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BACKGROUND: Cross-sectional and longitudinal studies have inconsistently linked cognitive performance and change over time to an elevated level of homocysteine (Hcy), with few conducted among urban adults. METHODS: Longitudinal data [Visit 1 (2004-2009) and Visit 2 (2009-2013)] were analyzed from up to 1430 selected Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants. Baseline and follow-up blood Hcy was measured, while 11 cognitive function test scores were assessed at either of these two visits. Overall, sex- and race-stratified associations were evaluated using mixed-effects linear regression models, adjusting for key potential confounders. Interaction effects between Hcy and serum levels of folate and vitamin B-12 were also tested. RESULTS: We found that greater LnHcyv1 was significantly associated with poorer baseline attention based on higher Loge (TRAILS A, in seconds) [ß (SE): 0.101 (0.031), P = 0.001]. Heterogeneity was also found by sex and by race. Most notably, among men only, LnHcyv1 was associated with faster decline on the BVRT (# of errors), a measure of visuo-spatial memory (ß (SE): 0.297(0.115), P = 0.010, reduced model); while among African American adults only, an elevated and increasing LnHcy over time was associated with faster rate of decline on Loge (TRAILS B, in seconds) [ß (SE): +0.012 (0.005), p = 0.008], a measure of executive function. Interactions between Hcy, folate and vitamin B-12 blood exposures were also detected. CONCLUSIONS: In summary, sex- and race-specific adverse association between elevated Hcy and cognitive performance over time were detected among middle-aged urban adults, in domains of attention, visuo-spatial memory and executive functioning.
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Brain aging process is influenced by various lifestyle, environmental and genetic factors, as well as by age-related and often coexisting pathologies. Magnetic resonance imaging and artificial intelligence methods have been instrumental in understanding neuroanatomical changes that occur during aging. Large, diverse population studies enable identifying comprehensive and representative brain change patterns resulting from distinct but overlapping pathological and biological factors, revealing intersections and heterogeneity in affected brain regions and clinical phenotypes. Herein, we leverage a state-of-the-art deep-representation learning method, Surreal-GAN, and present methodological advances and extensive experimental results elucidating brain aging heterogeneity in a cohort of 49,482 individuals from 11 studies. Five dominant patterns of brain atrophy were identified and quantified for each individual by respective measures, R-indices. Their associations with biomedical, lifestyle and genetic factors provide insights into the etiology of observed variances, suggesting their potential as brain endophenotypes for genetic and lifestyle risks. Furthermore, baseline R-indices predict disease progression and mortality, capturing early changes as supplementary prognostic markers. These R-indices establish a dimensional approach to measuring aging trajectories and related brain changes. They hold promise for precise diagnostics, especially at preclinical stages, facilitating personalized patient management and targeted clinical trial recruitment based on specific brain endophenotypic expression and prognosis.
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INTRODUCTION: Relationships and interplay of an infection burden (IB) and periodontal pathogens or periodontal disease (Pd) markers with Alzheimer's disease (AD) and all-cause dementia among US adults were examined. METHODS: Less than or equal to 2997 participants from the National Health and Nutrition Survey III were linked to CMS-Medicare [≥45 years (1988-1994); ≤30 years follow-up]. RESULTS: Hepatitis C (hazard ratio = 3.33, p = 0.004) and herpes simplex virus 2 were strongly associated with greater all-cause dementia risk. Porphyromonas gingivalis and Streptococcus oralis were associated with greater AD risk at higher IB. The red-green periodontal pathogen cluster coupled with higher IB count increased the risk of all-cause dementia among minority racial groups. Pocket probing depth associated with dementia risk at lower IB in the overall sample. DISCUSSION: Select viruses and bacteria were associated with all-cause and AD dementia, while the IB interacted with Pd markers in relation to these outcomes. HIGHLIGHTS: Interplay of infection burden (IB) and periodontal disease with dementia was tested. ≤2997 participants from NHANES III were linked to Medicare. Hepatitis C and herpes simplex virus 2 strongly associated with dementia risk. Tetanus sero-positivity increased Alzheimer's disease (AD) risk. Porphyromonas gingivalis and Streptococcus oralis associated with AD at higher IB. Red-green periodontal cluster at high IB, increased dementia in racial minorities. Pocket probing depth associated with dementia risk at lower IB.
