also associated with smaller total cortical gray matter, frontal and parietal volumes, and larger lateral ventricle and WMH volumes. Conclusion: The high prevalence of CVD risk among Hispanic/Latino adults may be associated with accelerated brain aging.

Associations of Allostatic Load with Level of and Change in Cognitive Function Among Middle-Aged and Older Hispanic/Latino Adults: The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

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.

Gut Microbiome Multi-Omics and Cognitive Function in the Hispanic Community Health Study/Study of Latinos- Investigation of Neurocognitive Aging.

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.

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

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.

Association Between Hypertensive Disorders of Pregnancy and Interval Neurocognitive Decline: An Analysis of the Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia, are associated with cognitive decline later in life among U.S. Hispanic/Latina individuals. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is a prospective population-based study of Hispanic/Latino individuals aged 18-74 years from four U.S. communities. This analysis included parous individuals aged 45 years or older who participated in the HCHS/SOL clinic study visit 1 (2008-2011) neurocognitive assessment and subsequently completed a repeat neurocognitive assessment as part of the Study of Latinos-Investigation of Neurocognitive Aging ancillary study visit 2 (2015-2018). Hypertensive disorders of pregnancy were assessed retrospectively by self-report of any gestational hypertension, preeclampsia, or eclampsia. Cognitive functioning was measured at both study visits with the Brief Spanish-English Verbal Learning Test, Digit Symbol Substitution, and Word Fluency. A regression-based approach was used to define cognitive decline at visit 2 as a function of cognition at visit 1 after adjustment for age, education, and follow-up time. Linear regression models were used to determine whether hypertensive disorders of pregnancy or their component diagnoses were associated with standardized cognitive decline after adjustment for sociodemographic characteristics, clinical and behavioral risk factors, and follow-up time. RESULTS: Among 3,554 individuals included in analysis, the mean age was 56.2 years, and 467 of individuals (13.4%) reported at least one hypertensive disorder of pregnancy. Individuals with hypertensive disorders of pregnancy compared with those without were more likely to have higher mean systolic blood pressure, fasting glucose, and body mass index. After an average of 7 years of follow-up, in fully adjusted models, gestational hypertension was associated with a 0.17-SD relative decline in Digit Symbol Substitution scores (95% CI, -0.31 to -0.04) but not other cognitive domains (Brief Spanish-English Verbal Learning Test or Word Fluency). Neither preeclampsia nor eclampsia was associated with neurocognitive differences. CONCLUSION: The presence of preeclampsia or eclampsia was not associated with interval neurocognitive decline. In this cohort of U.S. Hispanic/Latina individuals, gestational hypertension alone was associated with decreased processing speed and executive functioning later in life.

Normative data for the Digit Symbol Substitution for diverse Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

INTRODUCTION: Executive functioning and processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we aimed to provide normative data for the Digit Symbol Substitution (DSS) test. METHODS: The target population for the Study of Latinos-Investigation of Neurocognitive Aging included six heritage backgrounds (n = 6177). Average age was 63.4 ± 8.3 years, 54.5% were female, and mean education was 11.0 ± 4.7 years. Participants were administered the DSS as part of a larger battery. Heritage-adjusted DSS scores, and percentile cut-points were created using survey-adjusted regression and quantile regression models. RESULTS: Age, education, sex, heritage, and language preference were associated with DSS scores. DISCUSSION: Significant correlates of DSS performance should be considered when evaluating cognitive performance. Representative DSS norms for Hispanics/Latinos will advance assessment and accuracy of neurocognitive disorder diagnosis in clinical practice. To facilitate interpretation, we provide norms to reduce test biases and developed an online dashboard. Highlights: Normative data for the Digit Symbol Substitution (DSS) for diverse Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) This study is the first to develop norms for the DSS test across four regions of the United States.Factors such as age, education, sex, and Hispanic/Latino heritage and language preference are associated with differences in executive functioning and information processing speed.We created norms and an online dashboard (https://solincalab.shinyapps.io/dsst_shiny/) providing an easily accessible tool to evaluate processing speed and executive functioning in Hispanic/Latino adults.

