Frontiers in Aging

Background/Objective: Common measures of physical activity (PA) based on duration and intensity do not fully capture its complexity. Adding additional PA components of muscle strength, mechanical strain, and turning actions, can provide a more complete view of activity behavior. Furthermore, PA behaviors differ between men and women. Therefore, the goal of this study is to identify and cluster similar long-term PA patterns over time for each PA component, examined separately for men and women. Methods: We used data from 4963 participants (52% women; mean age 66 years, SD = 8.6) of the Longitudinal Aging Study Amsterdam (1992 to 2019). PA component scores were assigned to self-reported activities, and Sequence Analysis with Optimal Matching was used to identify and cluster similar activity patterns over a period of 10 years, separately for each component and stratified by sex. Results: PA components varied by sex and displayed a unique mix of trajectories, including predominately low, medium, or high activity, increasing or decreasing patterns, and trajectories characterized by early or late mortality. Importantly, trajectories remained independent, indicating that changes in one PA component were not linked to changes in others. Conclusion: Older men and women follow distinct and independent long term PA trajectories across components, underscoring that PA behaviour cannot be described by a single dimension. Significance/Implications: The observed independence and heterogeneity of trajectories suggest that muscle strength, mechanical strain, and turning actions capture meaningful and distinct aspects of PA that are not reflected by traditional measures alone. Future PA-strategies could incorporate these dimensions and acknowledge sex-specific patterns to better reflect natural movement. The independence of components suggests that future interventions should target multiple dimensions, as changes in one component may not translate to others. Such an approach may support more tailored and sustainable PA interventions in later life.

Walking impairments in Parkinsons disease (PD), including reduced speed, cadence, and stride length, and increased variability, impair mobility and raise fall risk. Conventional treatments may fail to address these deficits, underscoring the need for complementary non-invasive alternatives. This study examined whether combining rhythmic auditory cueing with transcranial direct current stimulation (tDCS) over the supplementary motor area (SMA), a critical region for internally-generated movement, would enhance gait performance in PD. Thirty-three participants with PD and thirty-two healthy controls completed two sessions (anodal vs. sham tDCS) with gait assessed during stimulation, immediately after stimulation, and 15 minutes after stimulation under two auditory conditions: walking in silence and walking to music paced 10% faster than baseline cadence. Spatiotemporal, variability, and stability gait parameters were analyzed using linear mixed-effects models. Rhythmic auditory cueing significantly increased cadence and speed during, immediately after, and especially 15 minutes after stimulation, suggesting sustained effects of rhythmic entrainment. Anodal tDCS produced faster cadence, as well as lower stride time variability and stride width, particularly in individuals with PD. Although both music and anodal tDCS affected gait, no interaction was observed, indicating independent effects. Individuals with PD had greater gait variability overall, and adjusted temporal gait parameters less to music than healthy controls did. Anodal stimulation reduced walking variability in PD, reducing the group differences observed under sham conditions. These findings suggest that rhythmic cueing and SMA stimulation target complementary mechanisms, highlighting the promise of combined tDCS-music interventions for gait rehabilitation in PD.