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The plasma proteome can mediate associations between periodontal disease (Pd) and brain white matter integrity (WMI). We screened 5089 UK Biobank participants aged 40-70 years for poor oral health problems (POHP). We examined the association between POHP and WMI (fractional anisotropy (FA), mean diffusivity (MD), Intracellular Volume Fraction (ICVF), Isotropic Volume Fraction (ISOVF) and Orientation Diffusion (OD)), decomposing the total effect through the plasma proteome of 1463 proteins into pure mediation, pure interaction, neither, while adjusting for socio-demographic and cardiovascular health factors. Similarly, structural equations modeling (SEM) was conducted. POHP was more prevalent among men (12.3% vs. 9.6%), and was associated with lower WMI on most metrics, in a sex-specific manner. Of 15 proteins strongly associated with POHP, growth differentiation factor 15 (GDF15) and WAP four-disulfide core domain 2 (WFDC2; also known as human epididymis protein 4; HE4) were consistent mediators. Both proteins mediated 7-8% of total POHP effect on FAmean. SEM yielded significant total effects for FAmean, MDmean and ISOVFmean in full models, with %mediated by common latent factor (GDF15 and WFDC2) ranging between 13% (FAmean) and 19% (ISOVFmean). For FA, mediation by this common factor was found for 16 of 49 tract-specific and global mean metrics. Protein metabolism, immune system, and signal transduction were the most common pathways for mediational effects. POHP was associated with poorer WMI, which was partially mediated by GDF15 and WFDC2.
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BACKGROUND: Homelessness and housing instability disproportionately affect U.S. veterans with psychiatric disorders, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), hepatitis C, and Alzheimer's disease and related disorders (ADRD). We examined housing status and/or HIV/AIDS in relation to ADRD risk and evaluated hepatitis C, substance use, and mental health disorders as mediators and/or moderators of hypothesized relationships, among U.S. veterans ≥50 years of age seeking Department of Veterans Affairs (VA) healthcare services. METHODS: A retrospective cohort study was conducted using linked VA Homeless Operations Management and Evaluation System and Corporate Data Warehouse databases (2017-2023) on 3â 275 098 eligible veterans yielding 133 388 ADRD cases over 5 years of follow-up. Multivariable regression and causal mediation analyses were performed, controlling for demographic and clinical characteristics. RESULTS: Taking stably housed veterans without HIV/AIDS as referent, ADRD risk was higher among veterans with homelessness/housing instability alone (adjusted hazard ratio [aHR]â =â 1.67, 95% confidence interval [CI]: 1.63,1.72), lower among veterans with HIV/AIDS alone (aHRâ =â 0.65, 95% CI: 0.58,0.73), but similar to veterans with homelessness/housing instability and HIV/AIDS (aHRâ =â 1.01, 95% CI: 0.79,1.29). In adjusted models, hepatitis C and psychiatric disorders were positively related to homelessness/housing instability and ADRD risk, but negatively related to HIV/AIDS. Statistically significant mediation and/or moderation of hepatitis C and psychiatric disorders were observed, although <10% of total effects were explained by these characteristics, controlling for confounders. CONCLUSIONS: Among older veterans, ADRD diagnoses over 5 years were less among those with HIV/AIDS, but more among those with homelessness/housing instability, and these relationships were partly explained by hepatitis C and psychiatric disorders.
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Enfermedad de Alzheimer , Infecciones por VIH , Hepatitis C , Personas con Mala Vivienda , Trastornos Mentales , Veteranos , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Veteranos/estadística & datos numéricos , Veteranos/psicología , Persona de Mediana Edad , Hepatitis C/epidemiología , Hepatitis C/complicaciones , Enfermedad de Alzheimer/epidemiología , Personas con Mala Vivienda/estadística & datos numéricos , Personas con Mala Vivienda/psicología , Estudios Retrospectivos , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Trastornos Mentales/epidemiología , Anciano , Vivienda/estadística & datos numéricos , Factores de Riesgo , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/psicología , Demencia/epidemiologíaRESUMEN
Background: Loneliness, dementia, and mortality are interconnected. Objective: We aimed at understanding mediating pathways and interactions between loneliness and dementia in relation to mortality risk. Methods: The study tested bi-directional relationships between dementia, loneliness, and mortality, by examining both interactions and mediating effects in a large sample of older US adults participating in the nationally representative Health and Retirement Study. Out of≤6,468 older participants selected in 2010, with mean baseline age of 78.3 years and a follow-up time up to the end of 2020, 3,298 died at a rate of 64 per 1,000 person-years (P-Y). Cox proportional hazards and four-way decomposition models were used. Results: Algorithmically defined dementia status (yes versus no) was consistently linked with a more than two-fold increase in mortality risk. Dementia status and Ln(odds of dementia) were strongly related with mortality risk across tertiles of loneliness score. Loneliness z-score was also linked to an elevated risk of all-cause mortality regardless of age, sex, or race or ethnicity, and its total effect (TE) on mortality was partially mediated by Ln(odds of dementia), z-scored, (≤40% of the TE was a pure indirect effect). Conversely, a small proportion (<5%) of the TE of Ln(odds of dementia), z-scored, on mortality risk was explained by the loneliness z-score. Conclusions: In sum, dementia was positively associated with all-cause mortality risk, in similar fashion across loneliness score tertiles, while loneliness was associated with mortality risk. TE of loneliness on mortality risk was partially mediated by dementia odds in reduced models.
