The Journals of Gerontology: Series A

Gait variability is a critical functional indicator of dynamic balance and neurocognitive decline in health. Its translation into clinical practice is, however, challenged by a lack of age-related normative trajectories and reference values under real-world ecological settings. Furthermore, the conventional metrics used to estimate gait variability (Coefficient of Variation, CV; Standard Deviation, SD) have a fundamental methodological flaw: the inherent sensitivity of conventional metrics to th...

ObjectivesGrowth Mindset and Grit have been proposed as key psychological resources for resilience and adaptation, yet their manifestation and social distribution in later life remain underexplored. This study examines the structure, distribution, and correlates of Growth Mindset and Grit in older adulthood using proxy indicators in the English Longitudinal Study of Ageing (ELSA). MethodsProxy indicators reflecting learning behaviour, personality traits, affect, and beliefs were used to derive ...

Background Older adults' walking has so far been evaluated using standardised assessments of walking capacity within a clinical setting. By taking the evaluation out of the laboratory into the real world, this study provides first evidence of the ability of Digital Mobility Outcomes (DMOs) to detect changes over time and the Minimal Important Difference (MID) in patients after proximal femoral fracture (PFF). This will guide the implementation of DMOs in research and clinical care. Methods For t...

Biological ageing begins before birth, with early-life exposures shaping late-life health. These exposures drive health inequities early, yet specific exposures and the composition of the ageing exposome remain largely undefined. This gap may persist as the field lacks agnostic investigations accounting for non-linearity, interactions and subtle signals. We aimed to identify exposures predictive of epigenetic ageing accumulated during childhood and adolescence and explore the composition of the...

Background and ObjectivesAssociations of common infections with Alzheimer disease (AD) risk have been reported. A hypothesized mechanism to explain these is cerebral amyloid-beta (A{beta}) aggregation as a defence in response to infection, with subsequent tau accumulation. However, few studies have assessed associations of infections with tau and A{beta} pathology. We investigated associations of serological measures of several common infections with plasma p-tau217 and A{beta} status measured b...

Introduction: Neurodegenerative diseases (NDDs) including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and non-AD dementias share chronic neuroinflammatory mechanisms that contribute to neuronal injury and disease progression. While anti-inflammatory therapies (AITs) are associated with reduced neurodegenerative disease risk, knowledge regarding the impact of biological sex and treatment duration across multiple NDDs remains li...

OBJECTIVEUsing two cohorts and synthetic datasets, we estimated effects of prospectively reported alcohol use on memory outcomes across middle age. METHODSData were from National Longitudinal Study of Youth 1979 (NLSY79, n=7540, alcohol reports from ages 18-26), Health and Retirement Study (HRS age 50-56 at enrollment, n=13,090), and a synthetic cohort matching early life exposure information from 3,259 NLSY79 participants to later life memory information from 5,451 HRS participants. Covariate-...

BackgroundThe relationship between hip osteoarthritis (hip OA) and Alzheimers disease (AD) presents a critical paradox within the emerging "bone-brain axis": widespread phenotypic comorbidity sharply contradicts evolutionary theories of biological antagonism. This study integrates longitudinal and multi-omic analyses to determine whether this clinical overlap masks an underlying genetic neuroprotection. MethodsWe analyzed longitudinal phenotypic data from 261,767 UK Biobank participants using C...

Ambient air pollution has been associated with increased incidence of chronic disease and is estimated to contribute towards 4.2 million early deaths annually. Whilst the health impacts are well described, less is understood about the underlying biological mechanisms, particularly when considering the co-occurrence of multiple pollutants. Using an atmospheric chemistry transportation model (EMEP4UK), we generate pre-baseline sampling pollution exposure estimates for eight pollutants in Generatio...

Suicide is one of the worlds leading public health problems, with more than 720,000 deaths annually. Suicide has traditionally been studied from an individual perspective. However, research has increasingly highlighted the influence of community-level factors on suicide risk. This study aimed to (1) analyse the spatial distribution of suicide mortality at the provincial level in Spain (2018-2022); (2) perform stratified analyses by sex and age group; and (3) compare suicide risk across differen...

