Reliability and validity of the UK Biobank cognitive tests

UK Biobank is a health resource with data from over 500,000 adults. The cognitive assessment in UK Biobank is brief and bespoke, and is administered without supervision on a touchscreen computer. Psychometric information on the UK Biobank cognitive tests are limited. Despite the non-standard nature of these tests and the limited psychometric information, the UK Biobank cognitive data have been used in numerous scientific publications. The present study examined the validity and short-term test-retest reliability of the UK Biobank cognitive tests. A sample of 160 participants (mean age = 62.59, SD = 10.24) was recruited who completed the UK Biobank cognitive assessment and a range of well-validated cognitive tests ('reference tests'). Fifty-two participants returned 4 weeks later to repeat the UK Biobank tests. Correlations were calculated between UK Biobank tests and reference tests. Two measures of general cognitive ability were created by entering scores on the UK Biobank cognitive tests, and scores on the reference tests, respectively, into separate principal component analyses and saving scores on the first principal component. Four-week test-retest correlations were calculated for UK Biobank tests. UK Biobank cognitive tests showed a range of correlations with their respective reference tests, i.e. those tests that are thought to assess the same underlying cognitive ability (mean Pearson r = 0.53, range = 0.22 to 0.83, p≤.005). The measure of general cognitive ability based on the UK Biobank cognitive tests correlated at r = 0.83 (p < .001) with a measure of general cognitive ability created using the reference tests. Four-week test-retest reliability of the UK Biobank tests were moderate-to-high (mean Pearson r = 0.55, range = 0.40 to 0.89, p≤.003). Despite the brief, non-standard nature of the UK Biobank cognitive tests, some tests showed substantial concurrent validity and test-retest reliability. These psychometric results provide currently-lacking information on the validity of the UK Biobank cognitive tests

Health literacy, cognitive ability and health

Poorer health literacy—the ability to acquire, understand and use health information to make better health decisions—has been associated with worse health outcomes. Poorer cognitive ability has also been found to predict increased risk of morbidity and mortality. Health literacy is often assessed using brief tests of health-related reading comprehension and numeracy. Scores on tests of health literacy have moderate-to-strong correlations with cognitive ability test scores. Despite this, few studies have investigated the associations of both health literacy and cognitive ability with respect to health outcomes. This thesis examined whether health literacy and cognitive ability, when studied together, have unique associations with health. The first study in this thesis investigated the unique contributions of health literacy and cognitive ability to smoking status in a sample of 8,734 middle-aged and older adults from the English Longitudinal Study of Ageing (ELSA). Limited health literacy (OR=1.13, 95% CI 1.03-1.25) and poorer cognitive ability (OR per SD=0.94, 95% CI 0.89-0.99) were associated with increased odds of reporting ever smoking. These associations were attenuated and non-significant after adjusting for education and social class. In participants who reported ever smoking, limited health literacy (OR=1.34, 95% CI 1.17-1.54) and poorer cognitive ability (OR=0.88, 95% CI 0.81- 0.95) were associated with being a current smoker, and this remained significant even after adjusting for socioeconomic variables. The second study investigated whether health literacy and cognitive ability were independently associated with diabetes, using a sample of ELSA participants (n=8,669). When examined concurrently, adequate health literacy (OR=0.82, 95% CI 0.69-0.98) and higher cognitive ability (OR per SD=0.78, 95% CI 0.70-0.86) were independently associated with lower odds of self-reported diabetes. Adjusting for health behaviours attenuated these associations and they were no longer significant. Individuals who did not have diabetes were then followed up for up to 10 years. Adequate health literacy (HR=0.72, 95% CI 0.59-0.87) and higher cognitive ability (HR=0.79, 95% CI 0.71-0.88) were associated with a lower risk of developing diabetes. These associations were attenuated by health behaviours and education. The third study sought to determine the role of cognitive ability, measured in childhood and in older age, in the association between health literacy and mortality. Using data from 795 elderly participants from the Lothian Birth Cohort 1936, this study found that lower scores on two tests of health literacy—the Newest Vital Sign (OR per 1 point increase=0.89, 95% CI 0.80-0.99) and the shortened Test of Functional Health Literacy in Adults (OR per 1 point increase=0.95, 95% CI 0.91- 0.98)—were significantly associated with increased risk of mortality. These associations were almost unchanged when childhood cognitive ability was added to the model. When additionally adjusting for cognitive ability in older age, the health literacy-mortality associations were attenuated and no longer significant. Cognitive ability in older adulthood, but not childhood cognitive ability, accounted for most of the association between health literacy and mortality. The genetic architecture of health literacy, cognitive ability, and health was examined in the fourth study. This study investigated whether polygenic profile scores for cognitive, education, and health-related traits were associated with performance on a test of health literacy using 5,783 ELSA participants. Greater odds of having adequate health literacy were associated with higher polygenic scores for better cognitive ability (OR per SD increase=1.34, 95% CI 1.26-1.42) and more years of schooling (OR=1.29, 95% CI 1.21-1.36). Reduced odds of having adequate health literacy were associated with higher polygenic scores for poorer self-rated health (OR=0.92, 95% CI 0.87-0.99) and schizophrenia (OR=0.91, 95% CI 0.85- 0.96). The association between health literacy, cognitive ability and health may, in part, be due to shared genetic influences. This thesis provided an examination of the role of health literacy and cognitive ability in various aspects of health, including health behaviours, morbidity, and mortality. The findings suggest that that at least some of the associations between health literacy and health may be accounted for by cognitive ability, and that the association between health literacy and cognitive ability may be partly due to shared genetic aetiology. The degree of attenuation may depend on the health outcome used and the health literacy and cognitive ability measures used