Background: The 2025/2026 COVID-19 vaccine season introduced updated formulations targeting the LP.8.1 lineage. This study assessed the absolute vaccine effectiveness (aVE) of mRNA-1283 and BNT162b2 on COVID-19 outcomes in adults aged [≥]65 years. Methods: Background: The 2025/2026 COVID-19 vaccine season introduced updated formulations targeting the LP.8.1 lineage. This study assessed the absolute vaccine effectiveness (aVE) of mRNA-1283 and BNT162b2 on COVID-19 outcomes in adults aged [≥]65 years. Methods: This retrospective study used linked electronic health record and administrative claims data through Jan 31, 2026. Adults [≥]65 years who received the mRNA-1283 or BNT162b2 2025/2026 COVID-19 vaccine were matched to unvaccinated individuals. Inverse probability of treatment weighting was applied to matched cohorts of each vaccine to balance covariates. Each vaccine was evaluated independently against its own unvaccinated comparator group. aVE against COVID-19 related hospitalization and medically-attended COVID-19 was estimated using Cox proportional hazards models; aVE = 100 x (1 - hazard ratio [HR]). Results: We identified 233,072 mRNA-1283 recipients and 422,610 BNT162b2 recipients [≥]65 years. The aVE (95% confidence interval) of mRNA-1283 against COVID-19 related hospitalization and medically-attended COVID-19 was 59.3% (39.0%, 72.9%) and 42.0% (35.0%, 48.3%) among adults [≥]65 years and 66.9% (45.9%, 79.8%) and 50.2% (42.1%, 57.2%) in [≥]75 years, respectively. The aVE of BNT162b2 against COVID-19 related hospitalization and medically-attended COVID-19 was 48.3% (32.4%, 60.5%) and 41.2% (36.2%, 45.8%) in [≥]65 years and 45.9% (26.0%, 60.4%) and 44.0% (37.8%, 49.6%) in [≥]75 years, respectively. Conclusions: This is the first real-world evidence showing that mRNA-1283 prevents COVID-19-related hospitalizations and medically attended events in vulnerable older adults at highest risk of severe disease. These findings support mRNA-1283 as an important public health tool for reducing the ongoing burden of COVID-19.Results: We identified 233,072 mRNA-1283 recipients and 422,610 BNT162b2 recipients [≥]65 years. The aVE (95% confidence interval) of mRNA-1283 against COVID-19 related hospitalization and medically-attended COVID-19 was 59.3% (39.0%, 72.9%) and 42.0% (35.0%, 48.3%) among adults [≥]65 years and 66.9% (45.9 %, 79.8%) and 50.2% (42.1%, 57.2%) in [≥]75 years, respectively. The aVE of BNT162b2 against COVID-19 related hospitalization and medically-attended COVID-19 was 48.3% (32.4%, 60.5%) and 41.2% (36.2%, 45.8%) in [≥]65 years and 45.9% (26.0%, 60.4%) and 44.0% (37.8%, 49.6%) in [≥]75 years, respectively. Conclusions: This is the first real-world evidence showing that mRNA-1283 prevents COVID-19-related hospitalizations and medically attended events in vulnerable older adults at highest risk of severe disease. These findings support mRNA-1283 as an important public health tool for reducing the ongoing burden of COVID-19.

IntroductionIndividuals with COPD can be classified according to their levels of physical activity (PA) and physical capacity (PC). The relationship between nutrition and body composition within these classifications remains unclear. ObjectivesTo compare the body composition and food intake of people with COPD and verify the associations. MethodsCross-sectional exploratory analysis study in which body composition and food intake were assessed in individuals with COPD. Classification was based on six-minute walk test (PC) and accelerometry(PA): Quadrant "can do, dont do" (I-preserved PC, low PA); quadrant "can do, do do" (II-preserved PC, preserved PA). Results72 individuals with COPD, 39 in quadrant I and 33 in quadrant II, with mean ages of (69 {+/-} 6) (67 {+/-} 7), respectively. Group I had a higher proportion of males, whereas group II had a higher proportion of females. A positive trend in skeletal muscle mass (p=0.011) (B= 2.883) and a negative trend in basal metabolic rate (p=0.010) (B=-0.092) for group I. ConclusionBrazilians with COPD classified in quadrants I and II showed similar results in terms of body composition and food intake. A positive trend in skeletal muscle mass was observed for the group I. These findings align with the pathophysiological model of COPD, in which the preservation of muscle mass and adequate protein intake support functional capacity and the maintenance of higher physical activity levels.

Altered iron homeostasis has long been implicated in Parkinson's Disease (PD), although the mechanisms have not been clear. Given the critical role of PD-related activating mutations in LRRK2 (leucine-rich repeat protein kinase 2) within membrane trafficking pathways we examined the impact of a homozygous mutant LRRK2G2019S on iron homeostasis within the RAW macrophage cell line with high iron capacity. Proteomics analysis revealed a dysregulation of iron-related proteins in steady state with highly elevated levels of ferritin light chain and a reduction of ferritin heavy chain. LRRK2G2019S mutant cells showed efficient ferritinophagy upon iron chelation, but upon iron overload there was a near complete block in the degradation of the ferritinophagy adaptor NCOA4. These conditions lead to an accumulation of phosphorylated Rab8 at the plasma membrane, which is selectively inhibited by LRRK type II kinase inhibitors. Iron overload then leads to increased oxidative stress and ferroptotic cell death. These data implicate LRRK2 as a key regulator of iron homeostasis and point to the need for an increased focus on the mechanisms of iron dysregulation in PD.

