Dietary patterns among U.S. food insecure cancer survivors and the risk of mortality: NHANES 1999-2018.

PURPOSE: Food insecurity-the lack of unabated access to nutritious foods-is a consequence many cancer survivors face. Food insecurity is associated with adverse health outcomes and lower diet quality in the general public. The goal of this analysis was to extract major and prevailing dietary patterns among food insecure cancer survivors from observed 24-h recall data and evaluate their relationship to survival after a cancer diagnosis. METHODS: We implemented two dietary patterns analysis approaches: penalized logistic regression and principal components analysis. Using nationally representative data from the National Health and Nutrition Examination Survey (NHANES) study, we extracted three dietary patterns. Additionally, we evaluated the HEI-2015 for comparison. Cox proportional hazards models assessed the relationship between the diet quality indices and survival after a cancer diagnosis. RESULTS: There were 981 deaths from all causes and 343 cancer-related deaths. After multivariable adjustment, we found higher risks of all-cause mortality associated with higher adherence to Pattern #1 (HR 1.25; 95% CI 1.09-1.43) and Pattern #2 (HR 1.15; 95% CI 1.01-1.31) among cancer survivors. CONCLUSION: Among all cancer survivors, higher adherence to major and prevailing dietary patterns from the U.S. food insecure cancer survivor population may lead to worse survival outcomes.

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.

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.

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.

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.

Associations Between Diet Quality and Proinflammatory Cytokines in Newly Diagnosed Head and Neck Cancer Survivors.

Background: Head and neck squamous cell carcinoma (HNSCC) is a class of heterogenous cancers involving the upper aerodigestive tract. We previously demonstrated the utility of a priori diet quality indices for predicting survival after an HNSCC diagnosis. The aim of this analysis was to evaluate the role of those a priori diet quality indices and proinflammatory cytokines in newly diagnosed HNSCC survivors. Methods: We analyzed cross-sectional data from a sample (n = 146; mean age 59.6 y; 79.3% male) from the University of Michigan Head and Neck Specialized Program of Research Excellence prospective longitudinal cohort study. Dietary intake was measured at pretreatment using a food frequency questionnaire. Serum samples were also collected at pretreatment. Covariate-adjusted proportional odds and logistic regression models were used to assess the relationship between 6 diet quality indices (Alternative Healthy Eating Index [AHEI]-2010, Alternate Mediterranean Diet, Dietary Approaches to Stop Hypertension [DASH], and 3 low-carbohydrate indices) and serum measures of a panel of 10 inflammatory cytokines and a cytokine summary composite score. Results: Higher scores on the AHEI-2010 and DASH diet quality indices were associated with higher odds of lower cytokine value scores for several cytokines and for the cytokine summary composite score (AHEI-2010-odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.10, 2.20; DASH-OR: 1.65; 95% CI 1.15, 2.36). Conclusions: Higher scores on the AHEI-2010 and DASH diet quality indices may be associated with lower proinflammatory cytokine levels in HNSCC survivors.

Hospital-treated prevalent infections, the plasma proteome and incident dementia among UK older adults.

The plasma proteome can mediate the association of hospital-treated infections with dementia incidence. We screened up to 37,269 UK Biobank participants aged 50-74 years for the presence of a prevalent hospital-treated infection, subsequently tested as a predictor for ≤1,463 plasma proteins and dementia incidence. Four-way decomposition models decomposed infection-dementia total effect into pure mediation, pure interaction, neither or both through the plasma proteome. Hospital-treated infections increased dementia two-fold. The strongest mediation effect was through the growth differentiation factor 15 (GDF15) protein. Top 17 proteomic mediators explained collectively 5% of the total effect, while pathway analysis of all mediators (k = 221 plasma proteins) revealed top pathways including the immune system, signal transduction, metabolism, disease and metabolism of proteins, with the GDF15 cluster reflecting most strongly the "transmembrane receptor protein tyrosine kinase signaling pathway". The association of hospital-treated infections with dementia was partially mediated through GDF15 and other plasma proteomic markers.

Empirical Dietary Patterns Associated with Food Insecurity in U.S. Cancer Survivors: NHANES 1999-2018.

(1) Background: Food insecurity (FI) is a public health and sociodemographic phenomenon that besets many cancer survivors in the United States. FI in cancer survivors may arise as a consequence of financial toxicity stemming from treatment costs, physical impairment, labor force egress, or a combination of those factors. To our knowledge, an understanding of the dietary intake practices of this population has not been delineated but is imperative for addressing the needs of this vulnerable population; (2) Methods: Using data from NHANES, 1999-2018, we characterized major dietary patterns in the food insecure cancer survivor population using: i. penalized logistic regression (logit) and ii. principal components analysis (PCA). We validated these patterns by examining the association of those patterns with food insecurity in the cancer population; (3) Results: Four dietary patterns were extracted with penalized logit and two with PCA. In the pattern validation phase, we found several patterns exhibited strong associations with FI. The FI, SNAP, and Household Size patterns (all extracted with penalized logit) harbored the strongest associations and there was evidence of stronger associations in those moderately removed from a cancer diagnosis (≥2 and <6 years since diagnosis); (4) Conclusions: FI may play an influential role on the dietary intake patterns of cancer survivors in the U.S. The results highlight the relevance of FI screening and monitoring for cancer survivors.

Adherence to a priori-Defined Diet Quality Indices Throughout the Early Disease Course Is Associated With Survival in Head and Neck Cancer Survivors: An Application Involving Marginal Structural Models.

