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Age and Ageing

◐ Oxford University Press (OUP)

Preprints posted in the last 30 days, ranked by how well they match Age and Ageing's content profile, based on 28 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Prioritising Research through Engagement with older Adult Care Homes and potential for mapping to existing data sources: the PREACH study

Irvine, L.; Micklewright, K.; Myles, B.; Davies, M.; Killett, A.; Goodman, C.; Burton, J. K.

2026-10-06 geriatric medicine 10.64898/2026.10.01.26364274 medRxiv
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Background: Care home research often fails to address issues that matter most to residents, families, and staff. Priority-setting exercises can help reduce this lack of inclusivity, but few have received significant resident responses. Objectives: To identify research priorities of UK care home stakeholders (including residents; relatives; care staff, managers and owners; healthcare professionals; policymakers and researchers), and to assess whether these priorities can be addressed using existing research datasets. Methods: PREACH was an 18-month research priority-setting study involving 1063 stakeholders, across 50 care homes, including 381 residents. Participants submitted ideas of what care home research should focus on through 1) care home activity sessions or 2) an online survey. Responses underwent content analysis to identify themes, and these themes were mapped against a national repository of care home trial data. Results: Fifty-one themes were identified. The most frequent priority across all stakeholder groups was access to meaningful activities for residents (22%). Relatives and residents emphasised social connection and day-to-day experience, whereas staff more often highlighted system pressures. No stakeholder-prioritised topics were directly addressable using existing secondary datasets. Conclusions: Collaboration with care home teams to reach large numbers of residents offers a practical route to producing more relevant and timely care home research. Care home stakeholders consistently prioritise quality of life, meaningful activity and staffing over disease-specific or health-focused research. Existing research datasets measure relatively few of the priorities identified by residents, highlighting the need for resident-centred outcome measures and data collection.

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Restoring Physical Resilience: Consistent Functional and Sarcopenia Gains Across Two Vivifrail Cohorts

Fernandez-Ortega, J.; Loza-Herbella, J.; Rangel-Garcia, J. A.; Fernandez-Revelles, A. B.

2026-10-16 geriatric medicine 10.64898/2026.10.14.26365508 medRxiv
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Objectives: To evaluate change in physical function and probable sarcopenia following a 36-week community multicomponent exercise programme (Vivifrail model) across two consecutive cycles, and to assess the consistency of this change between cohorts. Study design: Quasi-experimental, single-arm, repeated-measures service evaluation. Ninety-two older adults (2025-2026 cohort; mean age 75.9 years, 88.0% women) completed baseline and post-intervention assessments; an independent 2024-2025 cohort (n = 86) was analysed jointly for replication (n = 178). Main outcome measures: Short Physical Performance Battery (SPPB) score (primary); Timed Up and Go (TUG), handgrip strength, 6-metre walk time and Mini-Mental State Examination (MMSE) (secondary); probable sarcopenia (EWGSOP2), SPPB-based frailty category, and a fall-risk indicator computed identically in both cohorts. Results: SPPB improved by a mean of 1.33 points (Cohen's d = 0.96; p < .001), with concordant improvement in all four secondary outcomes (all q < .005). 72.8% reached the substantial minimal clinically important difference. Probable sarcopenia fell from 17.4% to 5.4% (p = .006), and frailty category shifted toward higher functional levels (p < .001). Effect sizes were consistent between cohorts for SPPB, handgrip and 6-metre walk; the Time x Cohort interaction was significant for TUG only. In the pooled sample, elevated fall risk fell from 19.7% to 11.2% (p = .002). Conclusions: A 36-week multicomponent exercise programme was associated with clinically meaningful, reproducible improvement in physical function and a reduction in probable sarcopenia across two independent cohorts. The single-arm design precludes causal inference.

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High-intensity progressive resistance training to prevent falls in community-dwelling adults aged 80 years and older with reduced muscle strength: protocol for the ReFit randomised controlled trial

Berg, J.; Tommerdal, K. H.; Coombes, J. S.; Follestad, T.; Salvesen, O. O.; Madssen, E.; Selbaek, G.; Dalen, H.; Bjornelv, G. M. W.; Devlin, B. L.; Steinsbekk, A.; Stensvold, D.; Singh, M. F.; Wisloff, U.

