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One of the hallmarks of diabetes is impaired endothelial function. Previous studies showed that HDL can exert protective effects on endothelium stimulating NO production and protecting from inflammation and suggested that HDL in obese people with diabetes and dyslipidemia may have lower endothelial protective function. We aimed to investigate whether type 2 diabetes impairs HDL endothelium protective functions in people with otherwise normal lipid profile. In a case-control study (n = 41 per group) nested in the Cooper Center Longitudinal Study we tested the ability of HDL to protect endothelium by stimulating endothelial nitric oxide synthase activity and suppressing NFκB-mediated inflammatory response in endothelial cells. In parallel we measured HDL protein composition, sphinogosine-1-phosphate and P-selectin. Despite similar levels of plasma HDL-C the HDL in individuals with type 2 diabetes lost almost 40% of its ability to stimulate eNOS activity (P<0.001) and 20% of its ability to suppress TNFα-dependent NFκB-mediated inflammatory response in endothelial cells (P<0.001) compared to non-T2D controls despite similar BMI and lipid profile (HDL-C, LDL-C, TC, TG). Significantly, the ability of HDL to stimulate eNOS activity was negatively associated with plasma levels of P-selectin, an established marker of endothelial dysfunction (r = -0.32, P<0.001). Furthermore, sphingosine-1-phosphate (S1P) levels were decreased in diabetic plasma (P = 0.017) and correlated with HDL-mediated eNOS activation. Collectively, our data suggest that HDL in individuals with type 2 diabetes loses its ability to maintain proper endothelial function independent of HDL-C, perhaps due to loss of S1P, and may contribute to development of diabetic complications.

Physical exercise, particularly aerobic exercise, is documented as providing a low cost regimen to counter well-documented cognitive declines including memory, executive function, visuospatial skills, and processing speed in normally aging adults. Prior aging studies focused largely on the effects of medium to long term (>6 months) exercise training; however, the shorter term effects have not been studied. In the present study, we examined changes in brain blood flow, cognition, and fitness in 37 cognitively healthy sedentary adults (57-75 years of age) who were randomized into physical training or a wait-list control group. The physical training group received supervised aerobic exercise for 3 sessions per week 1 h each for 12 weeks. Participants' cognitive, cardiovascular fitness and resting cerebral blood flow (CBF) were assessed at baseline (T1), mid (T2), and post-training (T3). We found higher resting CBF in the anterior cingulate region in the physical training group as compared to the control group from T1 to T3. Cognitive gains were manifested in the exercise group's improved immediate and delayed memory performance from T1 to T3 which also showed a significant positive association with increases in both left and right hippocampal CBF identified earlier in the time course at T2. Additionally, the two cardiovascular parameters, VO2 max and rating of perceived exertion (RPE) showed gains, compared to the control group. These data suggest that even shorter term aerobic exercise can facilitate neuroplasticity to reduce both the biological and cognitive consequences of aging to benefit brain health in sedentary adults.

BackgroundHigh triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) impart risk for heart disease. This study examines the relationships of TG/HDL-C ratio to mortality from all causes, coronary heart disease (CHD), or cardiovascular disease (CVD).Subjects and MethodsSurvival analysis was done in 39,447 men grouped by TG/HDL-C ratio cut point of 3.5 and for metabolic syndrome. National Death Index International Classification of Diseases (ICD-9 and ICD-10) codes were used for CVD and CHD deaths occurring from 1970 to 2008. Incidence of type 2 diabetes mellitus (DM) according to ratio was estimated in 22,215 men. Triglyceride/HDL-C ratio and cross-product of TG and fasting blood glucose (TyG index) were used in analysis.ResultsMen were followed up for 581,194 person-years. Triglyceride/HDL-C ratio predicted CHD, CVD, and all-cause mortality after adjustment for established risk factors and non–HDL-C. Mortality rates were higher in individuals with a high ratio than in those with a low ratio. Fifty-five percent of men had metabolic syndrome that was also predictive of CHD, CVD, and all-cause mortality. Annual incidence of DM was 2 times higher in men with high TG/HDL-C ratio than in those with a low ratio. Individuals with high TG/HDL-C ratio had a higher incidence of DM than those with a low ratio. The TyG index was not equally predictive of causes of mortality to TG/HDL-C, but both were equally predictive of diabetes incidence.ConclusionsTriglyceride/HDL-C ratio predicts CHD and CVD mortality as well as or better than do metabolic syndrome in men. Also, a high ratio predisposes to DM. The TyG index does not predict CHD, CVD, or all-cause mortality equally well, but like TG/HDL-C ratio, it predicts DM incidence.

