Middle-aged Participants Research Articles

Financial hardship experience in middle- and older-aged patients with advanced lung cancer

PurposeAdvancements in medical treatments have resulted in increased medical costs for cancer patients. More than half of the patients with advanced lung cancer reported unmet financial needs. The purpose of this study is to examine the differences in the prevalence and correlates of financial hardship between middle- and older-aged patients with advanced lung cancer, and its impact on multiple health-related outcomes.MethodsThis study presents a cross-sectional analysis involving 226 patients with advanced lung cancer, who were enrolled in a randomized controlled trial conducted between 2018 and 2020. Data collection was performed through self-reported questionnaires and electronic medical records. Multivariable logistic and linear regression models were adopted for analysis.Results58.0% reported experiencing financial hardships. Middle-aged participants who were single and had a lower education level were more likely to experience financial difficulties. However, males and higher performance status were associated with a lower likelihood of experiencing financial difficulties among older-aged participants. Financial hardship was significantly associated with anxiety (p < 0.001), depression (p < 0.001), sleep disturbances (p < 0.001), quality of life, global health status (p = 0.002), functional scale score (p < 0.001), symptom scale score (p < 0.001), and lung cancer-specific scale score (p < 0.001).ConclusionsMore than half of the patients with advanced lung cancer experienced financial hardships caused by cancer or its treatment, with a higher prevalence reported in middle-aged patients. Different sociodemographic and clinical variables correlated with financial hardship in middle- and older-aged participants, respectively. More attention should be paid to middle-aged patients with advanced lung cancer, particularly during routine assessments.

Association of combined healthy lifestyle factors with incident osteoporosis in patients with and without type 2 diabetes.

The association between type 2 diabetes mellitus (T2DM), lifestyle factors, and the risk of osteoporosis (OP) is well-established. However, the impact of a healthy lifestyle on diabetes-related osteoporosis needs further investigation. Our objective was to explore if a combination of healthy lifestyle factors could mitigate the risk of OP in individuals with type 2 diabetes. This longitudinal analysis included 237,725 middle-aged and older participants. An overall lifestyle score, ranging from 0 to 7, was calculated by assigning a point for each of the seven healthy lifestyle factors, including no current smoking, non-excessive alcohol consumption, regular physical activity, healthy diet, adequate sleep duration, less sedentary behavior, and adequate sunshine exposure. During a median follow-up 12.21 years, 5760 OP cases were documented. Participants with T2DM showed a higher risk of OP than those without diabetes. Compared with participants without diabetes who had a lifestyle score of 6-7, the hazard ratios (HRs) for OP were 1.58 (95% CI 1.23-2.03), 1.62 (95% CI 1.16-2.25), and 2.58 (95% CI 1.64-4.05) for participants with T2DM who had a lifestyle score of 4, 3, and 0-2, respectively. There was a graded association between higher lifestyle scores and lower risks of incident OP among participants without diabetes as well as among those with T2DM. We estimated that the population attributable fraction for not adhering to 6-7 lifestyle behaviors was 15.7%. Participants with T2DM who adhered to a variety of healthy lifestyle factors demonstrated a substantially reduced risk of developing OP.

Sex-specific associations of urinary mixed-metal concentrations with femoral bone mineral density among older people: an NHANES (2017-2020) analysis.

Heavy metal exposure is an important cause of reduced bone mineral density (BMD). Epidemiological studies focusing on the effects of mixed heavy metal exposure on BMD in middle-aged and older people are scarce. In single-metal studies, men and women have shown distinct responses of BMD to environmental metal exposure. This study therefore aimed to elucidate the association between mixed heavy metal exposure and BMD and to investigate whether it is sex-specific. Data from the 2017-2020 National Health and Nutrition Examination Survey were selected for this cross-sectional study. The study used three statistical methods, i.e., linear regression, Bayesian kernel machine regression (BKMR) modeling, and weighted quartiles (WQS) regression, to explore the association between the urinary concentrations of 11 metals (barium, cadmium, cobalt, cesium, manganese, molybdenum, lead, antimony, tin, thallium, and Tungsten), either individually or as a mixture, and total femoral BMD. A total of 1,031 participants were included in this study. Femoral BMD was found to be higher in men than women. A significant negative correlation between the urinary concentrations of the 10 metals and femoral BMD was found in the overall cohort. Further gender sub-stratified analyses showed that in men, urinary metal concentrations were negatively correlated with femoral BMD, with cobalt and barium playing a significant and non-linear role in this effect. In women, although urinary metal concentrations negatively modulated femoral BMD, none of the correlations was statistically significant. Antimony showed sex-specific differences in its effect. The urinary concentrations of 10 mixed heavy metals were negatively correlated with femoral BMD in middle-aged and older participants, and this effect showed gender differences. These findings emphasize the differing role of mixed metal exposure in the process of BMD reduction between the sexes but require further validation by prospective studies.