Improving diversity in U.S. Alzheimers disease (AD) research is a pressing need. By 2050, Hispanic and Latino Americans will comprise 30% of the population. Hispanics are 1.5 times more likely and Blacks are twice as likely to develop AD compared to Whites, yet both remain vastly underrepresented in clinical trials research. Aging and AD research mentorship of underrepresented STEM undergraduates is designed to promote entry into related professions by students committed to decreasing disparities in AD research participation and clinical care. The NIA-funded MADURA program recruited 93 students from backgrounds historically underrepresented in STEM majors and/or from NIH-defined disadvantaged backgrounds. Trainees were placed in aging/AD research labs and received weekly training and mentorship from faculty research PIs and other types of supervisors (postdoctoral researchers, graduate students, research assistant staff...) Our study examined student ratings of the program and mentor behaviors, using a program-specific survey and the Mentoring Competency Assessment-21 (MCA-21). Trainees were highly satisfied with both mentoring relationships and the overall program. Student rated MCA-21 competency areas were quite high for both P.I.s and other types of research mentors. However, there were striking differences in associations between competencies and relationship and program satisfaction, by mentor type. For PI mentors, no MCA-21 competencies were associated with relationship satisfaction, but five of six competencies were associated with relationship satisfaction for other mentor types. Similarly, no PI mentor competencies were significantly correlated with overall placement satisfaction, but all six competencies were correlated with overall placement satisfaction for other mentor types. The authors discuss the likelihood of differing student expectations of faculty PI versus other types of research mentors, recommendations for assessing role-specific student expectations (including functions primarily possible only for senior faculty PIs), and utilizing nearer-peer plus PI faculty mentors to comprehensively address the gamut of mentee needs.

Walking speed is widely used to assess gait recovery following stroke, yet it provides limited insight into how walking performance is mechanically organized. This study examined how center of mass (COM) work organization and propulsion-support coupling vary across walking speeds in individuals with post stroke hemiparesis to distinguish recovery of gait organization from recovery of limb level mechanical function. Eleven individuals with post stroke hemiparesis performed treadmill walking across speeds ranging from 0.2 to 0.7 m/s while ground reaction forces were recorded. Limb specific COM power and work were computed using an individual limbs framework, and interlimb asymmetry in net and positive work, along with the propulsion-support ratio (PSR), were quantified. A qualitative transition in gait organization was observed: at lower walking speeds, COM power exhibited a simplified two phase pattern, whereas at higher walking speeds (approximately >=0.5 m/s), a structured four phase COM power pattern emerged, including identifiable push off and preload phases. Despite this recovery of gait organization, interlimb work asymmetry remained elevated and paretic PSR remained reduced across all speeds, indicating persistent limb level mechanical deficits. These findings demonstrate that increases in walking speed and the emergence of typical COM power structure reflect recovery of gait organization rather than restoration of underlying limb level mechanical capacity. Consequently, walking speed alone is insufficient to characterize gait recovery after stroke, and biomechanically informed measures of COM work organization and propulsion-support coupling provide complementary insight by distinguishing organizational recovery from limb-level mechanical recovery.

Methods: DigiCog is a single-center cross-sectional study conducted within the Luxembourgish Predi-COVID cohort (NCT04380987). Participants aged 25-65 years, with and without persistent COVID-19 symptoms, are invited to participate. Cognitive assessments are performed during face-to-face sessions by trained nurses and neuropsychologists using both the VMTech device and standardized neuropsychological tests. Additional data on PCC symptom status, CR, sociodemographic characteristics, fatigue, and psychological factors are also collected. Agreement between digital and standard cognitive assessments will be evaluated using Cohen's kappa coefficient, with sensitivity, specificity, and receiver operating characteristic analyses as secondary measures. Cognitive performance will be compared between participants with and without PCC, and associations with CR proxies will be explored.