2026-09-24 sports medicine 10.64898/2026.09.23.26363212 medRxiv
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IntroductionFalls are a major cause of injury-related morbidity, mortality, and healthcare utilisation among older adults, with the greatest burden occurring in those aged [&ge;]80 years. Multicomponent exercise programmes that include balance and resistance exercises reduce falls, whereas the effect of resistance training delivered as a standalone fall-prevention intervention remains uncertain. Existing resistance-training trials have generally been small, underpowered for fall outcomes, and have produced inconsistent findings, despite reduced muscle strength being an important modifiable risk factor in the oldest old. The resistance training prescription used in these studies has not always aligned with recommendations for optimal strength adaptations in terms of intensity or progressive overload, which may explain this uncertain efficacy. Therefore, this study aims to determine whether 12 months of high-intensity progressive resistance training reduces fall rates in community-dwelling adults aged [&ge;]80 years with reduced muscle strength. Methods and analysisThis single-centre, randomised controlled trial conducted in Trondheim, Norway, includes 241 community-dwelling adults aged [&ge;]80 years with reduced muscle strength. Participants are randomly assigned (1:1) to either standard care with written physical activity guidance or a twice-weekly high-intensity progressive resistance training intervention for 12 months. The primary outcome is the rate of falls over 12 months. Secondary outcomes include time to first fall, fall-related injuries, muscular function, physical performance, balance, body composition, cardiometabolic health, cognition, and participant-reported outcomes. Cost-effectiveness is assessed from a healthcare perspective over the 12-month intervention period using costs and quality-adjusted life years. Analyses follow the intention-to-treat principle, using negative binomial regression for the primary outcome. The first participant was included on 30 March 2023, and the last participant was included on 29 September 2025. The 12-month intervention period is expected to be completed by September 2026. Ethics and disseminationThe study has received approval from the Regional Committee for Medical and Health Research Ethics in Norway (REK; reference number 462261). All participants provided written informed consent before participating. Findings will be shared via peer-reviewed publications, conference presentations, and communication with stakeholders and the public. Trial registration numberClinicalTrials.gov (NCT05691166), registered 11 January 2023. Available at: https://clinicaltrials.gov/study/NCT05691166

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Prehabilitative Exercise Mitigates Immobilization-Induced Atrophy Through Muscle Reserve Rather Than Resistance to Disuse: The PRE-EX Randomized Controlled Trial

Soendenbroe, C.; Pedersen, S. D.; Pulevic, L.; El Khoury, A.; Christiansen, H. L.; Linden, F. H.; Magnusson, S. P.; Svensson, R. B.; Schjerling, P.; Kjaer, M.; Mackey, A. L.

2026-09-27 rehabilitation medicine and physical therapy 10.64898/2026.09.25.26363998 medRxiv
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Periods of limb immobilization are common in clinical care and lead to rapid losses of muscle mass and strength. We therefore examined whether prehabilitative exercise improves outcomes after disuse by increasing pre-immobilization muscle reserve or by attenuating the biological response to immobilization. Here, we report the primary and muscle-focused secondary outcomes of the PRE-EX (PREhabilitative EXercise) randomized controlled trial (ClinicalTrials.gov: NCT06205784). Fifty-four healthy younger and older women completed four weeks of supervised resistance exercise or no training before eight days of unilateral limb immobilization, followed by four weeks of rehabilitation. From baseline to pre-immobilization, prehabilitation increased quadriceps cross-sectional area (CSA) by 6.7%, maximal voluntary contraction (MVC) by 15.2%, and muscle fiber CSA by 17.7%. Immobilization subsequently reduced quadriceps CSA by 3.2% over 5 days and MVC by ~20%, with similar relative losses in the Prehab and No-train groups. Consequently, quadriceps CSA, the studys primary outcome, remained greater in Prehab than in No-train after immobilization and following rehabilitation, while MVC was greater following rehabilitation. Prehabilitation did not preserve markers of neuromuscular innervation or produce a detectable post-immobilization transcriptomic signature. Instead, immobilization elicited an extensive transcriptional response comprising more than 7000 differentially expressed genes, characterized by activation of inflammatory, proteolytic, stress, and denervation-associated programs together with suppression of mitochondrial and muscle-structural pathways. Network analysis further linked these coordinated molecular programs to disuse-related changes in muscle size, strength, and morphology. The effects of prehabilitation and the subsequent response to immobilization were similar in younger and older women. These findings demonstrate that short-term prehabilitative exercise mitigates the consequences of limb immobilization by establishing greater muscle and strength reserve before disuse, rather than by attenuating the physiological or molecular response to immobilization.

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Physical Activity Initiation and Incident Mobility Difficulty Among Older Adults: A Sequential Target Trial Emulation

Liang, J.

2026-10-15 epidemiology 10.64898/2026.10.14.26365469 medRxiv
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Although physical activity is associated with better physical functioning, the effects of initiating regular physical activity among older adults with persistent inactivity remain unclear. We conducted a sequential target trial emulation using Health and Retirement Study (HRS) data to estimate the effect of physical activity initiation versus noninitiation on incident mobility difficulty. Participants were included in the analysis if they were aged [&ge;]65 years at the previous wave, reported no regular physical activity at the previous two waves, and had no mobility, activities of daily living (ADL), or instrumental activities of daily living (IADL) difficulties at baseline. Stabilized inverse probability of treatment weighting was applied to adjust for measured confounding. Weighted cumulative incidence was then estimated with death treated as a competing event, and risk differences were calculated at approximately 2, 4, and 6 years. At 2 years, the cumulative incidence of mobility difficulty was 32.75% among initiators and 39.73% among noninitiators, with a risk difference of -6.98 percentage points (95% CI, -13.11 to -0.88). At 4 and 6 years, risk differences were -2.90 percentage points (95% CI, -9.77 to 4.29) and -5.44 percentage points (95% CI, -12.27 to 1.99), respectively. Initiating regular moderate or vigorous physical activity was associated with a lower risk of incident mobility difficulty at approximately 2 years among older adults with persistent inactivity. This difference was less evident at later follow-up, and no clear differences were observed for incident ADL or IADL difficulty.