Sex-specific relationships of inflammatory biomarkers with blood pressure in older adults

Emerging evidence indicates an association between blood pressure and inflammation, yet this relationship remains unclear in older adults, despite the elevated prevalence of hypertension. We investigated the association between blood pressure, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and white blood cell (WBC) count in a cohort of 3571 older adults aged 65 and above, and 587 middle-aged participants (55–59 years old). In women aged 65 and above, the relationship between inflammatory markers and blood pressure was consistent, with hs-CRP and WBC emerging as predictors of high blood pressure. For hs-CRP, the adjusted odds ratio (OR) was 1.5 (95% CI, 1.07 to 2.10, P = 0.02), and for WBC, the adjusted OR was 1.41 (95% CI, 1.02 to 1.94, P = 0.04), comparing the highest to the lowest quartiles. In men, only the WBC count was significantly associated with an increased OR for high BP (adjusted OR 1.49, 95% CI, 1.09 to 2.02, P = 0.01) across quartiles. Across the entire study population, in a fully adjusted model, all inflammatory markers were modestly associated with blood pressure levels, while the effect of being over 65 years was the most significant predictor of high blood pressure (OR 1.84, 95% CI, 1.50 to 2.25, P < 0.001). The link between key inflammation markers and blood pressure in older adults varies by sex and biomarker type and may differ from the relationship observed in younger individuals. These relationships are likely to be affected by factors linked to age.

Sleep-wake behaviors associated with cognitive performance in middle-aged participants of the Hispanic Community Health Study/Study of Latinos

ObjectivesMany sleep-wake behaviors have been associated with cognition. We examined a panel of sleep-wake/activity characteristics to determine which are most robustly related to having low cognitive performance in midlife. Secondarily, we evaluate the predictive utility of sleep-wake measures to screen for low cognitive performance. MethodsThe outcome was low cognitive performance defined as being >1 standard deviation below average age/sex/education internally normalized composite cognitive performance levels assessed in the Hispanic Community Health Study/Study of Latinos. Analyses included 1006 individuals who had sufficient sleep-wake measurements about 2years later (mean age=54.9, standard deviation= 5.1; 68.82% female). We evaluated associations of 31 sleep-wake variables with low cognitive performance using separate logistic regressions. ResultsIn individual models, the strongest sleep-wake correlates of low cognitive performance were measures of weaker and unstable 24-hour rhythms; greater 24-hour fragmentation; longer time-in-bed; and lower rhythm amplitude. One standard deviation worse on these sleep-wake factors was associated with ∼20%-30% greater odds of having low cognitive performance. In an internally cross-validated prediction model, the independent correlates of low cognitive performance were: lower Sleep Regularity Index scores; lower pseudo-F statistics (modellability of 24-hour rhythms); lower activity rhythm amplitude; and greater time in bed. Area under the curve was low/moderate (64%) indicating poor predictive utility. ConclusionThe strongest sleep-wake behavioral correlates of low cognitive performance were measures of longer time-in-bed and irregular/weak rhythms. These sleep-wake assessments were not useful to identify previous low cognitive performance. Given their potential modifiability, experimental trials could test if targeting midlife time-in-bed and/or irregular rhythms influences cognition.

Association between short-term glucose fluctuations and cognition in patients with acute ischemic stroke complicated by type 2 diabetes mellitus

