Catharine R. Gale

Importance While systemic inflammation has been implicated in the aetiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS) is untested. Objective To quantify the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with ALS occurrence. Design, Setting, Participants UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centres between 2006 and 2010. Exposure Venous blood was collected at baseline in the full cohort and assayed for CRP. Repeat measurement was made 3-7 years later in a representative subgroup (N=14,514) enabling correction for regression dilution. Main Outcome(s) and Measure(s) ALS as ascertained via national hospitalisation and mortality registries. We computed multi-variable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles. Results In an analytical sample of 400,884 individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalisations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviours, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalisations (1.20; 1.00, 1.39). There was evidence of dose-response effects across tertiles of CRP for both outcomes (p for trend≤0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalisations (1.37; 1.05, 1.76) ascribed to ALS. Conclusions and Relevance Higher levels of CRP, a blood-based biomarker widely captured in clinical practice, were associated with a higher subsequent risk of ALS. Question Is C-reactive protein (CRP), a marker of systemic inflammation widely used in clinical practice, associated with later risk of amyotrophic lateral sclerosis (ALS)? Findings Following 11 years disease surveillance in 400,884 individuals (218,203 women), after adjustment for covariates and correction for regression dilution, a one standard deviation higher CRP levels were associations with both mortality (hazard ratio; 95% confidence interval: 1.62; 1.27, 2.08) and hospitalisations (1.37; 1.05, 1.76) ascribed to ALS. Meaning In the present study, CRP has a dose-response relationship with the risk of later ALS.

Background: The onset of psychological distress most commonly occurs in adolescence and, in keeping with other exposures, is time-varying across the life course. Most studies of its association with mortality risk are, however, conducted in middle- and older-aged populations with a single baseline assessment. This may lead to an underestimation of the magnitude of distress–mortality relationship. Methods: We used data from the 1970 British Cohort Study, a prospective cohort study. Psychological distress and covariates were collected at ages 5, 10, and 26. Vital status was ascertained between ages 26 and 44 years. Results: Eighteen years of mortality surveillance of 5,901 individuals (3,221 women) gave rise to 74 deaths. After adjustment for a series of confounding factors which included early life socioeconomic status, birth characteristics, and cognition, relative to the unaffected group, distress in childhood only was associated with around a 50% elevation in mortality risk (hazard ratio = 1.45; 95% confidence interval = 0.84, 2.51), whereas distress in adulthood only was related to a doubling of risk (1.95; 0.90, 4.21). In study members with persistent distress symptoms (childhood and adulthood), there was a tripling of the death rate (3.10; 1.42, 6.74) (P value for trend across these categories: 0.002). Conclusion: The suggestion of a strong association between life-course distress and death warrants replication in a study with a greater number of events.

Poorer performance on standard tests of pre-morbid cognitive function is related to an elevated risk of death from lower respiratory tract infections but the link with coronavirus (COVID‑19) mortality is untested. Participants in UK Biobank, aged 40 to 69 years at study induction (2006–10), were administered a reaction time test, an indicator of information processing speed, and also had their verbal-numeric reasoning assessed. Between April 1st and September 23rd 2020 there were 388 registry-confirmed deaths (138 women) ascribed to COVID-19 in 494,932 individuals (269,602 women) with a reaction time test result, and 125 such deaths (38 women) in the subgroup of 180,198 people (97,794 women) with data on verbal-numeric reasoning. In analyses adjusted for age, sex, and ethnicity, a one standard deviation slower reaction time was related to a higher rate of death from COVID-19 (hazard ratio; 95% confidence interval: 1.18; 1.09, 1.28), as was a one standard deviation disadvantage on the verbal-numeric reasoning test (1.32; 1.09, 1.59). While there was some attenuation in these relationships after adjustment for additional covariates which included socio-economic status and lifestyle factors, the two pre-pandemic indicators of cognitive function continued to be related to COVID-19 mortality.

