An undue emphasis on rural older adults in the Chief Medical Officer's annual report 2023?

The Chief Medical Officer's annual report 2023 presents an incomplete and skewed picture of the geography of older people in England. We show that there are higher absolute numbers of older people in urban areas in England and Wales, in contrast to key messages from the CMO report which suggest greater need in rural areas based on relative metrics. The absolute size of the urban-rural difference in the population of older people is projected to grow by 2043. Older adults in urban areas are much more likely to live in deprived areas than older adults in rural areas. The absolute number and prevalence of older adults in poorer health is also higher in urban areas, leading to greater health care needs. Policy-makers need to consider both absolute and relative demographic trends as well as making use of direct measures of health when planning how health care services for older adults are distributed geographically in England.

Generational differences in physical health and disability in the United States and Europe.

Objectives: Declines in mortality have typically been associated with improvements in physical health across generations. While life expectancy in most high-income countries continues to increase, there is evidence that younger generations, particularly in the United States (US), are less healthy than previous generations at the same age. We compared generational trends in physical health in the US, England, and continental Europe to explore whether other regions have experienced a similar pattern of worsening health across cohorts. Methods: Using data from nationally representative studies of adults aged ≥50 years from the US (Health and Retirement Study, n=26,939), England (English Longitudinal Study of Ageing, n=14,992) and 11 continental European countries (Survey of Health, Ageing and Retirement in Europe, n=72,595), we estimated differences in the age-adjusted prevalence of self-reported chronic disease and disability and observer-measured health indicators across pseudo-birth cohorts (born <1925, 1925-1935, 1936-1945, 1946-1954, 1955-1959). Results: Age-adjusted prevalence of doctor-diagnosed chronic disease increased across cohorts in all regions. Trends in disability prevalence were more regionally varied. Still, in both the US and Europe, we observed a structural break in disability trends, with declines observed in pre-war cohorts slowing, stalling, or reversing for cohorts born since 1945. Discussion: In all regions, we found evidence for worsening health across cohorts, particularly for those born since 1945. While more chronic disease in younger cohorts need not necessarily translate to worse quality of life or higher rates of functional limitation, there is some suggestion that worsening chronic disease morbidity may be spilling over into worsening disability.

BugSigDB captures patterns of differential abundance across a broad range of host-associated microbial signatures.

The literature of human and other host-associated microbiome studies is expanding rapidly, but systematic comparisons among published results of host-associated microbiome signatures of differential abundance remain difficult. We present BugSigDB, a community-editable database of manually curated microbial signatures from published differential abundance studies accompanied by information on study geography, health outcomes, host body site and experimental, epidemiological and statistical methods using controlled vocabulary. The initial release of the database contains >2,500 manually curated signatures from >600 published studies on three host species, enabling high-throughput analysis of signature similarity, taxon enrichment, co-occurrence and coexclusion and consensus signatures. These data allow assessment of microbiome differential abundance within and across experimental conditions, environments or body sites. Database-wide analysis reveals experimental conditions with the highest level of consistency in signatures reported by independent studies and identifies commonalities among disease-associated signatures, including frequent introgression of oral pathobionts into the gut.

Biological expressions of early life trauma in the immune system of older adults.

BACKGROUND: Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. METHODS: Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. FINDINGS: Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (ß = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (ß = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. INTERPRETATION: Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course.

Midlife Health in Britain and the US: A comparison of Two Nationally Representative Cohorts.