BackgroundWe explored the efficacy of AS01E-adjuvanted respiratory syncytial virus prefusion F protein-based vaccine (adjuvanted RSVPreF3) in subpopulations of participants with underlying medical conditions in the multi-country, phase 3 AReSVi-006 trial (conducted May/2021-May/2024). MethodsMedically stable [≥]60-year-olds were 1:1-randomised to receive one adjuvanted RSVPreF3 or placebo dose pre-RSV season 1. In exploratory post-hoc analyses in subgroups of participants with underlying conditions (including COPD, asthma, diabetes, obesity [BMI[≥]30 kg/m2]), we evaluated efficacy of one vaccine dose against RSV-related lower respiratory tract disease (RSV-LRTD), acute respiratory illness (RSV-ARI), and RSV-ARI-related complications (e.g., pneumonia, COPD/asthma exacerbation, cardiovascular events). We also evaluated (post-hoc) RSV-ARI-related systemic corticosteroid and antibiotics use in participants with COPD or asthma. ResultsThe efficacy analyses comprised 12,468 vaccine and 12,498 placebo recipients. Efficacy against RSV-LRTD over three RSV seasons was similar among participants with COPD (75.1%, 95% CI: 40.2-91.4), asthma (65.8%, 31.0-84.7), diabetes (69.8%, 37.5-87.1), and obesity (74.1%, 56.4-85.5) as in the overall study population (62.9%, 97.5% CI: 46.7-74.8). Efficacy was also observed against RSV-ARI in these subgroups. Efficacy against RSV-ARI-related complications was 74.4% (95% CI: 11.2-95.2) in participants with COPD and 60.8% (-9.9-88.7) in those with asthma. Among participants with COPD, 15.4% (1.9-45.4) of RSV-ARI episodes in vaccine vs 22.4% (12.5-35.3) in placebo recipients were treated with systemic corticosteroids, and 46.2% (19.2-74.9) vs 56.9% (43.2-69.8) with antibiotics. ConclusionsPost-hoc analyses of the AReSVi-006 trial suggest that adjuvanted RSVPreF3 may help prevent RSV-ARI, RSV-LRTD, and RSV-related complications in medically stable older adults with underlying medical conditions like COPD and asthma. Trial registrationClinicalTrials.gov: NCT04886596 SummaryPost-hoc analyses of the AReSVi-006 trial suggest that 1 dose of adjuvanted RSVPreF3 may help prevent RSV-related illness and complications over 3 consecutive RSV seasons in subgroups of [≥]60-year-olds with chronic medical conditions, e.g., COPD and asthma.

Objectives. The association between skeletal muscle gene expression and knee osteoarthritis (OA) was examined among older adult participants of the Study of Muscle, Mobility and Aging (SOMMA). Methods. Inclusion criteria included knee radiographs and bulk RNA sequencing (RNAseq) in vastus lateralis muscle, resulting in 523 participants (56% female). Radiographic knee OA was determined by Kellgren-Lawrence (KL) grades. Differential gene expression was analyzed using a control group (KL [≤] 1, n = 326) and two nested case groups: (a) KL [≥] 2 (n = 197), (b) KL [≥] 3 (n = 112). Results. Compared with controls, there were 27 and 41 genes associated (FDR [≤] 0.05) with KL [≥] 2 and KL [≥] 3, respectively, and 16 genes significantly associated in both contrasts. For 15 of the 16 genes, the association magnitude was larger with more severe OA (KL [≥] 3). Genes associated in both contrasts included brain-derived neurotrophic factor (BDNF) and interferon regulatory factor-2 (IRF2). Gene sets enriched in KL [≥] 2 and KL [≥] 3 contrasts included DNA repair and branched chain amino acid (BCAA) catabolism. Conclusions. Our results in older adult SOMMA participants indicate that knee OA is associated with genes and pathways expressed in skeletal muscle that are involved in pain sensitization, BCAA catabolism, muscle function preservation, calcium transport and storage, inflammation, and extracellular matrix remodeling. Additional longitudinal studies will be needed to determine how these genes could affect the progression of knee OA.