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Cultural and linguistic adaptation of a personalised post-diagnostic dementia intervention for Bangladeshi families in the UK: an iterative adaptation study

Budgett, J.; Lang, I.; Sen, A.; Hussain, M.; Yilmaz, M.; Birks, Y.; Cooper, C.

2026-10-14 psychiatry and clinical psychology 10.64898/2026.10.13.26365344 medRxiv
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People from UK South Asian communities experience barriers to accessing dementia care. Evidence suggests that evidence-based psychosocial dementia interventions can be successfully adapted for different cultural contexts, but further evidence is needed on how adaptations are developed and refined in practice. We aimed to adapt GRACE-family (Goal diRected, Accessible and Evidence-based Care), an evidence-based, manualised post-diagnostic dementia intervention, comprising 4-8 sessions for family carers and where possible, people with dementia, for Bengali-speaking communities. In a theory-informed process, a co-adaptation group encompassing lived, academic and clinical/professional experience developed consensus regarding which intervention functions were core. They then explored how adaptation might, while retaining these, account for cultural and linguistic contexts, informed by focus groups with memory service and Bengali community organisation staff (n=14). We developed a prototype adaptation, then piloted it with four Bangladeshi families supporting a person with dementia. Post-intervention, participants were asked about goal attainment, intervention acceptability, and qualitatively interviewed. Pilot data and a focus group with Sylheti-speaking family carers informed further refinements (n=6). Across data sources, two themes informed adaptation: (1) stigma, trust and community networks shaped access to dementia support; (2) flexible delivery was needed to respond to diverse language, communication and cultural needs. 3/4 pilot families completed the prototype intervention, which was in English as initial consultation cautioned against developing a written manual in a predominantly spoken language. Participants reported improvement on 7/8 personalised goals set, and all considered the intervention acceptable. Pilot delivery identified challenges using English-language materials during interpreter-mediated sessions. Iterative refinements added standard Bengali materials and spoken Sylheti audiovisual resources to broaden delivery options and facilitator training for culturally responsive and interpreter-mediated delivery. Our co-adaptation approach enabled stakeholders to advise from different, including experiential perspectives. It may inform future approaches to cultural and linguistically adaptations of psychological interventions for minoritised communities.

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Neighborhood socioeconomic status and environmental burden show diverging associations with cognitive impairment in community-dwelling older adults

Bonta, K. M.; Corbett, E.; Alemu, M. K.; Darge, B. D.; HIlderbrand, L. K.; Richardson, K. A.; Ogonuwe, S. S.; Blum, I. M.; Shen, K.; McGuire, M. K.; Pandhi, D. H.; Gallagher, L. W.; Hunter, J. M.; Grant, F.; Simmons, W.; Davis, L.; Shields, P.; Cooper, S.; Rouse, M.; Wilson-Lawson, K. S.; Hughes-Culp, C.; Howard, M.; Monroe, M.; Coleman, M.; Leath, D.; Butsch, J.; Davis, N.; Henry, J.; Gregory, P.; Scharre, D.; Grant, J. G.

2026-10-15 psychiatry and clinical psychology 10.64898/2026.10.13.26365488 medRxiv
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OBJECTIVE: Research on neighborhood context and cognitive health often relies on composite indices that collapse neighborhood socioeconomic status (SES) and aspects of the built environment into a single score. This study examined the extent to which neighborhood SES and built environment were associated with late-life cognitive impairment. METHOD: Participants were 281 predominantly Black older adults who completed the Self-Administered Gerocognitive Exam (SAGE), a brief cognitive screening measure. Participants also provided their home address to obtain four neighborhood metrics: Two composite measures of neighborhood disadvantage, the Environmental Justice Index (EJI) and the EJI Social-Environmental Rank, as well as the EJI Social Vulnerability Rank as a measure of neighborhood SES, and the EJI Environmental Burden Rank to measure exposure to hazardous aspects of the built environment. RESULTS: Lower neighborhood SES was associated with higher odds of cognitive impairment. In contrast, greater environmental burden was associated with lower odds of impairment, with years of education as a moderator; the association was strongest among individuals with high levels of education. The two composite scores were not associated with cognitive impairment. CONCLUSION: Composite measures of neighborhood features may obscure distinct pathways of their effects on cognition.

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Multimorbidity and Medication Order Patterns in Skilled Nursing Facilities: A Real-World Evidence Study

Ashraf, H.; Tsasis, P.; Mathers, K. E.; DiSanto, L.; Wong, A.; Sharma, D.; Heffernan, J. M.; Wagner, B.; Saumur, T. M.

