Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA): health assessment protocol, participant profile and patterns of participation.

BACKGROUND: The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) is a prospective, longitudinal study of a representative cohort of older adults living in Northern Ireland, United Kingdom. Its aim is to explore the social, behavioural, economic and biological factors of ageing and how these factors change as people age. The study has been designed to maximize comparability with other international studies of ageing thereby facilitating cross-country comparisons. This paper provides an overview of the design and methodology of the health assessment which was carried out as part of Wave 1. METHODS: Three thousand, six hundred and fifty five community dwelling adults, aged 50 years and over participated in the health assessment as part of Wave 1 of NICOLA. The health assessment included a battery of measurements across various domains that addressed key indicators of ageing namely: physical function, vision and hearing, cognitive function, and cardiovascular health. This manuscript describes the scientific rationale for the choice of assessments, provides an overview of the core objective measures carried out in the health assessment and describes the differences in characteristics of participants who took part in the health assessment compared to those who did not take part. RESULTS: The manuscript highlights the importance of incorporating objective measures of health in population based studies as a means of complementing subjective measures and as a way to advance our understanding of the ageing process. The findings contextualize NICOLA as a data resource within Dementias Platform UK (DPUK), the Gateway to Global Ageing (G2G) and other existing networks of population based longitudinal studies of ageing. CONCLUSION: This manuscript can help inform design considerations for other population based studies of ageing and facilitate cross-country comparative analysis of key life-course factors affecting healthy ageing such as educational attainment, diet, the accumulation of chronic conditions (including Alzheimer's disease, dementia and cardiovascular disease) as well as welfare and retirement policies.

A peer support dietary change intervention for encouraging adoption and maintenance of the Mediterranean diet in a non-Mediterranean population (TEAM-MED): lessons learned and suggested improvements.

Peer support interventions for dietary change may offer cost-effective alternatives to interventions led by health professionals. This process evaluation of a trial to encourage the adoption and maintenance of a Mediterranean diet in a Northern European population at high CVD risk (TEAM-MED) aimed to investigate the feasibility of implementing a group-based peer support intervention for dietary change, positive elements of the intervention and aspects that could be improved. Data on training and support for the peer supporters; intervention fidelity and acceptability; acceptability of data collection processes for the trial and reasons for withdrawal from the trial were considered. Data were collected from observations, questionnaires and interviews, with both peer supporters and trial participants. Peer supporters were recruited and trained to result in successful implementation of the intervention; all intended sessions were run, with the majority of elements included. Peer supporters were complimentary of the training, and positive comments from participants centred around the peer supporters, the intervention materials and the supportive nature of the group sessions. Attendance at the group sessions, however, waned over the intervention, with suggested effects on intervention engagement, enthusiasm and group cohesion. Reduced attendance was reportedly a result of meeting (in)frequency and organisational concerns, but increased social activities and group-based activities may also increase engagement, group cohesion and attendance. The peer support intervention was successfully implemented and tested, but improvements can be suggested and may enhance the successful nature of these types of interventions. Some consideration of personal preferences may also improve outcomes.

The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

Assessment of the Vitreomacular Interface Using High-Resolution OCT in a Population-Based Cohort Study of Older Adults.

PURPOSE: To describe the prevalence of vitreomacular interface (VMI) features and their associated risk factors in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) Study. DESIGN: Cross-sectional population-based study. PARTICIPANTS: Noninstitutionalized Northern Irish adults 40 years of age or older. METHODS: Using geographic stratification, a representative sample of people in Northern Ireland was invited to participate in the NICOLA Study. SD OCT images of participants were graded for vitreomacular traction (VMT), macular hole (MH), and epiretinal membrane (ERM) according to the International Vitreomacular Traction Study Group. A subsample was graded in more detail to estimate the prevalence of VMA and VMA area detailing size and location of VMA. Descriptive analysis and risk factors for each VMI feature were determined using generalized estimating equations. Results were standardized to the Northern Ireland population census (2011). MAIN OUTCOME MEASURES: Cohort profile, standardized prevalence, and risk factor associations of each VMI feature. RESULTS: Three thousand three hundred fifty-one NICOLA participants had gradable SD OCT images available for at least 1 eye. The prevalence of VMT was 0.5% (CI, 0.31%-0.70%), that for MH was 0.3% (CI, 0.23%-0.52%), and that for ERM was 7.6% (CI, 7.0%-8.3%). A detailed VMA analysis was performed on a subsample consisting of the first 1481 participants. The prevalence of VMA was 22.6% (CI, 21.1-24.2), and VMA area ranged from 0.25 to 42.7 mm2 (mean, 12.53 mm2; standard deviation, 6.90 mm2). In multivariate analyses, increased age was associated with an increased odds ratio (OR) of VMT, MH, and ERM. VMA area was positively associated with younger age and normal blood pressure. ERM and MH were present more often in more myopic eyes, associated with an increase in levels of high-density lipoprotein (HDL) cholesterol and triglycerides. CONCLUSIONS: The epidemiologic characteristics of VMI features indicated that VMI interactions throughout life are age dependent. Vitreous separation reduced to a greater extent in the horizontal meridians compared with the vertical, differing from previous studies. Future longitudinal studies of the evolution of these VMI changes over time would be of great interest.

