Lower mental health related quality of life precedes dementia diagnosis: findings from the EPIC-Norfolk prospective population-based study.

Lower Health Related Quality of Life (HRQoL) precedes dementia in older adults in the USA. We explore prospective associations between HRQoL and dementia in British adults in mid and late-life, when interventions to optimise cognitive ageing may provide benefit. 7,452 community-dwelling participants (57% women; mean age 69.3 ± 8.3 years) attended the European Prospective Investigation of Cancer-Norfolk study's third health check (3HC) and reported their HRQoL using Short-Form 36 (SF-36). Cox Proportional Hazard regression models explored associations between standard deviation differences in baseline Physical Component (PCS) and Mental Component Summary (MCS) scores, as well as eight SF-36 sub-scales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health), and incident dementia over ten years. Logistic regression models explored cross-sectional relationships at the 3HC between HRQoL and objective global cognitive function (n = 4435; poor cognition = lowest performance decile). The cohort was examined as a whole and by age-group (50-69, ≥ 70), considering socio-demographics and co-morbidity. Higher MCS scores were associated with lower chance of incident dementia (Hazard Ratio [HR] = 0.74, 95% CI 0.68-0.81) and lower odds of poor cognition (Odds Ratio [OR] = 0.82, 0.76-0.89), with findings similar by age-group. Higher PCS scores were not associated with dementia in the whole cohort (HR = 0.93, 0.84-1.04) or considering age-groups; and were only associated with poor cognition in younger participants (OR = 0.81, 0.72-0.92). Similarly, associations between higher scores on subscales pertaining to mental, but not physical, HRQoL and lower dementia incidence were observed. Lower mental HRQoL precedes dementia diagnosis in middle-aged and older British adults.

Prediction of acute myeloid leukaemia risk in healthy individuals.

The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4-8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.

Considerations for the use of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) in cross-country comparisons of cognitive aging and dementia.

INTRODUCTION: Informant reports are a critical component of dementia diagnoses, but the comparability of informant reports across countries is not well understood. METHODS: We compared the performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) using population-representative surveys in the United States (N = 3183), England (N = 1050), and India (N = 4047). RESULTS: Analyses of regression splines and comparisons of model fit showed strong associations between IQCODE and objective cognition at low cognitive functioning in the United States and England; in India, the association was weaker but consistent over the range of cognition. Associations between IQCODE score and informant generation (analysis of variance [ANOVA] p = 0.001), caregiver status (p < 0.001), and years known by the informant (p = 0.015) were different across countries after adjusting for objective cognition. DISCUSSION: In India, the IQCODE was less sensitive to impairments at the lowest levels of cognitive functioning. Country-specific adjustments to IQCODE scoring based on informant characteristics may improve cross-national comparisons. HIGHLIGHTS: Associations between IQCODE and cognitive testing were similar in the United States and England but differed in India. In India, the IQCODE may be less sensitive to impairments among those with low cognition and no education. Informant characteristics may differentially impact informant reports of decline across countries. Adjustments or culturally sensitive adaptations may improve cross-national comparability.

Measurement differences in the assessment of functional limitations for cognitive impairment classification across geographic locations.

INTRODUCTION: The measurement of dementia in cross-national contexts relies on the assessment of functional limitations. We aimed to evaluate the performance of survey items on functional limitations across culturally diverse geographic settings. METHODS: We used data from the Harmonized Cognitive Assessment Protocol Surveys (HCAP) in five countries (total N = 11,250) to quantify associations between items on functional limitations and cognitive impairment. RESULTS: Many items performed better in the United States and England compared to South Africa, India, and Mexico. Items on the Community Screening Instrument for Dementia (CSID) had the least variability across countries (SD = 0.73 vs. 0.92 [Blessed] and 0.98 [Jorm IQCODE]), but also the weakest associations with cognitive impairment (median odds ratio [OR] = 2.23 vs. 3.01 [Blessed] and 2.75 [Jorm IQCODE]). DISCUSSION: Differences in cultural norms for reporting functional limitations likely influences performance of items on functional limitations and may affect the interpretation of results from substantive studies. HIGHLIGHTS: There was substantial cross-country variation in item performance. Items from the Community Screening Instrument for Dementia (CSID) had less cross-country variability but lower performance. There was more variability in performance of instrumental activities of daily living (IADL) compared to activities of daily living (ADL) items. Variability in cultural expectations of older adults should be taken into account. Results highlight the need for novel approaches to assessing functional limitations.