Health literacy, cognitive ability and smoking:A cross-sectional analysis of the English Longitudinal Study of Ageing

Objectives: We used logistic regression to investigate whether health literacy and cognitive ability independently predicted whether participants have ever smoked and, in ever smokers, whether participants still smoked nowadays. Design: Cross-sectional study. Setting This study used data from Wave 2 (2004-05) of the English Longitudinal Study of Ageing, which is a cohort study of adults who live in England and who, at baseline, were aged 50 years and older. Participants 8734 (mean age=65.31 years, SD=10.18) English Longitudinal Study of Ageing participants who answered questions about their current and past smoking status, and completed cognitive ability and health literacy tests at Wave 2. Primary and secondary outcome measures The primary outcome measures were whether participants reported ever smoking at Wave 2 and whether ever smokers reported still smoking at Wave 2. Results: In models adjusting for age, sex, age left full-time education and occupational social class, limited health literacy (OR=1.096, 95% CI 0.988 to 1.216) and higher general cognitive ability (OR=1.000, 95% CI 0.945 to 1.057) were not associated with reporting ever smoking. In ever smokers, limited compared with adequate health literacy was associated with greater odds of being a current smoker (OR=1.194, 95% CI 1.034 to 1.378) and a 1 SD higher general cognitive ability score was associated with reduced odds of being a current smoker (OR=0.878, 95% CI 0.810 to 0.951), when adjusting for age, sex, age left full-time education and occupational social class. Conclusions: When adjusting for education and occupation variables, this study found that health literacy and cognitive ability were independently associated with whether ever smokers continued to smoke nowadays, but not with whether participants had ever smoked.</p

Role of cognitive ability in the association between functional health literacy and mortality in the Lothian Birth Cohort 1936:A prospective cohort study

Objectives: We investigated the role that childhood and old age cognitive ability play in the association between functional health literacy and mortality.Design: Prospective cohort studySetting: This study used data from the Lothian Birth Cohort 1936 (LBC1936) study, which recruited participants living in the Lothian region of Scotland when aged 70 years, most of whom had completed an intelligence test at age 11 years.Participants: 795 members of the LBC1936 with scores on tests of functional health literacy and cognitive ability in childhood and older adulthood.Primary and secondary outcome measures: Participants were followed up for 8 years to determine mortality. Time to death in days was used as the primary outcome measure.Results: Using Cox regression, higher functional health literacy was associated with lower risk of mortality adjusting for age and sex, using the Shortened Test of Functional Health Literacy in Adults (HR 0.95, 95% CI 0.92 to 0.98), the Newest Vital Sign (HR 0.88, 95% CI 0.80 to 0.97) and a functional health literacy composite measure (HR 0.77, 95% CI 0.65 to 0.92), but not the Rapid Estimate of Adult Literacy in Medicine (HR 0.95, 95% CI 0.90 to 1.01). Adjusting for childhood intelligence did not change these associations. When additionally adjusting for fluid-type cognitive ability in older age, associations between functional health literacy and mortality were attenuated and non-significant.Conclusions: Current fluid ability, but not childhood intelligence, attenuated the association between functional health literacy and mortality. Functional health literacy measures may, in part, assess fluid-type cognitive abilities, and this may account for the association between functional health literacy and mortality.</p