Background: Hereditary transthyretin amyloidosis (hATTR) manifests as cardiomyopathy and/or polyneuropathy. The V142I variant predominantly causes cardiac disease in African Americans, though neurological involvement may be underrecognized. We characterized neuropathy documentation and treatment patterns in a predominantly V142I cohort. Methods: Retrospective review of 54 hATTR patients at a major academic medical center. Neuropathy was classified as: objective (abnormal EMG), possible polyneuropathy (documented symptoms suggestive of polyneuropathy), symptoms only (neuropathic symptoms without specialist evaluation), or unclear. Treatment with stabilizers (tafamidis, acoramidis, diflunisal) and gene silencers (patisiran, vutrisiran, eplontersen) was assessed. Results: Of 54 patients (88.9% African American, 85.2% V142I), 51 (94.4%) had confirmed cardiac involvement. Among cardiac patients, 40/42 eligible (95.2%) received stabilizers. Overall, 16 patients (29.6%) received gene silencers, with 13 (24.1%) receiving both a stabilizer and gene silencer concurrently. Possible neuropathy (objective, possible polyneuropathy, or symptoms) was documented in 30 patients (55.6%). Gene silencer use was highest among those with objective neuropathy (8/17, 47.1%) versus symptoms only (1/10, 10.0%). All three patients without confirmed cardiac disease received gene silencers. Conclusions: In this V142I-predominant cohort with 94.4% cardiac involvement, stabilizer use was high (95.2%) among eligible patients. Over half had possible neuropathy based on clinical documentation, though EMG completion was limited (57.4%). Gene silencer use was associated with objective neuropathy documentation and non-cardiac phenotype. These findings support systematic neurological assessment in hATTR, even when cardiac disease predominates.

BackgroundEarly recognition of dementia-related changes is critical for timely intervention. The AD8 Dementia Screening Interview (AD8) detects subtle cognitive and functional changes, yet its broader associations with health and wellbeing among Chinese-speaking older adults remain underexplored. MethodsA cross-sectional study was conducted with 144 community-dwelling Chinese older adults (mean age 73.1 years; 81.3% female). Participants completed sociodemographic, health, functional, and psychosocial measures, including the AD8 and the Geriatric Depression Scale (GDS-15). Exploratory Factor Analysis (EFA) assessed the dimensionality of the AD8, and binary logistic regression examined associations between AD8 items and demographic, health, functional, and psychosocial outcomes. ResultsChronic disease was prevalent (68.1 percent), and 13.2 percent reported a mental health disorder. EFA identified three domains: memory impairment, executive and interest decline, and functional recall difficulties, explaining 61.7 percent of the variance. Logistic regression showed predictive roles for judgment problems (AD8_1), repetition (AD8_3), financial difficulties (AD8_6), tool-use difficulties (AD8_4), and daily memory problems (AD8_8). Financial and executive difficulties were associated with age and mobility challenges, while repetition predicted psychological disorders and hopelessness. Judgment problems were linked to lower life satisfaction and happiness but greater helplessness. Worthlessness was predicted by financial, tool-use, and memory difficulties, whereas intact temporal recall (AD8_5) was protective. Several outcomes including boredom, low energy, and staying home were not significant. ConclusionDistinct AD8 items predicted vulnerabilities across physical, psychological, and social domains. Findings highlight the multidimensional value of the AD8 as a culturally relevant screening and risk stratification tool for community-based assessments of Chinese older adults. Summary Statement Implications for PracticeO_ST_ABSWhat does this research add to existing knowledge in gerontology?C_ST_ABSThis study shows that specific AD8 items identify early multidimensional vulnerability among community-dwelling Chinese-speaking older adults. Difficulties with judgment, repetition, financial management, tool use, and daily memory were associated with functional limitations and psychosocial distress, extending the AD8 beyond dementia screening alone. The identification of three AD8 domains supports a broader understanding of early cognitive change as involving cognitive, functional, and emotional processes. The findings contribute culturally specific evidence from an under-researched population in gerontological research. What are the implications of this new knowledge for nursing care with older people?For nursing practice, the AD8 provides a brief, feasible tool to support holistic assessment in community and aged care settings. Key AD8 indicators can guide nurses in identifying older people at risk of functional decline and emotional vulnerability, enabling earlier, person-centred interventions. The findings highlight the importance of culturally and linguistically appropriate assessment when caring for diverse ageing populations. How could the findings be used to influence policy or practice or research or education?The results support integrating brief cognitive screening into routine nursing assessments and community-based aged care services to promote early identification and ageing in place. Nursing education should emphasise interpreting cognitive screening within psychosocial and cultural contexts. Longitudinal research is needed to assess intervention effectiveness. Key Points[tpltrtarr] Early cognitive changes matter for older Chinese-speaking adults, because difficulties with judgment, repetition, financial management, and tool use (AD8 domains) were consistently linked to poorer functional and psychosocial outcomes. [tpltrtarr]Beyond dementia screening, the AD8 proved useful for detecting vulnerabilities in wellbeing and daily functioning, extending its role beyond diagnostic sensitivity. [tpltrtarr]A cultural focus is vital, as this study is among the first to examine AD8 associations in older Chinese-speaking adults, underscoring the need for culturally tailored screening. [tpltrtarr]The psychosocial impact of cognitive changes was evident, with strong associations to helplessness, worthlessness, and reduced life satisfaction, reinforcing the overlap between cognitive and emotional health. [tpltrtarr]In practice, integrating AD8 screening into community and primary care could help identify at-risk individuals early and support targeted interventions in culturally and linguistically diverse populations.