Background: Older adults in the United States (US) have worse health and wider socioeconomic inequalities in health compared to Britain. Less is known about how health in the two countries compares in midlife, a time of emerging health decline, including inequalities in health. Methods: We compare measures of smoking status, alcohol consumption, obesity, self-rated health, cholesterol, blood pressure, and glycated haemoglobin using population-weighted modified Poisson regression in the 1970 British Cohort Study (BCS70) in Britain (N= 9,665) and the National Longitudinal Study of Adolescent to Adult Health (Add Health) in the US (N=12,297), when cohort members were aged 34-46 and 33-43, respectively. We test whether associations vary by early- and mid-life socioeconomic position. Findings: US adults had higher levels of obesity, high blood pressure and high cholesterol. Prevalence of poor self-rated health, heavy drinking, and smoking was worse in Britain. We found smaller socioeconomic inequalities in midlife health in Britain compared to the US. For some outcomes (e.g., smoking), the most socioeconomically advantaged group in the US was healthier than the equivalent group in Britain. For other outcomes (hypertension and cholesterol), the most advantaged US group fared equal to or worse than the most disadvantaged groups in Britain. Interpretation: US adults have worse cardiometabolic health than British counterparts, even in early midlife. The smaller socioeconomic inequalities and better overall health in Britain may reflect differences in access to health care, welfare systems, or other environmental risk factors. Funding: ESRC, UKRI, MRC, NIH, European Research Council, Leverhulme Trust.

Life expectancy changes since COVID-19.

The COVID-19 pandemic triggered an unprecedented rise in mortality that translated into life expectancy losses around the world, with only a few exceptions. We estimate life expectancy changes in 29 countries since 2020 (including most of Europe, the United States and Chile), attribute them to mortality changes by age group and compare them with historic life expectancy shocks. Our results show divergence in mortality impacts of the pandemic in 2021. While countries in western Europe experienced bounce backs from life expectancy losses of 2020, eastern Europe and the United States witnessed sustained and substantial life expectancy deficits. Life expectancy deficits during fall/winter 2021 among people ages 60+ and <60 were negatively correlated with measures of vaccination uptake across countries (r60+ = -0.86; two-tailed P < 0.001; 95% confidence interval, -0.94 to -0.69; r<60 = -0.74; two-tailed P < 0.001; 95% confidence interval, -0.88 to -0.46). In contrast to 2020, the age profile of excess mortality in 2021 was younger, with those in under-80 age groups contributing more to life expectancy losses. However, even in 2021, registered COVID-19 deaths continued to account for most life expectancy losses.

Structural adjustment programmes and infectious disease mortality.

International financial organisations like the International Monetary Fund (IMF) play a central role in shaping the developmental trajectories of fiscally distressed countries through their conditional lending schemes, known as 'structural adjustment programmes'. These programmes entail wide-ranging domestic policy reforms that influence local health and welfare systems. Using novel panel data from 187 countries between 1990 and 2017 and an instrumental variable technique, we find that IMF programmes lead to over 70 excess deaths from respiratory diseases and tuberculosis per 100,000 population and that IMF-mandated privatisation reforms lead to over 90 excess deaths per 100,000 population. Thus structural adjustment programmes, as currently designed and implemented, are harmful to population health and increase global infectious disease burdens.

Older Adults in the United States Have Worse Cardiometabolic Health Compared to England.

Explanations for lagging life expectancy in the United States compared to other high-income countries have focused largely on "deaths of despair," but attention has also shifted to the role of stalling improvements in cardiovascular disease and the obesity epidemic. Using harmonized data from the U.S. Health and Retirement Study and English Longitudinal Study of Ageing, we assess differences in self-reported and objective measures of health, among older adults in the United States and England and explore whether the differences in body mass index (BMI) documented between the United States and England explain the U.S. disadvantage. Older adults in the United States have a much higher prevalence of diabetes, low high-density lipoprotein cholesterol, and high inflammation (C-reactive protein) compared to English adults. While the distribution of BMI is shifted to the right in the United States with more people falling into extreme obesity categories, these differences do not explain the cross-country differences in measured biological risk. We conclude by considering how country differences in health may have affected the burden of coronavirus disease 2019 mortality in both countries.

Diverging destinies: 'social' data within the TwinsUK cohort.