Oscillatory coupling between respiration, heart rate, and cortical function is fundamental to physiological regulation yet remains poorly characterized in humans. Diminished respiratory heart rate variability (RespHRV)--the rhythmic heart rate modulation accompanying respiration--has emerged as a transdiagnostic biomarker of mental and physical health, reduced in anxiety, depression, cardiovascular disease, and aging (Beauchaine & Thayer, 2015; Menuet & Gourine et al., 2025). However, the cortic...

BackgroundA coronary artery calcium (CAC) score of 0 is widely considered to indicate low short- to intermediate-term risk for coronary artery disease (CAD) and is frequently used to defer lipid-lowering therapy. However, a subset of individuals with CAC=0 still experience events, highlighting residual risk not captured by imaging alone. Polygenic risk scores (PRS) quantify lifelong inherited susceptibility, but conventional approaches rely on predefined ancestry labels despite human genetic div...

Objective: Minimum unit pricing (MUP) aims to reduce use of cheap, high strength alcoholic beverages that drive harm, yet concerns remain about inequitable effects for structurally vulnerable groups. As part of the Costs, Harms, Expenditures and Alcohol Prices (CHEAP) study, we linked individual-level, product-specific alcohol consumption data from a customized survey with provincial retail price data to estimate prices per standard drink (PPSD) and examine their association with alcohol-related...

Type 2 diabetes (T2D) affects 11.1% of the global population, underscoring the need for biomarkers that inform treatment response and glycemic outcomes. We evaluated the association between the FTO variant rs9939609-A and glycemic control in a Mexican population. A total of 174 individuals living with T2D from Merida and Sisal, Yucatan, were included, of whom 85% were receiving oral hypoglycemic agents as main treatment. Glycemic control was defined cross-sectionally as good ([≤]130 mg/dL, n=...

BackgroundStroke is a leading cause of mortality and disability globally. However, information about stroke burden in the Philippines is limited. We sought to analyze stroke burden in the Philippines from 1990 to 2023. MethodsIncidence, prevalence, mortality, and disability-adjusted life-years (DALYs) estimates from the Global Burden of Disease Study 2023 data were used as indicators to analyze the burden of stroke by sex and age. Temporal trends in both crude and age-standardized rates were an...

Background: Quantitative genome wide association studies (GWAS) primarily rely on additive linear models that compare average phenotypic differences between genotype groups. While effective for detecting common variants of moderate effect in large sample sizes, such approaches inherently reduce high resolution phenotypic data to summary statistics (group averages), potentially limiting the detection of subtle genotype phenotype relationships. Genomic Informational Field Theory (GIFT) is a recent...

IntroductionAtmospheric conditions under climate change increase pressure on healthcare systems. Especially, the intensive care units (ICU) are vulnerable due to low buffer capacity and high utilization rates. MethodsDaily ICU cases from 2009 to 2023 were derived from the German statutory health insurance data of eleven regional AOK insurances. Cases were stratified by age and sex. Generalized additive models were used to investigate the associations between daily ICU cases and lagged atmospher...

IntroductionThe eligibility of anti-amyloid disease-modifying therapies (DMTs) and their integration into clinical practice in some institutions requires a specific range of Mini-Mental State Examination (MMSE) scores. Reliance on this pencil-and-paper psychometric instrument imposes operational burdens and risks perpetuating health disparities due to the tests known educational and cultural biases. This study evaluates the efficacy of the Digital Clock and Recall (DCR) - a rapid, FDA-listed dig...

BackgroundPropofol dosing guidelines recommend age-based reductions because hypnotic sensitivity increases in older adults. Most real-world evaluations of induction practice, however, have relied on total weight-normalized dose (mg/kg) rather than estimating cerebral exposure using pharmacokinetic models. Because age-related pharmacokinetic changes alter the relationship between administered dose and peak effect-site concentration (Ce,max), mg/kg surrogates may misrepresent true age-dependent ex...

BackgroundNo randomized clinical trial comparing the most established new modalities of treatment for patients with localized prostate cancer has been published, and there is scarce comparative effectiveness research assessing Patient-Reported Outcome Measures (PROMs). Objectiveto compare the impact of active surveillance, robot-assisted radical prostatectomy (RARP), Intensity-modulated radiotherapy (IMRT), and real-time brachytherapy on patients, through PROMs, from pre-treatment to five years...