Cognitive function and skeletal size and mineral density at age 6-7 years: Findings from the Southampton Women's Survey.

INTRODUCTION: Poor cognitive function and osteoporosis commonly co-exist in later life. In women, this is often attributed to post-menopausal estrogen loss. However, a common early life origin for these conditions and the associations between cognitive function and bone mineral density (BMD) in childhood have not previously been explored. We examined these relationships at age 6-7 years in the Southampton Women's Survey (SWS) mother-offspring cohort. METHODS: Child occipitofrontal circumference (OFC), a proxy for brain volume, intelligence quotient (IQ) [Wechsler Abbreviated Scale of Intelligence] and visual recognition and working memory [CANTAB® Delayed Matching to Sample (DMS) and Spatial Span Length (SSP), respectively] were assessed. Whole-body-less-head (WBLH) and lumbar spine dual-energy X-ray absorptiometry [Hologic Discovery] (DXA) were performed to measure bone area (BA), bone mineral content (BMC), BMD and bone mineral apparent density (BMAD). Linear regression was used to examine associations between age and sex standardized variables (ß represent standard deviation (SD) difference per SD of cognitive function). RESULTS: DXA was performed in 1331 children (mean (SD) age 6.8 (0.33) years, 51.5 % male), with OFC, IQ, DMS and SSP assessed in 1250, 551, 490 and 460, respectively. OFC (ß = 0.25 SD/SD, 95%CI 0.20,0.30), IQ (ß = 0.11 SD/SD, 95%CI 0.02,0.19), and DMS (ß = 0.11, SD/SD, 95%CI 0.01,0.20) were positively associated with WBLH BA, with similar associations for lumbar spine BA. OFC and DMS were also positively associated with WBLH BMC, but only OFC was associated with BMD (WBLH: ß = 0.38 SD/SD, 95%CI 0.33,0.43; LS: ß = 0.19 SD/SD, 95%CI 0.13,0.24). CONCLUSION: Childhood brain volume was positively associated with measures of skeletal size and BMD, whereas IQ and memory were associated only with skeletal size. These findings suggest that common early life determinants for skeletal growth and BMD and cognitive function should be explored to identify potential early-life approaches to preventing osteoporosis and cognitive decline.

Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: Prospective cohort study.

BACKGROUND: While systemic inflammation has been implicated in the etiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS), a condition with high case-fatality, is untested. Accordingly, we quantified the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with subsequent ALS occurrence. METHODS: We used data from UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centers between 2006 and 2010. Venous blood was collected at baseline in the full cohort and assayed for CRP, and repeat measurement was made 3-7 years later in a representative subgroup (N = 14,514) enabling correction for regression dilution. ALS was ascertained via national hospitalization and mortality registries until 2021. We computed multivariable 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 initially ALS-free individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalizations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviors, 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 hospitalizations (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 hospitalizations (1.37; 1.05, 1.76). CONCLUSIONS: Higher levels of CRP, a blood-based biomarker widely captured in clinical practice, is associated with moderately increased future risk of amyotrophic lateral sclerosis.

Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: prospective cohort study.

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 Outcomes and Measures: 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. Key Points: 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.

Explaining Ethnic Differentials in COVID-19 Mortality: A Cohort Study.

Ethnic inequalities in coronavirus disease 2019 (COVID-19) hospitalizations and mortality have been widely reported, but there is scant understanding of how they are embodied. The UK Biobank prospective cohort study comprises approximately half a million people who were aged 40-69 years at study induction, between 2006 and 2010, when information on ethnic background and potential explanatory factors was captured. Study members were prospectively linked to a national mortality registry. In an analytical sample of 448,664 individuals (248,820 women), 705 deaths were ascribed to COVID-19 between March 5, 2020, and January 24, 2021. In age- and sex-adjusted analyses, relative to White participants, Black study members experienced approximately 5 times the risk of COVID-19 mortality (odds ratio (OR) = 4.81, 95% confidence interval (CI): 3.28, 7.05), while there was a doubling in the South Asian group (OR = 2.05, 95% CI: 1.30, 3.25). Controlling for baseline comorbidities, social factors (including socioeconomic circumstances), and lifestyle indices attenuated this risk differential by 34% in Black study members (OR = 2.84, 95% CI: 1.91, 4.23) and 37% in South Asian individuals (OR = 1.57, 95% CI: 0.97, 2.55). The residual risk of COVID-19 deaths in ethnic minority groups may be ascribed to a range of unmeasured characteristics and requires further exploration.