Characterizing cognitive profiles in diverse middle-aged and older Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL).

Introduction: We investigated cognitive profiles among diverse, middle-aged and older Hispanic/Latino adults in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) cohort using a cross-sectional observational study design. Methods: Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.6%), and 38.4% reported less than a high school education. We used latent profile analysis of demographically adjusted z scores on SOL-INCA neurocognitive tests spanning domains of verbal memory, language, processing speed, and executive function. Results: Statistical fit assessment indices combined with clinical interpretation suggested five profiles: (1) a Higher Global group performing in the average-to-high-average range across all cognitive and instrumental activity of daily living (IADL) tests (13.8%); (2) a Higher Memory group with relatively high performance on memory tests but average performance across all other cognitive/IADL tests (24.6%); (3) a Lower Memory group with relatively low performance on memory tests but average performance across all other cognitive/IADL tests (32.8%); (4) a Lower Executive Function group with relatively low performance on executive function and processing speed tests but average-to-low-average performance across all other cognitive/IADL tests (16.6%); and (5) a Lower Global group performing low-average-to-mildly impaired across all cognitive/IADL tests (12.1%). Discussion: Our results provide evidence of heterogeneity in the cognitive profiles of a representative, community-dwelling sample of diverse Hispanic/Latino adults. Our analyses yielded cognitive profiles that may assist efforts to better understand the early cognitive changes that may portend Alzheimer's disease and related dementias among diverse Hispanics/Latinos. Highlights: The present study characterized cognitive profiles among diverse middle-aged and older Hispanic/Latino adults.Latent profile analysis of neurocognitive test scores was the primary analysis conducted.The target population consists of middle-aged and older Hispanic/Latino adults enrolled in the Hispanic Community Health Study/Study of Latinos and ancillary Study of Latinos - Investigation of Neurocognitive Aging.

Associations Between Self-Reported Visual and Hearing Functioning and Cognitive Function Among Hispanics/Latino: Hispanic Community Health Study.

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.

Hearing Loss and Associated 7-Year Cognitive Outcomes Among Hispanic and Latino Adults.

Importance: Hearing loss appears to have adverse effects on cognition and increases risk for cognitive impairment. These associations have not been thoroughly investigated in the Hispanic and Latino population, which faces hearing health disparities. Objective: To examine associations between hearing loss with 7-year cognitive change and mild cognitive impairment (MCI) prevalence among a diverse cohort of Hispanic/Latino adults. Design, Setting, and Participants: This cohort study used data from a large community health survey of Hispanic Latino adults in 4 major US cities. Eligible participants were aged 50 years or older at their second visit to study field centers. Cognitive data were collected at visit 1 and visit 2, an average of 7 years later. Data were last analyzed between September 2023 and January 2024. Exposure: Hearing loss at visit 1 was defined as a pure-tone average (500, 1000, 2000, and 4000 Hz) greater than 25 dB hearing loss in the better ear. Main outcomes and measures: Cognitive data were collected at visit 1 and visit 2, an average of 7 years later and included measures of episodic learning and memory (the Brief-Spanish English Verbal Learning Test Sum of Trials and Delayed Recall), verbal fluency (word fluency-phonemic fluency), executive functioning (Trails Making Test-Trail B), and processing speed (Digit-Symbol Substitution, Trails Making Test-Trail A). MCI at visit 2 was defined using the National Institute on Aging-Alzheimer Association criteria. Results: A total of 6113 Hispanic Latino adults were included (mean [SD] age, 56.4 [8.1] years; 3919 women [64.1%]). Hearing loss at visit 1 was associated with worse cognitive performance at 7-year follow-up (global cognition: ß = -0.11 [95% CI, -0.18 to -0.05]), equivalent to 4.6 years of aging and greater adverse change (slowing) in processing speed (ß = -0.12 [95% CI, -0.23 to -0.003]) equivalent to 5.4 years of cognitive change due to aging. There were no associations with MCI. Conclusions and relevance: The findings of this cohort study suggest that hearing loss decreases cognitive performance and increases rate of adverse change in processing speed. These findings underscore the need to prevent, assess, and treat hearing loss in the Hispanic and Latino community.

