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Background: Sleep-related disorders have been associated with cognitive decline and neurodegeneration. American Indians are at increased risk for dementia. Here, we aim to characterize, for the first time, the associations between sleep characteristics and subsequent cognitive performance in a sample of aging American Indians. Methods: We performed analyses on data collected in two ancillary studies from the Strong Heart Study, which occurred approximately 10 years apart with an overlapping sample of 160 American Indians (mean age at follow-up 73.1, standard deviation 5.6; 69.3% female and 80% with high school completion). Sleep measures were derived by polysomnography and self-reported questionnaires, including sleep timing and duration, sleep latency, sleep stages, indices of sleep-disordered breathing, and self-report assessments of poor sleep and daytime sleepiness. Cognitive assessment included measures of general cognition, processing speed, episodic verbal learning, short and long-delay recall, recognition, and phonemic fluency. We performed correlation analyses between sleep and cognitive measures. For correlated variables, we conducted separate linear regressions. We analyzed the degree to which cognitive impairment, defined as more than 1.5 standard deviations below the average Modified Mini Mental State Test score, is predicted by sleep characteristics. All regression analyses were adjusted for age, sex, years of education, body mass index, study site, depressive symptoms score, difference in age from baseline to follow-up, alcohol use, and presence of APOE e4 allele. Results: We found that objective sleep characteristics measured by polysomnography, but not subjective sleep characteristics, were associated with cognitive performance approximately 10 years later. Longer sleep latency was associated with worse phonemic fluency (β = -0.069, p = 0.019) and increased likelihood of being classified in the cognitive impairment group later in life (odds ratio 1.037, p = 0.004). Longer duration with oxygen saturation < 90% was associated with better immediate verbal memory, and higher oxygen saturation with worse total learning, short and long-delay recall, and processing speed. Conclusion: In a sample of American Indians, sleep characteristics in midlife were correlated with cognitive performance a decade later. Sleep disorders may be modifiable risk factors for cognitive impairment and dementia later in life, and suitable candidates for interventions aimed at preventing neurodegenerative disease development and progression. [ABSTRACT FROM AUTHOR]

Objective: Modified Mini-Mental State Examination (3MSE) is often used to screen for dementia, but little is known about psychometric validity in American Indians. Methods: We recruited 818 American Indians aged 65–95 for 3MSE examinations in 2010–2013; 403 returned for a repeat examination in 2017–2019. Analyses included standard psychometrics inferences for interpretation, generalizability, and extrapolation: factor analysis; internal consistency-reliability; test-retest score stability; multiple indicator multiple cause structural equation models. Results: This cohort was mean age 73, majority female, mean 12 years education, and majority bilingual. The 4-factor and 2nd-order models fit best, with subfactors for orientation and visuo-construction (OVC), language and executive functioning (LEF), psychomotor and working memory (PMWM), verbal and episodic memory (VEM). Factor structure was supported for both research and clinical interpretation, and factor loadings were moderate to high. Scores were generally consistent over mean 7 years. Younger participants performed better in overall scores, but not in individual factors. Males performed better on OVC and LEF, females better on PMWM. Those with more education performed better on LEF and worse on OVC; the converse was true for bilinguals. All differences were significant, but small. Conclusion: These findings support use of 3MSE for individual interpretation in clinic and research among American Indians, with moderate consistency, stability, reliability over time. Observed extrapolations across age, sex, education, and bilingual groups suggest some important contextual differences may exist. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Accurate epidemiologic estimates for dementia are lacking for American Indians, despite substantive social and health disparities. METHODS: The Strong Heart Study, a population‐based cohort of 11 American Indian tribes, conducted detailed cognitive testing and examinations over two visits approximately 7 years apart. An expert panel reviewed case materials for consensus adjudication of cognitive status (intact; mild cognitive impairment [MCI]; dementia; other impaired/not MCI) and probable etiology (Alzheimer's disease [AD], vascular bain injury [VBI], traumatic brain injury [TBI], other). RESULTS: American Indians aged 70–95 years had 54% cognitive impairment including 10% dementia. VBI and AD were primary etiology approximately equal proportions (>40%). Apolipoprotein (APO) Eε4 carriers were more common among those with dementia (p = 0.040). Plasma pTau, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were higher among those with cognitive impairment, but not amyloid beta (Aβ). Cognitive intact had mean 3MSE 92.2 (SD 6.4) and mean Montreal Cognitive Assessment (MoCA) score of 21.3 (SD 3.2). DISCUSSION: This is the first population‐based study to estimate the prevalence of vascular and Alzheimer's dementias in a population‐based study of American Indians. Highlights: The Strong Heart Study is a population‐based cohort of American Indian tribes, conducted over 30+ years and three US geographic regions (Northern Plains, Southern Plains, Southwest).Our teams conducted detailed cognitive testing, neurological examination, and brain imaging over two visits approximately 7 years apart. An expert panel reviewed collected materials for consensus‐based adjudication of cognitive status (intact; MCI; dementia; other impaired/not MCI) and probable underlying etiology (AD; VBI; TBI; other).In this cohort of American Indians aged 70–95, 54% were adjudicated with cognitive impairment, including approximately 35% MCI and 10% dementia. These data expand on prior reports from studies using electronic health records, which had suggested prevalence, and incidence of dementia in American Indians to be more comparable to the majority population or non‐Hispanic White individuals, perhaps due to latent case undercounts in clinical settings.Vascular and neurodegenerative injuries were approximately equally responsible for cognitive impairment, suggesting that reduction of cardiovascular disease is needed for primary prevention.Traumatic injury was more prevalent than in other populations, and common among those in the "other/not MCI" cognitive impairment category.Mean scores for common dementia screening instruments—even among those adjudicated as unimpaired—were relatively low compared to other populations (mean unimpaired 3MSE 92.2, SD 6.4; mean unimpaired MoCA 21.3, SD 3.2), suggesting the need for cultural and environmental adaptation of common screening and evaluation instruments. [ABSTRACT FROM AUTHOR]

