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Supplemental Material for Spousal Cognitive Status and Risk for Declining Cognitive Function and Dementia: The Atherosclerosis Risk in Communities Study by Mark Lee, Ryan T. Demmer, Anna Kucharska-Newton, B. Gwen Windham, Priya Palta, Tetyana Shippee, Pamela L. Lutsey in Journal of Aging and Health.

Background Increased carotid intima-media thickness, interadventitial diameter, presence of carotid plaque, and lower distensibility are predictors for cardiovascular disease. These indices likely relate to cerebrovascular disease, and thus may constitute a form of vascular contributions to dementia and Alzheimer disease-related dementia. Therefore, we assessed the relationship of carotid measurements and arterial stiffness with incident dementia in the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results A total of 12459 ARIC participants with carotid arterial ultrasounds in 1990 to 1992 were followed through 2017 for dementia. Dementia cases were identified using in-person and phone cognitive status assessments, hospitalization discharge codes, and death certificate codes. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for incident dementia. Participants were aged 57±6 at baseline, 57% were women, and 23% were Black individuals. Over a median follow-up time of 24years, 2224 dementia events were ascertained. After multivariable adjustments, the highest quintile of carotid intima-media thickness and interadventitial diameter in midlife was associated with increased risk of dementia (HR [95% CIs], 1.25 [1.08-1.45]; and 1.22 [1.04-1.43], respectively) compared with its respective lowest quintile. Presence of carotid plaque did not have a significant association with dementia (HR [95% CI], 1.06 [0.97-1.15]). Higher distensibility was associated with lower risk of dementia (HR [95% CI] highest versus lowest quintile, 0.76 [0.63-0.91]). Conclusions Greater carotid intima-media thickness, interadventitial diameter, and lower carotid distensibility are associated with an increased risk of incident dementia. These findings suggest that both atherosclerosis and carotid stiffness may be implicated in dementia risk.

Additional file 1. Supplementary Table 1.

Additional file 1. Table S1. Associations of Carotid-Femoral Pulse Wave Velocity (cfPWV) quartiles with incident AF in the ARIC cohort by sex and race, 2011–2017.

We examined associations of individual- and neighborhood-level life-course (LC) socioeconomic status (SES) with incident dementia in the Atherosclerosis Risk in Communities cohort. Individual- and neighborhood-level SES were assessed at 3 life epochs (childhood, young adulthood, midlife) via questionnaire (2001-2002) and summarized into LC-SES scores. Dementia was ascertained through 2013 using cognitive exams, telephone interviews, and hospital and death certificate codes. Cox regression was used to estimate hazard ratios of dementia by LC-SES scores in race-specific models. The analyses included data from 12,599 participants (25% Black) in the United States, with a mean age of 54 years and median follow-up of 24 years. Each standard-deviation greater individual LC-SES score was associated with a 14% (hazard ratio (HR)=0.86, 95% confidence interval (CI): 0.81, 0.92) lower risk of dementia in White and 21% (HR=0.79, 95% CI: 0.71, 0.87) lower risk in Black participants. Education was removed from the individual LC-SES score and adjusted for separately to assess economic factors of LC-SES. A standard-deviation greater individual LC-SES score, without education, was associated with a 10% (HR=0.90, 95% CI: 0.84, 0.97) lower dementia risk in White and 15% (HR=0.85, 95% CI: 0.76, 0.96) lower risk in Black participants. Neighborhood LC-SES was not associated with dementia. We found that individual LC-SES is a risk factor for dementia, whereas neighborhood LC-SES was not associated.

Supplemental material, Supplemental_Tables for Impact of oral anticoagulation choice on healthcare utilization for the primary treatment of venous thromboembolism by Pamela L Lutsey, Richard F MacLehose, J’Neka S Claxton, Rob F Walker, Terrence J Adam, Alvaro Alonso and Neil A Zakai in Vascular Medicine

OBJECTIVE: We aimed to assess the association between migraine headache and incident dementia. BACKGROUND: Migraine is a risk factor for white matter hyperintensities and ischemic stroke, which are both associated with increased risk of dementia. However, it is unknown whether migraine is independently associated with dementia. METHODS: History of migraine was ascertained via questionnaire. Adjudicated cases of dementia were identified using cognitive tests, neuropsychological exams, and clinician review of suspected cases. Incident dementia was identified using adjudicated cases, follow-up calls, and surveillance of hospital and death codes. We assessed hazards of incident dementia by migraine status. Sex differences were also examined and stratified results were presented. RESULTS: Analysis included 12,495 White and African American participants ages 51–70 with a median follow-up time of 21 years. Prevalence of dementia was 18.5% (1821/9955) among those with no migraine history, 15.8% (196/1243) among those with severe non-migraine heading, and 16.7% (233/1397) among migraineurs. There was no association between migraine and incident dementia [hazard ratio: 1.04 (0.91, 1.20)]. There was also no statistically significant interaction between sex and migraine status on risk of dementia. CONCLUSION: Despite evidence of brain abnormalities in migraineurs, there was no association between migraine and incident dementia in this prospective cohort.