Rapid systematic review to identify key barriers to access, linkage, and use of local authority administrative data for population health research, practice, and policy in the United Kingdom.

BACKGROUND: Improving data access, sharing, and linkage across local authorities and other agencies can contribute to improvements in population health. Whilst progress is being made to achieve linkage and integration of health and social care data, issues still exist in creating such a system. As part of wider work to create the Cambridge Child Health Informatics and Linked Data (Cam-CHILD) database, we wanted to examine barriers to the access, linkage, and use of local authority data. METHODS: A systematic literature search was conducted of scientific databases and the grey literature. Any publications reporting original research related to barriers or enablers of data linkage of or with local authority data in the United Kingdom were included. Barriers relating to the following issues were extracted from each paper: funding, fragmentation, legal and ethical frameworks, cultural issues, geographical boundaries, technical capability, capacity, data quality, security, and patient and public trust. RESULTS: Twenty eight articles were identified for inclusion in this review. Issues relating to technical capacity and data quality were cited most often. This was followed by those relating to legal and ethical frameworks. Issue relating to public and patient trust were cited the least, however, there is considerable overlap between this topic and issues relating to legal and ethical frameworks. CONCLUSIONS: This rapid review is the first step to an in-depth exploration of the barriers to data access, linkage and use; a better understanding of which can aid in creating and implementing effective solutions. These barriers are not novel although they pose specific challenges in the context of local authority data.

Alcohol Consumption and Incident Cataract Surgery in Two Large UK Cohorts.

PURPOSE: To examine the association of alcohol consumption and type of alcoholic beverage with incident cataract surgery in 2 large cohorts. DESIGN: Longitudinal, observational study. PARTICIPANTS: We included 469 387 participants of UK Biobank with a mean age of 56 years and 23 162 participants of European Prospective Investigation of Cancer (EPIC)-Norfolk with a mean age of 59 years. METHODS: Self-reported alcohol consumption at baseline was ascertained by a touchscreen questionnaire in UK Biobank and a food-frequency questionnaire in EPIC-Norfolk. Cases were defined as participants undergoing cataract surgery in either eye as ascertained via data linkage to National Health Service procedure statistics. We excluded participants with cataract surgery up to 1 year after the baseline assessment visit or those with self-reported cataract at baseline. Cox proportional hazards models were used to examine the associations of alcohol consumption with incident cataract surgery, adjusted for age, sex, ethnicity, Townsend deprivation index, body mass index (BMI), smoking, and diabetes status. MAIN OUTCOME MEASURES: Incident cataract surgery. RESULTS: There were 19 011 (mean cohort follow-up of 95 months) and 4573 (mean cohort follow-up of 193 months) incident cases of cataract surgery in UK Biobank and EPIC-Norfolk, respectively. Compared with nondrinkers, drinkers were less likely to undergo cataract surgery in UK Biobank (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.93) and EPIC-Norfolk (HR, 0.90; 95% CI, 0.84-0.97) after adjusting for covariables. Among alcohol consumers, greater alcohol consumption was associated with a reduced risk of undergoing cataract surgery in EPIC-Norfolk (P < 0.001), whereas a U-shaped association was observed in the UK Biobank. Compared with nondrinkers, subgroup analysis by type of alcohol beverage showed the strongest protective association with wine consumption; the risk of incident cataract surgery was 23% and 14% lower among those in the highest category of wine consumption in EPIC-Norfolk and UK Biobank, respectively. CONCLUSIONS: Our findings suggest a lower risk of undergoing cataract surgery with low to moderate alcohol consumption. The association was particularly apparent with wine consumption. We cannot exclude the possibility of residual confounding, and further studies are required to determine whether this association is causal in nature.

Is there a dose-response relationship between musical instrument playing and later-life cognition? A cohort study using EPIC-Norfolk data.