The Controlled Oral Word Association (COWA) test is used to assess phonemic fluency and executive function. Formal validation of test scores is important for accurate cognitive evaluation. However, there is a dearth of psychometric validation among American Indian adults. Given high burden of dementia risk and key contextual factors associated with cognitive assessments, this represents a critical oversight. In a large, longitudinal population-based cohort study of adult American Indians, we examined several validity inferences for COWA, including scoring, generalization, and extrapolation inferences, by investigation of factor structure, internal consistency, test–retest reliability, and differential test functioning. We found adequate unidimensional model fit, with high factor loadings. Internal consistency reliability and test–retest reliability were 0.88 and 0.77, respectively, for the full group. COWA scores were lowest among the oldest, lowest education, bilingual speakers; group effects for sex and bilingual status were small; age effect was medium; and education effect was largest. However, Wide Range Achievement Test (WRAT) score effect was stronger than education effect, suggesting better contextualization may be needed. These results support interpretation of total COWA score, including across sex, age, or language use strata. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Identification of Alzheimer's disease (AD) needs inexpensive, noninvasive biomarkers, with validation in all populations. METHODS: We collected plasma markers in older American Indian individuals: phosphorylated‐tau181 (pTau181); amyloid‐beta (Aβ) 40,42; glial fibrillary acidic protein (GFAP); and neurofilament light chain (NfL). Plasma markers were analyzed for discriminant properties with cognitive status and etiology using receiver operating characteristic (ROC) analysis. RESULTS: PTau181, GFAP, NfL plasma values were significantly associated with cognition, but Aβ were not. Discriminant performance was moderate for individual markers, with pTau181, GFAP, NfL performing best, but an empirically selected panel of markers (age, sex, education, pTau181, GFAP, NfL, Aβ4240 ratio) had excellent discriminant performance (AUC > 0.8). DISCUSSION: In American Indian individuals, pTau181 and Aβ values suggested more common pathology than in majority populations. Aβ was less informative than in other populations; however, all four markers were needed for a best‐performing dementia diagnostic model. These data validate utility of AD plasma markers, while suggesting population‐specific diagnostic characteristics. [ABSTRACT FROM AUTHOR]

Background: Arsenic and cadmium are known cardiovascular toxicants that pose disproportionate risk to rural communities where environmental exposures are high. American Indians have high vascular risk, which may be attributable in part to these exposures. Objective: We examined urine metal concentrations in association with magnetic resonance imaging findings of vascular brain injury or cerebral atrophy in adult American Indians. Methods: We measured arsenic and cadmium in American Indian participants from the Strong Heart Study (1989-1991) and evaluated these associations with later (2010-2013) measures of infarct, hemorrhage, white matter hyperintensity (WMH) grade, brain and hippocampal volume, and sulcal and ventricle atrophy using nested multivariate regression analyses. Results: Among participants with available data (N = 687), the median urine arsenic:creatinine ratio was 7.54 [micro]g/g [interquartile range (IQR): 4.90-11.93] and the cadmium:creatinine ratio was 0.96 [micro]g/g (IQR: 0.61-1.51). Median time between metal measurement and brain imaging was 21 y (range: 18-25 y). Statistical models detected significant associations between arsenic and higher burden of WMH [grade increase = 0.014 (95% CI: 0.000, 0.028) per 10% increase in arsenic]; and between cadmium and presence of lacunar infarcts [relative risk (RR) = 1.024 (95% CI: 1.004, 1.045) per 10% increase in cadmium]. Discussion: This population-based cohort of American Indian elders had measured values of urine arsenic and cadmium several times higher than previous population- and clinic-based studies in the United States and Mexico, and comparable values with European industrial workers. Our findings of associations for arsenic and cadmium exposures with vascular brain injury are consistent with established literature. Environmental toxicant accumulation is modifiable; public health policy may benefit from focusing on reductions in environmental metals. https://doi.org/10.1289/EHP6930, Introduction Arsenic and cadmium are known environmental toxicants. Geographical regions characterized by subsistence or rural economies may have some of the most heavily arsenic- and cadmium-contaminated soil or groundwater, where [...]

Introduction: Distinguishing Alzheimer's disease (AD) patient subgroups may optimize positive clinical outcomes. Cortical atrophy is correlated with memory deficits, but these associations are understudied in American Indians. Methods: We collected imaging and cognition data in the Strong Heart Study (SHS), a cohort of 11 tribes across three regions. We processed 1.5T MRI using FreeSurfer and iterative principal component analysis. Linear mixed models estimated volumetric associations with diabetes. Results: Over mean 7 years follow‐up (N = 818 age 65–89 years), overall volume loss was 0.5% per year. Significant losses associated with diabetes were especially strong in the right hemisphere. Annualized hippocampal, parahippocampal, entorhinal atrophy were worse for men, older age, diabetes, hypertension, stroke; and associated with both encoding and retrieval memory losses. Discussion: Our findings suggest that diabetes is an important risk factor in American Indians for cortical atrophy and memory loss. Future research should examine opportunities for primary prevention in this underserved population. [ABSTRACT FROM AUTHOR]

Background: The apolipoprotein E (APOE) ε4 allele confers higher risk of neurodegeneration and Alzheimer's disease (AD), but differs by race/ethnicity. We examined this association in American Indians. Methods: The Strong Heart Study is a population‐based cohort of American Indians who were 64 to 95 years of age in 2010 to 2013. APOE ε4 status, brain imaging, and neuropsychological testing was collected in N = 811 individuals. Summary statistics, graphics, and generalized linear regressions—adjusted for sociodemographics, clinical features, and intracranial volume with bootstrap variance estimator—compared APOE ε4 carriers with non‐carriers. Results: APOE ε4 carriers comprised 22% of the population (0.7% homozygotes). Participants were mean 73 years, 67% female, and 54% had some college education. The majority were obese (>50%), hypertensive (>80%), and diabetic (>50%). Neither imaging findings nor multidomain cognitive testing showed any substantive differences between APOE ε4 carriers and non‐carriers. Conclusion: We found no evidence of neurodegenerative risk from APOE ε4 in American Indians. Additional studies are needed to examine potential protective features. [ABSTRACT FROM AUTHOR]

Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system (1,2). After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells (4). It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential (6). Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in [CD411.sup.+]c-[Kit.sup.+] haematopoietic progenitor cells (7), concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta-gonads-mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling (8), compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development., In the mouse, the first haemogenic areas appear in the yolk sac starting at day 7.5 of development (E7.5) (9). After the establishment of circulation and the onset of vascular [...]