2026-09-23 geriatric medicine 10.64898/2026.09.22.26363593 medRxiv
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BackgroundMultimorbidity is common among U.S. skilled nursing facilities (SNFs) residents and complicates pharmacologic management, yet real-world evidence on treatment patterns in this population remains limited. This study evaluated medication order rates and identified resident- and facility-level factors among SNF residents with multimorbidity. MethodsRetrospective, observational study using electronic health record (EHR) data from PointClickCares Life Sciences database. Participants were 728,222 residents active in a U.S. SNF on April 30, 2025 with at least one documented diagnosis of hypertension, hyperlipidaemia, type 2 diabetes (T2D), depression, or Alzheimers disease and related dementias (ADRD). The outcome was presence of guideline-recommended medication order for each condition, modelled with modified Poisson regression to estimate adjusted prevalence risk ratios (RRs) and 95% confidence intervals. ResultsMedication order rates were 79% for ADRD, 79.1% for T2D, 87.7% for hypertension, 83.3% for hyperlipidaemia, and 90.8% for depression. Rates varied across comorbidity combinations: ADRD was associated with lower medication order prevalence, while cardiometabolic multimorbidity profiles associated with higher prevalence. Black/African American identity had the lowest likelihoods of a medication order for 3 of 5 conditions (RRs of 0.93 to 0.92), while having hypertension or hyperlipidaemia medication order was associated with higher likelihood of having orders for 3 of remaining 4 conditions (RRs of 1.02 to 1.19). ConclusionsMost SNF residents with multimorbidity had a medication order for common chronic conditions, although important variability and disparities remain. Differences by comorbidity profile and social context underscore the need for targeted strategies supporting equitable, integrated prescribing and person-centred care in SNFs.

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The effects of route previewing on adaptive gait and gaze behaviour under cognitive dual-task conditions in older adults

McVeigh-Mellor, O.; Cocks, A. J.; OReilly, L.; Ellmers, T. J.; Kal, E.

2026-10-05 rehabilitation medicine and physical therapy 10.64898/2026.10.02.26364602 medRxiv
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Background: Safely walking through complex environments requires the use of visual information to plan and regulate steps, while managing competing cognitive demands. Age-related changes in visual control of gait and executive function may contribute to unsafe stepping behaviour, particularly under cognitive load. Route previewing may support visual motor planning, but its effects under dual task conditions in older adults are not well understood. Research Question: Does cognitive dual tasking influence gait and gaze behaviour during adaptive walking in older adults, and does previewing the walking route before gait initiation mitigate these effects? Methods: Thirty nine community dwelling older adults (Mage=73.4 years, SD=8.1; 14 male) completed four adaptive walking conditions, combining single and dual-task walking with and without previewing. Per condition, participants completed six trials across different 8-m long coloured walking routes. Gait characteristics were assessed using an instrumented walkway and video-analysis, while gaze behaviour was recorded using mobile eye tracking. Cognitive load was manipulated using a serial subtraction task. Gait and gaze outcomes were evaluated using linear mixed effects models. Results: Dual task performance significantly increased stepping errors, cross-steps, and double limb support, while reducing stride length (p < .001). It also significantly increased the number and duration of task irrelevant fixations (p < .001). After previewing, participants exhibited more efficient gaze behaviour, as evidenced by looking further ahead (larger forward gaze transitions) and fewer irrelevant gaze fixations (p < .002). Significant Task-by-Preview interactions revealed that previewing mitigated the negative effects of dual-tasking on stepping errors and cross steps (p < .001). Significance: Route previewing prior to gait initiation attenuates negative effects of cognitive load on adaptive gait in older adults, likely by supporting visual motor planning. These findings highlight the potential value of simple visual planning interventions for improving adaptive gait in older adults.

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Physical Frailty Accelerates Multimorbidity Accumulation Across Distinct Disease Patterns

Huang, Y.; Hu, Z.; Hao, M.; Li, X.; Tang, Y.; Jiang, S.; Wang, X.; Han, L.; Wang, J.; Li, Y.; Zhang, H.

2026-10-16 geriatric medicine 10.64898/2026.10.15.26365629 medRxiv
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Background Emerging evidence has linked frailty to individual chronic diseases, but whether it predicts a broad disease spectrum and accelerates multimorbidity accumulation over time remains unknown. This study aimed to systematically evaluate the associations of physical frailty with the burden of incident disease across a wide range of chronic conditions, and with the long-term rates of multimorbidity accumulation. Methods In this prospective cohort study of 466,864 UK Biobank participants , frailty status was assessed using the Fried frailty phenotype and categorized as robust, pre-frailty, or frailty. Chronic diseases were defined based on International Classification of Diseases (ICD)-10 codes, and disease patterns were identified using network analysis. Cox proportional hazards models were used to examine the associations of frailty status with incident chronic diseases, and linear mixed models were used to assess the annual rate of chronic disease accumulation. Results During a median follow-up of 13.8 years (IQR: 13.1-14.5), 536 incident chronic diseases across multiple systems were recorded. Physical frailty was associated with a significantly increased risk of 458 incident diseases (Bonferroni-corrected P < 0.05/536). In the overall cohort, compared with robust participants, those with pre-frailty ({beta} = 0.266, 95% confidence interval [CI]: 0.264-0.267) and frailty ({beta} = 0.941, 95% CI: 0.936-0.946) exhibited significantly faster rates of multimorbidity accumulation. This accelerated multimorbidity accumulation was consistently observed across strata of baseline disease burden, including participant with 0 ({beta} = 0.644, 95% CI: 0.635-0.653), 1 ({beta} =0.748, 95% CI: 0.727-0.768), [&ge;] 2 ({beta} =0.940, 95% CI: 0.933-0.947) chronic conditions at baseline. Similar associations were also found across distinct disease patterns, including neurodegenerative, metabolic, and psychiatric patterns. Conclusions Physical frailty predicts a broad range of incident diseases and is associated with accelerated multimorbidity accumulation. Incorporating frailty assessment into prevention strategies may help mitigate the growing burden of multimorbidity.

