Catharine R Gale’s research while affiliated with University of Southampton and other places

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Publications (393)


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

March 2024

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17 Reads

Bone

Rebecca J. Moon

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Sarah R. Crozier

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Nicholas C. Harvey

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

August 2023

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10 Reads

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6 Citations

Brain Behavior and Immunity

Background: While systemic inflammation has been implicated in the etiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS) 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) ascribed to ALS. 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
  • Preprint
  • File available

March 2023

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18 Reads

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1 Citation

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.

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Hazard Ratios for the Association Between Baseline Characteristics and later Hospitalisation for Amyotrophic Lateral Sclerosis, UK Biobank 2006 to 2020
Pre-Morbid Risk Factors for Amyotrophic Lateral Sclerosis: Prospective Cohort Study

October 2021

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18 Reads

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3 Citations

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.


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

September 2021

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39 Reads

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18 Citations

American Journal of Epidemiology

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 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 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 5th March, 2020 and 24th January, 2021. In age- and sex-adjusted analyses, relative to White participants, Black study members experienced around five times the risk of COVID-19 mortality (odds ratio; 95% confidence interval: 4.81; 3.28, 7.05), while there was a doubling in the South Asian group (2.05; 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 (2.84; 1.91, 4.23) and 37% in South Asian individuals (1.57; 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.

August 2021

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6 Reads

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1 Citation

Clinical Epidemiology

Background As a neurodegenerative disorder with high case-fatality, there is a need to identify primary, modifiable risk factors for amyotrophic lateral sclerosis (ALS). Their detection has, however, proved elusive and this may be ascribed to the scarcity of well-characterised, sufficiently-powered cohort studies necessary to explore the aetiology of this rare condition. Methods UK Biobank is an on-going, closed, prospective cohort study in which 502,524 participants (273,420 women) have been linked to national hospital and mortality registries. Baseline data collection took place between 2006 and 2010 when a range of psychosocial, physiological, and demographic data were captured. Results Approximately 11 years of event surveillance gave rise to 301 hospitalisations and 279 deaths ascribed to ALS. After left censoring to account for reverse causality and adjustment for 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 due to the disorder was the outcome of interest. Of the remaining 23 potential 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). Conclusions In the present study, a comprehensive array of potential risk indices were essentially unrelated to later ALS.


Hazard ratios for the association between baseline characteristics and hospitalisation for amyotrophic lateral sclerosis, UK Biobank 2006 to 2020
Pre-morbid risk factors for amyotrophic lateral sclerosis: prospective cohort study

July 2021

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17 Reads

Background: As a neurodegenerative disorder with high case-fatality, there is a need to identify primary, modifiable risk factors for amyotrophic lateral sclerosis (ALS). Their detection has, however, proved elusive and this may be ascribed to the scarcity of well-characterised, sufficiently-powered cohort studies necessary to explore the aetiology of this rare condition. Methods: UK Biobank is an on-going, closed, prospective cohort study in which 502,524 participants (273,420 women) have been linked to national hospital and mortality registries. Baseline data collection took place between 2006 and 2010 when a range of psychosocial, physiological, and demographic data were captured. Results: Approximately 11 years of event surveillance gave rise to 301 hospitalisations and 279 deaths ascribed to ALS. After left censoring to account for reverse causality and adjustment for 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 due to the disorder was the outcome of interest. Of the remaining 23 potential 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). Conclusions: In the present study, a comprehensive array of potential risk indices were essentially unrelated to later ALS.


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

June 2021

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14 Reads

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6 Citations

Epidemiology

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 of this characteristic. 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 5901 individuals (3221 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; 95% confidence interval: 1.45; 0.84, 2.51), while 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.


Fig. 1. HDL-C concentration (2006-10) and risk of subsequent hospitalisation for COVID-19 (2020) in UK Biobank (N = 317,306). Multiply adjusted odds ratios are adjusted for age, sex, ethnicity, education, number in household, area deprivation, body mass index, leisure time physical activity, alcohol intake, smoking habit, diagnosed diabetes, cardiovascular disease, or hypertension, cholesterol-lowering medication, LDL-cholesterol, triglycerides, haemoglobin, white blood cell, and platelet count. The reference group is HDL-C <1.0 mmol/L, comprising 28,619 participants at risk of whom 246 were hospitalised.
Fig. 2. HDL-C concentration (2006-10) and risk of death from COVID-19 (2020) in UK Biobank (N = 317,827). Multiply adjusted odds ratios are adjusted for age, sex, ethnicity, education number in household, area deprivation, body mass index, leisure time physical activity, alcohol intake, smoking habit, diagnosed diabetes, cardiovascular disease, or hypertension, cholesterol-lowering medication, LDL-cholesterol, triglycerides, haemoglobin, white blood cell, and platelet count. The reference group is HDL-C <1.0 mmol/L, comprising 28,699 participants at risk of whom 89 died of COVID-19.
Association of pre-pandemic high-density lipoprotein cholesterol with risk of COVID-19 hospitalisation and death: The UK Biobank cohort study

June 2021

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26 Reads

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13 Citations

Preventive Medicine Reports

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.


