Association between Residential Greenness and Allostatic Load: A Cohort Study.

The association between residential greenness and allostatic load (AL), a marker of composite physiological burden and predictor of chronic disease, remains understudied. This study comprised 212,600 UK Biobank participants recruited over 2007 and 2010 at the baseline. Residential greenness was modeled as the normalized difference vegetation index (NDVI) from high spatial resolution (0.50 m) color infrared imagery and measured within a 0.5 km radial catchment. AL was measured as a composite index from 13 biomarkers comprising three physiological systems (metabolic, cardiovascular, and inflammatory systems) and two organ systems (liver and kidney). Multilevel mixed-effects generalized linear models with a random intercept for UK Biobank assessment centers were employed to examine the association between residential greenness and AL. Each interquartile range (IQR = 0.24) increment in NDVI greenness was associated with lower AL (beta (ß) = -0.28, 95% confidence interval (CI) = -0.55, -0.01). Consistently, relative to the lowest NDVI greenness quintile, participants in the highest quintile had lower AL (ß = -0.64, 95% CI = -1.02, -0.26). The proportion of the association between greenness and AL mediated by the physical activity was 3.2%. In conclusion, residential greenness was protectively associated with AL, a composite marker of wear and tear and general health.

Dementias Platform UK: Bringing genetics into life.

INTRODUCTION: The Dementias Platform UK (DPUK) Data Portal is a data repository bringing together a wide range of cohorts. Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and an overlapping genetic component that is poorly understood. The DPUK collection of independent cohorts can facilitate research in neurodegeneration by combining their genetic and phenotypic data. METHODS: For genetic data processing, pipelines were generated to perform quality control analysis, genetic imputation, and polygenic risk score (PRS) derivation with six genome-wide association studies of neurodegenerative diseases. Pipelines were applied to five cohorts. DISCUSSION: The data processing pipelines, research-ready imputed genetic data, and PRS scores are now available on the DPUK platform and can be accessed upon request though the DPUK application process. Harmonizing genome-wide data for multiple datasets increases scientific opportunity and allows the wider research community to access and process data at scale and pace.

Associations of Urban Built Environment with Cardiovascular Risks and Mortality: a Systematic Review.

With rapid urbanization, built environment has emerged as a set of modifiable factors of cardiovascular disease (CVD) risks. We conducted a systematic review to synthesize evidence on the associations of attributes of urban built environment (e.g. residential density, land use mix, greenness and walkability) with cardiovascular risk factors (e.g. hypertension and arterial stiffness) and major CVD events including mortality. A total of 63 studies, including 31 of cross-sectional design and 32 of longitudinal design conducted across 21 geographical locations and published between 2012 and 2023 were extracted for review. Overall, we report moderately consistent evidence of protective associations of greenness with cardiovascular risks and major CVD events (cross-sectional studies: 12 of 15 on hypertension/blood pressure (BP) and 2 of 3 on arterial stiffness; and longitudinal studies: 6 of 8 on hypertension/BP, 7 of 8 on CVD mortality, 3 of 3 on ischemic heart disease mortality and 5 of 8 studies on stroke hospitalization or mortality reporting significant inverse associations). Consistently, walkability was associated with lower risks of hypertension, arterial stiffness and major CVD events (cross-sectional studies: 11 of 12 on hypertension/BP and 1 of 1 on arterial stiffness; and longitudinal studies: 3 of 6 on hypertension/BP and 1 of 2 studies on CVD events being protective). Sixty-seven percent of the studies were rated as "probably high" risk of confounding bias because of inability to adjust for underlying comorbidities/family history of diseases in their statistical models. Forty-six percent and 14% of the studies were rated as "probably high" risk of bias for exposure and outcome measurements, respectively. Future studies with robust design will further help elucidate the linkages between urban built environment and cardiovascular health, thereby informing planning policies for creating healthy cities.

Research-ready data: the C-Surv data model.

Research-ready data (data curated to a defined standard) increase scientific opportunity and rigour by integrating the data environment. The development of research platforms has highlighted the value of research-ready data, particularly for multi-cohort analyses. Following stakeholder consultation, a standard data model (C-Surv) optimised for data discovery, was developed using data from 5 population and clinical cohort studies. The model uses a four-tier nested structure based on 18 data themes selected according to user behaviour or technology. Standard variable naming conventions are applied to uniquely identify variables within the context of longitudinal studies. The data model was used to develop a harmonised dataset for 11 cohorts. This dataset populated the Cohort Explorer data discovery tool for assessing the feasibility of an analysis prior to making a data access request. Data preparation times were compared between cohort specific data models and C-Surv.It was concluded that adopting a common data model as a data standard for the discovery and analysis of research cohort data offers multiple benefits.

