Mediating and moderating effects of plasma proteomic biomarkers on the association between poor oral health problems and incident dementia: The UK Biobank study.

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.

Relationships of depression and antidepressant use with epigenetic age acceleration and all-cause mortality among postmenopausal women.

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.

Loneliness, Dementia Status, and Their Association with All-Cause Mortality Among Older US Adults.

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.

Association between Flavonoid Intake and Cognitive Executive Function among African American and White Adults in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) Study.

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.

Plasma proteomic biomarkers and the association between poor cardiovascular health and incident dementia: The UK Biobank study.

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 âˆ¼ 54 % of the total effect.

Serum neurofilament light chain as a prognostic marker of all-cause mortality in a national sample of US adults.

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.

Pathways explaining racial/ethnic and socio-economic disparities in brain white matter integrity outcomes in the UK Biobank study.

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.

Growth Differentiation Factor 15 and Diet Quality Trajectory Interact to Determine Frailty Incidence among Middle-Aged Urban Adults.

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.

Helicobacter pylori, persistent infection burden and structural brain imaging markers.

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.

Relationship of psychotropic medication use with physical function among postmenopausal women.

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.

Depressive symptoms and antidepressant use in relation to white blood cell count among postmenopausal women from the Women's Health Initiative.

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.

Pulmonary artery catheter receipt among cardiac surgery patients from the national inpatient sample (1999-2019): Prevalence, predictors and hospitalization charges.

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.

Negative aging stereotypes in U.S. military veterans: results from the National Health and Resilience in Veterans Study.

U.S. military veterans are an average 20 years older than non-veterans and have elevated rates of certain health conditions. While negative aging stereotypes have been linked to increased risk for various health conditions, little is known about the prevalence and correlates of these stereotypes in this population. Using data from a nationally representative sample of 4,069 U.S. veterans surveyed between 11/19 and 3/20, we examined (1) the current prevalence of negative aging stereotypes related to physical, mental, and cognitive health and (2) sociodemographic, health, and psychosocial factors associated with these stereotypes. Multivariable regression and relative weight analyses were conducted to identify independent correlates of negative aging stereotypes. Results revealed that 82.3%, 71.1%, and 30.0% of veterans endorsed negative aging stereotypes related to physical, cognitive, and emotional health, respectively. Older age (36.6% relative variance explained), grit (23.6%), and optimism (17.5%) explained the majority of the variance in negative age stereotypes related to physical aging; grit (46.6%), openness to experiences (31.5%), and older age (15.1%) in negative age stereotypes related to cognitive aging; and emotional stability (28.8%), purpose in life (28.8%), and grit (25.3%) in negative age stereotypes related to emotional aging. This study provides an up-to-date characterization of the prevalence and correlates of negative aging stereotypes in U.S. veterans. Results underscore the importance of targeting key correlates of negative aging stereotypes, such as lower grit, as part of efforts to promote health and functioning in this population.

Infection burden and its association with neurite orientation dispersion and density imaging markers in the UK Biobank.

BACKGROUND: Infection burden (IB), although linked to neurodegeneration, including Alzheimer's Disease (AD), has not been examined against neurite orientation, dispersion, and density imaging (NODDI) measures. METHODS: Among 38,803 UK Biobank adults (Age:40-70 years), we tested associations of total IB (IBtotal, 47.5 %) and hospital-treated IB (IBhosp, 9.7 %) with NODDI measures (5-15 years later), including volume fraction of Gaussian isotropic diffusion (ISOVF), intra-cellular volume fraction (ICVF) and orientation dispersion (OD) indices, using multiple linear regression models. RESULTS: Total and hospital-treated infection burdens (IBtotal and IBhosp) were associated with increased ISOVF, indicating increased free-water component. IBtotal was positively associated with OD, indicating that at higher IBtotal there was greater fanning of neurites. This was more evident in the lower cardiovascular health group. IBhosp was associated with higher OD, and lower ICVF at higher AD polygenic risk. Together, these findings indicate that both total and hospital-treated infections have effects on NODDI outcomes in the direction of poor brain health. These effects were largely homogeneous across cardiovascular health and AD polygenic risk groups, with some effects shown to be stronger at poor cardiovascular health and/or higher AD risk. CONCLUSIONS: Total and hospital-treated infections were associated with poorer white matter microstructure (higher ISOVF or OD or lower ICVF), with some heterogeneity across cardiovascular health and AD risk. Longitudinal studies with multiple repeats on neuroimaging markers in comparable samples are needed.