Pre-Morbid Risk Factors for Amyotrophic Lateral Sclerosis: Prospective Cohort Study.

AIM: In the absence of effective treatments for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder with high case fatality, there is a clear need to identify its primary risk factors. METHODS: UK Biobank is a prospective cohort study in which baseline data were captured between 2006 and 2010 in 502,649 participants aged 37 to 73 years. Follow-up for ALS hospitalisations and death was made via national registries. RESULTS: Eleven years of event surveillance gave rise to 301 hospitalisations and 279 deaths due to ALS. After adjustment for selected confounding factors, being older (hazard ratio per 10 year increase; 95% confidence interval: 1.92; 1.58, 2.33) and male (1.37; 1.00, 1.87) were associated with elevated rates of hospitalisation for ALS. Similar effects were apparent when death ascribed to the disorder was the outcome of interest. Of the remaining 23 social, biological, and behavioural risk indices, however, there was only a suggestion that taller people experienced an increased risk of hospitalisation (per SD increase: 1.31; 1.09, 1.59). CONCLUSION: In the present, large-scale study, other than well known associations, we did not find convincing evidence of links with ALS for other risk indices.

Association of pre-pandemic high-density lipoprotein cholesterol with risk of COVID-19 hospitalisation and death: The UK Biobank cohort study.

There is growing evidence of, and biological plausibility for, elevated levels of high-density lipoprotein cholesterol (HDL-C) being related to lower rates of respiratory disease. We tested whether pre-pandemic HDL-C within the normal range is associated with subsequent COVID-19 hospitalisations and death. We analysed data on participants from UK Biobank, a prospective cohort study, baseline data for which were collected between 2006 and 2010. Follow-up for COVID-19 was via hospitalisation records (1845 events in 317,306 individuals) and a national mortality registry (458 deaths in 317,833 individuals). After controlling for a series of confounding factors which included health behaviours, inflammatory markers, and socio-economic status, higher levels of HDL-C were related to a lower risk of later hospitalisation. The effect was linear (p-value for trend 0.001), whereby a 0.2 mmol/L increase in HDL-C was associated with a 7% lower risk (odds ratio; 95% confidence interval: 0.93; 0.90, 0.96). Corresponding relationships for mortality were markedly weaker, such that statistical significance at conventional levels were not apparent for both the linear trend (p-value 0.25) and the odds ratio per 0.2 mmol/L increase (0.98; 0.91, 1.05). While our finding for HDL-C and hospitalisations for COVID-19 raise the possibility that favourable modification of this cholesterol fraction via lifestyle changes or drug intervention may impact upon the risk of the disease, it warrants testing in other studies.

Life-course Psychological Distress and Total Mortality by Middle Age: The 1970 Birth Cohort Study.

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.

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 < 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.

Pre-pandemic Cognitive Function and COVID-19 Vaccine Hesitancy: Cohort Study.

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: p<0.0001). Limitations: 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.

Intelligence, health and death.

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.

Pre-pandemic cognitive function and COVID-19 mortality: prospective cohort study.

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 (COVID­19) 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.

Association of pre-pandemic high-density lipoprotein cholesterol with risk of COVID-19 hospitalisation and death: the UK Biobank cohort study.