The field of cognitive epidemiology studies the prospective associations between cognitive abilities and health outcomes. We review research in this field over the past decade and describe how our understanding of the association between intelligence and all-cause mortality has consolidated with the appearance of new, population-scale data. To try to understand the association better, we discuss how intelligence relates to specific causes of death, diseases/diagnoses and biomarkers of health through the adult life course. We examine the extent to which mortality and health associations with intelligence might be attributable to people’s differences in education, other indicators of socioeconomic status, health literacy and adult environments and behaviours. Finally, we discuss whether genetic data provide new tools to understand parts of the intelligence–health associations. Social epidemiologists, differential psychologists and behavioural and statistical geneticists, among others, contribute to cognitive epidemiology; advances will occur by building on a common cross-disciplinary knowledge base.

Background Whereas several predictors of COVID-19 vaccine hesitancy have been examined, the role of cognitive function following the widely publicised development of an inoculation is unknown. Objective To test 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 Oxford University/AstraZeneca vaccine. Design, Setting, and Participants We used individual-level data from a pandemic-focused study (COVID Survey), a prospective cohort study nested within 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 11740 individuals (6702 women) aged 16-95. Pre-pandemic scores on general cognitive function, ascertained from a battery of six tests, were captured in 2011/12 wave of the Main Survey. Measurements Self-reported intention to take up a vaccination for COVID-19. To summarise our results, we computed odds ratios with accompanying 95% confidence intervals for general cognitive function adjusted for selected covariates. 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: pLimitations Our outcome was based on intention rather than behaviour. Conclusions Erroneous social media reports might have complicated personal decision-making, leading to people with lower cognitive ability test scores being vaccine-hesitant. With people 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.

Background: Poorer performance on standard tests of cognitive function is related to an elevated risk of death from lower respiratory tract infections. Whether pre-pandemic measures of cognition are related to COVID-19 mortality is untested. Methods: UK Biobank, a prospective cohort study, comprises around half a million people who were aged 40 to 69 years at study induction between 2006 and 2010 when a reaction time test was administered to the full sample, and verbal-numeric reasoning assessed in a subgroup. Death from COVID-19 was ascertained from participant linkage to a UK-wide national registry. Results: Between April 1 ^st and September 23 ^rd 2020, there were 388 deaths (138 women) ascribed to COVID-19 in the 494,932 individuals (269,602 women) with a reaction time test result, and 125 such deaths (38 women) in the 180,198 (97,794 women) for whom there were data on verbal-numeric reasoning. In analyses adjusted for age, sex, and ethnicity, a one standard deviation (118.2 msec) slower reaction time was related to a higher rate of death from COVID-19 (hazard ratio; 95% confidence interval: 1.18; 1.09, 1.28). A one standard deviation disadvantage (2.16 point) on the verbal-numeric reasoning test was also associated with an elevated risk of death (1.32; 1.09, 1.59). Attenuation after adjustment for additional covariates followed a similar pattern for both measures of cognition. For verbal-numeric reasoning, for instance, the hazard ratios were 1.22 (0.98, 1.51) after control for socioeconomic status, 1.16 (0.96, 1.41) after lifestyle factors, 1.25 (1.04, 1.52) after co-morbidity, and 1.29 (1.01, 1.64) after physiological indices. Conclusions: In the present study, poorer performance on two pre-pandemic indicators of cognitive function, including reaction time, a knowledge-reduced measure, was related to death ascribed to COVID-19.

Recent findings suggest that psychological distress in childhood—a combination of symptoms of anxiety and depression—particularly when persistent across the life course is related to an elevated rate of cardiovascular disease mortality in older age. ¹ Several mechanisms have been implicated with one possibility being that people who experience distress in early life, and particularly its recurrence across the life course, may become more susceptible to vascular disease via differences in physiological development. There is, however, a paucity of studies holding data on early distress and biological risk factors for cardiovascular disease in adulthood.