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Demencia , Soledad , Humanos , Soledad/psicología , Masculino , Femenino , Demencia/mortalidad , Demencia/psicología , Anciano , Estados Unidos/epidemiología , Anciano de 80 o más Años , Factores de Riesgo , Mortalidad/tendencias , Modelos de Riesgos ProporcionalesRESUMEN
Neurofilament light chain (NfL) is a neuron-specific structural protein released into the extracellular space, including body fluids, upon neuroaxonal damage. Despite evidence of a link in neurological disorders, few studies have examined the association of serum NfL with mortality in population-based studies. Data from the National Health and Nutrition Survey were utilized including 2,071 Non-Hispanic White, Non-Hispanic Black and Hispanic adult participants and adult participants of other ethnic groups (20-85 years) with serum NfL measurements who were followed for ≤ 6 years till 2019. We tested the association of serum NfL with mortality in the overall population and stratified by sex with the addition of potential interactive and mediating effects of cardio-metabolic risk factors and nutritional biomarkers. Elevated serum NfL levels (above median group) were associated with mortality risk compared to the below median NfL group in the overall sample (P = 0.010), with trends observed within each sex group (P < 0.10). When examining Loge NfL as a continuum, one standard deviation of Loge NfL was associated with an increased mortality risk (HR = 1.88, 95% CI 1.60-2.20, P < 0.001) in the reduced model adjusted for age, sex, race, and poverty income ratio; a finding only slightly attenuated with the adjustment of lifestyle and health-related factors. Four-way decomposition indicated that there was, among others, mediated interaction between NfL and HbA1c and a pure inconsistent mediation with 25(OH)D3 in predicting all-cause mortality, in models adjusted for all other covariates. Furthermore, urinary albumin-to-creatinine ratio interacted synergistically with NfL in relation to mortality risk both on the additive and multiplicative scales. These data indicate that elevated serum NfL levels were associated with all-cause mortality in a nationally representative sample of US adults.
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INTRODUCTION: While research has shown a positive association between a higher sense of purpose in life and functional health, there is a gap in understanding its benefits for racially minoritized and low SES individuals. This study aimed to investigate the correlation between purpose in life and physical functional health in a diverse sample, hypothesizing that purpose in life would be negatively associated with functional difficulties, with potentially stronger associations in White and high SES groups. METHODS: Data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were utilized (166 participants, mean age 59.44 [SD = 8.28], 59.6% females, 65.06% Black participants, 40.36% below poverty). Purpose in life was measured by Ryff's Psychological Well-being Purpose in Life subscale. Functional health was measured by functional difficulties in mobility and daily living. Race (Black and White) and poverty status (above and below) were used as moderators to probe the purpose-functional health association using zero-inflated Poisson regression while adjusting for age, education, depressive symptomology, and previous functional difficulties in four hierarchical models. RESULTS: Results showed that purpose in life was negatively associated with functional difficulty, indicating fewer difficulties in mobility and daily activities among those with a high sense of purpose. While the association did not remain significant after including previous functional difficulty as a covariate in Model 4, suggesting that race may not be a consistent moderator, poverty status remained a consistent moderator. The association was stronger for individuals above the poverty level. DISCUSSION: These findings underscore the complex interplay between purpose in life, race, poverty status, and functional health, emphasizing the importance of considering socioeconomic factors in interventions aimed at eliminating functional health disparities among diverse adult populations.