Standardized neuropsychological instruments are used to evaluate cognitive impairment, but few have been psychometrically evaluated in American Indians. We collected Montreal Cognitive Assessment (MoCA) in 403 American Indians 70 to 95 years, as well as age, sex, education, bilingual status, depression symptoms, and other neuropsychological instruments. We evaluated inferences of psychometric validity, including scoring inference using confirmatory factor analysis and structural equation modeling, generalizability inference using reliability coefficient, and extrapolation inference by examining performance across different contexts and substrata. The unidimensional (total score) model had good fit criteria. Internal consistency reliability was high. MoCA scores were positively associated with crystallized cognition (ρ = 0.48, p < .001) and inversely with depression symptoms (ρ = −0.27, p < .001). Significant differences were found by education (d = 0.79, p < .05) depression (d = 0.484, p < .05), and adjudicated cognitive status (p = .0001) strata; however, MoCA was not sensitive or specific in discriminating cognitive impairment from normal cognition (area under the curve <0.5). MoCA scores had psychometric validity in older American Indians, but education and depression are important contextual features for score interpretability. Future research should evaluate cultural or community-specific adaptations, to improve test discriminability in this underserved population. [ABSTRACT FROM AUTHOR]

Introduction: Research on factors associated with late-life cognitive performance in diverse racial/ethnic groups is increasingly important due to the growing size and racial diversity of the elder population. Methods: Using data on American Indians (AIs) from the Strong Heart Study, we measured associations between mid-life physical activity (PA), assessed by a questionnaire or pedometer, and performance on tests of general cognitive function, phonemic fluency, verbal learning and memory, and processing speed. Cognitive tests were administered 7–21 years after PA measurements. To estimate associations, we used regression models with and without inverse-probability weights to account for potential attrition bias in the cohort. Results: Questionnaire and pedometer measures of PA were positively associated with cognitive function. Participants in the top quartile of questionnaire-based PA had Modified Mini-Mental State examination scores 3.2 (95% CI: 1.5–4.9) points higher than participants in the lowest quartile. Phonemic fluency scores also trended higher for participants in the top compared to the bottom categories for both PA measures: top questionnaire quartile = 2.7 (95% CI: 0.6–4.8) points higher and top pedometry tertile = 6.7 (95% CI: 2.7–10.7) points higher. We observed no associations between PA and tests assessing verbal learning and memory, or processing speed. Weighted model results were similar, but less precise. Conclusions: In this cohort of AIs with relatively low levels of PA, positive associations between mid-life PA and late-life cognitive performance were dose-dependent and of modest clinical significance. [ABSTRACT FROM AUTHOR]

Background: The Modified Mini‐Mental State Examination (3MSE) is a cognitive assessment tool covering multiple domains often used to screen for dementia. Psychometric studies have demonstrated consistent 3MSE test performance across multiple racial/ethnic populations, but American Indians have been underrepresented in clinical validity studies. Population‐based cohort data suggests relatively low score distributions in American Indians, emphasizing a critical need for formal psychometric assessments. Method: The Strong Heart Study recruited 818 American Indians aged 65‐95 years from 3 states for cognitive examinations in 2010‐13; 403 survivors repeated exams in 2017‐19. Participants self‐reported age, sex, education, and bilingual ability; trained personnel administered the 3MSE. We conducted psychometric analyses to support validity inferences, including scoring using confirmatory factor analysis, generalizability with internal consistency‐reliability estimates, and extrapolation via multiple indicator multiple cause models for differential item functioning. Result: Participants were mean 73 years (SD 5.9), 67.5% female, mean 12.6 years education, mean 3MSE score 88.4 (SD 9.7); at repeat examination (mean 6.7 years later) mean 3MSE score was 87.1 (9.5). For a scoring inference, factor analysis supported a 4‐factor/second‐order model (comparative fit index: 0.91). The four factors included verbal‐episodic memory (short, long recall; λ: 0.81‐0.82), language‐executive function (animal, command, naming, obey, repetition, similarities; λ: 0.40‐0.58), psychomotor‐working memory (reversal, writing; λ: 0.49‐0.65), and orientation‐visuoconstruction (orientation, pentagons, registration, spatial, temporal; λ: 0.11‐0.69). For generalizability, we detected acceptable internal consistency (>0.90 total score) and strong test‐retest reliability (Pearson's r: 0.47‐0.78, all p<0.05). For extrapolation and group differences, overall test performance was strongly associated with age and education, but not sex; language use (bilingual) was significant and strongly associated with psychomotor‐working memory factor (β: 0.12‐0.40, p<0.05), but not with the language‐executive function factor (β: 0.01‐0.10). Conclusion: Overall, these patterns of evidence support clinical interpretation of 3MSE scores among American Indian elders, with consideration of age and education and possibly also bilingual status or usual language use. Furthermore, these findings suggest that previously‐observed population differences in 3MSE score may result from unaddressed social determinants. Future research should address possible influence of socioeconomic, cultural, historical, or behavioral factors not currently addressed in neuropsychological practice. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is best defined in vivo using quantifiable, objective markers reflecting amyloid deposition (A), pathologic tau (T), and neurodegeneration (N). However, gold standards for ATN (imaging or cerebrospinal proteins) are expensive, invasive, and/or impractical in low resource settings. Circulating proteins offer a practical alternative. Candidate plasma markers include amyloid‐β (Aβ40&42), phosphorylated tau‐181 (ptau), glial fibrillary protein (GFAP), and neurofilament light chain (NfL). However, no such markers have been evaluated in American Indians. Method: The Strong Heart Study recruited 401 American Indians over 3 states in 2017‐2019 for MRI, cognitive testing, and clinical examination. MRI included T1 sequences, which were processed using FreeSurfer to quantify structural volumes. Neuropsychological testing incuded California Verbal Learning Test, which was operationalized into categories of memory impairment using indices of learning and recall. Plasma samples were sent to University of Gothenburg for Simoa Quanterix assay. Statistics included descriptive summary; multivariate regression; and receiver operating characteristic analysis. Result: The study population was mean age 78 (SD 4.7, range 70‐95); majority female (71%); and 21% APOE ε4 allele carriers. An estimated 31% had any memory impairment (13.8% retrieval, 6.5% storage, 10.7% encoding). Median plasma marker values were: ptau 5.0pg/mL (range: 1.5‐442), Aβ40 128pg/mL (116‐175), Aβ42 8.2pg/mL (6.7‐9.7), GFAP 150pg/mL (0‐651), and NfL 31.6pg/mL (9.7‐343); median Aβ42:40 ratio 0.06. Comparing APOEε4 carriers to non‐carriers (Table1), ptau was +12%, Aβ40 ‐0.8%, Aβ42 ‐8.4%, Aβ4240 ‐16.7% (P = 0.006), GFAP +16.1%, NfL +3.2%, but only Aβ4240 was significant. Linear regressions with brain volumes identified significant associations for Aβ42, Aβ40, GFAP, and NfL (but not ptau) with ventricle, cortical, and overall volume; NfL was also associated with entorhinal and hippocampal volume. GFAP and ptau were significantly higher in those with memory encoding deficit; NfL higher with encoding or retrieval deficit (Table2). Although not significant, Aβ40 was lower with storage deficit, and Aβ42 with encoding or storage deficit. AUC range for plasma markers to discriminate memory impaired from intact: 0.4‐0.6. Conclusion: These data are a first look at ATN plasma markers in a population‐based cohort of American Indians, an underrepresented group in AD research. Future research should address generalizability and measurement validity. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic studies often use self-report as proxy for clinical history. However, whether self-report correctly identifies prevalence in minority populations with health disparities and poor health-care access is unknown. Furthermore, overlap of clinical vascular events with covert vascular brain injury (VBI), detected by imaging, is largely unexamined. Methods: The Strong Heart Study recruited American Indians from 3 regions, with surveillance and adjudication of stroke events from 1989 to 2013. In 2010–2013, all 817 survivors, aged 65–95 years, underwent brain imaging, neurological history interview, and cognitive testing. VBI was defined as imaged infarct or hemorrhage. Results: Adjudicated stroke was prevalent in 4% of participants and separately collected, self-reported stroke in 8%. Imaging-defined VBI was detected in 51% and not associated with any stroke event in 47%. Compared with adjudication, self-report had 76% sensitivity and 95% specificity. Participants with adjudicated or self-reported stroke had the poorest performance on cognitive testing; those with imaging-only (covert) VBI had intermediate performance. Conclusion: In this community-based cohort, self-report for prior stroke had good performance metrics. A majority of participants with VBI did not have overt, clinically recognized events but did have neurological or cognitive symptoms. Data collection methodology for studies in a resource-limited setting must balance practical limitations in costs, accuracy, feasibility, and research goals. [ABSTRACT FROM AUTHOR]

