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<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Frailty, characterised by decreased physiological function and increased vulnerability to stressors, was associated with an increase in numerous adverse outcomes. Although the number of digital biomarkers for detecting frailty in older adults is increasing, there remains a lack of evidence regarding their effectiveness for early detection and follow-up in real-world, home-based settings.<div class="boxTitle">Methods</div>Five databases were searched from inception until 1 August 2024. Standardised forms were utilised for data extraction. The Quality Assessment of Diagnostic Accuracy Studies was used to assess the risk of bias and applicability of included studies. A meta-analysis was conducted to assess the overall sensitivity and specificity for frailty detection.<div class="boxTitle">Results</div>The systematic review included 16 studies, identifying digital biomarkers relevant for frailty detection, including gait, activity, sleep, heart rate, hand movements and room transition. Meta-analysis further revealed pooled sensitivity of 0.78 [95% confidence interval (CI): 0.70–0.86] and specificity of 0.79 (95% CI: 0.72–0.86) to classify robust and pre-frailty/frailty participants. The overall risk of bias indicated that all the included studies were characterised as having a high or unclear risk of bias.<div class="boxTitle">Conclusion</div>This study offers a thorough characterisation of digital biomarkers for detecting frailty, underscoring their potential for early prediction in home settings. These findings are instrumental in bridging the gap between evidence and practice, enabling more proactive and personalised healthcare monitoring. Further longitudinal studies involving larger sample sizes are necessary to validate the effectiveness of these digital biomarkers as diagnostic tools or prognostic indicators.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background and Aims</div>Poor physical performance (PPP) in terms of weakness and slow walking speed is closely associated with frailty during ageing. We aimed to analyse the associations between modifiable lifestyle factors, inflammation markers (hs-CRP, D-dimer, and fibrinogen), and the odds of PPP and state transitions between normal and PPP in older adults.<div class="boxTitle">Methods</div>A total of 3756 participants ($\ge$ 55 years) in wave 1 (2009–2013) and wave 2 (2014–2019) of the Healthy Aging Longitudinal Study in Taiwan (HALST) were analysed. A logistic regression model was used to assess the associations between lifestyle factors (physical activity [PA], diet, and psychosocial health), inflammation markers, comorbidities, and PPP (two or more of the criteria: grip strength, 6-minute walking distance, or gait speed among the lowest 20%).<div class="boxTitle">Results</div>In total, 229 and 149 of the 773 PPP participants at wave 1 reversed and persistent in PPP state at wave 2, respectively. Higher PA (OR 0.917, 95% CI 0.894–0.941), psychosocial health (OR 0.964, 95% CI 0.955–0.972), LDL-C, and education level had significant protective effects, whereas greater waist circumference, D-dimer, fibrinogen, longer sleeping time, and comorbidities were positively associated with PPP. Higher PA, psychosocial health, and diet scores were protective against conversion to PPP, and increased PA and higher psychosocial health score were significant for reversion.<div class="boxTitle">Conclusions</div>Older adults are encouraged to engage in various forms of PA and participate in societal events to increase their physical performance. To avoid further deterioration in physical frailty, screening for PPP may be adopted as a standard clinical practice for older adults.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Healthy life expectancy is a major challenge in many countries and one of the World Health Organisation’s main concerns for the current decade. With different animal models, from invertebrates to mammals, research into the biology of ageing has identified various biological and physiological processes that alter the quality of ageing. Twelve characteristics of ageing have been defined, and the aim of a growing number of studies is to find how to slow down or halt their onset. Unfortunately, the direct transposition of animal models to humans is too often disappointing, and the race to bring anti-ageing products to market is a source of misleading promises. The development of geroscience will enable the identification and validation, with more relevant clinical evidence, of pro-ageing targets to develop anti-ageing therapies and aim for healthy ageing.