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Healthy dietary patterns rich in flavonoids may benefit cognitive performance over time. Among socioeconomically disadvantaged groups, the association between flavonoid intake and measures of cognition is unclear. This study sought to identify associations between flavonoid intake and cognitive performance among Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study participants (n = 1947) across three study visits. Flavonoid intakes were assessed via two 24-h dietary recalls. Cognitive performance was assessed via the Trail Making Test (TMT)-A and TMT-B, which provide measures of attention and executive function, respectively. Mixed effects linear regression was used to model TMT scores over three study visits against visit 1 (v1) flavonoid intake, time (years from v1), and the interaction between v1 flavonoid intake and time, capturing both the cross-sectional association between flavonoid intake and time at v1 as well as the longitudinal association between v1 flavonoid intake and the change in TMT scores over time. Prior to adjustment, inverse cross-sectional associations at v1 were observed between (1) anthocyanidin intake and TMT-A scores for the overall sample and (2) total flavonoid, anthocyanidin, flavan-3-ol, flavone, and flavonol intake and TMT-B scores for the overall sample and among White adults. Only the association between anthocyanidin intake and TMT-B at v1 among White adults persisted after adjustment (for demographic characteristics such as age). One possible explanation for the few significant associations is universally low flavonoid intakes resulting from the consumption of an unhealthy dietary pattern.
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Negro o Afroamericano , Cognición , Función Ejecutiva , Flavonoides , Envejecimiento Saludable , Población Blanca , Humanos , Masculino , Femenino , Flavonoides/administración & dosificación , Cognición/efectos de los fármacos , Persona de Mediana Edad , Función Ejecutiva/efectos de los fármacos , Anciano , Estudios Transversales , Dieta/estadística & datos numéricos , Antocianinas/administración & dosificación , Características de la ResidenciaRESUMEN
The plasma proteome can mediate poor oral health problems (POHP)'s link to incident dementia. We screened 37,269 UK Biobank participants 50-74 years old (2006-2010) for prevalent POHP, further tested against 1463 plasma proteins and incident dementia over up to 15 years of follow-up. Total effect (TE) of POHP-dementia through plasma proteomic markers was decomposed into pure indirect effect (PIE), interaction referent (INTREF), controlled direct effect (CDE), or mediated interaction (INTMED). POHP increased the risk of all-cause dementia by 17% (P < 0.05). Growth differentiation factor 15 (GDF15) exhibited the strongest mediating effects (PIE > 0, P < 0.001), explaining 28% the total effect of POHP on dementia, as a pure indirect effect. A first principal component encompassing top 4 mediators (GDF15, IL19, MMP12, and ACVRL1), explained 11% of the POHP-dementia effect as a pure indirect effect. Pathway analysis including all mediators (k = 173 plasma proteins) revealed the involvement of the immune system, signal transduction, metabolism, disease, and gene expression, while STRING analysis indicated that top mediators within the first principal component were also represented in the two largest proteomic clusters. The dominant biological GO pathway for the GDF15 cluster was GO:0007169 labeled as "transmembrane receptor protein tyrosine kinase signaling pathway." Dementia is linked to POHP mediated by GDF15 among several proteomic markers.
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We investigated relations of depressive symptoms, antidepressant use, and epigenetic age acceleration with all-cause mortality risk among postmenopausal women. Data were analyzed from ≤1,900 participants in the Women's Health Initiative study testing four-way decomposition models. After a median 20.4y follow-up, 1,161 deaths occurred. Approximately 11% had elevated depressive symptoms (EDS+), 7% were taking antidepressant medication at baseline (ANTIDEP+), while 16.5% fell into either category (EDS_ANTIDEP+). Baseline ANTIDEP+, longitudinal transition into ANTIDEP+ and accelerated epigenetic aging directly predicted increased mortality risk. GrimAge DNA methylation age acceleration (AgeAccelGrim) partially mediated total effects of baseline ANTIDEP+ and EDS_ANTIDEP+ on all-cause mortality risk in socio-demographic factors-adjusted models (Pure Indirect Effect >0, P < 0.05; Total Effect >0, P < 0.05). Thus, higher AgeAccelGrim partially explained the relationship between antidepressant use and increased all-cause mortality risk, though only prior to controlling for lifestyle and health-related factors. Antidepressant use and epigenetic age acceleration independently predicted increased all-cause mortality risk. Further studies are needed in varying populations.