ObjectivesGlucose fluctuations are more harmful than persistent hyperglycemia for chronic complications of diabetes. However, the relationship between cognition and glucose fluctuations in patients with acute ischemic stroke (AIS) complicated by type 2 diabetes mellitus (T2DM) remains unclear. We aimed to evaluate the association between short-term glucose fluctuations and cognition in patients with AIS complicated by T2DM. DesignA cohort study with a 2-year follow-up. Setting and participantsWe included 554 patients with mild AIS (mean age: 62 years; 170 females and 384 males). MeasurementsGlucose variability (GV) was evaluated using glycated hemoglobin (HbA1c), stress hyperglycemia (SHR), standard deviation of blood glucose (SDBG), mean postprandial blood glucose (MPBG), mean amplitude of glycemic excursion (MAGE), and time in range (TIR). We evaluated the relationship between GV, fasting blood glucose (FBG) and cognition during the acute phase using linear regression analysis. We evaluated the relationship between GV, FBG and the occurrence of post-stroke cognitive impairment (PSCI) using a logistic regression model. Mediation analyses were fitted to explore whether the relationships of HbA1c with cognition were mediated by cerebral small vessel disease (CSVD). ResultsA clear pattern of age-related GV was observed. Higher SHR in middle-aged participants; higher HbA1c, and lower TIR in older participants; and higher MAGE, MPBG, and SDBG across a broad age range (50–80 years) were associated with cognitive impairment in the acute phase of AIS. Higher SHR and SDBG together with lower TIR in middle-aged participants, higher HbA1c in older participants, and higher FBG, MPBG, and MAGE across a broad age range (50–80 years) were associated with the occurrence of PSCI. The association between HbA1c and cognition was partially mediated (proportion: 7–16%) by CSVD. ConclusionsShort-term glucose fluctuations are associated with cognition and a higher risk of PSCI in patients with AIS complicated by T2DM. CSVD might play an important role in the relationship between short-term glucose fluctuations and cognition.

The effects of resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged adults.

Denervated myofibers and senescent cells are hallmarks of skeletal muscle aging. However, sparse research has examined how resistance training affects these outcomes. We investigated the effects of unilateral leg extensor resistance training (2 days/week for 8 weeks) on denervated myofibers, senescent cells, and associated protein markers in apparently healthy middle-aged participants (MA, 55 ± 8 years old, 17 females, 9 males). We obtained dual-leg vastus lateralis (VL) muscle cross-sectional area (mCSA), VL biopsies, and strength assessments before and after training. Fiber cross-sectional area (fCSA), satellite cells (Pax7+), denervated myofibers (NCAM+), senescent cells (p16+ or p21+), proteins associated with denervation and senescence, and senescence-associated secretory phenotype (SASP) proteins were analyzed from biopsy specimens. Leg extensor peak torque increased after training (p < .001), while VL mCSA trended upward (interaction p = .082). No significant changes were observed for Type I/II fCSAs, NCAM+ myofibers, or senescent (p16+ or p21+) cells, albeit satellite cells increased after training (p = .037). While >90% satellite cells were not p16+ or p21+, most p16+ and p21+ cells were Pax7+ (>90% on average). Training altered 13 out of 46 proteins related to muscle-nerve communication (all upregulated, p < .05) and 10 out of 19 proteins related to cellular senescence (9 upregulated, p < .05). Only 1 out of 17 SASP protein increased with training (IGFBP-3, p = .031). In conclusion, resistance training upregulates proteins associated with muscle-nerve communication in MA participants but does not alter NCAM+ myofibers. Moreover, while training increased senescence-related proteins, this coincided with an increase in satellite cells but not alterations in senescent cell content or SASP proteins. These latter findings suggest shorter term resistance training is an unlikely inducer of cellular senescence in apparently healthy middle-aged participants. However, similar study designs are needed in older and diseased populations before definitive conclusions can be drawn.

Longitudinal associations of polypharmacy and frailty with major cardiovascular events and mortality among more than half a million middle-aged participants of the UK Biobank

BackgroundStudies of the associations of polypharmacy and frailty with adverse health outcomes in middle-aged adults are limited. Furthermore, a potentially stronger association of polypharmacy with adverse health outcomes in frail than in non-frail adults is of interest. ObjectiveTo evaluate associations of frailty (assessed using a frailty index) and polypharmacy (defined as taking five or more drugs) with major cardiovascular events, cancer incidence, all-cause, cardiovascular disease-specific, and cancer-specific mortality. MethodsCox proportional hazards regression models were used to analyze 501,548 participants of the UK Biobank cohort study aged 40–69 years who were followed up for an average of 12 years. ResultsThe prevalence of pre-frailty and frailty were 43.2 % and 2.3 %, respectively, and that of polypharmacy was 18.3 %. Although strongly associated with each other, frailty and polypharmacy were independently, statistically significantly associated with major cardiovascular events, cardiovascular disease-specific, and all-cause mortality. In addition, the hazard ratios of polypharmacy were stronger among (pre-)frail than non-frail study participants. No profound associations with cancer incidence and cancer mortality were observed. No sex and age differences were observed. ConclusionsThis large cohort study showed that polypharmacy and frailty are independent risk factors for major cardiovascular events, cardiovascular disease-specific and all-cause mortality in both middle-aged (40–64 years) and older people (≥ 65 years). In addition, the hazard ratios of polypharmacy were stronger among (pre-)frail than non-frail study participants. This underlines the need to avoid polypharmacy as far as possible not only in older but also in middle-aged subjects (40–64 years), especially if they are pre-frail or frail.