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Predicting hospital length of stay (LOS) can potentially improve healthcare resource allocation. Recent studies suggest that point-of-care ultrasound (POCUS), specifically measurements of muscle thickness (MT), may be valuable in assessing patient outcomes, including LOS. This study investigates the hypothesis that quadriceps MT and echo intensity (EI) can predict patient outcomes, particularly LOS.<div class="boxTitle">Methods</div>Quadriceps MT and EI were measured using POCUS in patients admitted to a hospital’s acute medical unit. Predictor variables included age, sex, MT, EI and the Charlson Comorbidity Index (CCI). The outcome variable was hospital LOS.<div class="boxTitle">Results</div>One hundred twenty participants were included (average age 76 ± 7, with 64 women and 56 men). The mean LOS was 27 ± 31 days, and the mean MT was 20 ± 6 mm. Sex-based differences in MT were statistically significant (<span style="font-style:italic;">P</span> = .032). Patients with prolonged LOS over 30 days had lower MT (mean 17 mm vs. 21 mm, <span style="font-style:italic;">P</span> < .0001). One unit increase in MT was significantly associated with ~1.5 fewer days of hospital LOS, and one CCI score increase was associated with almost three more days of hospital LOS. Having low MT significantly increased the odds of staying in the hospital longer than 30 days by more than three times in all models.<div class="boxTitle">Conclusion</div>Muscle thickness is a strong predictor of hospital LOS, highlighting the potential of POCUS for assessing patient outcomes.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background and aims</div>Delirium carries an eight-fold risk of future dementia. Small vessel disease (SVD), best seen on magnetic resonance imaging (MRI), increases delirium risk, yet delirium is understudied in MRI research. We aimed to determine MRI feasibility, tolerability, image usability and prevalence of SVD lesions in delirium.<div class="boxTitle">Methods</div>This case–control feasibility study performed MRI (3D T1/T2-weighted), fluid-attenuated inversion recovery, susceptibility-weighted and diffusion-weighted imaging (DWI) on 20 medical inpatients >65 years: 10 with delirium ≥3 weeks and 10 without delirium, matched for vascular risk, Clinical Frailty Scale (CFS) and cognition. We excluded acute stroke, agitation necessitating sedation, mobility assistance of >2 and MRI contraindications. We measured scan duration, tolerability, image usability, acute infarcts and SVD features. Six months later, we recorded CFS and cognitive diagnoses.<div class="boxTitle">Results</div>Mean age was 83.5 years (delirium 78.7 vs non-delirium 88.4); 13/20 were female; 17/20 had premorbid cognitive decline/impairment or dementia. Acquisition took mean 26.8 min. MRI was well tolerated in 16/20 (7/10 in delirium arm; 9/10 in non-delirium arm). Also, 4/20 had early scan termination, but 20/20 had clinically interpretable images. We detected DWI-hyperintense lesions in 3/10 (30%) with delirium (2/10 small subcortical and 1/10 cortical) and in 3/10 (30%) without delirium (2/10 small subcortical; 1/10 cortical). Mean white matter hyperintensity Fazekas score was 6 in delirium versus 4.5 without.<div class="boxTitle">Conclusions</div>MRI is feasible, usable and tolerable in delirium, and we detected DWI-hyperintense lesions in one-third of all study participants, regardless of delirium status. This study indicates acute vascular contributions, including SVD, to both delirium- and non-delirium–related presentations, supporting the need for larger studies.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>The burden of dementia is increasing dramatically with the population aging. Tinnitus and chronic noise exposure are associated with neuropsychiatric diseases and cognitive decline, but relationships between tinnitus and noise exposure and incident dementia remain unclear.<div class="boxTitle">Methods</div>160 032 participants from the UK Biobank were included. Information on tinnitus, tinnitus severity, noise exposure (loud music and noisy workplace) was collected at baseline. Cox proportional hazards models were used to assess the associations of tinnitus, tinnitus severity and noise exposure with the risk of incident dementia. Logistic regression models were used to assess the associations between noise exposure and tinnitus.