Social disadvantage accelerates aging.

Social disadvantage, like advanced age, is a risk factor for a broad range of health conditions; however, whether it influences the aging process remains unclear. Here, using a multicohort approach, we investigated the associations of social disadvantage with age-related plasma proteins and age-related diseases. We found proteomic signatures of accelerated immune aging and 14 specific age-related proteins linked to social disadvantage during both early and later life.

Direct and indirect impacts of the COVID-19 pandemic on life expectancy and person-years of life lost with and without disability: A systematic analysis for 18 European countries, 2020-2022.

Background: The direct and indirect impacts of the COVID-19 pandemic on life expectancy (LE) and years of life lost with and without disability remain unclear. Accounting for pre-pandemic trends in morbidity and mortality, we assessed these impacts in 18 European countries, for the years 2020-2022.

Methods And Findings: We used multi-state Markov modeling based on several data sources to track transitions of the population aged 35 or older between eight health states from disease-free, combinations of cardiovascular disease, cognitive impairment, dementia, and disability, through to death.

Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline.

Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe.

Obesity and risk of diseases associated with hallmarks of cellular ageing: a multicohort study.

Background: Ageing hallmarks, characterising features of cellular ageing, have a role in the pathophysiology of many age-related diseases. We examined whether obesity is associated with an increased risk of developing such hallmark-related diseases.

Methods: In this multicohort study, we included people aged 38-72 years with data on weight, height, and waist circumference measured during a clinical examination at baseline between March 13, 2006, and Oct 1, 2010, from the UK Biobank with follow-up until Nov 12, 2021.

Identification of circulating proteins associated with general cognitive function among middle-aged and older adults.

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.

Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life.

A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer's disease (AD) and related dementias. However, there is limited understanding of the peripheral biological mechanisms relevant in the earliest phases of the disease. Here, we used a large-scale proteomics platform to examine the association of 4877 plasma proteins with 25-year dementia risk in 10,981 middle-aged adults.

Trajectories of cardiac troponin in the decades before cardiovascular death: a longitudinal cohort study.

Background: High-sensitivity cardiac troponin testing is a promising tool for cardiovascular risk prediction, but whether serial testing can dynamically predict risk is uncertain. We evaluated the trajectory of cardiac troponin I in the years prior to a cardiovascular event in the general population, and determine whether serial measurements could track risk within individuals.

Methods: In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period.

Estimating Dementia Risk Using Multifactorial Prediction Models.

Importance: The clinical value of current multifactorial algorithms for individualized assessment of dementia risk remains unclear.

Objective: To evaluate the clinical value associated with 4 widely used dementia risk scores in estimating 10-year dementia risk.

Design, Setting, And Participants: This prospective population-based UK Biobank cohort study assessed 4 dementia risk scores at baseline (2006-2010) and ascertained incident dementia during the following 10 years.

Paternal and Maternal Problem Drinking and Lifetime Problem Drinking of Their Adult Children.

Parents' alcohol use is associated with alcohol use of their adolescent offspring, but does this association extend to the adulthood of the offspring? We examined associations of paternal and maternal problem drinking with lifetime problem drinking of their adult offspring prospectively assessed in a population-based Finnish twin-family cohort (FinnTwin16). Problem drinking (Malmö-modified Michigan Alcoholism Screening Test) was self-reported separately by mothers and fathers when their children were 16. The children reported on an extended lifetime version of the same measure during their mid-twenties (21-28 years) and mid-thirties (31-37 years).

Severe Infection and Risk of Cardiovascular Disease: A Multicohort Study.

Background: The excess risk of cardiovascular disease associated with a wide array of infectious diseases is unknown. We quantified the short- and long-term risk of major cardiovascular events in people with severe infection and estimated the population-attributable fraction.

Methods: We analyzed data from 331 683 UK Biobank participants without cardiovascular disease at baseline (2006-2010) and replicated our main findings in an independent population from 3 prospective cohort studies comprising 271 329 community-dwelling participants from Finland (baseline 1986-2005).

Proteomic signatures for identification of impaired glucose tolerance.