Evaluating the harmonisation potential of diverse cohort datasets.

Data discovery, the ability to find datasets relevant to an analysis, increases scientific opportunity, improves rigour and accelerates activity. Rapid growth in the depth, breadth, quantity and availability of data provides unprecedented opportunities and challenges for data discovery. A potential tool for increasing the efficiency of data discovery, particularly across multiple datasets is data harmonisation.A set of 124 variables, identified as being of broad interest to neurodegeneration, were harmonised using the C-Surv data model. Harmonisation strategies used were simple calibration, algorithmic transformation and standardisation to the Z-distribution. Widely used data conventions, optimised for inclusiveness rather than aetiological precision, were used as harmonisation rules. The harmonisation scheme was applied to data from four diverse population cohorts.Of the 120 variables that were found in the datasets, correspondence between the harmonised data schema and cohort-specific data models was complete or close for 111 (93%). For the remainder, harmonisation was possible with a marginal a loss of granularity.Although harmonisation is not an exact science, sufficient comparability across datasets was achieved to enable data discovery with relatively little loss of informativeness. This provides a basis for further work extending harmonisation to a larger variable list, applying the harmonisation to further datasets, and incentivising the development of data discovery tools.

Neighbourhood residential density, urbanicity and incident dementia and Alzheimer's disease: A 12-year prospective cohort study from the UK Biobank.

INTRODUCTION: An increasing proportion of global population is exposed to urban densification in an aging society. However, little is known of the role of residential density and urbanicity on the risk of developing dementia including Alzheimer's disease. We examined long-term associations between residential density and urbanicity and risks of incident dementia and Alzheimer's disease. METHODS: This prospective cohort study included participants from the UK Biobank who lived at the same residential address, had no self-reported neurological conditions and without dementia at baseline. Residential density was measured as the number of dwelling units within 1-km street neighbourhood of participant's home address. A composite index of urbanicity was developed from neighbourhood-level z-standardized densities of housing, retail, public transport and street centrality. Hazard ratios were derived from Cox proportional hazard models adjusted for known risk factors. RESULTS: The analytic sample included 239,629 participants aged 38-72 years. During a median follow-up of 12.3 years (interquartile range 11.5-13.0 years), 2,176 participants developed dementia and 1,004 Alzheimer's disease. After adjustments for potential risk factors, each 1,000 units/Km2 increment in residential density was associated with higher risks of dementia (hazard ratio [HR]=1.10, 95% confidence interval [CI]: 1.06-1.15) and Alzheimer's disease (HR=1.10, 95% CI: 1.04-1.16). Consistently, categorical models showed that living in neighbourhoods of higher residential density and urbanicity were associated with higher risks of dementia (HR = 1.30, 95% CI: 1.12-1.51 for the highest density quintile compared to the lowest and HR = 1.21, 95% CI: 1.05-1.39 for the highest urbanicity quintile relative to the lowest). The associations were more pronounced in female, age >65 years, and among participants of the low income and those being frail and having shorter leucocyte telomere length (LTL). CONCLUSIONS: Higher residential density and urbanicity was found to be positively associated with elevated risks of dementia and Alzheimer's disease. Optimizing neighbourhood residential density maybe one of the upstream considerations for mitigating against neurodegenerative diseases.

Depression and memory function - evidence from cross-lagged panel models with unit fixed effects in ELSA and HRS.

BACKGROUND: Individuals with depression are often found to perform worse on cognitive tests and to have an increased risk of dementia. The causes and the direction of these associations are however not well understood. We looked at two specific hypotheses, the aetiological risk factor hypothesis and the reverse causality hypothesis. METHOD: We analysed observational data from two cohorts, English Longitudinal Study of Ageing (ELSA) and Health and Retirement Study (HRS), using cross-lagged panel models with unit fixed effects. Each model was run once with depression and repeated with cognition as the dependent variable and the other variable as the main explanatory variable. All models were estimated separately for contemporaneous effects and lagged effects up to 8 years in the past. We contrasted the results with models making the random effects assumption. RESULTS: Evidence from the fixed effects models is mixed. We find no evidence for the reverse causality hypothesis in ELSA and HRS. While there is no evidence for the aetiological risk factors hypothesis in ELSA, results from HRS indicate some effects. CONCLUSION: Our findings suggest that current levels of cognitive function do not influence future levels of depression. Results in HRS provide some evidence that current levels of depressive symptoms influence future cognition.