Background: Twins offer social scientists a unique opportunity to understand the interplay of social factors and physical and mental well-being. TwinsUK is the largest UK registry of adult mono- and dy-zygotic twins, but most of the research that utilises the cohorts' data to date has focused on the genetic underpinnings of complex disease. Methods: Following formal unstructured discussions with social scientists we identified key areas of research interest and annotated the historical data collections in TwinsUK where they could be applied to these research aims. Results: We present a summary of variables identified as of key interest to researchers from the social science sphere, spanning the following domains: 1: Parenting, child rearing and pregnancies; 2: Working habits and patterns; 3: Sleeping habits and patterns; 4: Social support; 5: Negative life events; 6: Spousal relationships. Conclusions: TwinsUK has a wide range of genetic and health data that would allow investigation of research questions focusing on these domains.

Quantifying impacts of the COVID-19 pandemic through life-expectancy losses: a population-level study of 29 countries.

BACKGROUND: Variations in the age patterns and magnitudes of excess deaths, as well as differences in population sizes and age structures, make cross-national comparisons of the cumulative mortality impacts of the COVID-19 pandemic challenging. Life expectancy is a widely used indicator that provides a clear and cross-nationally comparable picture of the population-level impacts of the pandemic on mortality. METHODS: Life tables by sex were calculated for 29 countries, including most European countries, Chile and the USA, for 2015-2020. Life expectancy at birth and at age 60 years for 2020 were contextualized against recent trends between 2015 and 2019. Using decomposition techniques, we examined which specific age groups contributed to reductions in life expectancy in 2020 and to what extent reductions were attributable to official COVID-19 deaths. RESULTS: Life expectancy at birth declined from 2019 to 2020 in 27 out of 29 countries. Males in the USA and Lithuania experienced the largest losses in life expectancy at birth during 2020 (2.2 and 1.7 years, respectively), but reductions of more than an entire year were documented in 11 countries for males and 8 among females. Reductions were mostly attributable to increased mortality above age 60 years and to official COVID-19 deaths. CONCLUSIONS: The COVID-19 pandemic triggered significant mortality increases in 2020 of a magnitude not witnessed since World War II in Western Europe or the breakup of the Soviet Union in Eastern Europe. Females from 15 countries and males from 10 ended up with lower life expectancy at birth in 2020 than in 2015.

Life Course Socioeconomic Disadvantage and the Aging Immune System: Findings From the Health and Retirement Study.

OBJECTIVES: Previous research has documented a consistent association between current socioeconomic status (SES) and cytomegalovirus (CMV). Early life is likely a critical period for CMV exposure and immune development, but less is known about early-life socioeconomic factors and CMV, particularly in older age populations. Using data from the Health and Retirement Study, we investigated the association between life course socioeconomic disadvantage and immune response to CMV among older adults. METHODS: Using ordered logit models, we estimated associations between several measures of socioeconomic disadvantage and the odds of being in a higher CMV Immunoglobulin G (IgG) response category in a sample of 8,168 respondents aged older than 50 years. RESULTS: We found a significant association between educational attainment and CMV IgG response. Those with less than a high school education had 2.00 (95% confidence interval [CI]: 1.67-2.40) times the odds of being in a higher CMV category compared to those with a college degree or greater. In addition, we also observed a significant association with parental education and CMV response. Individuals with parents having 8 years or less of schooling had 2.32 (95% CI: 2.00-2.70) times the odds of higher CMV response compared to those whose parents had greater than high school education. DISCUSSION: CMV IgG levels in older adults are associated with both early-life and adult SES. Life course socioeconomic disadvantage may contribute to disparities in immunological aging.

Association Between Immune Response to Cytomegalovirus and Cognition in the Health and Retirement Study.