Objectives: Insulin resistance is a substantial health issue for American Indians, with type 2 diabetes overrepresented in this population as compared with non-Hispanic whites. Insulin resistance and its related conditions in turn increase risk for dementia and cognitive impairment. The aim of the current study was to determine whether type 2 diabetes and insulin resistance at midlife was associated with later-life cognitive testing in a large sample of older American Indians, aged 65 and older.Methods: American Indian participants who underwent both fasting blood draw as part of the Strong Heart Study and had subsequent cognitive testing as part of the later adjunct Cerebrovascular Disease and its Consequences in American Indians study were included (n = 790). Regression models examined type 2 diabetes and impaired fasting glucose and subsequent cognitive test performance as part of a longitudinal study design. The relationship between a continuous measure of insulin resistance and later cognitive test performance was assessed using generalized estimating equations.Results: Controlling for demographic and clinical factors, verbal fluency and processing speed/working memory were significantly negatively associated with having type 2 diabetes and with insulin resistance, but not with impaired fasting glucose.Conclusion: In this sample of American Indians, type 2 diabetes at midlife was associated with subsequent lower performance on measures of executive function. These results may have important implications for future implementation of diagnostic and intervention services in this population. [ABSTRACT FROM AUTHOR]

BACKGROUND American Indians have excess risk of depression, which can contribute to cerebrovascular and cognitive disability, with effects on memory, processing speed, executive function, and visuospatial ability. However, studies examining depression and cognition in American Indians are limited; this study aims to report associations of depression with general cognition, verbal fluency and memory, and processing speed. DESIGN Cohort study. SETTING The Cerebrovascular Disease and its Consequences in American Indians study was an ancillary examination of Strong Heart Study participants from 3 U.S. regions. PARTICIPANTS All eligible were included in this analysis (N=818). MEASUREMENTS Participants completed evaluations for depressive symptomology, cognition, and physical function—including Center for Epidemiologic Studies Depression (CESD), Modified Mini‐Mental State Examination (3MSE), Wechsler Adult Intelligence Scale‐Fourth Edition coding (WAIS), Controlled Oral Word Association (COWA), California Verbal and Learning Test, Halstead finger tapping, grip strength, and Short Physical Performance Battery (SPPB) tests. Linear mixed models were adjusted for site, age, sex, education, income, marital status, alcohol, smoking, diabetes, hypertension, obesity, cholesterol, stroke, infarct, and hemorrhage. RESULTS: Symptoms of depression were common, with 20% (N=138) endorsing CES‐D scores of 16+. More depressive symptoms were associated with older age, female sex, lower education, lower income, non‐married status, not using alcohol, not smoking, hypertension, diabetes, and stroke. In adjusted analyses, processing speed (WAIS: β −0.13, 95%CI −0.25, −0.03), general cognition (3MSE: β −0.10, 95%CI −0.17, −0.03), verbal fluency (COWA: β −0.10, 95%CI −0.19, −0.01), and motor function (SPPB: β −0.05, 95%CI −0.07, −0.03) were significantly associated with more symptoms of depression. CONCLUSION: These findings maybe informative for health disparities populations, especially those with depressive risk. Clinicians may require particular training in cultural humility. Future studies should validate use of the CES‐D scale in this population; longitudinal studies may focus on causal mechanisms and potential secondary prevention, such as social support. J Am Geriatr Soc 68:1739‐1747, 2020. [ABSTRACT FROM AUTHOR]

Objective: American Indians experience substantial health disparities relative to the US population, including vascular brain aging. Poorer cognitive test performance has been associated with cranial magnetic resonance imaging findings in aging community populations, but no study has investigated these associations in elderly American Indians. Methods: We examined 786 American Indians aged 64 years and older from the Cerebrovascular Disease and its Consequences in American Indians study (2010–2013). Cranial magnetic resonance images were scored for cortical and subcortical infarcts, hemorrhages, severity of white matter disease, sulcal widening, ventricle enlargement, and volumetric estimates for white matter hyperintensities (WMHs), hippocampus, and brain. Participants completed demographic, medical history, and neuropsychological assessments including testing for general cognitive functioning, verbal learning and memory, processing speed, phonemic fluency, and executive function. Results: Processing speed was independently associated with the presence of any infarcts, white matter disease, and hippocampal and brain volumes, independent of socioeconomic, language, education, and clinical factors. Other significant associations included general cognitive functioning with hippocampal volume. Nonsignificant, marginal associations included general cognition with WMH and brain volume; verbal memory with hippocampal volume; verbal fluency and executive function with brain volume; and processing speed with ventricle enlargement. Conclusions: Brain-cognition associations found in this study of elderly American Indians are similar to those found in other racial/ethnic populations, with processing speed comprising an especially strong correlate of cerebrovascular disease. These findings may assist future efforts to define opportunities for disease prevention, to conduct research on diagnostic and normative standards, and to guide clinical evaluation of this underserved and overburdened population. [ABSTRACT FROM AUTHOR]