The implementation of recommendations for type 2 diabetes (T2D) screening and diagnosis focuses on the measurement of glycated hemoglobin (HbA1c) and fasting glucose. This approach leaves a large number of individuals with isolated impaired glucose tolerance (iIGT), who are only detectable through oral glucose tolerance tests (OGTTs), at risk of diabetes and its severe complications. We applied machine learning to the proteomic profiles of a single fasted sample from 11,546 participants of the Fenland study to test discrimination of iIGT defined using the gold-standard OGTTs.

Systematic comparison of family history and polygenic risk across 24 common diseases.

Family history is the standard indirect measure of inherited susceptibility in clinical care, whereas polygenic risk scores (PRSs) have more recently demonstrated potential for more directly capturing genetic risk in many diseases. Few studies have systematically compared how these overlap and complement each other across common diseases. Within FinnGen (N = 306,418), we leverage family relationships, up to 50 years of nationwide registries, and genome-wide genotyping to examine the interplay of family history and genome-wide PRSs.

Comment on "A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk".

A 27-protein signature has been proposed to predict cardiovascular disease, but its applicability in clinical decision-making remains unclear.

Risk of Macrovascular and Microvascular Disease in Diabetes Diagnosed Using Oral Glucose Tolerance Test With and Without Confirmation by Hemoglobin A1c: The Whitehall II Cohort Study.

Background: It is unclear whether replacing oral glucose tolerance test (OGTT) with hemoglobin A1c (HbA1c) measurement for diagnosing diabetes is justified. We aimed to assess the proportion of OGTT-diagnosed diabetes cases that can be confirmed by HbA1c and to examine whether individuals with OGTT diagnosis but nondiagnostic HbA1c are at higher risk of macrovascular and microvascular disease.

Methods: Participants were 5773 men and women from the population-based Whitehall II prospective cohort study in the United Kingdom.

Cross-Sectional Blood Metabolite Markers of Hypertension: A Multicohort Analysis of 44,306 Individuals from the COnsortium of METabolomics Studies.

Hypertension is the main modifiable risk factor for cardiovascular morbidity and mortality but discovering molecular mechanisms for targeted treatment has been challenging. Here we investigate associations of blood metabolite markers with hypertension by integrating data from nine intercontinental cohorts from the COnsortium of METabolomics Studies. We included 44,306 individuals with circulating metabolites (up to 813).

Body-mass index and risk of obesity-related complex multimorbidity: an observational multicohort study.

Background: The accumulation of disparate diseases in complex multimorbidity makes prevention difficult if each disease is targeted separately. We aimed to examine obesity as a shared risk factor for common diseases, determine associations between obesity-related diseases, and examine the role of obesity in the development of complex multimorbidity (four or more comorbid diseases).

Methods: We did an observational study and used pooled prospective data from two Finnish cohort studies (the Health and Social Support Study and the Finnish Public Sector Study) comprising 114 657 adults aged 16-78 years at study entry (1998-2013).

Aortic Pulse Wave Velocity as Adjunct Risk Marker for Assessing Cardiovascular Disease Risk: Prospective Study.

Background: Aortic pulse wave velocity is a noninvasive measure of aortic stiffness and arterial aging. Its current value in cardiovascular risk estimation practice is unknown. We aimed to establish whether aortic pulse wave velocity identified individuals with higher risk of incident major adverse cardiovascular events and improved performance of the American Heart Association/American College of Cardiology atherosclerotic cardiovascular disease risk score.

Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: three analyses of population cohort studies.

Objectives: To examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association.

Design: Multicohort study with three sets of analyses.

Setting: United Kingdom, Europe, and the United States.

Plasma proteins, cognitive decline, and 20-year risk of dementia in the Whitehall II and Atherosclerosis Risk in Communities studies.

Introduction: Plasma proteins affect biological processes and are common drug targets but their role in the development of Alzheimer's disease and related dementias remains unclear. We examined associations between 4953 plasma proteins and cognitive decline and risk of dementia in two cohort studies with 20-year follow-ups.

Methods: In the Whitehall II prospective cohort study proteins were measured using SOMAscan technology.