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.

Psychosocial factors associated with 7-year change in cognition among middle-aged and older Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) and Sociocultural ancillary studies.

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.

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.

Connections between reproductive health and cognitive aging among women enrolled in the HCHS/SOL and SOL-INCA.

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.

A polygenic risk score for Alzheimer's disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.

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-[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. DISCUSSION: A 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.

Association of anxiety and depressive symptoms with C-reactive protein in diverse Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: High sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups. METHODS: Depressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-<3 mg/L, intermediate; ≥ 3mg/L, high). RESULTS: Mean CES-D, STAI scores, and hsCRP levels were 7.0 (SD = 5.9), 17.0 (SD = 5.7), and 3.84 (SD = 7.85), respectively. Generalized linear modeling, adjusted for sociodemographic characteristics revealed significant associations between depression (exp(ß) = 1.12; p<0.01) and anxiety symptoms (exp(ß) = 1.10; p<0.05) with continuous hsCRP levels. For categorical values of hsCRP, one SD increase in CES-D and STAI scores was associated with a 10% and 8% increase in the RRRs of high vs. low hsCRP, respectively. However, these relationships between CES-D or STAI and hsCRP were no longer statistically significant after adjustment for CVD risk factors and medications. CONCLUSION: We found modest associations between anxiety and depressive symptoms and systemic inflammation measured by hsCRP among diverse Hispanics/Latinos that did not appreciably differ between heritage groups.

Childhood and Life-Course Socioeconomic Position and Cognitive Function in the Adult Population of the Hispanic Community Health Study/Study of Latinos.

The Hispanic/Latino population experiences socioeconomic adversities across the lifespan and is at greater risk of cognitive impairment, yet little is known about the role of life-course socioeconomic position (SEP) in cognitive function in this population. Using baseline data (2008-2011) from adults (aged 45-74 years) of the Hispanic Community Health Study/Study of Latinos, we assessed the association between childhood SEP and socioeconomic mobility with cognitive function, and whether this association was mediated by midlife SEP. Childhood SEP was assessed using parental education. An index combining participants' education and household income represented midlife SEP. Socioeconomic mobility was categorized as stable low, downward or upward mobility, and stable high-SEP. Cognitive function measures were modeled using survey linear regression with inverse-probability weighting, accounting for covariates. We used mediation analysis to estimate the indirect effect of childhood SEP on cognition through midlife SEP. High childhood SEP was associated with global cognition in adulthood (coefficient for parental education beyond high school vs. less than high school = 0.26, 95% confidence interval: 0.15, 0.37). This association was partially mediated through midlife SEP (indirect effect coefficient = 0.16, 95% confidence interval: 0.15, 0.18). Low SEP through the life course was associated with the lowest cognitive function. This study provides evidence that life-course SEP influences cognitive performance in adulthood.

Method comparison and estimation of causal effects of insomnia on health outcomes in a survey sampled population.

Applying causal inference methods, such as weighting and matching methods, to a survey sampled population requires properly incorporating the survey weights and design to obtain effect estimates that are representative of the target population and correct standard errors (SEs). With a simulation study, we compared various approaches for incorporating the survey weights and design into weighting and matching-based causal inference methods. When the models were correctly specified, most approaches performed well. However, when a variable was treated as an unmeasured confounder and the survey weights were constructed to depend on this variable, only the matching methods that used the survey weights in causal estimation and as a covariate in matching continued to perform well. If unmeasured confounders are potentially associated with the survey sample design, we recommend that investigators include the survey weights as a covariate in matching, in addition to incorporating them in causal effect estimation. Finally, we applied the various approaches to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and found that insomnia has a causal association with both mild cognitive impairment (MCI) and incident hypertension 6-7 years later in the US Hispanic/Latino population.