Background: Over 86% of American Indian and Alaska Native elders live in urban metropolitan areas, yet the extant epidemiological data on cognition and aging in this racial and ethnic population has been collected in reservation communities and may have limited generalizability to the larger population. Multi‐faceted, high quality data are needed to assess risk and protective factors in this underserved and understudied population. Method: We intend to collect medical history, lifestyle and behavioral history, neurocognitive battery, anthropometric measures, blood and urine samples, cranial 3T MRI, rsfMRI, and wrist actigraphy data from 1200 urban‐dwelling Native elders (age 55 and older) across 5 major metropolitan areas: Anchorage, AK; Seattle, WA; San Bernardino, CA; Phoenix, AZ; and Oklahoma City, OK. This initial cohort will be the first in a NIA‐funded longitudinal cohort study to evaluate the brain and cognitive health of this population as they advance in age. Result: Originally funded in the summer of 2019, data collection was initially delayed due to the pandemic, but was initiated at one site (Phoenix) in the summer of 2021 and is now underway at all 5 field sites, with a total of 260 participants enrolled as of the time of this writing. Conclusion: This study represents the largest effort to characterize the cognition and brain health of a generalizable sample of urban‐dwelling American Indian and Alaska Native elders to date. [ABSTRACT FROM AUTHOR]

Background: Clinical stroke is prevalent in American Indians, but the lifestyle risk factors for vascular brain injury have not been well-studied in this population. The purpose of this study was to correlate brain magnetic resonance imaging (MRI) findings with obesity, alcohol use, and smoking behaviors in elderly American Indians from the Strong Heart Study. Methods: Cranial MRI scans (n = 789) were analyzed for dichotomous measures of infarcts, hemorrhages, white matter hyperintensities (WMH), and cerebral atrophy and continuous measures of total brain, WMH, and hippocampal volume. Poisson regression was used to estimate prevalence ratios, and linear regression was used to estimate measures of association for continuous outcomes. Models were adjusted for the risk factors of interest as well as age, sex, study site, income, education, hypertension, diabetes, and low-density lipoprotein cholesterol. Results: Smoking was associated with increased hippocampal atrophy (p = 0.002) and increased prevalence of sulcal widening (p < 0.001). Relative to nonsmokers, smokers with more than 25 pack-years of smoking had a 27% (95% CI 7–47%) increased prevalence of high-grade sulci, p = 0.005. Body mass index was inversely associated with prevalence of nonlacunar infarcts and sulcal widening (all p = 0.004). Alcohol use was not significantly associated with any of the measured MRI findings. Conclusions: This study found similar associations between smoking and vascular brain injury among American Indians, as seen in other populations. In particular, these findings support the role of smoking as a key correlate for cerebral atrophy. [ABSTRACT FROM AUTHOR]

Background: Clinical stroke is prevalent in American Indians, but the risk factors for cerebrovascular pathology have not been well-studied in this population. The purpose of this study was to correlate abnormalities on brain magnetic resonance imaging (MRI) with clinical risk factors in a cohort of elderly American Indians. Methods: Brain MRI scans from 789 participants of the Strong Heart Study were analyzed for infarcts, hemorrhage, white matter disease, and measures of cerebral atrophy including ventricular and sulcal grade and total brain volume. Clinical risk factors included measures of hypertension, diabetes, and high levels of low-density lipoprotein (LDL) cholesterol. Regression models adjusted for potential confounders were used to estimate associations between risk factors and brain MRI outcomes. Results: -Hypertension was associated with the presence of infarcts (p = 0.001), ventricle enlargement (p = 0.01), and increased white matter hyperintensity volume (p = 0.01). Diabetes was associated with increased prevalence of cerebral atrophy (p < 0.001), ventricular enlargement (p = 0.001), and sulcal widening (p = 0.001). High LDL was not significantly associated with any of the measured cranial imaging outcomes. Conclusions: This study found risk factors for cerebrovascular disease in American Indians similar to those seen in other populations and provides additional evidence for the important roles of hypertension and diabetes in promoting cerebral infarcts and brain atrophy, respectively. [ABSTRACT FROM AUTHOR]

Telomeres are repeating regions of DNA that cap chromosomes. They shorten over the mammalian life span, especially in the presence of oxidative stress and inflammation. Telomeres may play a direct role in cell senescence, serving as markers of premature vascular aging. Leukocyte telomere length (LTL)may be associated with premature vascular brain injury and cerebral atrophy. However, reports have been inconsistent, especially among minority populations with a heavy burden of illness related to vascular aging. We examined associations between LTL and magnetic resonance imaging in 363 American Indians aged 64-93 years from the Strong Heart Study (1989-1991) and its ancillary study, Cerebrovascular Disease and Its Consequences in American Indians (2010-2013). Our results showed significant associations of LTL with ventricular enlargement and the presence of white matter hyperintensities. Secondary models indicated that renal function may mediate these associations, although small case numbers limited inference. Hypertension and diabetes showed little evidence of effectmodification. Results were most extreme among participants who evinced the largest decline in LTL. Although this study was limited to cross-sectional comparisons, it represents (to our knowledge) the first consideration of associations between telomere length and brain aging in American Indians. Findings suggest a relationship between vascular aging by cell senescence and severity of brain disease. [ABSTRACT FROM AUTHOR]

Background: More than six million American Indians live in the United States, and an estimated 1.6 million will be aged ≥65 years old by 2050 tripling in numbers since 2012. Physical functioning and related factors in this population are poorly understood. Our study aimed to assess lower body functioning and identify the prevalence and correlates of "good" functioning in a multi-tribe, community-based sample of older American Indians.Methods: Assessments used the Short Physical Performance Battery (SPPB). "Good" lower body functioning was defined as a total SPPB score of ≥10. Potential correlates included demographic characteristics, study site, anthropometrics, cognitive functioning, depressive symptomatology, grip strength, hypertension, diabetes mellitus, heart disease, prior stroke, smoking, alcohol use, and over-the-counter medication use for arthritis or pain. Data were collected between 2010 and 2013 by the Cerebrovascular Disease and Its Consequences in American Indians Study from community-dwelling adults aged ≥60 years (n = 818).Results: The sample's mean age was 73 ± 5.9 years. After adjustment for age and study site, average SPPB scores were 7.0 (95% CI, 6.8, 7.3) in women and 7.8 (95% CI, 7.5, 8.2) in men. Only 25% of the sample were classified with "good" lower body functioning. When treating lower body functioning as a continuous measure and adjusting for age, gender, and study site, the correlates of better functioning that we identified were younger age, male gender, married status, higher levels of education, higher annual household income, Southern Plains study site, lower waist-hip ratio, better cognitive functioning, stronger grip strength, lower levels of depressive symptomatology, alcohol consumption, and the absence of hypertension, diabetes mellitus, and heart disease. In our fully adjusted models, correlates of "good" lower body functioning were younger age, higher annual household income, better cognitive functioning, stronger grip, and the absence of diabetes mellitus and heart disease.Conclusions: These results suggest that "good" lower body functioning is uncommon in this population, whereas its correlates are similar to those found in studies of other older adult populations. Future efforts should include the development or cultural tailoring of interventions to improve lower body functioning in older American Indians. [ABSTRACT FROM AUTHOR]