Chronic infections and the subsequent immune response have recently been shown to be risk factors for cognitive decline and Alzheimer disease and related dementias (ADRD). While some studies have shown an association between cytomegalovirus (CMV), a chronic and highly prevalent infection, and cognition and/or ADRD, these studies have been limited by nonrepresentative and small samples. Using 2016 data on 5,617 adults aged 65 years or more from the Health and Retirement Study, we investigated the cross-sectional associations of both CMV serostatus and immunoglobulin G (IgG) antibody response with cognitive function using linear regression models adjusting for age, sex, race/ethnicity, and educational attainment. We further investigated potential effect-measure modification by educational attainment. Overall, both CMV seropositivity and higher IgG antibody response were associated with lower cognitive function, though the relationship was not statistically significant in adjusted models. Among participants with less than a high school diploma, CMV seropositivity and being in the first tertile of IgG response, relative to seronegative persons, were associated with lower scores on the Telephone Interview for Cognitive Status (-0.56 points (95% confidence interval: -1.63, 0.52) and -0.89 points (95% confidence interval: -2.07, 0.29), respectively), and the relationship was attenuated among those with higher education. Our results suggest that CMV may be a risk factor for cognitive impairment, particularly among persons with fewer educational resources.

Pathogen burden and leukocyte telomere length in the United States.

BACKGROUND: Prior studies in humans have suggested that telomere shortening may be accelerated by infection, but research on multiple pathogens and use of large population-based study samples has been limited. We estimated cross-sectional associations between seropositivity to five persistent pathogens (Herpes Simplex Virus Type-1 (HSV-1), Herpes Simplex Virus Type-2 (HSV-2), cytomegalovirus (CMV), Helicobacter pylori (H.pylori), and Hepatitis B) as well as total pathogen burden and leukocyte telomere length. Data were derived from the National Health and Nutrition Examination Survey (1999-2000) for individuals 20-49 years of age, N = 1708. We analyzed the influence of each pathogen separately, a pathogen count score and a latent class model of pathogen burden on log telomere length using linear regression models, adjusted for covariates. RESULTS: Individuals in a latent pathogen burden class characterized by high probabilities of infection with HSV-1, CMV, and H. pylori, had significantly decreased log telomere length (- 0.30 [95% CI: - 0.36, - 0.24]) compared to those in a latent class characterized by low probabilities of all five infections. There were limited significant associations using other pathogen measures. CONCLUSIONS: These results suggest that infection with specific combinations of pathogens may be one mechanism contributing to accelerated cellular senescence with possible origins early in the life course.

The social underpinnings of mental distress in the time of COVID-19 - time for urgent action.

We argue that predictions of a 'tsunami' of mental health problems as a consequence of the pandemic of coronavirus disease 2019 (COVID-19) and the lockdown are overstated; feelings of anxiety and sadness are entirely normal reactions to difficult circumstances, not symptoms of poor mental health.  Some people will need specialised mental health support, especially those already leading tough lives; we need immediate reversal of years of underfunding of community mental health services.  However, the disproportionate effects of COVID-19 on the most disadvantaged, especially BAME people placed at risk by their social and economic conditions, were entirely predictable. Mental health is best ensured by urgently rebuilding the social and economic supports stripped away over the last decade. Governments must pump funds into local authorities to rebuild community services, peer support, mutual aid and local community and voluntary sector organisations.  Health care organisations must tackle racism and discrimination to ensure genuine equal access to universal health care.  Government must replace highly conditional benefit systems by something like a universal basic income. All economic and social policies must be subjected to a legally binding mental health audit. This may sound unfeasibly expensive, but the social and economic costs, not to mention the costs in personal and community suffering, though often invisible, are far greater.

Early Signs of Gut Microbiome Aging: Biomarkers of Inflammation, Metabolism, and Macromolecular Damage in Young Adulthood.

