No clear evidence for relationships of Apolipoprotein E genotype with measures of common infections in three UK cohorts (preprint)

APOE genotype is the strongest genetic risk factor for late onset Alzheimer's disease, with the ϵ2 and ϵ4 alleles decreasing and increasing risk relative to the ϵ3 allele, respectively. Although evidence has been conflicting, several common infections have been associated with Alzheimer's disease risk, and interactions by APOE ϵ4 carriage have also been reported. Nevertheless, to date, no study has examined relationships between APOE genotype and measures of multiple common infections among large population-based studies. We investigated associations of APOE ϵ2 and ϵ4 carriage (i.e. non-carrier vs carrier) with serostatus and antibody titers to 14 common pathogens — encompassing herpesviruses, human polyomaviruses, C.trachomatis , H.pylori , and T.gondii — in three population—based cohorts (UK Biobank, National Survey of Health and Development, Southall and Brent Revisited). Pathogen serostatus was derived using validated antibody cut-offs for relevant antigens and included as an outcome assessing previous infection. Antibody titers were dichotomised among the seropositive subset for each antigen and included as binary outcomes assessing recent immunological responses. We conducted analyses in each cohort using mixed-models, including age, sex and genetic principal components as fixed-effects, and genetic relatedness as a random-effect. In secondary analyses, we additionally assessed i) relationships of APOE ϵ2 and ϵ4 dosage (i.e. number of copies of the allele of interest), and ii) relationships of APOE genotype with continuous antibody titers (rank-based inverse normal transformed). Findings were meta-analysed across cohorts (n=10,059) using random-effects models and corrected for multiple tests using the false discovery rate. We found no clear evidence of relationships between APOE genotype and serostatus or antibody titers to any pathogen, with no strong associations observed in any of our analyses following multiple testing correction. Investigations of APOE genotypes with the clinical manifestations of these pathogens, as well as expanding to include other viruses such as SARS-CoV-2, would also be warranted.

Examining the inter-relationships between social isolation and loneliness and their correlates among older British adults before and during the COVID-19 lockdown: evidence from four British longitudinal studies (preprint)

Background and Objectives: Unprecedented social restrictions during the COVID-19 pandemic have provided a new lens for considering the inter-relationship between social isolation and loneliness in later life. We present these inter-relationships before and during the COVID-19 restrictions and investigate to what extent demographic, socio-economic, and health factors associated with such experiences differed during the pandemic. Research Design and Method: We used data from four British longitudinal population-based studies (1946 MRC NSHD, 1958 NCDS, 1970 BCS, and ELSA). Rates, co-occurrences, and correlates of social isolation and loneliness are presented prior to and during the early stage of the COVID-19 pandemic and the inter-relationships between these experiences are elucidated in both periods. Results: Across the four studies, pre-pandemic proportions reporting social isolation ranged from 15 to 54%, with higher rates in older ages (e.g., 32% of 70-79 and 54% of those over 80). During the pandemic, the percentage of older people reporting both social isolation and loneliness and isolation only slightly increased. The inter-relationship between social isolation and loneliness did not change. Associations between socio-demographic and health characteristics and social isolation and loneliness also remained consistent, with greater burden among those with greater economic precarity (females, non-homeowners, unemployed, illness and greater financial stress). Discussion and Implications: There were already large inequalities in experiences of social isolation and loneliness and the pandemic had a small impact on worsening these inequalities. The concepts of loneliness and social isolation are not transferable and clarity is needed in how they are conceptualised, operationalised, and interpreted.

Disruption of long-term psychological distress trajectories during the COVID-19 pandemic: evidence from three British birth cohorts (preprint)