A novel deep proteomic approach in human skeletal muscle unveils distinct molecular signatures affected by aging and resistance training.

The skeletal muscle proteome alterations to aging and resistance training have been reported in prior studies. However, conventional proteomics in skeletal muscle typically yields wide protein abundance ranges that mask the detection of lowly expressed proteins. Thus, we adopted a novel deep proteomics approach whereby myofibril (MyoF) and non-MyoF fractions were separately subjected to protein corona nanoparticle complex formation prior to digestion and Liquid Chromatography Mass Spectrometry (LC-MS). Specifically, we investigated MyoF and non-MyoF proteomic profiles of the vastus lateralis muscle of younger (Y, 22±2 years old; n=5) and middle-aged participants (MA, 56±8 years old; n=6). Additionally, MA muscle was analyzed following eight weeks of resistance training (RT, 2d/week). Across all participants, the number of non-MyoF proteins detected averaged to be 5,645±266 (range: 4,888-5,987) and the number of MyoF proteins detected averaged to be 2,611±326 (range: 1,944-3,101). Differences in the non-MyoF (8.4%) and MyoF (2.5%) proteomes were evident between age cohorts, and most differentially expressed non-MyoF proteins (447/543) were more enriched in MA versus Y. Biological processes in the non-MyoF fraction were predicted to be operative in MA versus Y including increased cellular stress, mRNA splicing, translation elongation, and ubiquitin-mediated proteolysis. RT in MA participants only altered ~0.3% of MyoF and ~1.0% of non-MyoF proteomes. In summary, aging and RT predominantly affect non-contractile proteins in skeletal muscle. Additionally, marginal proteome adaptations with RT suggest more rigorous training may stimulate more robust effects or that RT, regardless of age, subtly alters basal state skeletal muscle protein abundances.

The Association between the Plasma Phospholipid Profile and Insulin Resistance: A Population-Based Cross-Section Study from the China Adult Chronic Disease and Nutrition Surveillance.

The dysfunction of phospholipid metabolism enzymes and the change in membrane phospholipid composition are associated with insulin resistance, indicating that phospholipids play an important role in the regulation of insulin sensitivity. The reflection of phospholipid changes in blood might provide clues for both mechanism understanding and intervention. Using a targeted phospholipidomic approach, 199 phospholipid molecular species were identified and quantified in the plasma of 1053 middle-aged participants from a national investigation. The associations of the phospholipid matrix, clusters, and molecular species with insulin resistance were investigated. A significant association was confirmed between the phospholipid matrix and the homeostatic-model assessment of insulin resistance (HOMA-IR) by a distance-based linear model. Furthermore, three clustered phospholipid modules and 32 phospholipid molecular species were associated with HOMA-IR with the strict control of demographic and lifestyle parameters, family history of diabetes, BMI, WC, and blood lipid parameters. The overall decline in lysophosphatidylcholines (LPCs), the decrease in saturated lysophosphatidylethanolamines (LPEs), the decrease in polyunsaturated/plasmenyl phosphatidylcholines (PCs), and the increase in polyunsaturated phatidylethanolamines (PEs) were the prominent characters of plasma phospholipid perturbation associated with insulin resistance. This suggested that PC- and PE-related metabolic pathways were widely involved in the process of insulin resistance, especially the disorder of LPC acylation to diacyl-PC.

