The UK Biobank cohort is a population-based cohort of 500,000 participants recruited in the United Kingdom (UK) between 2006 and 2010. Approximately 9.2 million individuals aged 40-69 years who lived ...within 25 miles (40 km) of one of 22 assessment centers in England, Wales, and Scotland were invited to enter the cohort, and 5.5% participated in the baseline assessment. The representativeness of the UK Biobank cohort was investigated by comparing demographic characteristics between nonresponders and responders. Sociodemographic, physical, lifestyle, and health-related characteristics of the cohort were compared with nationally representative data sources. UK Biobank participants were more likely to be older, to be female, and to live in less socioeconomically deprived areas than nonparticipants. Compared with the general population, participants were less likely to be obese, to smoke, and to drink alcohol on a daily basis and had fewer self-reported health conditions. At age 70-74 years, rates of all-cause mortality and total cancer incidence were 46.2% and 11.8% lower, respectively, in men and 55.5% and 18.1% lower, respectively, in women than in the general population of the same age. UK Biobank is not representative of the sampling population; there is evidence of a "healthy volunteer" selection bias. Nonetheless, valid assessment of exposure-disease relationships may be widely generalizable and does not require participants to be representative of the population at large.
IMPORTANCE: Genetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown. OBJECTIVE: To investigate whether a healthy lifestyle is associated ...with lower risk of dementia regardless of genetic risk. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017. EXPOSURES: A polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles. MAIN OUTCOMES AND MEASURES: Incident all-cause dementia, ascertained through hospital inpatient and death records. RESULTS: A total of 196 383 individuals (mean SD age, 64.1 2.9 years; 52.7% were women) were followed up for 1 545 433 person-years (median interquartile range follow-up, 8.0 7.4-8.6 years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 95% CI, 1.64-2.23). Of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 95% CI, 2.09-3.83). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 95% CI, 0.51-0.90). CONCLUSIONS AND RELEVANCE: Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.
OBJECTIVE:To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease.
METHODS:One thousand six hundred fifty-eight ...elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population–based Cardiovascular Health Study between 1992–1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992–1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimerʼs Disease and Related Disorders Association criteria.
RESULTS:During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval CI) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25 to <50 nmol/L) were 2.25 (95% CI1.23–4.13) and 1.53 (95% CI1.06–2.21) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95% CI1.02–4.83) and 1.69 (95% CI1.06–2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.
CONCLUSION:Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.
UK Biobank is a population-based cohort of half a million participants aged 40-69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multi-modal imaging study, ...with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.
Although dietary intake over a single 24-h period may be atypical of an individual’s habitual pattern, multiple 24-h dietary assessments can be representative of habitual intake and help in assessing ...seasonal variation. Web-based questionnaires are convenient for the participant and result in automatic data capture for study investigators. This study reports on the acceptability of repeated web-based administration of the Oxford WebQ – a 24-h recall of frequency from a set food list suitable for self-completion from which energy and nutrient values can be automatically generated. As part of the UK Biobank study, four invitations to complete the Oxford WebQ were sent by email over a 16-month period. Overall, 176 012 (53 % of those invited) participants completed the online version of the Oxford WebQ at least once and 66 % completed it more than once, although only 16 % completed it on all four occasions. The response rate for any one round of invitations varied between 34 and 26 %. On most occasions, the Oxford WebQ was completed on the same day that they received the invitation, although this was less likely if sent on a weekend. Participants who completed the Oxford WebQ tended to be white, female, slightly older, less deprived and more educated, which is typical of health-conscious volunteer-based studies. These findings provide preliminary evidence to suggest that repeated 24-h dietary assessment via the Internet is acceptable to the public and a feasible strategy for large population-based studies.
Polygenic risk scores (PRS) are proposed for use in clinical and research settings for risk stratification. However, there are limited investigations on how different PRS diverge from each other in ...risk prediction of individuals. We compared two recently published PRS for each of three conditions, breast cancer, hypertension and dementia, to assess the stability of using these algorithms for risk prediction in a single large population. We used imputed genotyping data from the UK Biobank prospective cohort, limited to the White British subset. We found that: (1) 20% or more of SNPs in the first PRS were not represented in the more recent PRS for all three diseases, by the same SNP or a surrogate with R
> 0.8 by linkage disequilibrium (LD). (2) Although the difference in the area under the receiver operating characteristic curve (AUC) obtained using the two PRS is hardly appreciable for all three diseases, there were large differences in individual risk prediction between the two PRS. For instance, for each disease, of those classified in the top 5% of risk by the first PRS, over 60% were not so classified by the second PRS. We found substantial discordance between different PRS for the same disease, indicating that individuals could receive different medical advice depending on which PRS is used to assess their genetic susceptibility. It is desirable to resolve this uncertainty before using PRS for risk stratification in clinical settings.
Introduction
Little is known about the association between speech‐in‐noise (SiN) hearing impairment and dementia.
Methods
In 82,039 dementia‐free participants aged ≥60 years were selected from the UK ...Biobank. Cox proportional‐hazards models were used to investigate whether SiN hearing impairment is associated with an increased risk of incident dementia.