Emerging links between gut microbiota and diseases of aging point to possible shared immune, metabolic, and cellular damage mechanisms, operating long before diseases manifest. We conducted 16S rRNA sequencing of fecal samples collected from a subsample (n = 668) of Add Health Wave V, a nationally representative longitudinal study of adults aged 32-42. An overlapping subsample (n = 345) included whole-blood RNA-seq. We examined associations between fecal taxonomic abundances and dried blood spot-based markers of lipid and glucose homeostasis and C-reactive protein (measured in Wave IV), as well as gene expression markers of inflammation, cellular damage, immune cell composition, and transcriptomic age (measured in Wave V), using Bayesian hierarchical models adjusted for potential confounders. We additionally estimated a co-abundance network between inflammation-related genes and bacterial taxa using penalized Gaussian graphical models. Strong and consistent microbiota associations emerged for HbA1c, glucose, C-reactive protein, and principal components of genes upregulated in inflammation, DNA repair, and reactive oxygen species, with Streptococcus infantis, Pseudomonas spp., and Peptoniphilus as major players for each. This pattern was largely echoed (though attenuated) for immunological cell composition gene sets, and only Serratia varied meaningfully by transcriptomic age. Network co-abundance indicated relationships between Prevotella sp., Bacteroides sp., and Ruminococcus sp. and gut immune/metabolic regulatory activity, and Ruminococcus sp, Dialister, and Butyrivibrio crossotus with balance between Th1 and Th2 inflammation. In conclusion, many common associations between microbiota and major physiologic aging mechanisms are evident in early-mid adulthood and suggest avenues for early detection and prevention of accelerated aging.

A systematic review of the impact of psychosocial factors on immunity: Implications for enhancing BCG response against tuberculosis.

BACKGROUND: Tuberculosis (TB) remains an urgent global public health priority, causing 1.5 million deaths worldwide in 2018. There is evidence that psychosocial factors modulate immune function; however, how this may influence TB risk or BCG vaccine response, and whether this pathway can be modified through social protection, has not been investigated. This paper aims to: a) systematically review evidence of how psychosocial factors influence the expression of biomarkers of immunity, and b) apply this general evidence to propose plausible TB-specific pathways for future study. METHODS: Papers reporting on the impact of psychosocial stressors on immune biomarkers in relation to infectious disease risk were identified through a search of the databases MEDLINE, PsycINFO, Global Health and PsycEXTRA alongside reference list and citation searching of key papers. Data extraction and critical appraisal were carried out using a standardised form. The findings were tabulated and synthesised narratively by infectious disease category, and used to propose plausible mechanisms for how psychosocial exposures might influence immune outcomes relevant to TB and BCG response. RESULTS: 27,026 citations were identified, of which 51 met the inclusion criteria. The literature provides evidence of a relationship between psychosocial factors and immune biomarkers. While the direction and strength of associations is heterogenous, some overarching patterns emerged: adverse psychosocial factors (e.g. stress) were generally associated with compromised vaccine response and higher antibody titres to herpesviruses, and vice versa for positive psychosocial factors (e.g. social support). CONCLUSIONS: The evidence identifies pathways linking psychosocial factors and immune response: co-viral infection and immune suppression, both of which are potentially relevant to TB and BCG response. However, the heterogeneity in the strength and nature of the impact of psychosocial factors on immune function, and lack of research on the implications of this relationship for TB, underscore the need for TB-specific research.

Gut bacterial taxonomic abundances vary with cognition, personality, and mood in the Wisconsin Longitudinal Study.

Animal studies have shown that the gut microbiome can influence memory, social behavior, and anxiety-like behavior. Several human studies show similar results where variation in the gut microbiome is associated with dementia, depression, and personality traits, though most of these studies are limited by small sample size and other biases. Here, we analyzed fecal samples from 313 participants in the Wisconsin Longitudinal Study, a randomly selected population-based cohort of older adults, with measured psycho-cognitive dimensions (cognition, mood, and personality) and key confounders. 16s V4 sequencing showed that Megamonas is associated with all measured psycho-cognitive traits, Fusobacterium is associated with cognitive and personality traits, Pseudoramibacter_Eubacterium is associated with mood and personality traits, Butyvibrio is associated with cognitive traits, and Cloacibacillus is associated with mood traits. These findings are robust to sensitivity analyses and provide novel evidence of shared relationships between the gut microbiome and multiple psycho-cognitive traits in older adults, confirming some of the animal literature, while also providing new insights. While we addressed some of the weaknesses in prior studies, further studies are necessary to elucidate temporal and causal relationships between the gut microbiome and multiple psycho-cognitive traits in well-phenotyped, randomly-selected population-based samples.