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Comorbidities of dementia in electronic health records: validation of a natural language processing app and comparison with data linkage

Mirza, L.; Bendayan, R.; Stewart, R.; Davis, K. A. S.

2026-10-19 health informatics 10.64898/2026.10.16.26365714 medRxiv
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Awareness of comorbidities in people with dementia is vital context for dementia research and clinical management. Natural Language Processing (NLP) applied to free text in the electronic health record (EHR) may help ascertain comorbidity presence. Our aim was to assess the validity of the MedCAT Comorbidity NLP app in a cohort of people with dementia. We used text from the EHR of South London and Maudsley NHS Mental Health Trust via Clinical Records Interactive Search (CRIS), linked to structured data from local primary care (Lambeth DataNet) and hospital admission data in a cohort of 3,543 people with dementia. We evaluated MedCAT Comorbidity, examining internal validity via manual review of text and external validity by cross-validation against linked primary care and hospital data; and comparison of the predictive value of comorbidity measures for mortality. Internal precision was highest for atrial fibrillation (100%) and lowest for diabetes (78%). Cross-validation with linked data varied substantially across conditions, with precision from 96% to 59% and recall 77% to 4%. The median number of comorbidities identified was two using any single source, or three when combined. MedCAT Comorbidity demonstrated predictive ability for mortality (HR 1.11 per condition), although the model fit was better using comorbidity from hospital admission data. In people with dementia, the MedCAT Comorbidity app showed high precision for most conditions during internal validation. The variability of precision and recall on external validity assessment partly reflects incomplete documentation. Results from the MedCAT comorbidity app can assist researchers in understanding comorbidity of cohorts, particularly when primary care or hospital data is not available. Our findings highlight the need to develop quality assurance protocols that include internal and external validity checks before deploying general data extraction apps for specific clinical subpopulations.

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Plasma Neurofilament Light Chain is Markedly Elevated in General Hospital Inpatients with Delirium

Kang, M. J.; Eratne, D.; Borchard, T.; Patel, K.; Malpas, C. B.; Dang, C.; Storer, M.; Bhalala, O. G.; Yu, J. J.; Santillo, A. F.; Forbes, M.; Zetterberg, H.; Farrand, S.; Loi, S. M.; Mitchell, P. B.; Hopwood, M.; Smith, J.; Chiang, C.; Velakoulis, D.

2026-10-20 geriatric medicine 10.64898/2026.10.18.26365854 medRxiv
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Objective: To determine whether plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are elevated in hospitalised patients with delirium relative to patients with dementia and primary psychiatric disorders (PPD). Methods and analysis: This was a cross-sectional observational study conducted at the Royal Melbourne Hospital, Melbourne, Australia, between April and October 2024, with comparator samples from a research biobank. In Phase 1 (Delirium Discovery Cohort), we measured plasma NfL and GFAP using the Single molecule array (Simoa) platform in hospitalised patients with delirium and compared them with dementia and PPD groups. Biomarker concentrations were the primary outcome and were compared using general linear models adjusted for age, sex, and estimated glomerular filtration rate, with bootstrapped confidence intervals. Discriminative performance was assessed as a secondary outcome using receiver operating characteristic (ROC) curve analysis. In Phase 2, we applied this threshold to independent dementia and PPD groups. Results: In Phase 1 (n =176), inpatients with delirium showed higher concentrations of both NfL and GFAP than patients with dementia ({beta} = 0.78; 95% CI [0.37, 1.20] and {beta} = 0.39 [0.07, 0.73] respectively) or PPD groups ({beta} = 1.17; [0.69, 1.66] and {beta} = 0.83 [0.51, 1.24] respectively). ROC curve analysis for differentiating delirium from dementia and PPD groups yielded an optimal NfL threshold of 24.1 pg/mL (AUC = 0.89, 96% sensitivity, 70% specificity). In comparison, GFAP showed lower accuracy (AUC = 0.85), and combining NfL with GFAP (AUC = 0.90) did not significantly improve performance. In Phase 2 (n = 154), the NfL threshold of > 24 pg/ml maintained strong performance (AUC = 0.95, 96% sensitivity, and 77% specificity). Conclusions: Plasma NfL shows promise as a biomarker for delirium in hospitalised patients, distinguishing it with high sensitivity from patients with dementia and PPD. Larger multicentre studies are needed to refine cut-offs, evaluate temporal dynamics, and determine integration into acute hospital delirium pathways.