Maintaining ideal cardiovascular health is associated with higher serum anti-aging protein klotho in the middle-aged and older populations

ObjectivesMaintaining ideal cardiovascular health (CVH) is believed to have potential anti-aging benefits. The American Heart Association (AHA) recently updated the “Life's Essential 8 (LE8)” metrics to measure ideal CVH, but its connection with the anti-aging protein klotho is still unclear. We aimed to explore the relationship between ideal cardiovascular health and serum anti-aging protein klotho in a nationally representative US middle-aged and older population. DesignA cross-sectional study. SettingThe National Health and Nutrition Examination Survey (2007−2016). ParticipantsA total of 9457 middle-aged and older participants. MeasurementsIdeal CVH scores and their components were defined according to the guidelines set by the AHA. Serum klotho detected by enzyme-linked immunosorbent assay. Weighted multivariable linear regression and restricted cubic spline were employed to examine the association between CVH score and klotho. Subgroup analyses were conducted, stratified by age (40−59 and 60−79), sex (Male and Female), race (Mexican American, non-Hispanic White, non-Hispanic Black, and Others) and chronic kidney disease (Yes and No) in fully adjusted models. ResultsA total of 9457 middle-aged and older participants were included in this study, with a mean age of 55.27 ± 0.17 years. The mean serum klotho level in the population was 849.33 ± 5.39 pg/mL. After controlling for potential confounders, the LE8 score showed a positive correlation with serum klotho levels (β: 1.32; 95% CI 0.73, 1.91), and a non-linear dose-response relationship was observed. Furthermore, we also discovered a positive relationship between health behaviors score and health factors score and serum klotho levels (β: 0.48; 95% CI 0.07, 0.88 and β: 1.05; 95% CI 0.54, 1.56, respectively), particularly a stronger correlation between health factors and serum klotho. In the subgroup analysis, we observed a significant interaction between LE8 score and sex and race. (P for interaction <0.05). ConclusionsLE8 and its subscale scores were positively associated with serum klotho levels in the middle-aged and older populations. Promoting the maintenance of ideal CVH can contribute to delaying the aging process.

Resilience to Physical and Emotional Stress

Resilience is the ability of an individual to successfully adapt to stressful and challenging situations. However, resilience encompasses not only the way we react to a specific stressful situation but also how we cope with accompanying physical, psychological, and social challenges. A resilient person is not immune to failures, losses, and the effects of stress. It is the way a person responds after the initial shock that stands out and distinguishes resilient individuals from others. The aim of this study is to examine differences in resilience and quality of life among early and middle-aged participants, as well as the relationship between these variables. We aim to determine the importance of self-efficacy, perseverance, social support, internal locus of control, and coping and adaptation strategies for preserving the physical and mental health of individuals under the impact of stressful life events.

Examining Sexual Well-being across the Lifespan: Assessing the Relationship between Sexual Satisfaction and Adjustment to Aging

IntroductionSexual satisfaction is relevant to aging well, throughout the lifespan.ObjectivesThis study aims to compare the perspectives of sexual satisfaction and adjustment to aging in three age cohorts, across the life span; and to analyze whether sexual satisfaction influences the perceptions of AtA.MethodsThis cross-sectional study comprised participants from three different age cohorts (18-44; 45-64; and 65+ years). Four measures were used to meet the defined objectives: (a) Adjustment to Aging Scale (ATAS); (b) New Sexual Satisfaction Scale (NISS-S); and (c) sociodemographic, health and lifestyle questionnaire. Data were subject to One-way ANOVAs and hierarchical regression analyses.ResultsSocial support emerged as the most relevant dimension in the multifactorial nature of AtA. Generational differences were found in sense of purpose and ambitions [F (2, 616) = 14.203, p = .000], social support [F (2, 616) = 10.65, p = .000] and body and health [F (2, 616) = 8.73, p = .000]. Participants aged 65 and older showed significantly lower levels of sense of purpose and ambition, body and health, and social support. Younger participants showed the highest score for body and health. Age-related decreases in sexual satisfaction were also found, as younger participants showed statistically higher levels of sexual satisfaction, followed by middle-aged and older participants. Sexual satisfaction predicts all the dimensions of AtA, exception made for aging in place and stability, where age is the main predictor. Ego-centered sexual satisfaction positively predicted sense of purpose and ambitions (β = .212, p &lt; .05) and social support (β = .311, p &lt; .001); while partner/sexual activity centered sexual satisfaction was a positive predictor of zest and spirituality (β = .255, p &lt; .01), body and health (β = .239, p &lt; .001), and social support (β = .168, p &lt; .05).ConclusionsSexual satisfaction decreases with age and is positively related to all dimensions of AtA, hence gerontological interventions and program policies with older people would strongly benefit of including sexual satisfaction as a relevant variable for aging well.Keywords: sexual well-being; sexual satisfaction; adjustment to aging; generational groups; lifespan.Disclosure of InterestNone Declared