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Antidepresivos , Metilación de ADN , Depresión , Epigénesis Genética , Posmenopausia , Humanos , Femenino , Antidepresivos/uso terapéutico , Depresión/genética , Depresión/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Envejecimiento/genética , MortalidadRESUMEN
BACKGROUND: The study examined how plasma proteome indicators may explain the link between poor cardiovascular health (CVH) and dementia risk. METHODS: The present study involved 28,974 UK Biobank participants aged 50-74y at baseline (2006-2010) who were followed-up for ≤ 15 y for incidence of dementia. CVH was calculated using Life's Essential 8 (LE8) total scores. The scores were standardized and reverse coded to reflect poor CVH (LE8z_rev). OLINK proteomics was available on this sample (k = 1,463 plasma proteins). The study primarily tested the mediating effects of the plasma proteome in LE8z_rev-dementia effect. The total effect was decomposed into "mediation only" or pure indirect effect (PIE), "interaction only" or interaction referent (INTREF), "neither mediation nor interaction" or controlled direct effect (CDE), and "both mediation and interaction" or mediated interaction (INTMED). RESULTS: The study found poorer CVH assessed by LE8z_rev increased the risk of all-cause dementia by 11 % [per 1 SD, hazard ratio, (HR) = 1.11, 95 % CI: 1.03-1.20, p = 0.005). The study identified 11 plasma proteins with strong mediating effects, with GDF15 having the strongest association with dementia risk (per 1 SD, HR = 1.24, 95 % CI: 1.16, 1.33, P < 0.001 when LE8z_rev is set at its mean value) and the largest proportion mediated combining PIE and INTMED (62.6 %; 48 % of TE is PIE), followed by adrenomedullin or ADM. A first principal component with 10 top mediators (TNFRSF1A, GDF15, FSTL3, COL6A3, PLAUR, ADM, GFRAL, ACVRL1, TNFRSF6B, TGFA) mediated 53.6 % of the LE8z_rev-dementia effect. Using all the significant PIE (k = 526) proteins, we used OLINK Insight pathway analysis to identify key pathways, which revealed the involvement of the immune system, signal transduction, metabolism, disease, protein metabolism, hemostasis, membrane trafficking, extracellular matrix organization, developmental biology, and gene expression among others. STRING analysis revealed that five top consistent proteomic mediators were represented in two larger clusters reflecting numerous interconnected biological gene ontology pathways, most notably cytokine-mediated signaling pathway for GDF15 cluster (GO:0019221) and regulation of peptidyl-tyrosine phosphorylation for the ADM cluster (GO:0050730). CONCLUSION: Dementia is linked to poor CVH mediated by GDF15 and ADM among several key proteomic markers which collectively explained â¼ 54 % of the total effect.
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Bancos de Muestras Biológicas , Biomarcadores , Enfermedades Cardiovasculares , Demencia , Proteómica , Humanos , Masculino , Anciano , Femenino , Reino Unido/epidemiología , Demencia/sangre , Demencia/epidemiología , Persona de Mediana Edad , Proteómica/métodos , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Proteoma/metabolismo , Incidencia , Factores de Riesgo , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/análisis , Biobanco del Reino UnidoRESUMEN
Pathways explaining racial/ethnic and socio-economic status (SES) disparities in white matter integrity (WMI) reflecting brain health, remain underexplored, particularly in the UK population. We examined racial/ethnic and SES disparities in diffusion tensor brain magnetic resonance imaging (dMRI) markers, namely global and tract-specific mean fractional anisotropy (FA), and tested total, direct and indirect effects through lifestyle, health-related and cognition factors using a structural equations modeling approach among 36,184 UK Biobank participants aged 40-70 y at baseline assessment (47% men). Multiple linear regression models were conducted, testing independent associations of race/ethnicity, socio-economic and other downstream factors in relation to global mean FA, while stratifying by Alzheimer's Disease polygenic Risk Score (AD PRS) tertiles. Race (Non-White vs. White) and lower SES predicted poorer WMI (i.e. lower global mean FA) at follow-up, with racial/ethnic disparities in FAmean involving multiple pathways and SES playing a central role in those pathways. Mediational patterns differed across tract-specific FA outcomes, with SES-FAmean total effect being partially mediated (41% of total effect = indirect effect). Furthermore, the association of poor cognition with FAmean was markedly stronger in the two uppermost AD PRS tertiles compared to the lower tertile (T2 and T3: ß±SE: -0.0009 ± 0.0001 vs. T1: ß±SE: -0.0005 ± 0.0001, P < 0.001), independently of potentially confounding factors. Race and lower SES were generally important determinants of adverse WMI outcomes, with partial mediation of socio-economic disparities in global mean FA through lifestyle, health-related and cognition factors. The association of poor cognition with lower global mean FA was stronger at higher AD polygenic risk.