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Use of routine clinical data in adults with chronic diseases for identifying risk of frailty: results from the UK Biobank study

LANDRE, B.; Silva, G. C.; Fayosse, A.; Meneghel Danilevicz, I.; Lieb, W.; Sabia, S.; Singh Manoux, A.; Sturmer, P.

2026-10-07 public and global health 10.64898/2026.10.05.26364730 medRxiv
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Frailty assessment is increasingly recommended for risk stratification in chronic disease management, but systematic clinical screening for frailty remains difficult to implement because it is resource-intensive. We investigated whether routinely collected clinical measures could be repurposed to prioritize adults with chronic diseases for clinical frailty assessment. We conducted a prediction study using UK Biobank data. A stacked ensemble model was developed using 12 routinely and low cost measured clinical variables to predict frailty. Gain metrics were used to quantify the proportion of frailty cases identified when screening was restricted to individuals with the highest predicted risk of frailty. We compared health profiles (mortality, polypharmacy, self-rated health, falls) of frail and non-frail individuals across different levels of predicted risk. The robustness of this screening strategy was evaluated across 3,284 modelling settings. Among 281,729 participants (mean age 57.9; 54.7% women) with at least one chronic condition, 5.8% were frail. In the validation sample (N validation=93,910, N training=187,819), screening only the 20% of participants with the highest predicted risk of frailty identified 55.6% of all frailty cases, corresponding to a 2.78-fold improvement compared to random screening. Overall, the model recovered 53.4% of the maximum achievable improvement over random screening. Frailty remained always associated with poor outcomes. Screening performance remained consistent across alternative modelling settings. Routinely collected clinical measures can improve the efficiency of frailty screening among adults living with chronic diseases by prioritizing individuals based on their level of risk. Since these data are already gathered during routine care, this risk-prioritization strategy could support scalable screening without increasing testing burden or clinical workload.

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Patterns of modifiable lifestyle, behavioural and health-related risk factors and their associations with incident dementia in UK Biobank

Uejima, Y.; Calvin, C. M.; Kuzma, E.; Littlejohns, T. J.

2026-09-25 epidemiology 10.64898/2026.09.24.26363838 medRxiv
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INTRODUCTION: Individual lifestyle, behavioural and health-related factors are associated with the risk of developing dementia. However, the co-occurrence of these factors, which are likely to form distinct patterns, in relation to dementia risk has been understudied. METHODS: The sample included 151,832 UK Biobank participants aged 60-69 years. Latent class analysis was used to identify patterns among participants with two or more of the following risk factors: high alcohol consumption, high body weight, depression, diabetes, poor diet, hypertension, physical inactivity, visual impairment, hearing impairment, sleep disturbance, smoking, social isolation, traumatic brain injury, and vitamin D deficiency. Multivariate Cox proportional hazards models were used to determine the associations between identified risk factor patterns and incident dementia ascertained through hospital and death records. RESULTS: Over a median follow-up of 13 years, 5,304 participants developed dementia. Six risk factor classes were identified. Compared to participants with zero or one risk factor, all classes were associated with dementia risk: 'multiple risk factors' (hazard ratio [HR] 2.38, 95% confidence interval [CI] 2.11-2.68), 'hearing loss and unhealthy lifestyle' (HR=1.37, 95% CI 1.22-1.55), 'sleep and psychosocial factors' (HR=1.34, 95% CI 1.20-1.49), 'poor cardiometabolic health' (HR=1.32, 95% CI 1.19-1.46), 'heavy drinking and unhealthy lifestyle' (HR=1.20, 95% CI 1.07-1.35), and 'vitamin D deficiency, sedentary and psychosocial factors' (HR=1.18, 95% CI 1.03-1.35). DISCUSSION: We identified risk factor patterns that were differentially associated with dementia risk. These findings suggest that accounting for the co-occurrence of risk factors might be an effective approach for risk stratification and developing effective dementia prevention strategies.

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Targeted Free Swimming for Women, Girls, and Older Adults in Tower Hamlets: A RE-AIM Evaluation Study Protocol

Clements, K.; Todorova, Y.; Makawa, A.; Asamoah, P. E.; Lester, P.; Ngina, D. M.; Sherar, L.

2026-10-07 public and global health 10.64898/2026.10.05.26361900 medRxiv
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Across the UK, older adults in deprived areas like Barnsley are spending more of their lives in poor health. Alongside increased loneliness, this creates barriers to leading active healthy lives that can lead to decreases in the quality of life of residents and increased pressure on healthcare services. To address these issues, Barnsley Council brought together over 80 providers of physical activity classes for adults aged 50 and over as part of a joined up partnership called the Barnsley Older People Physical Activity Alliance (BOPPAA). The evaluation will explore how effectively the joined up partnership (BOPPAA) works in helping older adults lead active health lives by collecting information on involvement in the classes, and speaking to residents and organisations to get their thoughts and opinions. The findings will be used to help understand how BOPPAA can be improved to better meet the needs of the local population.