OBJECTIVE: There is growing evidence of, and biological plausibility for, elevated levels of high-density lipoprotein cholesterol (HDL-C), being related to lower rates of severe infection. Accordingly, we tested whether pre-pandemic HDL-C within the normal range is associated with subsequent COVID-19 hospitalisations and death. APPROACH: We analysed data on 317,306 participants from UK Biobank, a prospective cohort study, baseline data for which were collected between 2006 and 2010. Follow-up for COVID-19 was via hospitalisation records and a national mortality registry. RESULTS: After controlling for a series of confounding factors which included health behaviours, inflammatory markers, and socio-economic status, higher levels of HDL-C were related to a lower risk of later hospitalisation for COVID-19. The effect was linear (p-value for trend 0.001) such that a 0.2 mmol/L increase in HDL-C was associated with a corresponding 9% reduction in risk (odds ratio; 95% confidence interval: 0.91; 0.86, 0.96). A very similar pattern of association was apparent when COVID-19 mortality was the outcome of interest (odds ratio per 0.2 mmol/l increase in HDL-C: 0.90; 0.81, 1.00); again, a stepwise effect was evident (p-value for trend 0.03). CONCLUSIONS: These novel results for HDL-C and COVID-19 events warrant testing in other studies.

Pre-pandemic cognitive function and COVID-19 mortality: prospective cohort study.

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 1st and September 23rd 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.

Explaining ethnic disparities in COVID-19 mortality: population-based, prospective cohort study.

Ethnic disparities in COVID-19 hospitalizations and mortality have been reported but there is scant understanding of how these inequalities are embodied. The UK Biobank prospective cohort study comprises around half a million people who were aged 40-69 years at study induction between 2006 and 2010 when information on ethnic background and potential explanatory factors was captured. Study members were linked to a national mortality registry. In an analytical sample of 448,664 individuals (248,820 women), 354 deaths were ascribed to COVID-19 between 5th March and the end of follow-up on 17th September 2020. In age- and sex-adjusted analyses, relative to White participants, Black study members experienced around seven times the risk of COVID-19 mortality (odds ratio; 95% confidence interval: 7.25; 4.65, 11.33), while there was a doubling in the Asian group (1.98; 1.02, 3.84). Controlling for baseline comorbidities, socioeconomic circumstances, and lifestyle factors explained 53% of the differential in risk for Asian people (1.37; 0.68, 2.77) and 27% in Black study members (4.28; 2.67, 6.86). The residual risk in ethnic minority groups for COVID-19 deaths may be ascribed to unknown genetic factors or unmeasured phenotypes, most obviously racial discrimination.

The influence of X chromosome variants on trait neuroticism.

Autosomal variants have successfully been associated with trait neuroticism in genome-wide analysis of adequately powered samples. But such studies have so far excluded the X chromosome from analysis. Here, we report genetic association analyses of X chromosome and XY pseudoautosomal single nucleotide polymorphisms (SNPs) and trait neuroticism using UK Biobank samples (N = 405,274). Significant association was found with neuroticism on the X chromosome for 204 markers found within three independent loci (a further 783 were suggestive). Most of the lead neuroticism-related X chromosome variants were located in intergenic regions (n = 397). Involvement of HS6ST2, which has been previously associated with sociability behaviour in the dog, was supported by single SNP and gene-based tests. We found that the amino acid and nucleotide sequences are highly conserved between dogs and humans. From the suggestive X chromosome variants, there were 19 nearby genes which could be linked to gene ontology information. Molecular function was primarily related to binding and catalytic activity; notable biological processes were cellular and metabolic, and nucleic acid binding and transcription factor protein classes were most commonly involved. X-variant heritability of neuroticism was estimated at 0.22% (SE = 0.05) from a full dosage compensation model. A polygenic X-variant score created in an independent sample (maximum N ≈ 7,300) did not predict significant variance in neuroticism, psychological distress, or depressive disorder. We conclude that the X chromosome harbours significant variants influencing neuroticism, and might prove important for other quantitative traits and complex disorders.

Childhood correlates of adult positive mental well-being in three British longitudinal studies.