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options. Masitinib, a tyrosine kinase inhibitor targeting microglial and mast cell activity in ALS pathogenesis, offers potential neuroprotection. This study presents a post-hoc analysis of long-term survivors treated with masitinib at 4.5 mg/kg/day in study AB10015, comparing observed survival to predicted and historical benchmarks. Methods: Study AB10015 was a randomized, double-blind, placebo-controlled trial assessing masitinib with riluzole in ALS patients. Overall survival (OS) was measured from symptom onset to death, encompassing the double-blind period and post-study follow-up, including an optional open-label program. The ENCALS model predicted survival of long-term survivors ([&ge;]5 years). A delay in the need for mechanical assistance, such as permanent ventilation, gastrostomy, tracheostomy, or wheelchair dependence, was used as a surrogate measure for quality of life (QoL). Results: Among 130 patients receiving masitinib 4.5 mg/kg/day, the 5-year survival rate from onset was 42.3%, increasing to 50.0% in patients with an ALSFRS-R progression rate from disease onset of <1.1 points/month (AB10015 primary efficacy population), and 52.9% in a subgroup of patients without complete loss of functionality at baseline. Half of the long-term survivors had satisfactory QoL, defined as no mechanical assistance. The median OS for long-term survivors (n=55) was 121 months versus the ENCALS-predicted 42 months, yielding a 79-month residual median survival gain. Long-term survivors were prevalent across ALS baseline prognostic factors, including slow or moderate disease progression rate ({Delta}FS), severe or moderate functional severity, bulbar or spinal site of onset, respiratory function, and age. Long-term survival was less likely in patients with complete loss of function at baseline or fast progressing disease ({Delta}FS [&ge;]1.1 points/month) at baseline. Conclusions: Masitinib treatment in ALS patients showed substantial survival benefit. Long-term survivors were largely independent of ALS prognostic factors, suggesting a subpopulation driven by microglial/mast cell activity. A recently identified biomarker detecting masitinib effect on pro-inflammatory microglia may help identify responsive patients.

INTRODUCTION: Alzheimer's disease (AD) and frontotemporal dementia (FTD) have considerable clinical and pathological overlap. While plasma proteomics has advanced in AD, deep comparative analyses with FTD-particularly in diverse, biomarker-confirmed Asian cohorts-remain limited. METHODS: Plasma from 101 individuals with known pTau217 status was profiled using Olink Explore-HT. Differential expression-pathway enrichment, penalized regression-GLMNET, single-cell transcriptomic integration, associations with cognitive measures and, cross-platform validation were performed. RESULTS: Among 5,400-proteins, 1,168 were differentially expressed in AD and 370 in FTD (FDR<0.05). Distinct and overlapping proteomic signatures were identified in AD and FTD, reflecting gliosis, synaptic dysfunction, immune activation, and metabolic pathways. Prioritized proteins correlated with cognitive performance and plasma phosphorylated tau, A{beta}42, and neurofilament light chain, linking circulating proteins to disease severity. Cross platform validation revealed strong concordance with large independent datasets. CONCLUSION: Comprehensive plasma proteomics in Asian cohort supports scalable framework for blood-based biologically informed targets for precision diagnosis and therapeutic stratification.