INTRODUCTION: Musical instrument playing provides intellectual stimulation, which is hypothesised to generate cognitive reserve that protects against cognitive impairment. Studies to date have classified musicianship as a binary entity. This investigation draws on the dataset of the European Prospective Investigation of Cancer Norfolk study to examine the effect of frequency of playing on later-life cognition. METHODS: We compared three categorisations of self-reported musical playing frequency in late mid-life (12-month period) against cognitive performance measured after a 4-11 year delay, adjusted for relevant health and social confounders. Logistic regression models estimated the adjusted association between frequency of musical playing and the likelihood of being in the top and bottom cognitive deciles. RESULTS: A total of 5,693 participants (745 musicians) provided data on music playing, cognition and all co-variables. Classification of musicianship by frequency of playing demonstrated key differences in socio-demographic factors. Musicians outperformed non-musicians in cognition generally. Compared with non-musicians, frequent musicians had 80% higher odds of being in the top cognitive decile (OR 1.80 [95% CI 1.19-2.73]), whereas musicians playing at any frequency had 29% higher odds (95% CI 1.03-1.62). There was evidence of a threshold effect, rather than a linear dose-response relationship. DISCUSSION: This study supports a positive association between late mid-life musical instrument playing and later-life cognition, although causation cannot be assumed. Musicians playing frequently demonstrated the best cognition. 'Musicians' are a heterogeneous group and frequency of music playing seems a more informative measure than binary classification. Ideally, this more nuanced measure would be collected for different life course phases.

Cardiovascular risk factors associated with polymyalgia rheumatica and giant cell arteritis in a prospective cohort: EPIC-Norfolk Study.

OBJECTIVES: PMR and GCA are associated with increased risk of vascular disease. However, it remains unclear whether this relationship is causal or reflects a common underlying propensity. The aim of this study was to identify whether known cardiovascular risk factors increase the risk of PMR and GCA. METHODS: Clinical records were examined using key word searches to identify cases of PMR and GCA, applying current classification criteria in a population-based cohort. Associations between cardiovascular risk factors and incident PMR and GCA were analysed using Cox proportional hazards. RESULTS: In 315 022 person years of follow-up, there were 395 incident diagnoses of PMR and 118 incident diagnoses of GCA that met the clinical definition. Raised diastolic blood pressure (>90 mmHg) at baseline/recruitment was associated with subsequent incident PMR [hazard ratio=1.35 (95% CI 1.01, 1.80) P=0.045], and ever-smoking was associated with incident GCA [hazard ratio=2.01 (95% CI 1.26, 3.20) P=0.003]. Estimates were similar when the analysis was restricted to individuals whose diagnoses satisfied the current classification criteria sets. CONCLUSION: PMR and GCA shares common risk factors with vascular disease onset, suggesting a common underlying propensity. This may indicate a potential for disease prevention strategies through modifying cardiovascular risk.

Usual physical activity and subsequent hospital usage over 20 years in a general population: the EPIC-Norfolk cohort.

BACKGROUND: While physical activity interventions have been reported to reduce hospital stays, it is not clear if, in the general population, usual physical activity patterns may be associated with subsequent hospital use independently of other lifestyle factors. OBJECTIVE: We examined the relationship between reported usual physical activity and subsequent admissions to hospital and time spent in hospital for 11,228 men and 13,786 women aged 40-79 years in the general population. METHODS: Participants from a British prospective population-based cohort study were followed for 20 years (1999-2019) using record linkage to document hospital usage. Total physical activity was estimated by combining workplace and leisure time activity reported in a baseline lifestyle questionnaire and repeated in a subset at a second time point approximately 12 years later. RESULTS: Compared to those reporting no physical activity, participants who were the most active had a lower likelihood of spending more than 20 days in hospital odds ratio (OR) 0.88 (95% confidence interval (CI) 0.81-0.96) over the next 20 years after multivariable adjustment for age, sex, smoking status, education, social class and body mass index. Participants reporting any activity had a mean of 0.42 fewer hospital days per year between 1999 and 2009 compared to inactive participants, an estimated potential saving to the National Health Service (NHS) of £247 per person per year, or approximately 7% of UK health expenditure. Participants who remained physically active or became active 12 years later had lower risk of subsequent hospital usage than those who remained inactive or became inactive, p-trend < 0.001. CONCLUSION: Usual physical activity in this middle-aged and older population predicts lower future hospitalisations - time spent in hospital and number of admissions independently of behavioural and sociodemographic factors. Small feasible differences in usual physical activity in the general population may potentially have a substantial impact on hospital usage and costs.

Retinal Vasculometry Associations with Cardiometabolic Risk Factors in the European Prospective Investigation of Cancer-Norfolk Study.