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

May 2021

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141 Reads

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44 Citations

Brain Behavior and Immunity

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. Accordingly, our objective was 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. 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 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. Study members self-reported their intention to take up a vaccination for COVID-19. 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 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.


Citations (58)


... Studies have found that elevated levels of CRP are associated with a higher risk of mortality and faster disease progression in ALS 32 . Furthermore, a recent prospective study has shown that higher CRP levels are associated with an increased risk of developing ALS 31 . Thirdly, albumin is a non-glycosylated plasma protein whose metabolism is affected by nutritional intake and inflammatory diseases. ...

Reference:

Lower creatinine-to-cystatin c ratio associated with increased risk of incident amyotrophic lateral sclerosis in the prospective UK biobank cohort
Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: Prospective cohort study
  • Citing Article
  • August 2023

Brain Behavior and Immunity

... CSF parameters included leukocyte counts, total protein, lactate, oligoclonal IgG bands (OCB), immunoglobulin (Ig) synthesis, and pNfH. In blood, CRP, [26][27][28] CK, 29,30 and NfL were tested. 31 For measurement of pNfH and NfL, CSF and blood samples from all participating centers were centrally analyzed at the CSF Laboratory of Ulm University. ...

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

... Nonetheless, monogenic ALS mutations may still exhibit incomplete penetrance or delayed onset [8], as exposure to certain environmental factors might modify the risk the mutations confer [8]. Many environmental risk factors have been studied in relation to ALS [9, 10], with some of the associations potentially varying by age, sex, and genetic factors [11][12][13][14][15]. ...

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

... Although there are various studies that demonstrate ethnic differences in COVID-19 mortality in different countries, their results are not directly applicable to Peru due to sociocultural and healthcare system differences that impact health indicators in each country [14][15][16][17][18][19]. Similarly, while one study compared the risk of infection and mortality from COVID-19 between native Amazonian peoples and the general population in Peru, it did not compare with the Andean indigenous peoples [8], who have different sociodemographic characteristics and access to healthcare compared to Amazonian peoples [11][12][13][14][15][16][17][18][19][20]. ...

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

American Journal of Epidemiology

... Stress across the life course included childhood adversity and stressful life events, which were shown to be significantly associated with mortality [34] and phenotypic age [35]. Childhood adversity was defined as at least one of the following four adverse experiences during childhood: continuous separation from mother for more than a year, parents frequently quarrelling, being sent away from home due to wrongdoing, or an experience so frightening that it was thought about years afterwards [36]. ...

Life-course Psychological Distress and Total Mortality by Middle Age: The 1970 Birth Cohort Study
  • Citing Article
  • June 2021

Epidemiology

... During the COVID-19 pandemic there have been several studies examining the effect of lipid/lipoprotein levels on the risk of developing COVID-19 infections. Studies using the UK Biobank and other large databases have found that decreased HDL-C and apolipoprotein A-I levels measured many years prior to COVID-19 infections were associated with an increased risk of COVID-19 infections while LDL-C, apolipoprotein B, Lp (a), and triglyceride levels were not consistently associated with an increased risk [1,2,[82][83][84][85][86][87][88][89][90][91]. For example, a 0.26 mmol/L (10 mg/dL) decrease in HDL-C or 10mg/dL decrease in Apo A-I levels were associated with an approximately 10% increased risk of severe COVID-19 infection [83]. ...

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

Preventive Medicine Reports

... majorities), rural (vs. urban) communities, more politically conservative or fundamentally religious groups, and in individuals with lower socioeconomic status or education level (e.g., [8][9][10][25][26][27][28][29][30][31]. ...

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

Brain Behavior and Immunity

... As previous studies have shown [10,69,70], post-COVID-19 syndrome is characterized by multiple symptoms such as fatigue, dizziness, problems with concentration, memory and executive functions that affect all daily activities. In our research, we used reaction time measurement because it is associated with a decrease in the speed of information processing [71]. It has also been shown that reaction time measurement can be used to estimate the risk of death from COVID-19 [71]. ...

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

European Journal of Epidemiology

... The gradient can be observed along multiple socioeconomic indicators, including family background and individual characteristics [2][3][4][5][6] . While some studies have documented the differential risk along parental income or parental education 7,8 , other studies point to the importance of one's own educational attainment or income for understanding mortality risk 5,[9][10][11][12][13] . Further, parental and individual factors are correlated and probably interact with each other 14,15 . ...

Intelligence, health and death
  • Citing Article
  • April 2021

Nature Human Behaviour

... A growing body of research focuses on the impact of pre-existing mental disorders on COVID-19 clinical outcomes among this vulnerable population. Preexisting mental disorders were associated with risk of severe COVID-19 clinical outcomes (hospitalization, intensive care unit [ICU] admission, invasive ventilation, or death) (8)(9)(10)(11). Recent studies also found a higher mortality rate among COVID-19 patients with mental disorders compared to the general population (12,13). Likewise, hospitalized COVID-19 patients with severe psychiatric disorders died at a younger age than those without a psychiatric disorder after controlling for other clinically relevant variables. ...

Pre-pandemic mental illness and risk of death from COVID-19
  • Citing Article
  • March 2021

The Lancet Psychiatry