Association of functional health literacy and cognitive ability with self-reported diabetes in the English Longitudinal Study of Ageing:A prospective cohort study

OBJECTIVES: We investigated whether functional health literacy and cognitive ability were associated with self-reported diabetes. DESIGN: Prospective cohort study. SETTING: Data were from waves 2 (2004–2005) to 7 (2014–2015) of the English Longitudinal Study of Ageing (ELSA), a cohort study designed to be representative of adults aged 50 years and older living in England. PARTICIPANTS: 8669 ELSA participants (mean age=66.7, SD=9.7) who completed a brief functional health literacy test assessing health-related reading comprehension, and 4 cognitive tests assessing declarative memory, processing speed and executive function at wave 2. PRIMARY OUTCOME MEASURE: Self-reported doctor diagnosis of diabetes. RESULTS: Logistic regression was used to examine cross-sectional (wave 2) associations of functional health literacy and cognitive ability with diabetes status. Adequate (compared with limited) functional health literacy (OR 0.71, 95% CI 0.61 to 0.84) and higher cognitive ability (OR per 1 SD=0.73, 95% CI 0.67 to 0.80) were associated with lower odds of self-reporting diabetes at wave 2. Cox regression was used to test the associations of functional health literacy and cognitive ability measured at wave 2 with self-reporting diabetes over a median of 9.5 years follow-up (n=6961). Adequate functional health literacy (HR 0.64; 95% CI 0.53 to 0.77) and higher cognitive ability (HR 0.77, 95% CI 0.69 to 0.85) at wave 2 were associated with lower risk of self-reporting diabetes during follow-up. When both functional health literacy and cognitive ability were added to the same model, these associations were slightly attenuated. Additionally adjusting for health behaviours and body mass index fully attenuated cross-sectional associations between functional health literacy and cognitive ability with diabetes status, and partly attenuated associations between functional health literacy and cognitive ability with self-reporting diabetes during follow-up. CONCLUSIONS: Adequate functional health literacy and better cognitive ability were independently associated with lower likelihood of reporting diabetes

Genetic contributions to health literacy

Higher health literacy is associated with higher cognitive function and better health. Despite its wide use in medical research, no study has investigated the genetic contributions to health literacy. Using 5783 English Longitudinal Study of Ageing (ELSA) participants (mean age = 65.49, SD = 9.55) who had genotyping data and had completed a health literacy test at wave 2 (2004-2005), we carried out a genome-wide association study (GWAS) of health literacy. We estimated the proportion of variance in health literacy explained by all common single nucleotide polymorphisms (SNPs). Polygenic profile scores were calculated using summary statistics from GWAS of 21 cognitive and health measures. Logistic regression was used to test whether polygenic scores for cognitive and health-related traits were associated with having adequate, compared to limited, health literacy. No SNPs achieved genome-wide significance for association with health literacy. The proportion of variance in health literacy accounted for by common SNPs was 8.5% (SE = 7.2%). Greater odds of having adequate health literacy were associated with a 1 standard deviation higher polygenic score for general cognitive ability [OR = 1.34, 95% CI (1.26, 1.42)], verbal-numerical reasoning [OR = 1.30, 95% CI (1.23, 1.39)], and years of schooling [OR = 1.29, 95% CI (1.21, 1.36)]. Reduced odds of having adequate health literacy were associated with higher polygenic profiles for poorer self-rated health [OR = 0.92, 95% CI (0.87, 0.98)] and schizophrenia [OR = 0.91, 95% CI (0.85, 0.96)). The well-documented associations between health literacy, cognitive function and health may partly be due to shared genetic etiology. Larger studies are required to obtain accurate estimates of SNP-based heritability and to discover specific health literacy-associated genetic variants.</p