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Persistent infections, whether viral, bacterial or parasitic, including Helicobacter pylori infection, have been implicated in non-communicable diseases, including dementia and other neurodegenerative diseases. In this cross-sectional study, data on 635 cognitively normal participants from the UK Biobank study (2006-21, age range: 40-70 years) were used to examine whether H. pylori seropositivity (e.g. presence of antibodies), serointensities of five H. pylori antigens and a measure of total persistent infection burden were associated with selected brain volumetric structural MRI (total, white, grey matter, frontal grey matter (left/right), white matter hyperintensity as percent intracranial volume and bi-lateral sub-cortical volumes) and diffusion-weighted MRI measures (global and tract-specific bi-lateral fractional anisotropy and mean diffusivity), after an average 9-10 years of lag time. Persistent infection burden was calculated as a cumulative score of seropositivity for over 20 different pathogens. Multivariable-adjusted linear regression analyses were conducted, whereby selected potential confounders (all measures) and intracranial volume (sub-cortical volumes) were adjusted, with stratification by Alzheimer's disease polygenic risk score tertile when exposures were H. pylori antigen serointensities. Type I error was adjusted to 0.007. We report little evidence of an association between H. pylori seropositivity and persistent infection burden with various volumetric outcomes (P > 0.007, from multivariable regression models), unlike previously reported in past research. However, H. pylori antigen serointensities, particularly immunoglobulin G against the vacuolating cytotoxin A, GroEL and outer membrane protein antigens, were associated with poorer tract-specific white matter integrity (P < 0.007), with outer membrane protein serointensity linked to worse outcomes in cognition-related tracts such as the external capsule, the anterior limb of the internal capsule and the cingulum, specifically at low Alzheimer's disease polygenic risk. Vacuolating cytotoxin A serointensity was associated with greater white matter hyperintensity volume among individuals with mid-level Alzheimer's disease polygenic risk, while among individuals with the highest Alzheimer's disease polygenic risk, the urease serointensity was consistently associated with reduced bi-lateral caudate volumes and the vacuolating cytotoxin A serointensity was linked to reduced right putamen volume (P < 0.007). Outer membrane protein and urease were associated with larger sub-cortical volumes (e.g. left putamen and right nucleus accumbens) at middle Alzheimer's disease polygenic risk levels (P < 0.007). Our results shed light on the relationship between H. pylori seropositivity, H. pylori antigen levels and persistent infection burden with brain volumetric structural measures. These data are important given the links between infectious agents and neurodegenerative diseases, including Alzheimer's disease, and can be used for the development of drugs and preventive interventions that would reduce the burden of those diseases.
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BACKGROUND: Elevated plasma growth differentiation factor 15 (GDF15) and poor diet quality may be associated with increased frailty incidence, although their interactive associations have not been assessed in urban middle-aged adults. OBJECTIVES: We aimed to examine GDF15 and its interactive association with diet quality in relation to frailty incidence among a sample of middle-aged urban adults. METHODS: The relationship between GDF15 and diet quality trajectories in relation to incident frailty was examined in a longitudinal study of participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (2004-2017). Serum GDF15 concentration and frailty incidence were primary exposure and outcome, respectively. Group-based trajectory models were used to assess diet quality trajectories (≤3 visits/participant, N = 945, N' = 2247 observations) using the Healthy Eating Index 2010 version (HEI-2010), Dietary Inflammatory Index, and mean adequacy ratio (MAR). Cox proportional hazards models were used, testing interactive associations of GDF15 and diet quality trajectories with frail/prefrail incidence (N = 400 frailty-free at first visit, N' = 604 observations, n = 168 incident frail/prefrail). RESULTS: Both elevated GDF15 and lower diet quality trajectories were associated with a lower probability of remaining nonfrail (≤13 y follow-up). Among females, the "high diet quality" HEI-2010 trajectory had a hazard ratio (HR) of 0.15 [95% confidence interval (CI): 0.04, 0.54; P = 0.004; fully adjusted model] when compared with the "low diet quality" trajectory group. Among males only, there was an antagonistic interaction between lower HEI-2010 trajectory and elevated GDF15. Specifically, the HR for GDF15-frailty in the higher diet quality trajectory group (high/medium combined), and among males, was 2.69 (95% CI: 1.06, 6.62; P = 0.032), whereas among the lower diet quality trajectory group, the HR was 0.94 (95% CI: 0.49, 1.80; P = 0.86). Elevated GDF15 was independently associated with frailty among African American adults. CONCLUSIONS: Pending replication, we found an antagonistic interaction between GDF15 and HEI-2010 trajectory in relation to frailty incidence among males.