SARS-CoV-2, influenza A/B and respiratory syncytial virus positivity and association with influenza-like illness and self-reported symptoms, over the 2022/23 winter season in the UK: a longitudinal surveillance cohort

BackgroundSyndromic surveillance often relies on patients presenting to healthcare. Community cohorts, although more challenging to recruit, could provide additional population-wide insights, particularly with SARS-CoV-2 co-circulating with other respiratory viruses.MethodsWe estimated the positivity and incidence of SARS-CoV-2, influenza A/B, and RSV, and trends in self-reported symptoms including influenza-like illness (ILI), over the 2022/23 winter season in a broadly representative UK community cohort (COVID-19 Infection Survey), using negative-binomial generalised additive models. We estimated associations between test positivity and each of the symptoms and influenza vaccination, using adjusted logistic and multinomial models.ResultsSwabs taken at 32,937/1,352,979 (2.4%) assessments tested positive for SARS-CoV-2, 181/14,939 (1.2%) for RSV and 130/14,939 (0.9%) for influenza A/B, varying by age over time. Positivity and incidence peaks were earliest for RSV, then influenza A/B, then SARS-CoV-2, and were highest for RSV in the youngest and for SARS-CoV-2 in the oldest age groups. Many test positives did not report key symptoms: middle-aged participants were generally more symptomatic than older or younger participants, but still, only ~ 25% reported ILI-WHO and ~ 60% ILI-ECDC. Most symptomatic participants did not test positive for any of the three viruses. Influenza A/B-positivity was lower in participants reporting influenza vaccination in the current and previous seasons (odds ratio = 0.55 (95% CI 0.32, 0.95)) versus neither season.ConclusionsSymptom profiles varied little by aetiology, making distinguishing SARS-CoV-2, influenza and RSV using symptoms challenging. Most symptoms were not explained by these viruses, indicating the importance of other pathogens in syndromic surveillance. Influenza vaccination was associated with lower rates of community influenza test positivity.

Association of Cognitive Reserve Indicator with Cognitive Decline and Structural Brain Differences in Middle and Older Age: Findings from the UK Biobank

BackgroundCognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to dementia risk in late life. However, the association between CR and cognitive changes and brain imaging measures, especially in midlife, is unclear.ObjectiveWe aimed to explore the association of CR with cognitive decline and structural brain differences in middle and older age.DesignThis longitudinal study was from the UK Biobank project where participants completed baseline surveys between 2006 to 2010 and were followed (mean follow-up: 9 years).SettingA population-based study.ParticipantsA total of 42,301 dementia-free participants aged 40–70 were followed-up to detect cognitive changes. A subsample (n=34,041) underwent brain magnetic resonance imaging scans.MeasurementsWe used latent class analysis to generate a CR indicator (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities. Cognitive tests for global and domain-specific cognition were administrated at baseline and follow-up. Total brain, white matter, grey matter, hippocampal, and white matter hyperintensity volumes (TBV, WMV, GMV, HV, and WMHV) were assessed at the follow-up examination. Data were analyzed using mixed-effects models and analysis of covariance.ResultsAt baseline, 16,032 (37.9%), 10,709 (25.3%), and 15,560 (36.8%) participants had low, moderate, and high levels of CR, respectively. Compared with low CR, high CR was associated with slower declines in global cognition (β [95% confidence interval]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). Participants with high CR had lower TBV, WMV, GMV, and WMHV, but higher HV when controlling for global cognition (corrected P <0.01 for all). The significant relationships between CR and cognition and TBV were present among both middle-aged (<60 years) and older (≥60 years) participants. The CR-cognition association remained significant despite reductions in brain structural properties.ConclusionsHigher CR is associated with slower cognitive decline, higher HV, and lower microvascular burden, especially in middle age. Individuals with high CR could tolerate smaller brain volumes while maintaining cognition. The benefit of CR for cognition is independent of structural brain differences. Our findings highlight the contribution of enhancing CR to helping compensate for neuroimaging alterations and ultimately prevent cognitive decline.