Pre-pandemic cognitive function and COVID-19 vaccine hesitancy: cohort study

Background Whereas several predictors of COVID-19 vaccine hesitancy have been reported, the role of cognitive function is largely unknown. Accordingly, our objective was to evaluate the association between scores from an array of cognitive function tests and self-reported vaccine hesitancy after the announcement of the successful testing of the first COVID-19 vaccine (Oxford University/AstraZeneca). Methods We used individual-level data from a pandemic-focused study ('COVID Survey'), a prospective cohort study nested within United Kingdom Understanding Society ('Main Survey'). In the week immediately following the announcement of successful testing of the first efficacious inoculation (November/December 2020), data on vaccine intentionality were collected in 11,740 individuals (6702 women) aged 16–95 years. Pre-pandemic scores on general cognitive function, ascertained from a battery of six tests, were captured in 2011/12 wave of the Main Survey. Study members self-reported their intention to take up a vaccination in the COVID-19 Survey. Results Of the study sample, 17.2% (N = 1842) indicated they were hesitant about having the vaccine. After adjustment for age, sex, and ethnicity, study members with a lower baseline cognition score were markedly more likely to be vaccine hesitant (odds ratio per standard deviation lower score in cognition; 95% confidence interval: 1.76; 1.62, 1.90). Adjustment for mental and physical health plus household shielding status had no impact on these results, whereas controlling for educational attainment led to partial attenuation but the probability of hesitancy was still elevated (1.52; 1.37, 1.67). There was a linear association for vaccine hesitancy across the full range of cognition scores (p for trend: p &lt; 0.0001). Conclusions Erroneous social media reports might have complicated personal decision-making, leading to people with lower cognitive ability being vaccine-hesitant. With individuals with lower cognition also experiencing higher rates of COVID-19 in studies conducted prior to vaccine distribution, these new findings are suggestive of a potential additional disease burden

Psychological correlates of free colorectal cancer screening uptake in a Scottish sample: A cross-sectional observational study

Objectives Colorectal cancer (CRC) screening uptake in Scotland is 56%. This study examined whether psychological factors were associated with CRC screening uptake. Design Cross-sectional observational study. Setting This study used data from the Healthy AGeing In Scotland (HAGIS) pilot study, a study designed to be representative of Scottish adults aged 50 years and older. Participants 908 (505 female) Scottish adults aged 50 to 80 years (mean age=65.84, SD=8.24), who took part in the HAGIS study (2016-2017). Primary and secondary outcome measures Self-reported participation in CRC screening was the outcome measure. Logistic regression was used to test whether scores on measures of health literacy, cognitive ability, risk aversion, time preference (e.g., present-oriented or future-oriented), and personality were associated with CRC screening when these psychological factors were entered individually and simultaneously in the same model. Results Controlling for age, age-squared, sex, living arrangement, and sex*living arrangement, a one-point increase in risk aversion (OR=0.66, 95% CI 0.51 to 0.85), and present-orientation (OR=0.86, 0.80 to 0.94) was associated with reduced odds of screening. Higher scores on health literacy (OR per one-point increase=1.20, 1.09 to 1.31), cognitive ability (OR per SD increase=1.51, 1.25 to 1.81), and the intellect personality trait (OR per one-point increase=1.05, 1.01 to 1.09) were associated with increased odds of screening. Higher risk aversion was the only psychological variable that was associated with CRC screening participation when all psychological variables were entered in the same models, and remained associated with CRC screening when additionally adjusting for deprivation and education. A backward elimination model retained two psychological variables as correlates of CRC screening; risk aversion and cognitive ability. Conclusion Individuals who are more risk averse are less likely to participate in free, home CRC screening

Difference in distribution functions:A new diffusion weighted imaging metric for estimating white matter integrity

Diffusion weighted imaging (DWI) is a widely recognized neuroimaging technique to evaluate the microstructure of brain white matter. The objective of this study is to establish an improved automated DWI marker for estimating white matter integrity and investigating ageing related cognitive decline. The concept of Wasserstein distance was introduced to help establish a new measure: difference in distribution functions (DDF), which captures the difference of reshaping one's mean diffusivity (MD) distribution to a reference MD distribution. This new DWI measure was developed using a population-based cohort (n=19,369) from the UK Biobank. Validation was conducted using the data drawn from two independent cohorts: the Sydney Memory and Ageing Study, a community-dwelling sample (n=402), and the Renji Cerebral Small Vessel Disease Cohort Study (RCCS), which consisted of cerebral small vessel disease (CSVD) patients (n=171) and cognitively normal controls (NC) (n=43). DDF was associated with age across all three samples and better explained the variance of changes than other established DWI measures, such as fractional anisotropy, mean diffusivity and peak width of skeletonized mean diffusivity (PSMD). Significant correlations between DDF and cognition were found in the UK Biobank cohort and the MAS cohort. Binary logistic analysis and receiver operator characteristic curve analysis of RCCS demonstrated that DDF had higher sensitivity in distinguishing CSVD patients from NC than the other DWI measures. To demonstrate the flexibility of DDF, we calculated regional DDF which also showed significant correlation with age and cognition. DDF can be used as a marker for monitoring the white matter microstructural changes and ageing related cognitive decline in the elderly