Background The purpose of this study was to: 1) examine the maintenance of Physical Education and physical activity during the distance learning time, 2) determine the resources educators are utilizing to deliver PE curricula, and 3) understand the challenges experienced by educators during distance learning. Methods A survey was sent to a cohort of school-based fitness assessment software users. Respondents were largely school-based individuals including PE teachers ( n  = 1789), school ( n  = 62) and district administrators ( n  = 64), nurses ( n  = 3), and “other” ( n  = 522). Results Of 2440 respondents, most were from a city or suburb (69.7%), elementary or middle school (72.3%), and had Title 1 status (60.4%), an indicator of low socioeconomic status. Most campuses were closed during the COVID-19 pandemic (97.8%). Of the schools closed during the pandemic, only 2.8% had no prior PE requirements and that increased to 21% during the pandemic. In schools that remained open during the pandemic, 7.7% had no prior PE requirements and this increased to 60.5%. Importantly, 79% of respondents reported that students were either “significantly less” or “somewhat less” physically active during the closure. For closed schools, the most frequently cited challenges included “student access to online learning“, “teacher/student communication” and “teacher remote work arrangements”. For open schools, the most commonly reported challenges included “social distancing”, “access to gymnasium/equipment”, and “concern for personal health and wellbeing”. Conclusion The COVID-19 pandemic has caused important reductions in PE requirements and time engaged in physical activity. Challenges experienced by teachers were identified for closed and open schools.

To investigate the association between serum vitamin D levels and depression in a large database of patients from the Cooper Clinic. We conducted a cross-sectional study of 12,594 participants seen at the Cooper Clinic from November 27, 2006, to October 4, 2010. Serum 25-hydroxyvitamin D [25(OH)D] was analyzed, and depression was defined as a Center for Epidemiologic Studies Depression Scale (CES-D) score of 10 or more. Those with and those without a history of depression represented 2 distinct populations with respect to CES-D scores; accordingly, they were analyzed separately. In the total sample, higher vitamin D levels were associated with a significantly decreased risk [odds ratio, 0.92 (95% confidence interval, 0.87-0.97)] of current depression based on CES-D scores. The finding was stronger in those with a prior history of depression [odds ratio, 0.90 (95% confidence interval, 0.82-0.98)] and not significant in those without a history of depression [odds ratio, 0.95 (95% confidence interval, 0.89-1.02)]. We found that low vitamin D levels are associated with depressive symptoms, especially in persons with a history of depression. These findings suggest that primary care patients with a history of depression may be an important target for assessment of vitamin D levels.

Background Schools are recommended to use a whole-of-school (WOS) approach to promote physical activity opportunities before, during, and after school. Yet, the barriers and facilitators to implementing a WOS approach successfully are not well understood. The R = MC 2 heuristic, which defines readiness for implementation as a combination of an organization’s motivation and capacity to implement, can enhance our understanding of implementation in the school setting. This study examines associations between constructs from the R = MC 2 heuristic and schools’ implementation of a WOS approach. Methods We conducted a secondary analysis of cross-sectional data from U.S. elementary schools participating in the NFL PLAY60 FitnessGram Project during the 2022–23 school year. From surveys administered to school staff, we created a WOS index (range = 0–12) comprising six physical activity practices: physical education, recess, before and after-school programs, classroom-based approaches, and active transport. We also assessed how six constructs from the R = MC 2 heuristic (i.e., culture, implementation climate, leadership, priority, resources utilization, resource availability) impact physical activity implementation using a series of questions measured on a 5-point Likert scale. We used linear regression models to determine associations between R = MC 2 constructs (independent variables) and WOS index scores (dependent variable), controlling for school-level characteristics (student enrollment, percentage of race/ethnicity and economically disadvantaged students served) and state-level clustering. Results The analytic sample consisted of 132 schools across 18 states. On average, school staff rated leadership (mean = 4.1, range = 1.5–5) and organizational culture (mean = 4.0, range = 2.25–5) the highest. The mean WOS index score was 6.1. Partially adjusted models indicated significant positive associations between each R = MC 2 construct and WOS index scores. Fully adjusted regression models revealed priority ( b  = 0.88; p  = 0.010; 95% CI = 0.19–1.56) and implementation climate ( b  = 0.69; p  = 0.047; 95% CI = 0.07–1.32) were positively and significantly associated with WOS index scores. Conclusions Our study provides insights into key implementation constructs associated with providing school-based physical activity opportunities. These findings can support the development of resources and implementation strategies which, in turn, can help schools address implementation-related disparities. This will help schools improve the quality and accessibility of opportunities for physical activity provided to students across the United States.