Pro-Inflammatory Diets Are Associated with Frailty in an Urban Middle-Aged African American and White Cohort.

Diet quality is a modifiable risk factor for frailty, but research on the association of frailty with dietary inflammatory potential is limited. The objective was to determine associations between diet quality assessed by the dietary inflammatory index (DII) with frailty status over time. Participants with both dietary and frailty data from the longitudinal Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were used (n = 2901, 43.5% male, 43.8% African American, 48.5 y mean baseline age, with a mean 8.7 y of follow-up). Group-based trajectory modeling identified two frailty (remaining non-frail or being pre-frail/frail over time) and three diet quality trajectory groups (high or medium pro-inflammatory and anti-inflammatory potentials). Multiple logistic regression found both medium pro-inflammatory and anti-inflammatory DII trajectory groups, compared to the high pro-inflammatory group, were positively associated with being non-frail over time for the overall sample, both sexes and races. Kaplan-Meier curves and log-rank test revealed anti-inflammatory DII scores were associated with lower risk for being pre-frail or frail. No longitudinal relationship existed between frailty status at baseline and annualized DII change, a check on reverse causality. This study contributes to our current knowledge providing longitudinal evidence of the link between anti-inflammatory DII score with lower frailty risk.

Pathways explaining racial/ethnic and socio-economic disparities in dementia incidence: the UK Biobank study.

BACKGROUND: Pathways explaining racial/ethnic disparities in dementia risk are under-evaluated. METHODS: We examine those disparities and their related pathways among UK Biobank study respondents (50-74 y, N = 323,483; 3.6% non-White minorities) using a series of Cox proportional hazards and generalized structural equations models (GSEM). RESULTS: After ≤15 years, 5,491 all-cause dementia cases were diagnosed. Racial minority status (RACE_ETHN, Non-White vs. White) increased dementia risk by 24% (HR = 1.24, 95% CI: 1.07-1.45, P = 0.005), an association attenuated by socio-economic status (SES), (HR = 1.12, 95% CI: 0.96-1.31). Total race-dementia effect was mediated through both SES and Life's Essential 8 lifestyle sub-score (LE8LIFESTYLE), combining diet, smoking, physical activity, and sleep factors. SES was inversely related to dementia risk (HR = 0.69, 95% CI: 0.67, 0.72, P < 0.001). Pathways explaining excess dementia risk among racial minorities included 'RACE_ETHN(-) → SES(-) → DEMENTIA', 'RACE_ETHN(-) → SES(-) → Poor cognitive performance, COGN(+) → DEMENTIA' and 'RACE_ETHN(-) → SES(+) → LE8LIFESTYLE(-) → DEMENTIA'. CONCLUSIONS: Pending future interventions, lifestyle factors including diet, smoking, physical activity, and sleep are crucial for reducing racial and socio-economic disparities in dementia.

Cardiovascular health, infection burden, and incident dementia in the UK Biobank.

INTRODUCTION: Among older adults, total and hospitalized infection may be associated with incidence of all-cause and Alzheimer's disease (AD) dementias, with variation by cardiovascular health (CVH). METHODS: We used Cox proportional hazards (PH) models to examine the relationships between International Classification of Diseases-10th revision (ICD-10)-specific viral and bacterial infectious agents and incident all-cause and AD dementia among 355,046 UK Biobank participants ≥50 years at baseline. Life's Essential 8 (LE8) index reflected CVH. RESULTS: In both sexes, total infection burden (yes vs. no) was associated with all-cause dementia, with significant interactions by LE8 tertiles, whereby this relationship was significant only in the lowest LE8 tertile. Hospital-treated infection burden (yes vs no) was significantly related to all-cause and AD dementia, with no significant interaction with LE8 tertile. Age group patterns were detected. DISCUSSION: AD and all-cause dementia were related to hospital-treated infections, while CVH modified the relationship of total infection burden with all-cause dementia. Highlights Secondary analysis on >355,000 UK Biobank participants ≥50 years at baseline. Alzheimer's disease and all-cause dementia are both related to hospital-treated infection. Cardiovascular health modifies association of infection burden with all-cause dementia.

Association of pulmonary artery catheter with in-hospital outcomes after cardiac surgery in the United States: National Inpatient Sample 1999-2019.