No studies, to date, have scrutinized the role of a priori dietary patterns on prognosis following a head and neck squamous cell carcinoma (HNSCC) diagnosis. The purpose of this analysis was to evaluate the associations between adherence to six a priori defined diet quality indices (including AHEI-2010, aMED, DASH, and three low-carbohydrate indices) throughout the first 3 years of observation and all-cause and cancer-specific mortalities in 468 newly diagnosed HNSCC patients from the University of Michigan Head and Neck Specialized Program of Research Excellence (UM-SPORE). The dietary intake data were measured using a food frequency questionnaire administered at three annual time points commencing at study entry. Deaths and their causes were documented throughout the study using various data sources. Marginal structural Cox proportional hazards models were used to evaluate the role of diet quality, as a time-varying covariate, on mortality. There were 93 deaths from all causes and 74 cancer-related deaths adjudicated throughout the observation period. There was a strong inverse association between adherence to the AHEI-2010, all-cause mortality (HR Q5-Q1 :0.07, 95% CI:0.01-0.43, p trend:0.04), and cancer-specific mortality (HR Q5-Q1 :0.15, 95% CI:0.02-1.07, p trend:0.04). Other more modest associations were noted for the low-carbohydrate indices. In sum, higher adherence to the AHEI-2010 and a plant-based low-carbohydrate index throughout the first 3 years since diagnosis may bolster survival and prognosis in newly diagnosed patients with HNSCC.

Healthcare Professionals' Views and Perspectives towards Aging.

Improving care for the older population is a growing clinical need in the United States. Ageism and other attitudes of healthcare professionals can negatively impact care for older adults. This study investigated healthcare professionals' (N = 140) views towards aging and characterized a confluence of factors influencing ageism perspectives in healthcare workers using path analysis models. These models proposed relationships between aging anxiety, expectations regarding aging, age, ageism, and knowledge. Aging anxiety had a less critical role in the final model than hypothesized and influenced ageism in healthcare workers through its negative effect (ß = -0.27) on expectations regarding aging. In contrast, aging knowledge (ß = -0.23), age (ß = -0.27), and expectations regarding aging (ß = -0.48) directly and inversely influenced ageism. Increased knowledge about the aging process could lower ageism amongst healthcare professionals and improve care for older adults. The results put forth in this study help to characterize and understand healthcare workers' complex views towards the aging population they often encounter. Moreover, these results highlight the need and utility of leveraging practitioner education for combating ageism in the clinical setting.

Pretreatment Adherence to a Priori-Defined Dietary Patterns Is Associated with Decreased Nutrition Impact Symptom Burden in Head and Neck Cancer Survivors.

Dietary intake is understood to contribute to nutrition impact symptoms (NIS) in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate the performance of four a priori-defined diet quality indices on the presence of NIS 1 year following diagnosis using data on 323 participants from the University of Michigan Head and Neck Specialized Program of Research Excellence (UM-SPORE). Pretreatment dietary intake was measured before treatment initiation using a food frequency questionnaire. NIS were measured along seven subdomains. Multivariable binary logistic regression models were constructed to evaluate relationships between pretreatment scores on a priori-defined diet quality indices (AHEI-2010, aMED, DASH, and a low-carbohydrate score) and the presence of individual symptoms in addition to a composite "symptom summary score" 1-year postdiagnosis. There were several significant associations between different indices and individual NIS. For the symptom summary score, there were significant inverse associations observed for aMED (ORQ5-Q1: 0.36, 95% CI: 0.14-0.88, ptrend = 0.04) and DASH (ORQ5-Q1: 0.38, 95% CI: 0.15-0.91, ptrend = 0.02) and the presence of NIS 1-year postdiagnosis. Higher adherence to the aMED and DASH diet quality indices before treatment may reduce NIS burden at 1-year postdiagnosis.

Carbohydrate Nutrition and the Risk of Cancer.

PURPOSE OF REVIEW: This review summarizes a selection of epidemiologic research assessing the associations between carbohydrate intake and cancer incidence and survival. Evidence for plausible biological mechanisms is also considered. RECENT FINDINGS: The mechanistic paradigm explaining the relationship between carbohydrates and cancer risk has been contested by numerous observational studies. Carbohydrates have conventionally been ascribed a deleterious role in the field of cancer research due to previous preclinical findings. A breadth of studies suggests that complex carbohydrate intake is inversely associated with risk of a number of cancer types. Data from studies assessing simple carbohydrates and cancer risk are mixed. Furthermore, recommendations for subsequent studies are framed.

Dietary Fiber, Whole Grains, and Head and Neck Cancer Prognosis: Findings from a Prospective Cohort Study.

No studies, to date, have examined the relationship between dietary fiber and recurrence or survival after head and neck cancer diagnosis. The aim of this study was to determine whether pretreatment intake of dietary fiber or whole grains predicted recurrence and survival outcomes in newly diagnosed head and neck cancer (HNC) patients. This was a prospective cohort study of 463 participants baring a new head and neck cancer diagnosis who were recruited into the study prior to the initiation of any cancer therapy. Baseline (pre-treatment) dietary and clinical data were measured upon entry into the study cohort. Clinical outcomes were ascertained at annual medical reviews. Cox proportional hazard models were fit to examine the relationships between dietary fiber and whole grain intakes with recurrence and survival. There were 112 recurrence events, 121 deaths, and 77 cancer-related deaths during the study period. Pretreatment dietary fiber intake was inversely associated with risk of all-cause mortality (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.14-0.95, ptrend = 0.04). No statistically significant associations between whole grains and prognostic outcomes were found. We conclude that higher dietary fiber intake, prior to the initiation of treatment, may prolong survival time, in those with a new HNC diagnosis.