Sick Individuals and Sick (Microbial) Populations: Challenges in Epidemiology and the Microbiome.

The human microbiome represents a new frontier in understanding the biology of human health. While epidemiology in this area is still in its infancy, its scope will likely expand dramatically over the coming years. To rise to the challenge, we argue that epidemiology should capitalize on its population perspective as a critical complement to molecular microbiome research, allowing for the illumination of contextual mechanisms that may vary more across populations rather than among individuals. We first briefly review current research on social context and the gut microbiome, focusing specifically on socioeconomic status (SES) and race/ethnicity. Next, we reflect on the current state of microbiome epidemiology through the lens of one specific area, the association of the gut microbiome and metabolic disorders. We identify key methodological shortcomings of current epidemiological research in this area, including extensive selection bias, the use of noncompositionally robust measures, and a lack of attention to social factors as confounders or effect modifiers.

Sociodemographic variation in the oral microbiome.

PURPOSE: Variations in the oral microbiome are potentially implicated in social inequalities in oral disease, cancers, and metabolic disease. We describe sociodemographic variation of oral microbiomes in a diverse sample. METHODS: We performed 16S rRNA sequencing on mouthwash specimens in a subsample (n = 282) of the 2013-2014 population-based New York City Health and Nutrition Examination Study. We examined differential abundance of 216 operational taxonomic units, and alpha and beta diversity by age, sex, income, education, nativity, and race/ethnicity. For comparison, we examined differential abundance by diet, smoking status, and oral health behaviors. RESULTS: Sixty-nine operational taxonomic units were differentially abundant by any sociodemographic variable (false discovery rate < 0.01), including 27 by race/ethnicity, 21 by family income, 19 by education, 3 by sex. We found 49 differentially abundant by smoking status, 23 by diet, 12 by oral health behaviors. Genera differing for multiple sociodemographic characteristics included Lactobacillus, Prevotella, Porphyromonas, Fusobacterium. CONCLUSIONS: We identified oral microbiome variation consistent with health inequalities, more taxa differing by race/ethnicity than diet, and more by SES variables than oral health behaviors. Investigation is warranted into possible mediating effects of the oral microbiome in social disparities in oral and metabolic diseases and cancers.

Tobacco exposure associated with oral microbiota oxygen utilization in the New York City Health and Nutrition Examination Study.

PURPOSE: The effect of tobacco exposure on the oral microbiome has not been established. METHODS: We performed amplicon sequencing of the 16S ribosomal RNA gene V4 variable region to estimate bacterial community characteristics in 259 oral rinse samples, selected based on self-reported smoking and serum cotinine levels, from the 2013-2014 New York City Health and Nutrition Examination Study. We identified differentially abundant operational taxonomic units (OTUs) by primary and secondhand tobacco exposure, and used "microbe set enrichment analysis" to assess shifts in microbial oxygen utilization. RESULTS: Cigarette smoking was associated with depletion of aerobic OTUs (Enrichment Score test statistic ES = -0.75, P = .002) with a minority (29%) of aerobic OTUs enriched in current smokers compared with never smokers. Consistent shifts in the microbiota were observed for current cigarette smokers as for nonsmokers with secondhand exposure as measured by serum cotinine levels. Differential abundance findings were similar in crude and adjusted analyses. CONCLUSIONS: Results support a plausible link between tobacco exposure and shifts in the oral microbiome at the population level through three lines of evidence: (1) a shift in microbiota oxygen utilization associated with primary tobacco smoke exposure; (2) consistency of abundance fold changes associated with current smoking and shifts along the gradient of secondhand smoke exposure among nonsmokers; and (3) consistency after adjusting for a priori hypothesized confounders.