Background: The Cerebrovascular Disease and its Consequences in American Indians study conducted cranial MRI examination of surviving participants of the Strong Heart Study, a longitudinal cohort of elderly American Indians. Methods: Of the 1,033 recruited participants, some were unable to complete the MRI (n = 22), some scans were unusable due to participant motion or technical errors (n = 13), and one community withdrew consent after data collection (n = 209), leaving 789 interpretable MRI scan images. Six image sequences were obtained in contiguous slices on 1.5T scanners. Neuroradiologists graded white matter hyperintensities (WMH), sulci, and ventricles on a 0-to 9-point scale, and recorded the presence of infarcts and hemorrhages. Intracranial, brain, hippocampal, and WMH volumes were estimated by automated image processing. Results: The median scores for graded measures were 2 (WMH) and 3 (sulci, ventricles). About one-third of participants had lacunar (20%) or other infarcts (13%); few had hemorrhages (5.7%). Findings of cortical atrophy were also prevalent. Statistical analyses indicated significant associations between older age and findings of vascular injury and atrophy; male gender was associated with findings of cortical atrophy. Conclusions: Vascular brain injury is the likely explanation in this elderly American Indian population for brain infarcts, hemorrhages, WMH grade, and WMH volume. Although vascular brain injury may play a role in other findings, independent degenerative other disease processes may underlie abnormal sulcal widening, ventricular enlargement, hippocampal volume, and total brain volume. Further examination of risk factors and outcomes with these findings may expand the understanding of neurological conditions in this understudied population. [ABSTRACT FROM AUTHOR]

Background: Estimates of hippocampal volume by magnetic resonance imaging have clinical and cognitive correlations and can assist in early Alzheimer disease diagnosis. However, little is known about the relationship between global or regional brain volumes and cognitive test performance in American Indians.Materials and Methods: American Indian participants (N=698; median age, 72 y) recruited for the Cerebrovascular Disease and its Consequences in American Indians study, an ancillary study of the Strong Heart Study cohort, were enrolled. Linear regression models assessed the relationship between magnetic resonance imaging brain volumes (total brain and hippocampi) and cognitive measures of verbal learning and recall, processing speed, verbal fluency, and global cognition.Results: After controlling for demographic and clinical factors, all volumetric measurements were positively associated with processing speed. Total brain volume was also positively associated with verbal learning, but not with verbal recall. Conversely, left hippocampal volume was associated with both verbal learning and recall. The relationship between hippocampal volume and recall performance was more pronounced among those with lower scores on a global cognitive measure. Controlling for APOE ε4 did not substantively affect the associations.Conclusions: These results support further investigation into the relationship between structural Alzheimer disease biomarkers, cognition, genetics, and vascular risk factors in aging American Indians. [ABSTRACT FROM AUTHOR]

Background: American Indians present with increased risk factors for Alzheimer's disease and related dementias (ADRDs). Intraindividual cognitive variability (IICV), which measures the variability in performance on neuropsychological tests within a person at a single time, has been proposed as a noninvasive marker of neurodegeneration and early dementia. In this study, we investigated the hypothesis that higher IICV was related to more features of neurodegeneration on magnetic resonance imaging (MRI) measurements among older American Indians. Method: American Indian participants over 64 years of age who underwent MRI and completed a battery of neuropsychological tests were included in the study (N = 750). Data from three neuropsychological tests were used to compute a multidomain IICV measure of cognition along with IICV measures representing the cognitive domains of memory, executive function and processing speed. Regression models estimated IICV associations with total brain volume, hippocampal volume, and graded white matter disease, adjusting for age, sex, education, BMI, and intracranial volume. Result: Memory, executive function and processing speed, and multidomain IICV measures were associated with total brain volume before correction for multiple comparisons. After correction with Bonferroni, only higher IICV of memory was associated with lower total brain volume (Beta = −0.20; 95%CI −0.332, −0.068; p = 0.009). Furthermore, additional adjustment of mean scores from the tests used for the variability measure resulted in loss of significance for all IICV measures, with only mean scores remaining significant. Measures of IICV were not associated with hippocampal volume or white matter disease. Conclusion: These findings suggest that IICV of memory may be associated with imaging measures related to neurodegenerative injury in older American Indians. However, these associations representing variability in cognition are smaller than those representing mean cognition. More research is needed to understand the clinical and etiologic associations for IICV measures. [ABSTRACT FROM AUTHOR]

The Cerebrovascular Disease and its Consequences in American Indians (CDCAI) Study recruited surviving members of a 20-year, longitudinal, population-based cohort of American Indians focused on cardiovascular disease, its risk factors, and its consequences. The goal of the CDCAI Study is to characterize the burden, risk factors, and manifestations of vascular brain injury identified on cranial MRI. The CDCAI Study investigators enrolled 1,033 participants aged 60 and older from 11 American Indian communities and tribes in the Northern Plains, Southern Plains, and Southwestern United States. In addition to cranial MRI performed according to standardized protocols, participants underwent extensive medical interview, clinical examination, neurocognitive testing, physical function evaluation, electrocardiogram, and provided blood and urine specimens. Participants also self-administered questionnaires covering demographics, quality of life, and medical history. This report describes the design, implementation, and some of the unique challenges of this study and data collection. [ABSTRACT FROM AUTHOR]