Hericium erinaceus (Lions Mane) is a functional mushroom with a long history of culinary and traditional use, as well as potential neurotrophic and mood modulating properties. Evidence for its effects on cognitive performance under real world conditions, however, remains limited. In this randomized, double blind, placebo controlled trial, adults aged 40 to 75 years with self reported cognitive difficulty completed a one week baseline followed by eight weeks of daily supplementation with 2 g of H. erinaceus fruiting body and mycelial biomass or placebo. Cognitive performance using a computerized battery, as well as daily subjective assessments of sleep and wellbeing, were collected remotely. 109 Participants were included in the primary analysis (H. erinaceus, n = 57; placebo, n = 52). H. erinaceus was associated with significantly greater improvement in visual attention and working memory (Juggle Factor task), subjective sleep quality, morning restedness, and mood compared with placebo (p < 0.05). No adverse events were reported in participants receiving H. erinaceus. Together, H. erinaceus supplementation modestly improved visual attention and was associated with faster improvements in sleep quality, restedness, and mood in adults with subjective cognitive concerns.

Objectives: Longer lifespans lead to longer time on retirement, despite the efforts to raise the retirement age. Therefore, it is important to study how the retirement years can be spent without diseases. This study examined socioeconomic and sociodemographic differences in healthy years spent on retirement. Methods: We followed a cohort of retired Finnish municipal employees (N=4231, average follow-up 15.4 years) on national administrative registers for major chronic diseases: cancer, coronary heart disease, cerebrovascular disease, diabetes, asthma or chronic obstructive pulmonary disease, dementia, mental disorders, and alcohol-related disorders. Median healthy years on retirement and age at first occurrence of illness (ICD-10 and ATC-based) in each combination of sex, occupational class, and age of retirement were predicted using Royston-Parmar models. Prevalence rates for each diagnostic group were calculated. Results: Most healthy years on retirement were spent by women having worked in semi-professional jobs who retired at age 60-62 (median predicted healthy years 11.6, 95% CI 10.4-12.7). The least healthy years on retirement were spent by men having worked in routine non-manual jobs who retired after age 62 (median predicted healthy years 6.5, 95% CI 4.4-9.5). Diabetes was slightly more common among lower occupational class women, and dementia among manual working women having retired at age 60-62. Discussion: Healthy years on retirement are not enjoyed equally by women and men and those who retire early or later. Policies aiming to increase the retirement age should consider the effects of these gaps on retirees and the equitability of those effects.

BackgroundIn long-term care facilities (LTCFs), close-contact identification often relies on staff recall and monitoring records because residents may be unable to self-report reliably. How these different record-generation processes relate to proximity-based sensor measurements in routine LTCF workflow remain unclear, and how such differences may influence contact-based decision-making in outbreak response is not well understood. MethodsWe conducted a five-day observational study in a Japanese LTCF using ultra-wideband (UWB) indoor positioning. Twenty-seven participants wore UWB tags, including 16 residents and 11 staff members; 10 staff members completed questionnaires. We compared UWB-derived proximity with questionnaire-derived contacts from staff self-report and monitoring-based proxy records, and assessed directional discrepancies under multiple distance-time thresholds. ResultsQuestionnaire-based records and UWB-derived proximity showed different patterns of discrepancy across contact types. Within this facility, resident-related monitoring-based proxy records showed relatively small directional discrepancies, whereas staff self-reports tended to identify additional resident-staff contacts under the baseline threshold ([&le;]1.0 m for [&ge;]15 min). Several alternative thresholds were associated with discrepancies closer to zero than the baseline, although the apparent ranking varied by summary metric. ConclusionsIn this single-facility observational study, different contact-list generation processes were associated with different patterns of discrepancy relative to a proximity-based operational measure. These findings support interpretation in terms of workflow-specific contact-list generation rather than a single universally optimal threshold and may help inform facility-level review of contact identification practices in LTCFs. These findings support aligning contact identification strategies with facility-specific workflows to improve the feasibility and effectiveness of IPC practices in LTCFs.