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Dieta , Fragilidad , Factor 15 de Diferenciación de Crecimiento , Humanos , Masculino , Factor 15 de Diferenciación de Crecimiento/sangre , Femenino , Fragilidad/epidemiología , Fragilidad/sangre , Persona de Mediana Edad , Incidencia , Estudios Longitudinales , Población Urbana , AncianoRESUMEN
To examine cross-sectional and longitudinal relationships of psychotropic medications with physical function after menopause. Analyses involved 4557 Women's Health Initiative Long Life Study (WHI-LLS) participants (mean age at WHI enrollment (1993-1998): 62.8 years). Antidepressant, anxiolytic, and sedative/hypnotic medications were evaluated at WHI enrollment and 3-year follow-up visits. Performance-based physical function [Short Physical Performance Battery (SPPB)] was assessed at the 2012-2013 WHI-LLS visit. Self-reported physical function [RAND-36] was examined at WHI enrollment and the last available follow-up visit-an average of 22 [±2.8] (range: 12-27) years post-enrollment. Multivariable regression models controlled for socio-demographic, lifestyle, and health characteristics. Anxiolytics were not related to physical function. At WHI enrollment, antidepressant use was cross-sectionally related to worse self-reported physical function defined as a continuous (ß = -6.27, 95% confidence interval [CI]: -8.48, -4.07) or as a categorical (< 78 vs. ≥ 78) (odds ratio [OR] = 2.10, 95% CI: 1.48, 2.98) outcome. Antidepressant use at WHI enrollment was also associated with worse performance-based physical function (SPPB) [< 10 vs. ≥ 10] (OR = 1.53, 95% CI: 1.05, 2.21) at the 2012-2013 WHI-LLS visit. Compared to non-users, those using sedative/hypnotics at WHI enrollment but not at the 3-year follow-up visit reported a faster decline in physical function between WHI enrollment and follow-up visits. Among postmenopausal women, antidepressant use was cross-sectionally related to worse self-reported physical function, and with worse performance-based physical function after > 20 years of follow-up. Complex relationships found for hypnotic/sedatives were unexpected and necessitate further investigation.
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Inflammation can play a role in the pathophysiology of depression, and specific types of antidepressants may have inflammatory or anti-inflammatory properties. Furthermore, depression and antidepressant use has been linked to white blood cell (WBC) count, a routinely measured inflammatory marker. We examined the cross-sectional and longitudinal relationships of depressive symptoms and/or antidepressant use with WBC count among postmenopausal women. Analyses of cross-sectional data at enrollment were performed on 125,307 participants, 50-79 years of age, from the Women's Health Initiative Clinical Trials and Observational Studies who met eligibility criteria, and a subset of those with 3-year follow-up data were examined for longitudinal relationships. Depressive symptoms were defined using the Burnam Algorithm whereas antidepressant use was defined using therapeutic class codes. WBC count (Kcell/ml) was obtained through laboratory evaluations of fasting blood samples. Multivariable regression modeling was performed taking sociodemographic, lifestyle and health characteristics into consideration. At enrollment, nearly 85% were non-users of antidepressants with no depressive symptoms, 5% were antidepressant users with no depressive symptoms, 9% were non-users of antidepressants with depressive symptoms, and 2% were users of antidepressants with depressive symptoms. In fully-adjusted models, cross-sectional relationships were observed whereby women in the 2nd (OR = 1.06, 95% CI: 1.01, 1.13), 3rd (OR = 1.06, 95% CI: 1.00, 1.12) or 4th (OR = 1.10, 95% CI: 1.05, 1.17) quartiles of WBC count were more likely to exhibit depressive symptoms, and women in the 4th quartile were more likely to be users of antidepressants (OR = 1.07, 95% CI: 1.00, 1.15), compared to women in the 1st quartile. Compared to women who exhibited no depressive symptoms at either visit, those with consistent depressive symptoms at enrollment and at 3-year follow-up had faster decline in WBC count (ß = -0.73, 95% CI: -1.33, -0.14) over time. No significant bidirectional relationships were observed between changes in depressive symptoms score and WBC count over time. In conclusion, depressive symptoms and/or antidepressant use were cross-sectionally related to higher WBC counts among postmenopausal women. Further evaluation of observed relationships is needed in the context of prospective cohort studies involving older adult men and women, with repeated measures of depression, antidepressant use, and WBC count.