Objective: Resting heart rate (RHR) is an established predictor of myocardial infarction (MI) and mortality, but the relationship between variation in RHR over a period of several years and health outcomes is unclear. We evaluated the relationship between long-term variation in RHR and the risks of incident MI and mortality among older adults.Methods: 1991 subjects without cardiovascular disease from the Cardiovascular Health Study were included. RHR was taken from resting ECGs at the first five annual study visits. RHR mean, trend and variation were estimated with linear regression. Subjects were followed for incident MI and death until December 2010. HRs for RHR mean, trend and variation are reported for differences of 10 bpm, 2 bpm/year and 2 bpm, respectively.Results: 262 subjects had an incident MI event (13%) and 1326 died (67%) during 12 years of median follow-up. In primary analyses adjusted for cardiovascular risk factors, RHR mean (HR 1.12; 95% CI 1.05 to 1.20) and variation (HR 1.08; 95% CI 1.03 to 1.13) were associated with the risk of death while trend was not. None of the RHR variables were significantly associated with the risk of incident MI events; however, CIs were wide and the MI associations with RHR variables were not significantly different from the mortality associations. Adjusting for additional variables did not affect estimates, and there were no significant interactions with sex.Conclusions: Variation in RHR over a period of several years represents a potential predictor of long-term mortality among older persons free of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Little is known about cognitive impairment and dementia in American Indians, who are underrepresented in most studies of Alzheimer's disease and related dementias. Method: The Strong Heart Study recruited 4,549 American Indians aged 45‐75 from 3 major geographic regions in 1989‐1991. In 2010‐2013 and again in 2017‐2019, all eligible surviving participants were recruited for comprehensive cranial magnetic resonance imaging, cognitive, and clinical examinations. Neurological data collected included history of stroke and neurological symptoms. Cognitive data included Modified Mini Mental Status Examination, Weschler Adult Intelligence Scale, Controlled Word Association Test, California Verbal Learning Test, Wide Range Achievement Test, Montreal Cognitive Assessment, Craft Story Recall, Benson Figure Copy, Number Span test, Category Fluency, Trail Making test, Multilingual Naming Test, Functional Activities Questionnaire. Physical function tests included Short Physical Performance Battery, dynamometric grip strength, and Halstead finger tapping test. Mood and quality of life tests included Short Form 36 and Centers for Epidemiologic Studies Depression scale. Clinical examination included anthropometric measures, blood pressure, and basic blood and urine laboratory assays including serum glucose, lipids, creatinine, and albumin. Neuroradiologists blinded to clinical data examined MRI for vascular and structural findings, including presence and location of infarcts, hemorrhages, white matter hyperintensities, sulcal widening, ventricle enlargement, and volumetric estimates of hippocampus, parahippocampal gyrus, thalamus, and frontal lobe. Neuropsychologist panels adjudicated cognitive impairment and dementia by case review. Result: This report describes the structure and methods used to collect these longitudinal data, including the cognitive examinations, the neuropsychological data cleaning, and the panel‐based case reviews. We also include basic epidemiologic description of the data, including changes in cranial imaging findings and cognitive and functional examinations between the two neurological examinations (approximate follow‐up time: 7 years). Conclusion: This report adds to existing literature with the first longitudinal description of cranial imaging and cognitive testing data in American Indian elders, as well as the first cognitive measurements related to Alzheimer's disease, in this population. These data may be used to estimate incidence and prevalence of vascular brain injury, structural atrophy, imaging markers related to Alzheimer's disease, and cognitive function in this understudied population. [ABSTRACT FROM AUTHOR]

Background: Carrying an APOE ε4 allele increases risk for Alzheimer's disease and related dementias. However, risk effects and prevalence of risk alleles are not consistent across races/ethnicities. Prevalence of cognitive impairment or dementia and attributable risk from APOE ε4 genotype are unknown in American Indians (AI). This project evaluated associations of APOE genotype with cranial imaging and cognitive testing markers of vascular and Alzheimer's dementias in a large, prospective, population‐based cohort of AI. Method: The Strong Heart Study recruited 4,549 AI aged 45‐75 from 13 tribal communities across 3 major geographic regions in 1989‐1991. In 2010‐2013, all eligible surviving participants, then aged 65‐95, underwent cognitive examination including 3MS, WAIS, COWA, and CVLT‐II long delay free recall and cranial magnetic resonance imaging (MRI). APOE was genotyped from blood using ABI PRISM Linkage Mapping and DNA sequencing. Result: Most participants carried either 3.3 (73%) or 4.3 genotypes (23%). Clinical risk factors for dementia were prevalent, including high body mass index (mean>30), hypertension (80%), diabetes (48%), high LDL (39‐44%), chronic kidney disease (27%), and prior stroke (8‐9%). APOE ε4 carriers did not differ from non‐carriers in clinical factors, with the exception of serum LDL (103.9 mg/dL vs 96.7 mg/dL, P=0.015). Findings from MRI were also similar between genotypes, including presence of infarcts or hemorrhages, brain volume, and grade (0‐9) for white matter hyperintensities, sulcal widening, and ventricle enlargement. APOE ε4 carriers had marginally more WMH volume than non‐carriers. Cognitive examination scores were also similar, including Modified Mini Mental Status Examination (3MSE), Weschler Adult Intelligence Scale coding test (WAIS), Controlled Oral Word Association test (COWA), California Verbal Learning Test long delay free recall (CVLT). Conclusion: Despite evidence for higher risk of Alzheimer's and related dementias from presence of APOE ε4 allele among individuals from other populations, our study found little evidence of such an effect in elderly AIs. These findings raise intriguing questions about the presence of as‐yet‐unknown protective factors. Limitations of this study include cross‐sectional analyses and possibility of selective survival before the MRI examination. Future research should directly examine whether longitudinal changes in cognition and brain structure are associated with APOE genotype. [ABSTRACT FROM AUTHOR]

BACKGROUND Recent reports have linked variability in visit-to-visit systolic blood pressure (SBP) to risk of mortality and stroke, independent of the effect of mean SBP level. This study aimed to evaluate whether variability in SBP is associated with all-cause mortality, incident myocardial infarction (MI), and incident stroke, independent of mean SBP or trends in SBP levels over time. METHODS The Cardiovascular Health Study is a longitudinal cohort study of vascular risk factors and disease in the elderly. Participants who attended their first 5 annual clinic visits and experienced no event before the 5th visit were eligible (n = 3,852). Primary analyses were restricted to participants not using antihypertensive medications throughout the first 5 clinic visits (n = 1,642). Intraindividual SBP variables were defined using each participant’s 5-visit blood pressure measures. Cox proportional hazards models estimated adjusted hazard ratios (HRs) per SD increase in intraindividual SBP variability, adjusted for intraindividual SBP mean and change over time. RESULTS Over a mean follow-up of 9.9 years, there were 844 deaths, 203 MIs, and 195 strokes. Intraindividual SBP variability was significantly associated with increased risk of mortality (HR = 1.13; 95% confidence interval (CI) = 1.05–1.21) and of incident MI (HR = 1.20; 95%CI = 1.06–1.36), independent of the effect from adjustment factors. Intraindividual SBP variability was not associated with risk of stroke (HR = 1.03; 95% CI = 0.89–1.21). CONCLUSIONS Long-term visit-to-visit SBP variability was independently associated with a higher risk of subsequent mortality and MI but not stroke. More research is needed to determine the relationship of BP variability with cardiovascular risk and the clinical implications. [ABSTRACT FROM AUTHOR]