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Memory and executive functioning show differential associations with scam susceptibility in middle to older adulthood

Molinare, C. P.; Zhang, B. Y.; Sanderson-Cimino, M.; Leguizamon, M.; Oyen, E.; Noriega-Makarskyy, D. T.; Axelrod, J.; Lim, A. C.; Wu, C.; Agarwal, M.; Mosqueda, L.; Han, S. D.

2026-10-06 psychiatry and clinical psychology 10.64898/2026.10.04.26364617 medRxiv
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Objectives: The rising prevalence of financial exploitation among older adults has prompted research on the cognitive mechanisms underlying financial decision making in later life. Prior work has demonstrated a link between cognitive impairment and financial vulnerability. The present study examined the unique contributions of composite measures of memory and executive functioning to scam susceptibility in middle-aged to older adults without dementia. Methods: One hundred and fifty-one participants (age= 68.2 {+/-} 8.0 years, 72.2% female, years of education= 16.4 {+/-} 2.2) completed standard neuropsychological measures from the Uniform Data Set (UDS), Version 3, and the California Verbal Learning Test, Second Edition, and a self-report scam susceptibility measure. Psychometrically robust composite scores, the UDS-M+ and UDS3-EF, were computed to represent memory and executive functioning domains. Linear regression models examined independent associations between UDS-M+ and UDS3-EF performance and scam susceptibility. Nested model comparisons evaluated unique contributions of the UDS-M+ and UDS3-EF when included in a joint model. Results: Lower UDS-M+ (b= -0.25, 95% CI [-0.45, -0.04], p= .018) and lower UDS3-EF (b= -0.33, 95% CI [-0.54, -0.12], p= .002) scores were independently associated with greater scam susceptibility after adjusting for age, sex, years of education, and income. However, only UDS3-EF remained significant in a joint model. Post hoc analyses revealed that only memory was associated with scam susceptibility in middle-aged adults whereas only executive functioning was significant in older adults. Conclusions: These findings highlight the importance of monitoring memory and executive functioning across middle to older adulthood when considering susceptibility to scams.

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Navigating Life After Dementia Diagnosis: Questions, Challenges, and Support Needs Among Dementia Dyads

Britt, K.; Harb, A.; Bailey, B.; Saffold, B.; Luo, X.; Brown, R. T.; Huang, B.

2026-10-09 geriatric medicine 10.64898/2026.10.07.26364992 medRxiv
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Background: Older adults living with mild cognitive impairment (MCI) or Alzheimer's disease and related dementias (AD/ADRD) and their care partners face substantial daily challenges that evolve with disease progression and extend far beyond the clinical setting, including symptom management, care coordination, healthcare navigation, and planning for future care needs. Understanding these challenges is essential for developing innovative solutions to provide ongoing and targeted support. In this study, we explored questions, challenges, and support needs experienced by dementia dyads following diagnosis to inform the development of an artificial intelligence (AI)-based chatbot designed to provide ongoing support for dementia dyads. Methods: We recruited 11 community-dwelling dyads comprising persons living with MCI or mild AD/ADRD and their care partners, one additional care partner, and 12 dementia care experts from academic medical centers, clinics, and aging organizations in the U.S. We conducted semi-structured interviews and analyzed them using conventional content analysis. Results: Participants described interconnected questions, challenges, and support needs that evolved while navigating life with MCI or AD/ADRD. Questions centered around day-to-day care management, medical concerns, behavioral symptom management, diagnosis and prognosis, safety, and resources and services. Challenges included care partner overwhelm, limited dementia knowledge, condition-related uncertainty, healthcare system navigation difficulties, financial constraints, and technology-related barriers. Participants identified needs for ongoing education, personalized care planning, resource navigation, logistical support and follow-up, culturally responsive care, and social and emotional support. Conclusions: Dementia dyads experience substantial informational, emotional, and practical support needs in the early stages of MCI and AD/ADRD. Findings suggest that post-diagnostic support should extend beyond information provision alone to provide ongoing, personalized, and practical guidance that helps dyads navigate changing needs, resources, and everyday dementia care. These findings are informing the development of an AI-based chatbot intended to complement existing dementia care by extending access to education, practical guidance, and resource navigation between clinical encounters.

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30-Day Heart Failure Readmission and Post-Discharge Healthcare Use Among Older Australians: A Linked-Data Mixed-Methods Study

Leong, C. S.; Kabir, A.; Barr, M. L.