Amateur Boxing and Dementia: Cognitive Impairment Within the 35-Year Caerphilly Cohort Study.

OBJECTIVE: To examine the long-term effects of amateur boxing in a representative population sample of men. DESIGN: The sample was examined every 5 years for 35 years. Cognition was assessed repeatedly from the third examination. Previous boxing experience and dementia were assessed at the fifth examination, and dementia assessed subsequently through medical records. SETTING AND ASSESSMENT OF RICK FACTORS: The Caerphilly Prospective Study investigates risk factors for a range of chronic diseases of diseases. These include life style and behavior, together with biological factors relevant to vascular disease. PARTICIPANTS: 1123 adult men aged 45 to 59 years at baseline, followed for 35 years. MAIN OUTCOME MEASURES: Cognitive impairment. RESULTS: A report by a subject of having boxed "seriously" when younger was associated with a 2-fold increase in cognitive impairment [odds ratio (OR) = 2.27; 95% confidence intervals = 1.18-4.38]. For amnestic (Alzheimer-like) impairment, this rises to OR = 2.78 (95% confidence limits 1.37-5.65). Having boxed is associated with an "advancement" in the onset of the dementia (4.8 years; 95% confidence limits 0.9-8.8 years). CONCLUSIONS: Amateur boxing is associated with an increased risk and an earlier onset of cognitive impairment and dementia.

Associations of perceived adverse lifetime experiences with brain structure in UK Biobank participants.

BACKGROUND: Adversity experiences (AEs) are major risk factors for psychiatric illness, and ample evidence suggests that adversity-related changes in brain structure enhance this vulnerability. To achieve greater understanding of the underlying biological pathways, increased convergence among findings is needed. Suggested future directions may benefit from the use of large population samples which may contribute to achieving this goal. We addressed mechanistic pathways by investigating the associations between multiple brain phenotypes and retrospectively reported AEs in early life (child adversity) and adulthood (partner abuse) in a large population sample, using a cross-sectional approach. METHODS: The UK Biobank resource was used to access imaging-derived phenotypes (IDPs) from 6,751 participants (aged: M = 62.1, SD = 7.2, range = 45-80), together with selected reports of childhood AEs and adult partner abuse. Principal component analysis was used to reduce the dimensionality of the data prior to multivariate tests. RESULTS: The data showed that participants who reported experiences of childhood emotional abuse ('felt hated by family member as a child') had smaller cerebellar and ventral striatum volumes. This result was also depicted in a random subset of participants; however, we note small effect sizes ( ηp2  < .01), suggestive of modest biological changes. CONCLUSIONS: Using a large population cohort, this study demonstrates the value of big datasets in the study of adversity and using automatically preprocessed neuroimaging phenotypes. While retrospective and cross-sectional characteristics limit interpretation, this study demonstrates that self-perceived adversity reports, however nonspecific, may still expose neural consequences, identifiable with increased statistical power.

Road traffic noise, noise sensitivity, noise annoyance, psychological and physical health and mortality.