PURPOSE: To examine associations between retinal vessel morphometry and cardiometabolic risk factors in older British men and women. DESIGN: Retinal imaging examination as part of the European Prospective Investigation into Cancer-Norfolk Eye Study. PARTICIPANTS: Retinal imaging and clinical assessments were carried out in 7411 participants. Retinal images were analyzed using a fully automated validated computerized system that provides novel measures of vessel morphometry. METHODS: Associations between cardiometabolic risk factors, chronic disease, and retinal markers were analyzed using multilevel linear regression, adjusted for age, gender, and within-person clustering, to provide percentage differences in tortuosity and absolute differences in width. MAIN OUTCOMES MEASURES: Retinal arteriolar and venular tortuosity and width. RESULTS: In all, 279 802 arterioles and 285 791 venules from 5947 participants (mean age, 67.6 years; standard deviation [SD], 7.6 years; 57% female) were analyzed. Increased venular tortuosity was associated with higher body mass index (BMI; 2.5%; 95% confidence interval [CI], 1.7%-3.3% per 5 kg/m2), hemoglobin A1c (HbA1c) level (2.2%; 95% CI, 1.0%-3.5% per 1%), and prevalent type 2 diabetes (6.5%; 95% CI, 2.8%-10.4%); wider venules were associated with older age (2.6 µm; 95% CI, 2.2-2.9 µm per decade), higher triglyceride levels (0.6 µm; 95% CI, 0.3-0.9 µm per 1 mmol/l), BMI (0.7 µm; 95% CI, 0.4-1.0 per 5 kg/m2), HbA1c level (0.4 µm; 95% CI, -0.1 to 0.9 per 1%), and being a current smoker (3.0 µm; 95% CI, 1.7-4.3 µm); smoking also was associated with wider arterioles (2.1 µm; 95% CI, 1.3-2.9 µm). Thinner venules were associated with high-density lipoprotein (HDL) (1.4 µm; 95% CI, 0.7-2.2 per 1 mmol/l). Arteriolar tortuosity increased with age (5.4%; 95% CI, 3.8%-7.1% per decade), higher systolic blood pressure (1.2%; 95% CI, 0.5%-1.9% per 10 mmHg), in females (3.8%; 95% CI, 1.4%-6.4%), and in those with prevalent stroke (8.3%; 95% CI, -0.6% to 18%); no association was observed with prevalent myocardial infarction. Narrower arterioles were associated with age (0.8 µm; 95% CI, 0.6-1.0 µm per decade), higher systolic blood pressure (0.5 µm; 95% CI, 0.4-0.6 µm per 10 mmHg), total cholesterol level (0.2 µm; 95% CI, 0.0-0.3 µm per 1 mmol/l), and HDL (1.2 µm; 95% CI, 0.7-1.6 µm per 1 mmol/l). CONCLUSIONS: Metabolic risk factors showed a graded association with both tortuosity and width of retinal venules, even among people without clinical diabetes, whereas atherosclerotic risk factors correlated more closely with arteriolar width, even excluding those with hypertension and cardiovascular disease. These noninvasive microvasculature measures should be evaluated further as predictors of future cardiometabolic disease.

Understanding the relationship between cognition and death: a within cohort examination of cognitive measures and mortality.

Despite several studies demonstrating an independent and inverse association between cognition and mortality, the nature of this association still remains unclear. To examine the association of cognition and mortality after accounting for sociodemographic, health and lifestyle factors and to explore both test and population characteristics influencing this relationship. In a population based cohort of 8585 men and women aged 48-92 years, who had cognitive assessments in 2006-2011 and were followed up till 2016 for mortality, we examined the relationship between individual cognitive tests as well as a global cognition score to compare their ability in predicting mortality and whether these differed by population characteristics. Risk of death was estimated using Cox proportional hazard regression models including sociodemographic, lifestyle and health variables, and self-reported comorbidities, as covariates in the models. Poor cognitive performance (bottom quartile of combined cognition score) was associated with higher risk of mortality, Hazard Ratio = 1.32 (95% Confidence Interval 1.09, 1.60); individual cognitive tests varied in their mortality associations and also performed differently in middle-age and older age groups. Poor cognitive performance is independently associated with higher mortality. This association is observed for global cognition and for specific cognitive abilities. Associations vary depending on the cognitive test (and domain) as well as population characteristics, namely age and education.