Background: Among cardiac measures, diastolic parameters demonstrate the earliest and most consistent age-related changes. This can be leveraged to develop a continuous left ventricular (LV) Diastolic Age from routine echocardiographic parameters. Analogous to how epigenetic clocks weight molecular markers against mortality risk, we calibrated Diastolic Age by weighting echocardiographic features against the validated PREVENT-Heart Failure (HF) risk score. Methods: We analyzed 1,952 participants from the Project Baseline Health Study (median age 50 [36-64] years, 54% female). The measure was derived using partial least-squares regression anchored on PREVENT-HF and calibrated within a healthy reference subgroup. External validation was performed in the WASE (n=1,708) and Stanford Cardiovascular Aging (n=313) cohorts. Associations with ASE-defined LV diastolic dysfunction (LVDD), epigenetic clocks, and major adverse cardiovascular events (MACE) were examined. Results: Diastolic Age correlated strongly with chronological age (r=0.78) with robust external validation (WASE r=0.76; Stanford r=0.82; calibration slopes {approx}1.0). It increased progressively across grades of diastolic dysfunction and discriminated LVDD with an AUC of 0.89 (95% CI 0.87-0.92), and was independently associated with hypertension, diabetes, and elevated C-reactive protein. While correlated with the Levine (r=0.76) and Horvath (r=0.41) epigenetic clocks, residual analyses indicated that Diastolic Age captures a distinct cardiac-specific dimension of biological aging. Over median follow-up of 4.2 years, it independently predicted MACE (HR 2.30, 95% CI 1.70-3.18), with accelerated diastolic aging across all age groups among those with events. Discrimination was comparable to ASE-defined LVDD (C-index 0.83 vs. 0.82). Conclusion: Diastolic Age provides a continuous, echocardiography-derived measure of cardiac biological aging that complements categorical diastolic grading and epigenetic aging clocks, and independently predicts cardiovascular outcomes.

Dementia incidence has been declining in Western societies for decades, but whether this reflects higher cognitive capacity entering old age, slower cognitive decline, or both remains unresolved. Analysing ~783,000 episodic memory assessments from ~219,000 individuals across five longitudinal cohorts, we find that later-born cohorts benefit from a double dividend: higher memory levels entering old age and slower rates of decline. The projected 20-year cohort advantage at age 80 is of sufficient magnitude to plausibly account for the observed 13% per-decade decline in dementia incidence reported in meta-analyses. Generational gains are disproportionately concentrated among the fastest-declining individuals, and are reflected in lower hippocampal atrophy rates in an independent sample. A formal bounding analysis shows that the double dividend is robust across a range of plausible period assumptions, consistent with environmental conditions operating across the lifespan having reshaped the architecture of human cognitive aging.

BackgroundInsecticides remain the cornerstone of mosquito vector control for malaria, dengue, and other mosquito-borne diseases, yet global patterns of deployment and their socioeconomic and environmental drivers are poorly characterized. Understanding where and why insecticides are used is essential for better targeting control efforts and ensuring they are effective, equitable, and efficient. MethodsWe analyzed annual country-level insecticide-use data from 122 countries (1990-2019), reported as standard spray coverage for insecticide-treated nets (ITNs), residual spraying (RS), spatial spraying (SS), and larviciding (LA). Generalized linear mixed models and hurdle models quantified associations between deployment and disease incidence, human development index (HDI), human population density, temperature, and precipitation. Models were evaluated using repeated cross-validation and applied to generate downscaled predictions of insecticide use at subnational administrative region level 2 (ADM2) globally. FindingsInsecticide deployment increased with malaria and dengue incidence, but this response was substantially stronger in higher-HDI countries, indicating that deployment depends on socioeconomic capacity as well as disease burden that leads to weaker scaling in lower-resource settings. Intervention types exhibited distinct patterns; ITN use tracked malaria burden, whereas infrastructure-intensive approaches (e.g., RS and SS) were concentrated in higher-HDI settings and increased with Aedes-borne disease incidence. Downscaled ADM2-level maps uncovered substantial within-country heterogeneity that is obscured at the national scale, highlighting regions where predicted deployment remains low relative to disease risk across sub-Saharan Africa, South Asia, and parts of Latin America. InterpretationGlobal insecticide deployment reflects not only epidemiological need but also economic and logistical capacity, creating mismatches between risk and control. High-resolution mapping can support more equitable allocation of interventions, guide insecticide resistance stewardship, and improve strategic planning as climate and urbanization reshape mosquito-borne disease risk.