BACKGROUND: Both physical and psychological health outcomes have been associated with exposure to environmental noise. Noise sensitivity could have the same moderating effect on physical and psychological health outcomes related to environmental noise exposure as on annoyance but this has been little tested. METHODS: A cohort of 2398 men between 45 and 59 years, the longitudinal Caerphilly Collaborative Heart Disease study, was established in 1984/88 and followed into the mid-1990s. Road traffic noise maps were assessed at baseline. Psychological ill-health was measured in phase 2 in 1984/88, phase 3 (1989/93) and phase 4 (1993/7). Ischaemic heart disease was measured in clinic at baseline and through hospital records and records of deaths during follow up. We examined the longitudinal associations between road traffic noise and ischaemic heart disease morbidity and mortality using Cox Proportional Hazard Models and psychological ill-health using Logistic Regression; we also examined whether noise sensitivity and noise annoyance might moderate these associations. We also tested if noise sensitivity and noise annoyance were longitudinal predictors of ischaemic heart disease morbidity and mortality and psychological ill-health. RESULTS: Road traffic noise was not associated with ischaemic heart disease morbidity or mortality. Neither noise sensitivity nor noise annoyance moderated the effects of road traffic noise on ischaemic heart disease morbidity or mortality. High noise sensitivity was associated with lower ischaemic heart disease mortality risk (HR = 0.74, 95%CI 0.57, 0.97). Road traffic noise was associated with Phase 4 psychological ill-health but only among those exposed to 56-60dBA (fully adjusted OR = 1.82 95%CI 1.07, 3.07). Noise sensitivity moderated the association of road traffic noise exposure with psychological ill-health. High noise sensitivity was associated longitudinally with psychological ill-health at phase 3 (OR = 1.85 95%CI 1.23, 2.78) and phase 4 (OR = 1.65 95%CI 1.09, 2.50). Noise annoyance predicted psychological ill-health at phase 4 (OR = 2.47 95%CI 1.00, 6.13). CONCLUSIONS: Noise sensitivity is a specific predictor of psychological ill-health and may be part of a wider construct of environmental susceptibility. Noise sensitivity may increase the risk of psychological ill-health when exposed to road traffic noise. Noise annoyance may be a mediator of the effects of road traffic noise on psychological ill-health.

Obtaining EQ-5D-5L utilities from the disease specific quality of life Alzheimer's disease scale: development and results from a mapping study.

PURPOSE: The Quality of Life Alzheimer's Disease Scale (QoL-AD) is commonly used to assess disease specific health-related quality of life (HRQoL) as rated by patients and their carers. For cost-effectiveness analyses, utilities based on the EQ-5D are often required. We report a new mapping algorithm to obtain EQ-5D indices when only QoL-AD data are available. METHODS: Different statistical models to estimate utility directly, or responses to individual EQ-5D questions (response mapping) from QoL-AD, were trialled for patient-rated and proxy-rated questionnaires. Model performance was assessed by root mean square error and mean absolute error. RESULTS: The response model using multinomial regression including age and sex, performed best in both the estimation dataset and an independent dataset. CONCLUSIONS: The recommended mapping algorithm allows researchers for the first time to estimate EQ-5D values from QoL-AD data, enabling cost-utility analyses using datasets where the QoL-AD but no utility measures were collected.

Conducting public involvement in dementia research: The contribution of the European Working Group of People with Dementia to the ROADMAP project.

BACKGROUND: Dementia outcomes include memory loss, language impairment, reduced quality of life and personality changes. Research suggests that outcomes selected for dementia clinical trials might not be the most important to people affected. OBJECTIVE: One of the goals of the 'Real world Outcomes across the Alzheimer's Disease spectrum for better care: Multi-modal data Access Platform' (ROADMAP) project was to identify important outcomes from the perspective of people with dementia and their caregivers. We review how ROADMAP's Public Involvement shaped the programme, impacted the research process and gave voice to people affected by dementia. DESIGN: The European Working Group of People with Dementia (EWGPWD) were invited to participate. In-person consultations were held with people with dementia and caregivers, with advance information provided on ROADMAP activities. Constructive criticism of survey content, layout and accessibility was sought, as were views and perspectives on terminology and key concepts around disease progression. RESULTS: The working group provided significant improvements to survey accessibility and acceptability. They promoted better understanding of concepts around disease progression and how researchers might approach measuring and interpreting findings. They effectively expressed difficult concepts through real-world examples. CONCLUSIONS: The role of the EWGPWD in ROADMAP was crucial, and its impact was highly influential. Involvement from the design stage helped shape the ethos of the programme and ultimately its meaningfulness. PUBLIC CONTRIBUTION: People with dementia and their carers were involved through structured consultations and invited to provide feedback on project materials, methods and insight into terminology and relevant concepts.

Exposure to light at night (LAN) and risk of obesity: A systematic review and meta-analysis of observational studies.