Background: Research on factors associated with late‐life cognitive performance in diverse racial/ethnic groups is increasingly important due to the growing size and racial diversity of the elder population. American Indian elders suffer disproportionately from health conditions and behaviors that increase the risk of cognitive impairment, such as hypertension, diabetes, smoking, physical inactivity, and obesity. To inform prevention efforts in the growing at‐risk population, a better understanding of the relationships between modifiable cognitive risk factors and cognitive impairment is critical. Method: Using data on 816 American Indians from the Strong Heart Study, we measured associations between mid‐life physical activity (PA), assessed by questionnaire, and performance on 4 cognitive tests administered ∼21 years later. Cognitive tests assessed general cognitive function, phonemic fluency, verbal learning and memory and processing speed domains. To estimate associations, we used regression models with and without inverse probability weights that accounted for potential attrition bias due to drop out between the PA and cognitive assessments. A subset of participants (n=165) had pedometer PA measured ∼12 years after the questionnaire PA assessment. In separate models, we also estimated associations between average daily steps and cognitive test scores. Result: Participants had mean ages of 52 years at the questionnaire‐based PA assessment and 73 years at cognitive testing. The pedometer subset was mostly sedentary at the time of measurement with 66% completing <5000 steps/day, on average. Nevertheless, both questionnaire and pedometer measures of PA were positively associated with cognitive performance in later life. Participants in the top quartile of questionnaire‐based PA had Modified Mini‐Mental State examination scores 3.2 (95%CI: 1.5‐4.9) points higher than participants in the lowest quartile. Phonemic fluency scores also trended higher for participants in the top compared to bottom quantiles for both PA measures. We observed no associations between PA and tests assessing verbal learning and memory, or processing speed. Weighted model results were similar to unweighted results, but less precise. Conclusion: In this cohort of American Indians with relatively low levels of PA, positive associations between mid‐life PA and late‐life cognitive performance were domain‐specific and of modest clinical significance. [ABSTRACT FROM AUTHOR]

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the ‘transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

Objectives: American Indians (AIs) generally consume less alcohol than the US general population; however, the prevalence of alcohol use disorder is higher. This is the first large cohort study to examine binge drinking as a risk factor for vascular brain injury (VBI). Methods: We used linear and Poisson regression to examine the association of self-reported binge drinking with VBI, measured via magnetic resonance imaging (MRI), in 817 older AIs who participated in the Strong Heart and Cerebrovascular Disease and Its Consequences in American Indians studies. Results: Any binge drinking at multiple time-points was associated with increased sulcal (β = 0.360, 95% CI [0.079, 0.641]) and ventricle dilatation (β = 0.512, 95% CI [0.174, 0.850]) compared to no binge drinking. Discussion: These observed associations are consistent with previous findings. Identifying how binge drinking may contribute to VBI in older AIs may suggest modifiable health behaviors for neurological risk reduction and disease prevention. [ABSTRACT FROM AUTHOR]

Information about the equality of psychometric properties of the medical outcomes study (MOS) Short Form-36 (SF-36), a health status measure, across gender and across the lifespan for American Indian adults is lacking. We tested measurement invariance (configural, metric, scalar invariance) of the physical and mental components between gender and over time in a sample of 2,709 (1,054 men, 1,654 women) American Indian older adults at three time points, and across a 6-year time frame. Measurement invariance of a 2-factor higher-order model was demonstrated between gender at each time point. Tests of longitudinal invariance indicated longitudinal measurement invariance over time. Multiple-group latent means analysis indicated men had significantly higher physical and mental component latent means compared to women at each time point, and longitudinal latent means analysis found physical and mental component latent means decreased over time. The 2-factor higher-order model SF-36 is valid for American Indian older adults over a 6-year time frame. Public Significance Statement: The medical outcomes study (MOS) Short Form-36 (SF-36) is a valid assessment for American Indian older adults. Men had significantly higher physical and mental scores compared to women, and physical and mental components scores decreased over time in the total sample. [ABSTRACT FROM AUTHOR]

The validation of the assessment of depression across ethnic groups is critical yet deficient for American Indian (AI) adults. Therefore, we assessed the psychometric properties of the Center for Epidemiological Studies-Depression (CES-D) in AI elders and tested differences in depression constructs between gender. Participants were 817 AI adults (68% women), mean age 73.2 years (SD = 6.1, range: 64–95) for women and 72.6 years (SD = 5.3, range: 65–90) for men., in the Cerebrovascular Disease and Its Consequences in AIs Study. We evaluated the factor structure of the 20-item and 12-item CES-D and tested measurement invariance between gender. Results demonstrated a poor fit for the 20-item CES-D and partial gender measurement invariance of the 12-item CES-D. AI female elders had significantly higher depression levels than AI male elders on the Depressed Affect subscale, the Somatic Symptoms subscale, and the Well-Being (reverse-coded) subscale. Further replication is needed, and we recommend future psychometric work with the 12-item CES-D with AI elders. Public Significance Statement: An abbreviated 12-item Center for Epidemiological Studies-Depression scale assesses depression in American Indian female and male elders. Female AI elders had higher levels on the Depressed Affect and Somatic Symptoms, and lower levels of Well-Being, than AI male elders. [ABSTRACT FROM AUTHOR]

Background Disproportionately high rates of alcohol use disorders are present in many American Indian/Alaska Native (AI/AN) communities, yet little information exists regarding the effectiveness of alcohol treatments in AI/AN populations. Contingency management is an intervention for illicit drug use in which tangible reinforcers (rewards) are provided when patients demonstrate abstinence as assessed by urine drug tests. Contingency management has not been widely studied as an intervention for alcohol problems because until recently, no alcohol biomarker has been available to adequately verify abstinence. Aims The HONOR Study is designed to determine whether a culturally-tailored contingency management intervention is an effective intervention for AI/AN adults who suffer from alcohol use disorders. Methods Participants include 400 AI/AN alcohol-dependent adults residing in one rural reservation, one urban community, as well as a third site to be decided, in the Western U.S. Participants complete a 4-week lead-in phase prior to randomization, then 12 weeks of either a contingency management intervention for alcohol abstinence, or a control condition where participants receive reinforcers for attending study visits regardless of alcohol use. Participants are then followed for 3-more months post-intervention. The primary study outcome is urinary ethyl glucuronide-confirmed alcohol abstinence; secondary outcomes include self-reported alcohol and drug use, HIV risk behaviors, and self-reported cigarette smoking. Discussion This will be the largest randomized, controlled trial of any alcohol for AI/ANs and the largest contingency management study targeting alcohol use disorders, thus providing important information to AI/AN communities and the alcohol treatment field in general. [ABSTRACT FROM AUTHOR]