Validation of the SQUASH physical activity questionnaire using accelerometry: The NEO study

ObjectiveTo investigate the construct validity of the SQUASH (Short QUestionnaire to ASsess Health-enhancing physical activity). DesignThis is a cross-sectional analysis using baseline measurements from middle-aged participants in the Netherlands Epidemiology of Obesity (NEO) study. The SQUASH consists of questions on eleven physical activities investigating days per week, average duration per day and intensity, leading to a summed score in Metabolic Equivalent of Task hours (MET h) per week. To assess convergent validity, a Spearman's rank correlation between SQUASH and ActiHeart was calculated. To assess extreme group validity, three groups expected to differ in SQUASH total physical activity outcome were compared. For discriminative validity, a Spearman's rank correlation between SQUASH physical activity and participant height was investigated. ResultsSQUASH data were available for 6550 participants (mean age 56 years, 44% men, mean BMI 26.3, 15% with knee OA, 13% with hand OA). Median physical activity (interquartile range) was 118 (76; 154) MET h/week according to SQUASH and 75 (58; 99) according to ActiHeart. Convergent validity was weak (rho ​= ​0.20). For all three extreme group comparisons, a statistically significant difference was present. Discriminative validity was present (rho ​= ​0.01). Compared with the reference quintile, those with a discrepancy SQUASH ​> ​ActiHeart and SQUASH ​< ​ActiHeart were relatively younger and more often male. ConclusionsThe construct validity of the SQUASH seems sub-optimal. Physical activity reported by the SQUASH was generally higher than reported by ActiHeart. Whether the differences between SQUASH and ActiHeart are e.g. due to different underlying domains, limitations to our study, or reflect true differences needs further investigation.

Submaximal, Low-Dose Eccentric vs Traditional Cycling Exercise: Reduced Oxygen Uptake and Pulmonary Artery Pressure Assessed by Echocardiography in Healthy Middle-aged Adults. A Randomized Controlled, Crossover Trial

ObjectiveTo investigate the ventilatory and circulatory differences between eccentric (ECC) and concentric (CON) cycling exercise at submaximal, low-dose intensity from onset to end-exercise in healthy middle-aged participants. DesignRandomized controlled crossover trial. SettingThe participants underwent 1 ECC and 1 CON test according to stepwise incremental exercise protocols at identical, submaximal intensities. Breath-by-breath analyses of ventilatory gas exchange and echocardiography were used to assess cardiopulmonary function during exercise. Participants24 healthy middle-aged, untrained participants (14 women, 10 men, 50±14 years) were included. Interventions1 ECC and 1 CON test at submaximal intensities. Main Outcome MeasureThe main outcome was oxygen uptake (V'O2). ResultsThe V'O2 increase was reduced by -422 mL/min (-52%, 95% confidence interval: -513 to -292, P<.001) during ECC, as well as the ventilatory drive. Echocardiographic parameters, heart rate (-14%), cardiac output (-21%), stroke volume (-15%), and pulmonary artery pressure by tricuspid regurgitation pressure gradient (TRPG) (-26%) were also significantly reduced during ECC compared with CON at identical intensities. Participants reported significantly less dyspnea and unchanged perceived leg fatigue in ECC. ConclusionECC was well tolerated, and significant reductions were observed in V'O2, ventilation, and right ventricular load compared with CON, even at low intensity levels. This study, conducted on healthy middle-aged participants, did not raise concerns that would hinder further investigation of the effects of ECC in patients with severely limited cardiopulmonary disease, and it calls for further research on this topic.

Sex differences in waist circumference obesity and eating speed: a cross-sectional study of Japanese people with normal body mass index.

Fast eating has been positively associated with visceral fat accumulation in normal-weight individuals according to body mass index (BMI). However, previous studies have not examined energy and nutrients, or adjusted for food intake. We examined the relationship between eating speed and visceral fat accumulation, using waist circumference as an index, in middle-aged participants who were considered to be of standard weight according to BMI, with nutrient intake added as an adjustment factor. We included 6,548 Japanese participants (3,875 men and 2,673 women) aged 40-74 years with BMI 18.5-25.0 kg/m2 who were enrolled in the Yamagata Cohort Study. Participants were divided into "fast," "normal," and "slow" eaters according to self-reported eating speed. Nutrient and food intake were evaluated using a food frequency questionnaire, and the difference in intake by eating speed and sex was compared. Logistic regression analysis was used to examine the relationship between waist circumference obesity (men ≥85 cm, women ≥90 cm, according to Japanese criteria) and eating speed, adjusted for nutrient intake and other lifestyle habits. In men, slow eaters had greater intakes of dietary protein, fat, polyunsaturated fatty acids (PUFA), omega-3 PUFA, total dietary fiber, soluble dietary fiber, insoluble dietary fiber, soybean products, fish, green and yellow vegetables, other vegetables, mushrooms, and seaweed in comparison with normal-speed eaters. In men, waist circumference obesity was significantly lower among slow eaters than in the group with normal eating speed. In women, waist circumference obesity was not significantly associated with eating speed and was not also associated with nutrient/food consumption except omega-6 PUFA. Eating slowly was associated with healthy dietary habits. Our results could help prevent waist circumference obesity in men with a BMI between 18.5 and 25.0 kg/m2. However, similar findings were not observed in women, suggesting a sex difference.