BACKGROUND: There is emerging evidence of the association between light at night (LAN) exposure and weight gain. OBJECTIVE: We aim to conduct a systematic review and meta-analysis of observational studies on the association between LAN exposure and risk of obesity in human subjects. METHODS: Peer-reviewed observational studies were systematically searched from MEDLINE (EBSCO), Academic Search Complete (EBSCO), CINAHL Plus (EBSCO) and PubMed up to December 24, 2019. Random-effects models were developed to estimate the associations between LAN exposure and weight-related outcomes of overweight and obesity as measured by body mass index (BMI), waist circumference, waist-hip-ratio and waist-to-height-ratio. The I2 statistic was used to assess the degree of heterogeneity across studies. The National Toxicology Program's Office of Health Assessment and Translation (OHAT) risk of bias rating tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline were respectively employed to assess the risk of bias and to appraise the quality of the generated evidence. RESULTS: A total of 12 studies (three with longitudinal and nine of cross-sectional design) published between 2003 and 2019 were included for systematic review, while seven of them fulfilling the inclusion/exclusion criteria were included in the meta-analysis. A higher LAN exposure was significantly associated with 13% higher odds of overweight (BMI≥25 kg/m2) (Summary Odds Ratio; SOR: 1.13, 95% CI: 1.10-1.16) with low heterogeneity (I2 = 27.27%), and 22% higher odds of obesity (BMI≥30 kg/m2) (SOR: 1.22, 95% CI: 1.07-1.38) with substantial heterogeneity (I2 = 85.96%). Stratifying analyses by the levels of measurement of LAN exposures (macro-, meso- and micro-levels) and time of LAN measurement (including before and while sleeping) consistently produced robust estimates, with higher exposure to LAN being positively associated with poorer weight outcomes. Assessment of risk of bias identified substantial detection bias for exposure, with over half of the pooled studies employing subjective LAN measures. The overall evidence of the association between LAN exposure and risk of obesity was rated as 'moderate' as per the GRADE guideline. CONCLUSIONS: Exposure to LAN was reported to be a significant risk factor for overweight and obesity. Prospectively designed future studies with objectively measured multi-level LAN exposures and weight outcomes are required.

Real-world evidence in Alzheimer's disease: The ROADMAP Data Cube.

INTRODUCTION: The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. METHODS: Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys. RESULTS: Information about 66 data sources and 13 outcome domains were integrated into a Data Cube. Gap analysis identified cognitive ability, functional ability/independence, behavioral/neuropsychiatric symptoms, treatment, comorbidities, and mortality as the outcomes collected most. Data were most lacking in caregiver-related outcomes. In general, electronic health records covered a broader, less detailed data spectrum than research cohorts. DISCUSSION: This integrated real-world AD data overview provides an intuitive visual model that facilitates initial assessment and identification of gaps in relevant outcomes data to inform future prospective data collection and matching of data sources and outcomes against research protocols.

Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies.

BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th-95th percentile 1·04-13·5]) from 71 011 participants from 37 studies. FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10-1·17), coronary disease excluding myocardial infarction (1·06, 1·00-1·11), heart failure (1·09, 1·03-1·15), fatal hypertensive disease (1·24, 1·15-1·33); and fatal aortic aneurysm (1·15, 1·03-1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91-0·97). In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively. INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.

Associations with Corneal Hysteresis in a Population Cohort: Results from 96 010 UK Biobank Participants.

PURPOSE: To describe the distribution of corneal hysteresis (CH) in a large cohort and explore its associated factors and possible clinical applications. DESIGN: Cross-sectional study within the UK Biobank, a large cohort study in the United Kingdom. PARTICIPANTS: We analyzed CH data from 93 345 eligible participants in the UK Biobank cohort, aged 40 to 69 years. METHODS: All analyses were performed using left eye data. Linear regression models were used to evaluate associations between CH and demographic, lifestyle, ocular, and systemic variables. Piecewise logistic regression models were used to explore the relationship between self-reported glaucoma and CH. MAIN OUTCOME MEASURES: Corneal hysteresis (mmHg). RESULTS: The mean CH was 10.6 mmHg (10.4 mmHg in male and 10.8 mmHg in female participants). After adjusting for covariables, CH was significantly negatively associated with male sex, age, black ethnicity, self-reported glaucoma, diastolic blood pressure, and height. Corneal hysteresis was significantly positively associated with smoking, hyperopia, diabetes, systemic lupus erythematosus (SLE), greater deprivation (Townsend index), and Goldmann-correlated intraocular pressure (IOPg). Self-reported glaucoma and CH were significantly associated when CH was less than 10.1 mmHg (odds ratio, 0.86; 95% confidence interval, 0.79-0.94 per mmHg CH increase) after adjusting for covariables. When CH exceeded 10.1 mmHg, there was no significant association between CH and self-reported glaucoma. CONCLUSIONS: In our analyses, CH was significantly associated with factors including age, sex, and ethnicity, which should be taken into account when interpreting CH values. In our cohort, lower CH was significantly associated with a higher prevalence of self-reported glaucoma when CH was less than 10.1 mmHg. Corneal hysteresis may serve as a biomarker aiding glaucoma case detection.