2026-10-12 cardiovascular medicine 10.64898/2026.10.09.26365178 medRxiv
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Abstract Background: Heart failure (HF) is a major public health challenge in ageing populations and a leading cause of unplanned hospital readmissions. Biological, social, and economic factors contribute to recurrent hospitalisation, but gaps remain in understanding how these factors interact and patterns of healthcare use following hospitalisation. Methods: We conducted an explanatory sequential mixed-methods study of patients aged ?60 years with an HF hospital admission between 2016 and 2020 who completed the Sax Institute?s 45 and Up Study baseline questionnaire. Data were linked to Admitted Patient Data Collection, Medicare Benefits Schedule, and Pharmaceutical Benefits Scheme data. HF readmission within 30 days of the index admission was the outcome. Cox proportional hazards models estimated crude and adjusted hazard ratios (HRs and adjHRs) with 95% confidence intervals (CIs). Kaplan-Meier curves and log-rank tests compared survival between groups. Time-series plots mapped healthcare interactions over 1 year following the index admission. Results: Among 4,252 patients with HF, 409 were readmitted within 30 days. Significant predictors included age ?80 years (adjHR, 1.30; 95%CI, 1.01?1.67), 1 chronic condition (adjHR, 2.49; 95%CI, 1.41?4.40), ?2 chronic conditions (adjHR, 1.75; 95%CI, 1.04?2.95), and alcohol consumption above national guidelines (adjHR, 1.45; 95%CI, 1.06?1.98). Time-series analysis indicated that participants with readmission had more frequent out-of-hospital health service contact following their initial HF admission than those without readmission. Conclusions: Older age, chronic conditions, and high alcohol intake increased 30-day HF readmission risk. Differences in healthcare use after admission highlight opportunities for targeted and coordinated post-discharge care.

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Patient-Reported Shared Decision-Making and Documented Advance Care Planning Among Adults With Alzheimer Disease and Related Dementias

Wang, X.; Macieira, T. G. R.; Hong, Y.-R.; Revere, L.; Xie, Z.

2026-10-19 geriatric medicine 10.64898/2026.10.15.26365674 medRxiv
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Objective To examine the association between patient-reported shared decision-making (SDM) and documented advance care planning (ACP) among adults with Alzheimer disease and related dementias (ADRD), and to assess whether this association differed between adults with and without ADRD. Design Retrospective observational study using linked survey and electronic health record (EHR) data. Setting and Participants Participants aged [&ge;]50 years in the All of Us Research Program who completed a patient-reported SDM measure and had linked EHR records. The primary analytic cohort included 3,635 adults with ADRD; 123,681 adults without ADRD comprised a secondary comparison cohort. Methods SDM was measured by how often clinicians asked participants about their opinions or preferences regarding medical care or treatment and was categorized as high (always/most of the time) or low (some of the time/ None of the time). Documented ACP was identified within 3 years before or after the SDM assessment. Modified Poisson regression with robust variance estimated prevalence ratios (PRs) and adjusted PRs (aPRs). Results Among adults with ADRD, 60.6% reported high SDM. Documented ACP prevalence was 5.1% among participants with high SDM and 3.6% among those with low SDM (P=0.027). High SDM was associated with greater ACP prevalence in the unadjusted model (PR, 1.44; 95% CI, 1.04-1.99); the association remained positive but was attenuated after full adjustment (aPR, 1.28; 95% CI, 0.93-1.77). Among adults without ADRD, high SDM was associated with documented ACP (aPR, 1.17; 95% CI, 1.03-1.33). Conclusions and Implications Among adults with ADRD, high SDM was associated with greater ACP prevalence in unadjusted analyses, although the fully adjusted association was not statistically significant. In contrast, higher SDM remained significantly associated with ACP among those without ADRD. The low prevalence of ACP highlights an important opportunity to expand discussions of current and future care preferences as a routine component of patient-centered care.

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Plasma metabolomic profiling of frailty in older adults at risk of dementia

Alldritt, I.; Michaelian, J. C.; Yu, R.; Deemer, S. E.; Mills, R. J.; Naismith, S. L.; Philp, A.

2026-10-08 geriatric medicine 10.64898/2026.10.06.26364906 medRxiv
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Background: Frailty is a prominent risk factor for dementia. Early detection of at-risk individuals may enable intervention to prevent or slow dementia pathology. Blood-based biomarker discovery could offer a path for early detection of frailty and cognitive decline. Methods: Older adults at risk of dementia underwent comprehensive multi-disciplinary assessment at the Healthy Brain Ageing (HBA) clinic, including geriatric, neurophysiological and mood evaluations, in addition to providing a fasted blood sample. Clinical data were used to calculate a deficit accumulation frailty index (FI) score. Additional cohorts attended either one (n=118) or two (n=73) subsequent visits over an average period of 4 years. Untargeted metabolomics was performed on plasma samples, and metabolites were clustered by similarity. Linear regression was used to assess association of clusters with FI. Finally, change in plasma abundance over time was assessed. Results: At assessment, participants had a mean (SD) age of 68.10 (8.07) years; 72.2% were female. Hierarchical clustering identified 10 clusters of metabolites, of which 6 were significantly associated with FI (p<0.05) at baseline and contained similar classes of metabolite. Differential abundance analysis found unique temporal regulation of metabolite abundance in each cluster, but across clusters severity of frailty impacted direction of change in plasma abundance over time. Conclusions: Frailty index was associated with carboxylic acids and derivatives, fatty acyls and organooxygen compounds across multiple clusters, and a large number of lipids were linked to frailty score, potentially implicating dysregulation of energy metabolism in the pathophysiology of frailty and forming a panel of predictive biomarkers of at risk patients.