Is cardiorespiratory fitness associated with cognitive outcomes in mid-adulthood? Findings from the 1958 British birth cohort.

Identifying causal factors to intervene on to delay age-related declines in cognitive function is urgently needed. We examined associations between non-exercise testing cardiorespiratory fitness (NETCRF; estimated using sex, age, body mass index, resting heart rate, and physical activity) at 45 years and cognitive function outcomes (immediate and delayed verbal memory; verbal fluency; visual processing speed) at 50 years in 8130 participants from the 1958 British birth cohort. In unadjusted models, higher NETCRF was associated with better cognitive function across all outcomes. When adjusted for confounding factors, associations disappeared. In this cohort, associations between 45 years NETCRF and 50 years cognitive function likely result from confounding factors.

Obesity in early adulthood and physical functioning in mid-life: Investigating the mediating role of c-reactive protein.

INTRODUCTION: Obesity in adulthood is associated with reduced physical functioning (PF) at older ages. However, mechanisms underpinning this association are not well understood. We investigated whether and the extent to which C-reactive protein (CRP) mediates the association between early-adult obesity and mid-life PF. METHODS: We used data from 8495 participants in the 1958 British birth cohort study. Body mass index (BMI), CRP and PF were measured at 33, 45 and 50y, respectively. Poor PF was defined as the lowest (sex-specific) 10% on the Short-form 36 Physical Functioning subscale. We accounted for prospectively measured confounders in early-life (e.g., social class at birth) and in mid-adulthood (e.g., 42y comorbidities). We decomposed the total effect of early-adult obesity on mid-life PF into direct and indirect (via CRP) effects, by employing a mediation analysis based on parametric g-computation. RESULTS: The estimated total effect of obesity at 33y on poor PF at 50y, expressed as an odds ratio (OR), was 2.41 (95% CI: 1.89, 3.08). The direct effect of obesity on poor PF (i.e., not operating via CRP), was 1.97 (95% CI: 1.51, 2.56), with an indirect effect of 1.23 (95% CI: 1.10, 1.37). As such, the proportion of the total effect which was mediated by the effect of obesity on CRP at 45y, was 23.27% (95% CI: 8.64%, 37.90%). CONCLUSION: Obesity in early-adulthood was associated with over twice the odds of poor PF in mid-life, with approximately 23% of the obesity effect operating via a downstream effect on CRP. As current younger generations are likely to spend greater proportions of their life course in older age and with obesity, both of which are associated with poor PF, there is an urgent need to identify mechanisms, and thus potential modifiable intermediaries, linking obesity to poor PF.

Parental obesity and risk factors for cardiovascular disease among their offspring in mid-life: findings from the 1958 British Birth Cohort Study.

BACKGROUND: Few studies have investigated whether parental adiposity is associated with offspring cardiovascular health or the underlying pathways. Studying these associations may help to illuminate the paradox of increasing prevalence of obesity and declining trends in cardiovascular disease (CVD) mortality, which may be partially explained by beneficial adaptations to an obesogenic environment among people exposed to such environments from younger ages. OBJECTIVE: To investigate associations between parental body mass index (BMI) and risk factors for CVD among their offspring in mid-life and to test whether associations of offspring BMI with CVD risk factors were modified by parental BMI. METHODS: Data from parents and offspring in the 1958 British birth cohort were used (N=9328). Parental BMI was assessed when offspring were aged 11 years; offspring BMI, waist circumference and CVD risk factors (lipid levels, blood pressure, glycosylated haemoglobin (HbA1c) and inflammatory and haemostatic markers) were measured at 44-45 years. RESULTS: Higher parental BMI was associated with less favourable levels of offspring risk factors for CVD. Most associations were maintained after adjustment for offspring lifestyle and socioeconomic factors but were largely abolished or reversed after adjustment for offspring adiposity. For some CVD risk factors, there was evidence of effect modification; the association between higher BMI and an adverse lipid profile among offspring was weaker if maternal BMI had been higher. Conversely, offspring BMI was more strongly associated with HbA1c if parental BMI had been higher. CONCLUSIONS: Intergenerational influences may be important in conferring the effect of high BMI on CVD risk among offspring.

Comparison of innovator and generic salbutamol inhalers: a double-blind randomized study of efficacy and tolerance.

Preliminary feedback from physicians and pharmacists in Trinidad suggests that generic pressurized metered dose inhalers (pMDIs) of salbutamol are not as effective as Ventolin and that they have poor patient acceptance. This study was designed to compare the clinical efficacy and tolerance of two generic inhalers available in Trinidad (Asthalin and Salomol) with Ventolin in stable asthmatics. Twenty-one physician-diagnosed stable asthmatics were administered the inhalers in a Latin-square randomized double-blind study with 80% power to identify differences in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) before and 0.25, 0.5, 1, 2 and 3 h after inhalation. Pulse and blood pressure were recorded at similar time points. Seventeen patients completed the study. Within 15 min basal respiratory function significantly increased following inhalation from all three inhalers with a gradual decline over the observation period. Asthalin produced the highest changes in FEV1, PEFR and the longest duration of effect (p < 0.001). Respiratory function tests did not differ between Ventolin and Salomol. Pulse was not affected by treatments and mean arterial blood pressure fell after Asthalin. Ventolin was not superior to the generic pMDIs in improving pulmonary function. Fifteen patents reported cough sensation after Asthalin. Throat irritation and cough sensation after inhaling Asthalin may negate patient compliance. We suggest that optimizing particle size and cascade impact in the Asthalin inhaler may improve patient tolerance and acceptance with enhanced treatment outcome with cost-efficacy.