Baseline Assessment of 25-Hydroxyvitamin D Assay Performance: A Vitamin D Standardization Program (VDSP) Interlaboratory Comparison Study.

The Vitamin D Standardization Program (VDSP) coordinated an interlaboratory study to assess the comparability of measurements of total 25-hydroxyvitamin D [25(OH)D] in human serum, which is the primary marker of vitamin D status. A set of 50 individual donor samples were analyzed by 15 different laboratories representing national nutrition surveys, assay manufacturers, and clinical and/or research laboratories to provide results for total 25(OH)D using both immunoassays (IAs) and LC tandem MS (MS/MS). The results were evaluated relative to bias compared with the target values assigned based on a combination of measurements at Ghent University (Belgium) and the U.S. National Institute of Standards and Technology using reference measurement procedures for the determination of 25(OH)D2 and 25(OH)D3. CV and mean bias for each laboratory and assay platform were assessed and compared with previously established VDSP performance criteria, namely CV ≤ 10% and mean bias ≤ 5%. Nearly all LC-MS/MS results achieved VDSP criteria, whereas only 50% of IAs met the criterion for a ≤10% CV and only three of eight IAs achieved the ≤5% bias. These results establish a benchmark for the evaluation of 25(OH)D assay performance and standardization activities in the future.

Baseline Assessment of 25-Hydroxyvitamin D Reference Material and Proficiency Testing/External Quality Assurance Material Commutability: A Vitamin D Standardization Program Study.

The Vitamin D Standardization Program (VDSP) coordinated a study in 2012 to assess the commutability of reference materials and proficiency testing/external quality assurance materials for total 25-hydroxyvitamin D [25(OH)D] in human serum, the primary indicator of vitamin D status. A set of 50 single-donor serum samples as well as 17 reference and proficiency testing/external quality assessment materials were analyzed by participating laboratories that used either immunoassay or LC-MS methods for total 25(OH)D. The commutability test materials included National Institute of Standards and Technology Standard Reference Material 972a Vitamin D Metabolites in Human Serum as well as materials from the College of American Pathologists and the Vitamin D External Quality Assessment Scheme. Study protocols and data analysis procedures were in accordance with Clinical and Laboratory Standards Institute guidelines. The majority of the test materials were found to be commutable with the methods used in this commutability study. These results provide guidance for laboratories needing to choose appropriate reference materials and select proficiency or external quality assessment programs and will serve as a foundation for additional VDSP studies.

Plasma Lutein and Zeaxanthin Are Associated With Better Cognitive Function Across Multiple Domains in a Large Population-Based Sample of Older Adults: Findings from The Irish Longitudinal Study on Aging.

BACKGROUND: Low blood serum or plasma concentrations of the xanthophyll carotenoids lutein and zeaxanthin have been implicated in poorer cognitive health in older adults. However, equivocal results from smaller studies and clinical trials highlight the need for large population-based studies with comprehensive measures of cognitive function and adjustment for multiple confounders to examine such associations in more depth. METHODS: In the current study, we investigated the association between plasma lutein and zeaxanthin and domain-specific cognitive performance in 4,076 community-dwelling adults aged 50 years or older from The Irish Longitudinal Study on Ageing. Mixed-effects models were fitted with adjustment for demographic and socioeconomic factors, health conditions, and health behaviors. RESULTS: Higher plasma lutein and zeaxanthin were independently associated with better composite scores across the domains of global cognition, memory, and executive function. We also found evidence that higher plasma zeaxanthin, but not lutein, was associated with better processing speed. These associations were consistent across domains. CONCLUSIONS: Further investigation of the prognostic value of carotenoid concentrations, and their changes, on cognition in similar population-based samples longitudinally is warranted.

Combining vitamin C and carotenoid biomarkers better predicts fruit and vegetable intake than individual biomarkers in dietary intervention studies.

PURPOSE: The aim of this study was to determine whether combining potential biomarkers of fruit and vegetables is better at predicting FV intake within FV intervention studies than single biomarkers. DESIGN: Data from a tightly controlled randomised FV intervention study (BIOFAV; all food provided and two meals/day on weekdays consumed under supervision) were used. A total of 30 participants were randomised to either 2, 5 or 8 portions FV/day for 4 weeks, and blood samples were collected at baseline and 4 weeks for plasma vitamin C and serum carotenoid analysis. The combined biomarker approach was also tested in three further FV intervention studies conducted by the same research team, with less strict dietary control (FV provided and no supervised meals). RESULTS: The combined model containing all carotenoids and vitamin C was a better fit than either the vitamin C only (P < 0.001) model or the lutein only (P = 0.006) model in the BIOFAV study. The C-statistic was slightly lower in the lutein only model (0.85) and in the model based upon factor analysis (0.88), and much lower in the vitamin C model (0.68) compared with the full model (0.95). Results for the other studies were similar, although the differences between the models were less marked. CONCLUSIONS: Although there was some variation between studies, which may relate to the level of dietary control or participant characteristics, a combined biomarker approach to assess overall FV consumption may more accurately predict FV intake within intervention studies than the use of a single biomarker. The generalisability of these findings to other populations and study designs remains to be tested. Clinical trial Registration Number NCT01591057 ( www.clinicaltrials.gov ).