To examine associations of pulmonary artery catheter (PAC) use with in-hospital death and hospital length of stay (days) overall and within subgroups of hospitalized cardiac surgery patients. Secondary analyses of 1999-2019 National Inpatient Sample data were performed using 969,034 records (68% male, mean age: 65 years) representing adult cardiac surgery patients in the United States. A subgroup of 323,929 records corresponded to patients with congestive heart failure, pulmonary hypertension, mitral/tricuspid valve disease and/or combined surgeries. We evaluated PAC in relation to clinical outcomes using regression and targeted maximum likelihood estimation (TMLE). Hospitalized cardiac surgery patients experienced more in-hospital deaths and longer stays if they had ≥ 1 subgroup characteristics. For risk-adjusted models, in-hospital deaths were similar among recipients and non-recipients of PAC (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.96, 1.12), although PAC was associated with more in-hospital deaths among the subgroup with congestive heart failure (OR 1.14, 95% CI 1.03, 1.26). PAC recipients experienced shorter stays than non-recipients (ß = - 0.40, 95% CI - 0.64, - 0.15), with variations by subgroup. We obtained comparable results using TMLE. In this retrospective cohort study, PAC was associated with shorter stays and similar in-hospital death rates among cardiac surgery patients. Worse clinical outcomes associated with PAC were observed only among patients with congestive heart failure. Prospective cohort studies and randomized controlled trials are needed to confirm and extend these preliminary findings.

Cardiovascular health, infection burden and their interactive association with brain volumetric and white matter integrity outcomes in the UK Biobank.

BACKGROUND: Cardiovascular health is associated with brain magnetic resonance imaging (MRI) markers of pathology and infections may modulate this association. METHODS: Using data from 38,803 adults (aged 40-70 years) and followed-up for 5-15 years, we tested associations of prevalent total (47.5%) and hospital-treated infection burden (9.7%) with brain structural and diffusion-weighted MRI (i.e., sMRI and dMRI, respectively) common in dementia phenome. Poor white matter tissue integrity was operationalized with lower global and tract-specific fractional anisotropy (FA) and higher mean diffusivity (MD). Volumetric sMRI outcomes included total, gray matter (GM), white matter (WM), frontal bilateral GM, white matter hyperintensity (WMH), and selected based on previous associations with dementia. Cardiovascular health was measured with Life's Essential 8 score (LE8) converted to tertiles. Multiple linear regression models were used, adjusting for intracranial volumes (ICV) for subcortical structures, and for demographic, socio-economic, and the Alzheimer's Disease polygenic risk score for all outcomes, among potential confounders. RESULTS: In fully adjusted models, hospital-treated infections were inversely related to GM (ß ± SE: -1042 ± 379, p = 0.006) and directly related to WMH as percent of ICV (Loge transformed) (ß ± SE:+0.026 ± 0.007, p < 0.001). Both total and hospital-treated infections were associated with poor WMI, while the latter was inversely related to FA within the lowest LE8 tertile (ß ± SE:-0.0011 ± 0.0003, p < 0.001, PLE8×IB < 0.05), a pattern detected for GM, Right Frontal GM, left accumbens and left hippocampus volumes. Within the uppermost LE8 tertile, total infection burden was linked to smaller right amygdala while being associated with larger left frontal GM and right putamen volumes, in the overall sample. Within that uppermost tertile of LE8, caudate volumes were also positively associated with hospital-treated infections. CONCLUSIONS: Hospital-treated infections had more consistent deleterious effects on volumetric and white matter integrity brain neuroimaging outcomes compared with total infectious burden, particularly in poorer cardiovascular health groups. Further studies are needed in comparable populations, including longitudinal studies with multiple repeats on neuroimaging markers.

Diet Quality Trajectories over Adulthood in a Biracial Urban Sample from the Healthy Aging in Neighborhoods of Diversity across the Life Span Study.

Limited investigation has been done on diet quality trajectories over adulthood. The main study objectives were to determine the diet quality group trajectories (GTs) over time and to detect changes in a socio-economically and racially diverse middle-aged cohort. Data from three waves of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were used to determine diet quality with group-based trajectory modeling (GBTM). Three quality indices-the Healthy Eating Index (HEI), the Dietary Inflammatory Index (DII), and the Mean Adequacy Ratio (MAR)-were explored. The rate of change in quality over time was determined by mixed-effects regression analysis. Three diet quality GTs, low, middle, and high quality, were identified for each index and confirmed with spaghetti plots. Within each GT, only small changes in diet quality scores were observed, with improvements for the HEI and DII indices and a slight decline in MAR scores. Weighted kappa values revealed that the DII had better agreement with the HEI-2010 and MAR indices compared with the agreement between the HEI-2010 and MAR. Bayesian estimates revealed that the annualized rate of change in diet quality per person across the GTs was similar. There was minimal change in diet quality over time, regardless of the diet quality index used.