Area deprivation and age related macular degeneration in the EPIC-Norfolk Eye Study.

OBJECTIVES: To investigate the relationship between area deprivation, individual socio-economic status (SES) and age related macular degeneration (AMD). STUDY DESIGN: Cross sectional study nested within a longitudinal cohort study. METHODS: Data were collected in the EPIC-Norfolk Eye Study by trained nurses, using standardized protocols and lifestyle questionnaires. The English Index of multiple deprivation 2010 (IMD) was derived from participants' postcodes. AMD was identified from standardized grading of fundus photographs. Logistic regression was used to examine associations between IMD, SES and AMD. RESULTS: 5344 pairs (62.0% of total 8623) of fundus photographs were of sufficient quality for grading of AMD. Of 5182 participants with complete data, AMD was identified in 653 participants (12.60%, 95%CI = 11.7-13.5%). Multivariable logistic regression showed that people living in the most affluent 5% of areas had nearly half the odds of AMD compared to those living in comparatively more deprived areas (OR = 0.56, 95% CI = 0.36-0.89, P = 0.02), after adjusting for age, sex, education, social class and smoking. CONCLUSIONS: The authors found that living in the most affluent areas exerted a protective effect on AMD, independently of education and social class. Further investigation into underlying mechanisms will inform potential interventions to reduce health inequalities relating to AMD.

Daytime napping and the risk of all-cause and cause-specific mortality: a 13-year follow-up of a British population.

Epidemiologic studies have reported conflicting results on the relationship between daytime napping and mortality risk, and there are few data on the potential association in the British population. We investigated the associations between daytime napping and all-cause or cause-specific mortality in the European Prospective Investigation Into Cancer-Norfolk study, a British population-based cohort study. Among the 16,374 men and women who answered questions on napping habits between 1998 and 2000, a total of 3,251 died during the 13-year follow-up. Daytime napping was associated with an increased risk of all-cause mortality (for napping less than 1 hour per day on average, hazard ratio = 1.14, 95% confidence interval: 1.02, 1.27; for napping 1 hour or longer per day on average, hazard ratio = 1.32, 95% confidence interval: 1.04, 1.68), independent of age, sex, social class, educational level, marital status, employment status, body mass index, physical activity level, smoking status, alcohol intake, depression, self-reported general health, use of hypnotic drugs or other medications, time spent in bed at night, and presence of preexisting health conditions. This association was more pronounced for death from respiratory diseases (for napping less than 1 hour, hazard ratio = 1.40, 95% confidence interval: 0.95, 2.05; for napping 1 hour or more, hazard ratio = 2.56, 95% confidence interval: 1.34, 4.86) and in individuals 65 years of age or younger. Excessive daytime napping might be a useful marker of underlying health risk, particularly of respiratory problems, especially among those 65 years of age or younger. Further research is required to clarify the nature of the observed association.

Systemic medication and intraocular pressure in a British population: the EPIC-Norfolk Eye Study.

OBJECTIVE: To determine the association between systemic medication use and intraocular pressure (IOP) in a population of older British men and women. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We included 7093 participants from the European Prospective Investigation into Cancer-Norfolk Eye Study. Exclusion criteria were a history of glaucoma therapy (medical, laser, or surgical), IOP asymmetry between eyes of >5 mmHg, and missing data for any covariables. The mean age of participants was 68 years (range, 48-92) and 56% were women. METHODS: We measured IOP using the Ocular Response Analyzer. Three readings were taken per eye and the best signal value of the Goldmann-correlated IOP value considered. Participants were asked to bring all their medications and related documentation to the health examination, and these were recorded by the research nurse using an electronic case record form. The medication classes examined were angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, α-blockers, ß-blockers, calcium channel blockers, diuretics, nitrates, statins, insulin, biguanides, sulfonylureas, aspirin, and other nonsteroidal anti-inflammatory drugs. We examined associations between medication use and IOP using multivariable linear regression models adjusted for age, sex, and body mass index. Models containing diabetic medication were further adjusted for glycosylated hemoglobin levels. MAIN OUTCOME MEASURES: Mean IOP of the right and left eyes. RESULTS: Use of systemic ß-blockers (-0.92 mmHg; 95% CI, -1.19, -0.65; P<0.001) and nitrates (-0.63 mmHg; 95% CI, -1.12, -0.14; P = 0.011) were independently associated with lower IOP. The observed associations between statin or aspirin use with IOP were no longer significant after adjustment for ß-blocker use. CONCLUSIONS: This is the first population-based study to demonstrate and quantify clinically significant differences in IOP among participants using systemic ß-blockers or nitrates. Lower IOP observed in participants using statins or aspirin was explained by concurrent systemic ß-blocker use. The study findings may have implications for the management of glaucoma patients with comorbidity, and may provide insight into the pathophysiologic processes underlying IOP.