BACKGROUND: Previous evidence has shown how experiences within childhood, such as parenting and socioeconomic conditions, are associated later on in life with adult mental well-being. However, these studies tend to focus on childhood experiences in isolation, and fewer studies have investigated how multiple aspects of the childhood environment, including both socioeconomic and psychosocial aspects, are associated with adult positive mental well-being. Using data from three British birth cohort studies, we investigated how prospective measures of the childhood environment up to the age of 16 years were associated with midlife adult mental well-being and whether similar associations were replicated across different generations. METHODS: Childhood environment comprised socioeconomic circumstances, psychosocial factors (child-rearing and parenting, family instability) and parental health. The Warwick-Edinburgh Mental Wellbeing Scale, a validated instrument measuring both hedonic and eudaemonic aspects of well-being, was administered in mid-life. We modelled associations between childhood environment domains and well-being. RESULTS: Despite changes in social context in all three studies, poorer quality parent-child relationships and poor parental mental health were strongly and independently associated with poorer adult mental well-being. Socioeconomic circumstances were also associated with adult mental well-being, but the association was weaker than for the measures of parenting or parental mental health. CONCLUSION: These findings confirm that parenting and parental mental health, as well as socioeconomic circumstances, are important for adult mental well-being. Interventions in early childhood aimed at reducing socioeconomic adversity and offering support to parents might be warranted, to enhance adult mental well-being later on in the life course.

Overweight, obesity, and risk of hospitalization for COVID-19: A community-based cohort study of adults in the United Kingdom.

The role of obesity and overweight in occurrence of COVID-19 is unknown. We conducted a large-scale general population study using data from a community-dwelling sample in England (n = 334,329; 56.4 ±8.1 y; 54.5% women) with prospective linkage to national registry on hospitalization for COVID-19. Body mass index (BMI, from measured height and weight) was used as an indicator of overall obesity, and waist-hip ratio for central obesity. Main outcome was cases of COVID-19 serious enough to warrant a hospital admission from 16 March 2020 to 26 April 2020. Around 0.2% (n = 640) of the sample were hospitalized for COVID-19. There was an upward linear trend in the likelihood of COVID-19 hospitalization with increasing BMI, that was evident in the overweight (odds ratio, 1.39; 95% CI 1.13 to 1.71; crude incidence 19.1 per 10,000) and obese stage I (1.70;1.34 to 2.16; 23.3 per 10,000) and stage II (3.38; 2.60 to 4.40; 42.7 per 10,000) compared to normal weight (12.5 per 10,000). This gradient was little affected after adjustment for a wide range of covariates; however, controlling for biomarkers, particularly high-density lipoprotein cholesterol and glycated hemoglobin, led to a greater degree of attenuation. A similar pattern of association emerged for waist-hip ratio. In summary, overall and central obesity are risk factors for COVID-19 hospital admission. Elevated risk was apparent even at modest weight gain. The mechanisms may involve impaired glucose and lipid metabolism.

Inflammation as a risk factor for the development of frailty in the Lothian Birth Cohort 1936.

BACKGROUND: Research suggests that frailty is associated with higher inflammation levels. We investigated the longitudinal association between chronic inflammation and frailty progression. METHODS: Participants of the Lothian Birth Cohort 1936, aged 70 at baseline were tested four times over 12 years (wave 1: n = 1091, wave 4: n = 550). Frailty was assessed by; the Frailty Index at waves 1-4 and Fried phenotype at waves 1, 3 and 4. Two blood-based inflammatory biomarkers were measured at wave 1: Fibrinogen and C-reactive protein (CRP). RESULTS: Fully-adjusted, linear mixed effects models showed higher Fibrinogen was significantly associated with higher wave 1 Frailty Index score (ß = 0.011, 95% CI[0.002,0.020], p < .05). Over 12 year follow-up, higher wave 1 CRP (ß = 0.001, 95% CI[0.000,0.002], p < .05) and Fibrinogen (ß = 0.004, 95% CI[0.001,0.007], p < .05) were significantly associated with increased Frailty Index change. For the Fried phenotype, wave 1 Pre-frail and Frail participants had higher CRP and Fibrinogen than Non-frail participants (p < .001). Logistic regression models calculated risk of worsening frailty over follow-up and we observed no significant association of CRP or Fibrinogen in minimally-adjusted nor fully-adjusted models. CONCLUSIONS: Findings showed a longitudinal association of higher wave 1 CRP and Fibrinogen on worsening frailty in the Frailty Index, but not Fried Phenotype. A possible explanation for this disparity may lie in the conceptual differences between frailty measures (a biopsychosocial vs physical approach). Future research, which further explores different domains of frailty, as well the associations between improving frailty and inflammation levels, may elucidate the pathway through which inflammation influences frailty progression. This may improve earlier identification of those at high frailty risk.