Supplemental material, Supplementary_tables for Association of Life’s Simple 7 with reduced clinically manifest abdominal aortic aneurysm: The ARIC study by Abayomi O Oyenuga, Aaron R Folsom, Pamela L Lutsey and Weihong Tang in Vascular Medicine

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

Supplementary_Figure_II_and_Legend for The Association of Biomarkers of Inflammation and Extracellular Matrix Degradation With the Risk of Abdominal Aortic Aneurysm: The ARIC Study by Weihong Tang, Lu Yao, Ron C. Hoogeveen, Alvaro Alonso, David J. Couper, Pamela L. Lutsey, Carol C. Steenson, Weihua Guan, David W. Hunter, Frank A. Lederle, and Aaron R. Folsom in Angiology

Supplementary_Tables_v5_2clean for The Association of Biomarkers of Inflammation and Extracellular Matrix Degradation With the Risk of Abdominal Aortic Aneurysm: The ARIC Study by Weihong Tang, Lu Yao, Ron C. Hoogeveen, Alvaro Alonso, David J. Couper, Pamela L. Lutsey, Carol C. Steenson, Weihua Guan, David W. Hunter, Frank A. Lederle, and Aaron R. Folsom in Angiology

BackgroundHispanics/Latinos are purportedly at increased risk for neurocognitive decline and dementias. Without dementia cures, low-cost, well-tolerated public health means for mitigating neurocognitive decline are needed.ObjectiveWe examined associations between neurocognition and cardiovascular health (CVH) metrics (Life's Simple 7; LS7) among diverse Hispanics/Latinos. We hypothesized that higher LS7 would be associated with healthier brain function (neurocognitive performance).MethodsWe used baseline (2008-2011) Hispanic Community Health Study/Study of Latinos (HCHS/SOL; N = 9,623; ages 45-74 years) to examine neurocognition in relation to CVH LS7 scores.ResultsIn age and sex adjusted models, a one unit LS7 score increase (range = 0-14) was associated with higher neurocognitive function on the B-SEVLT sum (0.23 [p

BackgroundDisordered mineral metabolism is characteristic of decreased kidney function. However, the prospective associations between circulating levels of vitamin D binding protein, vitamin D, and end-stage renal disease (ESRD) have not been extensively evaluated in epidemiologic studies.Study designNested case-control study.Setting & participantsMiddle-aged black and white men and women from 4 US communities.PredictorsBaseline levels of vitamin D binding protein, 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) were measured in blood samples collected at study visit 4 (1996-1998)of the ARIC (Atherosclerosis Risk in Communities) Study.OutcomeESRD cases (n=184) were identified through hospitalization diagnostic codes from 1996 to 2008 and were frequency matched to controls (n=251) on categories of estimated glomerular filtration rate, albuminuria, diabetes mellitus, sex, and race.MeasurementsLogistic regression was used to estimate the association between mineral metabolism biomarkers (vitamin D binding protein, 25(OH)D, and 1,25(OH)2D) and incident ESRD, adjusting for age, sex, race, estimated glomerular filtration rate, albuminuria, diabetes mellitus, hypertension, education, specimen type, and serum levels of calcium, phosphate, and parathyroid hormone.ResultsHigher vitamin D binding protein levels were associated with elevated risk for incident ESRD (OR, 1.76; 95% CI, 1.22-2.54; P=0.003). Higher free and bioavailable 25(OH)D levels were associated with reduced risk for incident ESRD (ORs of 0.65 [95% CI, 0.46-0.92; P=0.02] and 0.63 [95% CI, 0.43-0.91; P=0.02] forfree and bioavailable 25[OH]D, respectively). There was no association between ESRD and overall levels of 25(OH)D(OR, 0.83; 95% CI, 0.58-1.19; P=0.3) or 1,25(OH)2D (OR, 0.73; 95% CI, 0.48-1.13; P=0.2).LimitationsLack of direct measurement of free and bioavailable vitamin D.ConclusionsIn the general population, blood levels of vitamin D binding protein were positively associatedand blood levels of free and bioavailable 25(OH)D were inversely associated with new-onset ESRD during follow-up.