Dietary patterns and hearing loss in older men enrolled in the Caerphilly Study.

The association between dietary patterns (DP) and prevalence of hearing loss in men enrolled in the Caerphilly Prospective Study was investigated. During 1979-1983, the study recruited 2512 men aged 45-59 years. At baseline, dietary data were collected using a semi-quantitative FFQ, and a 7-d weighed food intake (WI) in a 30 % subsample. Five years later, pure-tone unaided audiometric threshold was assessed at 0·5, 1, 2 and 4 kHz. Principal component analysis (PCA) identified three DP and multiple logistic and ordinal logistic regression models examined the association with hearing loss (defined as pure-tone average of frequencies 0·5, 1, 2 and 4 kHz >25 dB). Traditional, healthy and high-sugar/low-alcohol DP were found with both FFQ and WI data. With the FFQ data, fully adjusted models demonstrated significant inverse association between the healthy DP and hearing loss both as a dichotomous variable (OR=0·83; 95 % CI 0·77, 0·90; P<0·001) and as an ordinal variable (OR=0·87; 95 % CI 0·81, 0·94; P<0·001). With the WI data, fully adjusted models showed a significant and inverse association between the healthy DP and hearing loss (OR=0·85; 95 % CI 0·73, 0·99; P<0·03), and a significant association between the traditional DP (per fifth increase) and hearing loss both as a dichotomous variable (OR=1·18; 95 % CI 1·02, 1·35; P=0·02) and as an ordinal variable (OR=1·17; 95 % CI 1·03, 1·33; P=0·02). A healthy DP was significantly and inversely associated with hearing loss in older men. The role of diet in age-related hearing loss warrants further investigation.

Predicting incident dementia 3-8 years after brief cognitive tests in the UK Biobank prospective study of 500,000 people.

INTRODUCTION: Prospective studies reporting associations between cognitive performance and subsequent incident dementia have been subject to attrition bias. Furthermore, the extent to which established risk factors account for such associations requires further elucidation. METHODS: We used UK Biobank baseline cognitive data (n ≤ 488,130) and electronically linked hospital inpatient and death records during three- to eight-year follow-up, to estimate risk of total dementia (n = 1051), Alzheimer's disease (n = 352), and vascular dementia (n = 169) according to four brief cognitive tasks, with/without adjustment for constitutional and modifiable risk factors. RESULTS: We found associations of cognitive task performance with all-cause and cause-specific dementia (P <  .01); these were not accounted for by established risk factors. Cognitive data added up to 5% to the discriminative accuracy of receiver operating characteristic curve models; areas under the curve ranged from 82% to 86%. DISCUSSION: This study offers robust evidence that brief cognitive testing could be a valuable addition to dementia prediction models.

The relationship between alcohol use and long-term cognitive decline in middle and late life: a longitudinal analysis using UK Biobank.

Background: Using UK Biobank data, this study sought to explain the causal relationship between alcohol intake and cognitive decline in middle and older aged populations. Methods: Data from 13 342 men and women, aged between 40 and 73 years were used in regression analysis that tested the functional relationship and impact of alcohol on cognitive performance. Performance was measured using mean reaction time (RT) and intra-individual variation (IIV) in RT, collected in response to a perceptual matching task. Covariates included body mass index, physical activity, tobacco use, socioeconomic status, education and baseline cognitive function. Results: A restricted cubic spline regression with three knots showed how the linear (ß1 = -0.048, 95% CI: -0.105 to -0.030) and non-linear effects (ß2 = 0.035, 95% CI: 0.007-0.059) of alcohol use on mean RT and IIV in RT (ß1 = -0.055, 95% CI: -0.125 to -0.034; ß2 = 0.034, 95% CI: 0.002-0.064) were significant adjusting for covariates. Cognitive function declined as alcohol use increased beyond 10 g/day. Decline was more apparent as age increased. Conclusions: The relationship between alcohol use and cognitive function is non-linear. Consuming more than one UK standard unit of alcohol per day is detrimental to cognitive performance and is more pronounced in older populations.

Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.