Cognitive function in a general population of men and women: a cross sectional study in the European Investigation of Cancer-Norfolk cohort (EPIC-Norfolk).

BACKGROUND: Although ageing is strongly associated with cognitive decline, a wide range of cognitive ability is observed in older populations with varying rates of change across different cognitive domains. METHODS: Cognitive function was measured as part of the third health examination of the European Prospective Investigation of Cancer in Norfolk (EPIC-Norfolk 3) between 2006 and 2011 (including measures from the pilot phase from 2004 to 2006). This was done using a battery consisting of seven previously validated cognitive function tests assessing both global function and specific domains. The battery included a shortened version of the Extended Mental State Exam (SF-EMSE); letter cancellation task; Hopkins Verbal Learning Test (HVLT); Cambridge Neuropsychological Test Automated Battery Paired Associates Learning Test (CANTAB-PAL); Visual Sensitivity Test (VST); Shortened version of the National Adult Reading Test (Short-NART) and a task to test for prospective memory. We report the distribution of cognitive function in different cognitive domains by age and sex and compare the utility of a number of assessment tests in a general population of older men and women. RESULTS: Cognitive test data were available for 8585 men and women taking part in EPIC-Norfolk 3. Increasing age was generally associated with declining mean cognitive function, but there was a wide range observed within each age group as well as variability across different cognitive domains. Some sex differences were also observed. CONCLUSION: Descriptive data are presented for this general population sample of older men and women. There is a wide range of cognitive performance seen in this population. Though average performance declines with age, there is large individual variability across different cognitive domains. These variations may provide insights into the determinants of cognitive function in later life.

Unraveling the role of plasma proteins in dementia: insights from two cohort studies in the UK, with causal evidence from Mendelian randomization.

Population-based proteomics offer a groundbreaking avenue to predict dementia onset. This study employed a proteome-wide, data-driven approach to investigate protein-dementia associations in 229 incident all-cause dementia (ACD) among 3,249 participants from the English Longitudinal Study of Ageing (ELSA) over a median 9.8-year follow-up, then validated in 1,506 incident ACD among 52,745 individuals from the UK Biobank (UKB) over median 13.7 years. NEFL and RPS6KB1 were robustly associated with incident ACD; MMP12 was associated with vascular dementia in ELSA. Additional markers EDA2R and KIM1 (HAVCR1) were identified from sensitivity analyses. Combining NEFL and RPS6KB1 with other factors yielded high predictive accuracy (area under the curve (AUC)=0.871) for incident ACD. Replication in the UKB confirmed associations between identified proteins with various dementia subtypes. Results from reverse Mendelian Randomization also supported the role of several proteins as early dementia biomarkers. These findings underscore proteomics' potential in identifying novel risk screening targets for dementia.

The physical capability of community-based men and women from a British cohort: the European Prospective Investigation into Cancer (EPIC)-Norfolk study.