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Depresión , Posmenopausia , Anciano , Femenino , Humanos , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Depresión/epidemiología , Recuento de Leucocitos , Estudios Prospectivos , Salud de la Mujer , Persona de Mediana EdadRESUMEN
Despite limited evidence to support its efficacy, use of pulmonary artery catheter (PAC), a relatively expensive medical device, for monitoring clinical status and guiding therapeutic interventions, has become standard of care in many settings, and especially during and after cardiac surgery. We examined the prevalence and predictors of PAC use and its association with hospitalization charges among cardiac surgery patients generally and for each selected subgroup of high-risk or complex surgical procedures. We conducted an analysis on 1,442,528 records from the National Inpatient Sample (1999-2019) that included cardiac surgery patients ≥18 years of age. Subgroups were categorized based on the presence of specific disorders like tricuspid or mitral valve disease, pulmonary hypertension, heart failure, or cardiac surgery combinations. Multivariable regression models were constructed to assess predictors of PAC use as well as PAC use as a predictor of loge hospitalization charges controlling for patient and hospital characteristics. Based on International Classification of Diseases procedure codes, PAC use was prevalent among 7.15 % of cardiac surgery hospitalizations, and hospitalization charges were estimated at $191,345, with no differences according to PAC use. Overall, being female, having Charlson comorbidity index (CCI) > 0, and non-payer (versus Medicare) status were independently associated with PAC use. Among the subgroup with the selected conditions, being female, having CCI>0, and being a Medicaid (versus Medicare) recipient were independently associated with PAC use, whereas elective admission was inversely related to PAC use. Among the subgroup without the selected conditions, having a CCI >0, elective admission, and non-payer (vs. Medicare) status were independently associated with PAC use. PAC use was not independently related to hospitalization charges overall or among subgroups. In conclusion, approximately 7 % of cardiac surgery hospitalizations received a PAC, with no differences in charges according to PAC use and disparities in PAC use driven by sex, elective admission, CCI and health insurance status. Large randomized trials are required to characterize the safety, efficacy, and cost-effectiveness of PAC use among distinct groups of patients undergoing cardiac surgery.
RESUMEN
This study examines the association between personality and cognitive errors in the Healthy Aging in Neighborhoods of Diversity across the Life Span study, a sample diverse across race (Black, White) and SES (above, below 125% of the federal poverty line). Participants (N=1,062) completed a comprehensive personality questionnaire and were administered a brief mental status screener of cognitive errors. Higher neuroticism was associated with more cognitive errors, whereas higher openness and conscientiousness were associated with fewer errors. These associations were independent of age, sex, race, poverty status, and education and were generally not moderated by these factors. These findings support the associations between personality and cognition across race and SES.
RESUMEN
Circulating cell-free mitochondrial DNA (ccf-mtDNA) acts as a damage-associated molecular pattern molecule and may be cargo within extracellular vesicles (EVs). ccf-mtDNA and select mitochondrial DNA (mtDNA) haplogroups are associated with cardiovascular disease. We hypothesized that ccf-mtDNA and plasma EV mtDNA would be associated with hypertension, sex, self-identified race, and mtDNA haplogroup ancestry. Participants were normotensive (n = 107) and hypertensive (n = 108) African American and White adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span study. ccf-mtDNA levels were higher in African American participants compared with White participants in both plasma and EVs, but ccf-mtDNA levels were not related to hypertension. EV mtDNA levels were highest in African American participants with African mtDNA haplogroup. Circulating inflammatory protein levels were altered with mtDNA haplogroup, race, and EV mtDNA. Our findings highlight that race is a social construct and that ancestry is crucial when examining health and biomarker differences between groups.