Geographic disparities of dietary inflammatory index and its association with hypertension in middle-aged and elders in China: results from a nationwide cross-sectional study.

Geographic distribution of dietary inflammatory index (DII) in China has not been thoroughly evaluated and evidence on the association between DII and hypertension among Chinese middle-aged and older population was inadequate. To investigate the geographic disparities of DII and its association with hypertension among Chinese middle-aged and elders. Data was from the China Adults Chronic Diseases and Nutrition Surveillance (CACDNS 2015) for middle-aged and older participants. The DII for each participant was determined through a combination of 3 days 24 h dietary recall interviews and a food frequency questionnaire. Spatial analysis was employed to investigate the geographic distribution of DII in China. Restricted cubic spline models and binary logistic regression analysis were used to assess the relationship between DII and hypertension. The least absolute shrinkage and selection operator (LASSO) regression was applied for identifying key hypertension-related factors, which was then included in the establishment of a risk prediction nomogram model, with the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) being built to evaluate its discriminatory power for hypertension. A total of 52,087 middle-aged and older participants were included in the study, among whom 36.6% had hypertension. it revealed that a clear spatial correlation in the national distribution of DII scores (Moran I: 0.252, p = 0.001), with higher DII scores concentrated in the northwest region and lower DII scores concentrated in the southeast region. Hypertensive participants had higher DII scores compared to those without hypertension (OR: 1.507 vs. 1.447, p = 0.003). Restricted cubic spline models and binary logistic regression analysis demonstrated a positive association between DII and hypertension after adjusting for potential confounding factors. There was a significant increasing trend in the proportion of hypertensive individuals as DII scores increase (p for trend = 0.004). The nomogram model, constructed using key factors identified through LASSO regression, demonstrated a robust discriminative capacity, with an area under the curve (AUC) of 73.2% (95% CI, 72.4-74.0%). Decision curve analysis confirmed the reliability and effectiveness of the nomogram model. Sensitivity analysis conducted within the subpopulation aged under 45 years yielded results consistent with the primary analysis. In Chinese adults middle-aged and older, geographic disparities in dietary inflammatory potential are notable, with lower levels observed in the southeastern coastal regions of China and higher levels in the northwestern regions. Meanwhile, there is a positive association between the inflammatory potential of the diet and hypertension. Additional research is needed to investigate regional disparities in dietary inflammatory potential and pinpoint specific dietary patterns associated with lower inflammation.

Acute Treatment with the Nootropic CILTEP® Does Not Improve Cognitive Performance in Healthy Middle-Aged Participants

This study investigated the acute effects of the dietary nootropic stack CILTEP®. It contains a combination of ingredients that have been individually reported to improve cognitive performance. Especially, the ingredients luteolin, which is considered a phosphodiesterase type 4 (PDE4) inhibitor, and forskolin, an adenylate cyclase stimulator, were of interest since they can increase the second messenger cAMP and thus also intracellular signaling. Numerous studies have shown that inhibition of PDE4 can improve memory in animals and humans. We examined whether acute dosing of 3 capsules of CILTEP® would improve cognitive function in healthy participants aged 30 to 40 (n = 33). We used a randomized, double-blind, placebo-controlled, two-way cross-over design. Our test battery was aimed at measuring memory performance, attention, and sensorimotor speed. The primary outcome measures were the performance on the verbal learning task and the spatial pattern separation task. Secondary outcomes included other cognitive tests, event-related potentials (ERPs), and assessment of the activity of the enzyme beta-glucuronidase and its effect on the bioavailability of luteolin, heart rate, and blood pressure. No relevant effects of acute CILTEP® treatment were found on any measure of the test battery or ERPs. Blood plasma concentrations of luteolin increased, yet about 2000 times too low to likely exert any PDE4 inhibition. CILTEP® treatment did neither affect heart rate nor blood pressure. In summary, there is no evidence that a single standardized dose of 3 capsules of CILTEP® can improve cognitive function in healthy middle-aged participants.