Results
Over 11 years of follow‐up (median = 10.1), 1285 participants developed dementia. Insufficient and poor SiN hearing were associated with a 61% (hazard ratio HR = 1.61, 95% confidence CI 1.41–1.84) and 91% (HR = 1.91, 95% CI 1.55–2.36) increased risk of developing dementia, respectively, compared to normal SiN hearing. The association remained similar when restricting to follow‐up intervals of ≤3, >3 to <6, >6 to <9, and >9 years. There was limited evidence for mediation through depressive symptoms and social isolation.
Discussion
SiN hearing impairment is independently associated with incident dementia, providing further evidence for hearing impairment as a potential modifiable dementia risk factor.
Abstract INTRODUCTION Higher neuroticism might be associated with dementia risk. Here we investigated modification by genetic predisposition to dementia, mediation by mental health and vascular ...conditions, neuroimaging outcomes, and cognitive function. METHODS Cox proportional‐hazards models were used to assess the association between neuroticism score and incident dementia over up to 15 years in 1,74,164 participants. Cross‐sectional analyses on dementia‐related neuroimaging outcomes and cognitive function were conducted in 39,459 dementia‐free participants. RESULTS Higher neuroticism was associated with an 11% higher risk of incident dementia, especially vascular dementia (15% higher risk), regardless of genetic predisposition to dementia. Mental and vascular conditions mediated the association of neuroticism with all‐cause dementia and vascular dementia. Neuroticism was associated with higher cerebrovascular pathology, lower gray matter volume, and worse function across multiple cognitive domains. DISCUSSION Neuroticism could represent a risk factor for dementia, and vascular and mental health might drive these associations. Highlights Neuroticism was associated with an increased risk of incident all‐cause dementia, particularly vascular dementia. Associations were not modified by genetic predisposition to dementia. Associations were largely mediated by mental and vascular conditions. Neuroticism was associated with increased cerebrovascular pathology and lower gray matter volume. Neuroticism was associated with worse function across multiple cognitive domains.
We aimed to identify potential novel predictors for breast cancer among post-menopausal women, with pre-specified interest in the role of polygenic risk scores (PRS) for risk prediction. We utilised ...an analysis pipeline where machine learning was used for feature selection, prior to risk prediction by classical statistical models. An "extreme gradient boosting" (XGBoost) machine with Shapley feature-importance measures were used for feature selection among Formula: see text 1.7 k features in 104,313 post-menopausal women from the UK Biobank. We constructed and compared the "augmented" Cox model (incorporating the two PRS, known and novel predictors) with a "baseline" Cox model (incorporating the two PRS and known predictors) for risk prediction. Both of the two PRS were significant in the augmented Cox model (Formula: see text). XGBoost identified 10 novel features, among which five showed significant associations with post-menopausal breast cancer: plasma urea (HR = 0.95, 95% CI 0.92-0.98, Formula: see text), plasma phosphate (HR = 0.68, 95% CI 0.53-0.88, Formula: see text), basal metabolic rate (HR = 1.17, 95% CI 1.11-1.24, Formula: see text), red blood cell count (HR = 1.21, 95% CI 1.08-1.35, Formula: see text), and creatinine in urine (HR = 1.05, 95% CI 1.01-1.09, Formula: see text). Risk discrimination was maintained in the augmented Cox model, yielding C-index 0.673 vs 0.667 (baseline Cox model) with the training data and 0.665 vs 0.664 with the test data. We identified blood/urine biomarkers as potential novel predictors for post-menopausal breast cancer. Our findings provide new insights to breast cancer risk. Future research should validate novel predictors, investigate using multiple PRS and more precise anthropometry measures for better breast cancer risk prediction.
OBJECTIVE Metabolic syndrome (MetS) has been linked to dementia. In this study, we examined the association of MetS with neuroimaging and cognition in dementia-free adults, offering insight into the ...impact of MetS on brain health prior to dementia onset. RESEARCH DESIGN AND METHODS We included 37,395 dementia-free adults from the UK Biobank database. MetS was defined as having at least three of the following components: larger waist circumference; elevated levels of triglycerides, blood pressure, HbA1c; or reduced HDL cholesterol levels. Multivariable-adjusted linear regression was used to assess associations of MetS with structural neuroimaging and cognitive domains. RESULTS MetS was associated with lower total brain (standardized β: −0.06; 95% CI −0.08, −0.04), gray matter (β: −0.10; 95% CI −0.12, −0.08) and hippocampal (for left side, β: −0.03, 95% CI −0.05, −0.01; for right side, β: −0.04, 95% CI −0.07, −0.02) volumes, and greater white matter hyperintensity (WMH) volume (β: 0.08; 95% CI 0.06, 0.11). Study participants with MetS performed poorer on cognitive tests of working memory (β: −0.10; 95% CI −0.13, −0.07), verbal declarative memory (β: −0.08; 95% CI −0.11, −0.05), processing speed (β: −0.06; 95% CI −0.09, −0.04), verbal and numerical reasoning (β: −0.07; 95% CI −0.09, −0.04), nonverbal reasoning (β: −0.03; 95% CI −0.05, −0.01), and on tests of executive function, where higher scores indicated poorer performance (β: 0.05; 95% CI 0.03, 0.08). More MetS components were also associated with less brain volume, greater WMH, and poorer cognition across all domains. CONCLUSIONS MetS was associated poorer brain health in dementia-free adults, characterized by less brain volume, greater vascular pathology, and poorer cognition. Further research is necessary to understand whether reversal or improvement of MetS can improve brain health.
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