Background Identifying lifestyle factors that independently or jointly lower dementia risk is a public health priority given the limited treatment options available to patients. In this cohort study, we examined the associations between Mediterranean or Dietary Approaches to Stop Hypertension (DASH) diet adherence and cardiorespiratory fitness (CRF) with later-life dementia, and assessed whether the associations between dietary pattern and dementia are modified by CRF. Methods Data are from 9,095 adults seeking preventive care at the Cooper Clinic (1987–1999) who completed a 3-day dietary record and a maximal exercise test. Alzheimer’s disease and related disorders or senile dementia (i.e., all-cause dementia) was identified from Medicare administrative claims (1999–2019). Illness-death models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between Mediterranean or DASH diet adherence (primary exposure), CRF (secondary exposure), and all-cause dementia, adjusted for demographic and clinical factors. An interaction term was included between diet score and CRF to assess effect modification by CRF. Results The mean age at baseline was 50.6 (standard deviation [SD]: 8.4) years, and a majority of the study sample were men (77.5%) and White (96.4%). 1449 cases of all-cause dementia were identified over a mean follow-up of 9.2 (SD: 5.8) years. Neither Mediterranean nor DASH diet adherence was associated with dementia risk in fully adjusted models (HR per SD of Mediterranean diet score: 1.00, 95% CI: 0.94, 1.05; HR per SD of DASH diet score: 1.02, 95% CI: 0.96, 1.08). However, participants with higher CRF had a decreased hazard of dementia (HR, per metabolic equivalent of task [MET] increase, Mediterranean model: 0.95, 95% CI: 0.92, 0.98; HR, per MET increase, DASH model: 0.96, 95% CI: 0.92, 0.97). No effect modification by CRF was observed in the association between diet and dementia. Conclusions In this sample of apparently healthy middle-aged adults seeking preventive care, higher CRF at midlife was associated with a lower risk of all-cause dementia, though adherence to a Mediterranean or DASH diet was not, and CRF did not modify the diet-dementia association. CRF should be emphasized in multimodal interventions for dementia prevention and investigated among diverse samples.

Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56-75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health.

ObjectiveThis study aimed to examine the association of midlife fitness and body mass index (BMI) with incident dementia later in life.Design and participantsA cohort study of 6428 individuals (mean age 50.9±7.6 years) from the Cooper Center Longitudinal Study.MeasuresCardiorespiratory fitness and BMI were assessed twice (1970–1999) during visits to the Cooper Clinic, a preventive medicine clinic in Dallas, Texas. These measures were examined as continuous and categorical variables. As continuous variables, fitness and BMI were examined at baseline (averaged of two examinations) and as absolute change between exams (mean time 2.1±1.8 years). Variables were categorised: unfit versus fit and normal versus overweight/obese. Medicare claims data were used to obtain all-cause dementia incidence (1999–2009). Mean follow-up between midlife examinations and Medicare surveillance was 15.7 ((SD=6.2) years. Multivariable models were used to assess the associations between fitness, BMI and dementia.ResultsDuring 40 773 person years of Medicare surveillance, 632 cases of dementia were identified. After controlling for BMI and covariates, each 1-metabolic equivalent increment in fitness was associated with 5% lower (HR 0.95; 95% CI 0.90 to 0.99) dementia risk. In comparison, after controlling for fitness and covariates, each 1 kg/m2 increment in BMI was associated with a 3.0% (HR 1.03; 95% CI 1.00 to 1.07) higher risk for dementia, yet without significance (p=0.051). Similar findings were observed when the exposures were categorised. Changes in fitness and BMI between examinations were not related to dementia. Jointly, participants who were unfit and overweight/obese had the highest (HR 2.28 95% CI 1.57 to 3.32) dementia risk compared with their fit and normal weight counterparts.ConclusionLower midlife fitness is a risk marker for dementia irrespective of weight status. Being unfit coupled with overweight/obese status might increase one’s risk for dementia even further.

The deleterious health effects of prolonged sitting and physical inactivity are well-established, yet these behaviors are pervasive in modern culture. To inform interventions aimed at reducing sedentary behavior and increasing lifestyle activity, this study examined psychological and behavioral economic factors that may be associated with these behaviors. This cross-sectional study was conducted among 4072 adults in Israel. Participants completed a survey pertaining to lifestyle behaviors and economic preferences using an online platform in September 2020. The psychological and behavioral economic factors of interest were patience, self-control, risk-taking, grit, and general self-efficacy. Sedentary behavior and lifestyle activity (e.g., time spent moving about) was assessed using the Rapid Assessment Disuse Index (RADI) tool (higher score indicative of more sitting and less activity). Multivariable linear and logistic regression analyses examined the association between psychological and behavioral economic factors and RADI score. Among 4072 participants, those who were impatient (vs. patient, β: −1.13; 95% CI: −1.89, −0.38) had higher grit (β: −1.25, 95% CI: −1.73, −0.77), and those who were more risk-seeking (β: −0.23; 95% CI: −0.33, −0.13) had lower RADI scores (i.e., less sedentary, more active). Significant associations for grit and risk-taking were also observed when the RADI score was dichotomized, such that individuals who had higher grit or were more risk-seeking were more likely to be non-sedentary/active. No significant associations were observed for self-control or general self-efficacy. Higher grit and more risk-seeking were associated with a decreased propensity for sedentary behaviors and inactivity; these factors may provide targets for interventions aimed at reducing sedentary behavior and increasing lifestyle activity.