BACKGROUND: The European Working Group for Sarcopenia in Older People (EWGSOP) published a case-finding algorithm for sarcopenia, recommending muscle mass measurement in older adults with low grip strength (women <20 kg; men <30 kg) or slow walking speed (≤0.8 m/s). However, the implications of adopting this algorithm into clinical practice are unclear. Therefore, we aimed to explore the physical capability of men and women from a British population-based cohort study. METHODS: In the European Prospective Investigation into Cancer-Norfolk study, 8,623 community-based adults (48-92 years old) underwent assessment of grip strength, walking speed, timed chair stands and standing balance. The proportion of older men and women (≥65 years) fulfilling EWGSOP criteria for muscle mass measurement was estimated. Additionally, cross-sectional associations of physical capability with age and sex were explored using linear and logistic regression. RESULTS: Approximately 1 in 4 older participants (28.8%) fulfilled criteria for muscle mass measurement with a greater proportion of women than men falling below threshold criteria (33.6% versus 23.6%). Even after adjustment for anthropometry, women were 12.4 kg (95% Confidence Interval [CI] 12.0, 12.7) weaker, took 12.0% (95% CI 10.0, 14.0) longer to perform five chair stands and were 1.82 (95% CI 1.48, 2.23) times more likely to be unable to hold a tandem stand for 10 seconds than men, although usual walking speed was similar. Physical capability was inversely associated with age and per year, walking speed decreased by 0.01 m/s (95% CI 0.01, 0.01) and grip strength decreased by 0.49 kg (men; 95% CI 0.46, 0.51) and 0.25 kg (women; 95% CI 0.23, 0.27). Despite this, there was still variation within age-groups and not all older people had low physical capability. CONCLUSIONS: Every effort to optimise functional health in later life should be made since poor function is not inevitable. However, if the EWGSOP sarcopenia case-finding algorithm is endorsed, large proportions of older people could qualify for muscle mass measurement which is not commonly available. Considering population ageing, further discussion is needed over the utility of muscle mass measurement in clinical practice.

Association Between Retinal Nerve Fiber Layer Thickness and Incident Dementia in the European Prospective Investigation into Cancer in Norfolk Cohort.

BACKGROUND: Retinal nerve fiber layer (RNFL) thickness may reflect cerebral status. OBJECTIVE: This study assessed the relationship between RNFL thickness and incident all-cause dementia in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) Eye Study. METHODS: Glaucoma detection with variable corneal compensation (GDx-VCC) and Heidelberg Retinal Tomograph II (HRT II) derived global mean RNFL thickness from dementia-free participants at baseline within the EPIC-Norfolk Eye Study were analyzed. Incident dementia was identified through linkage to electronic medical records. Cox proportional hazard mixed-effects regression models adjusted for key confounders were used to examine the associations between RNFL thickness and incident dementia in four separate models. RESULTS: 6,239 participants were included with 322 cases of incident dementia and mean age of 67.5-years old, with 49.7% women (median follow-up 13.2-years, interquartile range (11.7 to 14.6 years). Greater RNFL thickness (GDx-VCC) was not significantly associated with a lower risk of incident dementia in the full adjusted model [HR per quartile increase 0.95; 95% CI 0.82-1.10]. Similarly, RNFL thickness assessed with HRT II was also not associated with incident dementia in any model (full adjusted model; HR per quartile increase: 1.06; [95% CI 0.93-1.19]. Gender did not modify any associations under study. CONCLUSION: GDx-VCC and HRT II derived RNFL thickness are unlikely to be useful predictors of incident dementia. Higher resolution optical imaging technologies may clarify whether there are useful relationships between neuro-retinal morphology and brain measures.

Evaluation of routinely collected records for dementia outcomes in UK: a prospective cohort study.

OBJECTIVES: To evaluate the characteristics of individuals recorded as having a dementia diagnosis in different routinely collected records and to examine the extent of overlap of dementia coding across data sources. Also, to present comparisons of secondary and primary care records providing value for researchers using routinely collected records for dementia outcome capture. STUDY DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: A cohort of 25 639 men and women in Norfolk, aged 40-79 years at recruitment (1993-1997) followed until 2018 linked to routinely collected to identify dementia cases. Data sources include mortality from death certification and National Health Service (NHS) hospital or secondary care records. Primary care records for a subset of the cohort were also reviewed. PRIMARY OUTCOME MEASURE: Diagnosis of dementia (any-cause). RESULTS: Over 2000 participants (n=2635 individuals) were found to have a dementia diagnosis recorded in one or more of the data sources examined. Limited concordance was observed across the secondary care data sources. We also observed discrepancies with primary care records for the subset and report on potential linkage-related selection bias. CONCLUSIONS: Use of different types of record linkage from varying parts of the UK's health system reveals differences in recorded dementia diagnosis, indicating that dementia can be identified to varying extents in different parts of the NHS system. However, there is considerable variation, and limited overlap in those identified. We present potential selection biases that might occur depending on whether cause of death, or primary and secondary care data sources are used. With the expansion of using routinely collected health data, researchers must be aware of these potential biases and inaccuracies, reporting carefully on the likely extent of limitations and challenges of the data sources they use.