Importance Mental health disorders were among the leading global contributors to years lived with disability prior to the COVID-19 pandemic onset, and growing evidence suggests that population mental health outcomes have worsened since the pandemic started. The extent that these changes have altered common age-related trends in psychological distress, where distress typically rises until mid-life and then falls in both sexes, is unknown. Objective To analyse whether long-term pre-pandemic psychological distress trajectories have altered during the pandemic, and whether these changes have been different across generations and by sex. Design Cross-cohort study with prospective data collection over a 40-year period (earliest time point: 1981; latest time point: February/March 2021). Setting Population-based (adult general population), Great Britain. Participants Members of three nationally representative birth cohorts which comprised all people born in Great Britain in a single week of 1946, 1958, or 1970, and who participated in at least one of the data collection waves conducted after the start of the pandemic (40.6%, 42.8%, 39.4%, respectively). Exposure(s) Time, COVID-19 pandemic. Main Outcome(s) and Measure(s) Psychological distress factor scores, as measured by validated self-reported questionnaires. Results 16,389 participants (2,175 from the 1946 birth cohort, 52.8% women; 7,446 from the 1958 birth cohort, 52.4% women; and 6,768 from the 1970 birth cohort, 56.2% women) participated in the study. By September/October 2020, psychological distress levels had reached or exceeded the levels of the peak in the pre-pandemic life-course trajectories, with larger increases in younger cohorts: Standardised Mean Differences (SMD) and 95% confidence intervals (CIs) of -0.02 [-0.07, 0.04], 0.05 [0.02, 0.07], and 0.09 [0.07, 0.12] for the 1946, 1958, and 1970 birth cohorts, respectively. Increases in distress were larger among women than men, widening the pre-existing inequalities observed in the pre-pandemic peak and in the most recent pre-pandemic assessment. Conclusions and Relevance Pre-existing long-term psychological distress trajectories of adults born between 1946 and 1970 were disrupted during the COVID-19 pandemic, particularly among women, who reached the highest levels ever recorded in up to 40 years of follow-up data. This may impact future trends of morbidity, disability, and mortality due to common mental health problems.

Psychological Distress Before and During the COVID-19 Pandemic: Sociodemographic Inequalities in 11 UK Longitudinal Studies (preprint)

Background: How population mental health has evolved across the COVID-19 pandemic under varied lockdown measures is poorly understood, with impacts on health inequalities unclear. We investigated changes in mental health and sociodemographic inequalities from before and across the first year of the pandemic in 11 longitudinal studies. Methods: Data from 11 UK longitudinal population-based studies with pre-pandemic measures of psychological distress were analysed and estimates pooled. Trends in the prevalence of poor mental health were assessed across the pandemic at three time periods: initial lockdown (TP1, Mar-June 20); easing of restrictions (TP2, July-Oct 20); and a subsequent lockdown (TP3, Nov 20-Mar 21). Multi-level regression was used to examine changes in psychological distress compared to pre-pandemic; with stratified analyses by sex, ethnicity, education, age, and UK country. Results: Across the 11 studies (n=54,609), mental health had deteriorated from pre-pandemic scores across all three pandemic time periods (TP1 Standardised Mean Difference (SMD): 0.13 (95% CI: 0.03, 0.23); TP2 SMD: 0.18 (0.09, 0.27); TP3 SMD: 0.20 (0.09, 0.31)). Changes in psychological distress across the pandemic were higher in females (TP3 SMD: 0.23 (0.11, 0.35)) than males (TP3 SMD: 0.16 (0.06, 0.26)), and slightly lower in below-degree level educated persons at some time periods (TP3 SMD: 0.18 (0.06, 0.30)) compared to those who held degrees (TP3 SMD: 0.26 (0.14, 0.38)). Increased distress was most prominent amongst adults aged 35-44 years (TP3 SMD: 0.49 (0.15, 0.84)). We did not find evidence of changes in distress differing by ethnicity or UK country. Conclusions: The substantial deterioration in mental health seen in the UK during the first lockdown did not reverse when lockdown lifted, and a sustained worsening is observed across the pandemic. Mental health declines have not been equal across the population, with females, those with higher degrees, and younger adults more affected.

Study Problems and Depressive Symptoms in Adolescents During the COVID-19 Outbreak: Poor Parent-child Relationship as a Vulnerability (preprint)

Background Little is known about the prevalence of and risk factors for adolescent mental health problems during the COVID-19 outbreak. We aimed to investigate the prevalence of depressive symptoms, their association with study-relevant problems, and the moderating effect of parent-child relationship among Chinese adolescents during the school closures.Results Using data from 6435 adolescents, we found that the prevalence of depressive symptoms was 17.7%. All the study problem measures were associated with more severe depressive symptoms. There was a moderating effect of the parental relationship on the associations between study problems and depressive symptoms. The association between number of study problems and depressive symptoms was stronger in adolescents with a poor parent-child relationship (regression coefficient 4.34 [95% CI 2.97, 5.72]) than those with a good or normal relationship (2.55 [2.35, 2.75]), p for interaction 0.002, on multivariable adjustment.Conclusions Study problems due to school closures were particularly problematic for adolescents who had poor parent-child relationships. Public health initiatives could help students to adjust study habits and improve parent-child relationships, thereby protecting against the development of depression.