The assessment of vascular function during dietary intervention trials in human subjects.

The potential to reduce cardiovascular morbidity through dietary modification remains an area of intense clinical and scientific interest. Any putatively beneficial intervention should be tested within a randomised controlled trial which records appropriate endpoints, ideally incident CVD and death. However, the large sample sizes required for these endpoints and associated high costs mean that the majority of dietary intervention research is conducted over short periods among either healthy volunteers or those at only slightly increased risk, with investigators using a diverse range of surrogate measures to estimate arterial health in these studies. The present review identifies commonly employed techniques, discusses the relative merits of each and highlights emerging approaches.

Resting energy expenditure in non-ventilated, non-sedated patients recovering from serious traumatic brain injury: comparison of prediction equations with indirect calorimetry values.

BACKGROUND & AIMS: Little is known about energy requirements in brain injured (TBI) patients, despite evidence suggesting adequate nutritional support can improve clinical outcomes. The study aim was to compare predicted energy requirements with measured resting energy expenditure (REE) values, in patients recovering from TBI. METHODS: Indirect calorimetry (IC) was used to measure REE in 45 patients with TBI. Predicted energy requirements were determined using FAO/WHO/UNU and Harris-Benedict (HB) equations. Bland-Altman and regression analysis were used for analysis. RESULTS: One-hundred and sixty-seven successful measurements were recorded in patients with TBI. At an individual level, both equations predicted REE poorly. The mean of the differences of standardised areas of measured REE and FAO/WHO/UNU was near zero (-9 kcal) but the variation in both directions was substantial (range -591 to +573 kcal). Similarly, the differences of areas of measured REE and HB demonstrated a mean of 1.9 kcal and range -568 to +571 kcal. Glasgow coma score, patient status, weight and body temperature were significant predictors of measured REE (p<0.001; R(2)=0.47). CONCLUSIONS: Clinical equations are poor predictors of measured REE in patients with TBI. The variability in REE is substantial. Clinicians should be aware of the limitations of prediction equations when estimating energy requirements in TBI patients.

A clinical, renal and immunological assessment of surface modifying additive treated (SMART) cardiopulmonary bypass circuits.

Biocompatible cardiopulmonary bypass (CPB) circuits aim to reduce contact activation and its physiological consequences. We investigated the hypothesis that use of Surface Modifying Additive (SMA)-treated circuits (Sorin Group Ltd) compared with non-SMA circuits would be associated with preservation of blood pressure during CPB and modulation of perioperative subclinical renal function (urinary alpha-1-microglobulin (alpha-1-m)) and plasma and urinary cytokine changes. In a study of low-risk CABG patients (n=40), randomized to SMA (n=20) versus non-SMA circuits (n=20), we found better preserved blood pressure at CPB initiation in SMA patients (p <0.05), particularly in ACE-inhibited SMA patients (n =11) versus ACE-inhibited non-SMA patients (n =10) (p <0.05). Plasma anti-inflammatory IL-10, as well as urinary alpha-1-m, were elevated 48 hours postoperatively (p <0.05). SMA patients also had lower blood loss (p <0.05). SMA circuits have some clinical benefit, especially in ACE-inhibited patients.

Rapid isolation of VLDL subfractions: assessment of composition and susceptibility to copper-mediated oxidation.

VLDLs, synthesized and released by the liver, are a heterogeneous group of particles of varying composition and metabolic fates. A method is described for the rapid isolation of VLDL into four subfractions (A-D) and assessment of their susceptibility to oxidation. The total isolation procedure required less than 3.5 h, and was achieved by gradient ultracentrifugation. Each subfraction was assessed for triglyceride, cholesterol, and apolipoprotein B (apoB) composition and for the presence of contaminants such as albumin and urate. The oxidation potential, in the presence of copper ions, of each subfraction was also assessed. This rapid procedure produced VLDL fractions analogous to those produced by a previously reported but more prolonged isolation method. Comparison of the two procedures demonstrated that lipid and apoB were similar, while the rapid procedure produced subfractions void of albumin and urate contamination and lower in preformed hydroperoxides. Compositional changes were found between the subfractions: as the subfractions became smaller and more dense (A-->D), there was a decrease in the ratio of triglyceride to apoB and an increase in the ratio of cholesterol to apoB, also arachidonic acid was increased in subfraction D compared with subfractions A, B, and C. The smaller subfractions were more susceptible to oxidation, a trend similar to that reported previously for the oxidation of LDL subfractions.