<div class="boxTitle">Results</div>During a median follow-up of 12.8 years, 2219 incident dementias were recorded. Compared with participants without tinnitus, those with tinnitus had a 10% increased risk of dementia (hazard ratios [HR]: 1.10, 95% CI: 1.00–1.20). Among the participants with tinnitus, compared with those with the lowest tinnitus severity, those with slight and moderate or severe tinnitus had 23% (95%CI: 1.03–1.46) and 64% (95%CI: 1.35–2.00) increased risks of dementia, respectively. Furthermore, compared with participants without exposure to noise, those with exposure to noise for more than 5 years had a 12% increased risk of dementia (HR: 1.12, 95%CI: 1.00–1.26). In addition, the longer time the participants exposed to noise, the higher the odds of having tinnitus (<span style="font-style:italic;">P</span> for linear trend <.001).<div class="boxTitle">Conclusions</div>Tinnitus, tinnitus severity and long-term noise exposure were associated with incident dementia, and long-term noise exposure were related to tinnitus. Tinnitus and noise exposure are public health issues vital for dementia prevention.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>We hypothesised that morbidity burden was higher in real-life patients with oral anticoagulant-related intracerebral haemorrhage (OAC-ICH) than direct oral anticoagulant (DOAC) trial-life patients (pivotal trial participants) and explored if pre-stroke morbidity was comparable (i) in real-life patients on DOAC or vitamin K antagonist (VKA) with ICH, and (ii) in trial-life patients versus real-life patients with OAC-ICH.<div class="boxTitle">Methods</div>The COOL-ICH cohort included 401 acute, consecutive patients with OAC-ICH (272 VKA-ICH, 129 DOAC-ICH) from the Capital Region of Denmark. Risk-factors and morbidity in trial-life patients were retrieved from publications.<div class="boxTitle">Results</div>Risk-factors, CHADS2 and Charlson Comorbidity Index were comparable in DOAC vs VKA users in real-life. Pre-stroke modified Rankin Scale (mRS) was higher in DOAC users than in VKA users (median mRS 1 vs 0, <span style="font-style:italic;">P</span> = 0.002). More DOAC users were women (53% vs 39%, <span style="font-style:italic;">P</span> = 0.009). Compared to trial-life patients, age and proportion of women were higher in real-life patients. CHADS2-scores were comparable.<div class="boxTitle">Conclusion</div>In conclusion, burden of risk-factors and comorbidities were similar in real-life patients with DOAC-ICH and VKA-ICH, as well as in real-life patients compared to trial-life patients. However, real-life patients especially those on DOAC, were older and more frequently women than trial-life patients. It is reassuring that burden of comorbidity was similar in real-life and trial-life patients. Nevertheless, this report underlines the importance of recruiting adequate numbers of older people and women to cardio-vascular trials to ensure sufficient safety data to advice prescriptions in these very prevalent sub-groups of patients.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Despite growing attention to well-being in dementia, few studies have defined meaning-based (eudaimonic) well-being in this population, mainly due to challenges posed by cognitive decline and self-report limitations. We developed and validated a novel tool for measuring meaning-based well-being in individuals with dementia, particularly those receiving residential or home care. The study included two samples: carers of 174 care home residents and carers of 420 community-dwelling individuals for whom respondents reported dementia. The Well-being in Dementia Inventory (WiDI) assesses six core dimensions: Self-Sufficiency, Functional Mastery, Goal-Based Mastery, Purposeful Engagement, Positive Interactions and Constructive Self-Perspective. Confirmatory Factor Analysis established the WiDI’s six-factor structure, underscoring its multidimensional nature and equivalence across community-dwelling individuals, regardless of gender, age group (younger-old/mid-older-old), or care context (family or professional). The scale exhibited high internal and inter-rater reliability, though very low scores in the care home sample inflated these statistics. Concurrent validity was confirmed through strong correlations with adapted indices of meaning-based well-being (e.g. the Scales of Psychological Well-being and the Mental Health Continuum Short Form, commonly used in non-dementia samples), indicating the WiDI’s conceptual consistency. These findings clarify how meaning-based well-being can be assessed in individuals with dementia and introduce the WiDI as a reliable and valid tool for assessing well-being, suggesting broad applicability across care settings. These results have important implications for practice and policy, advocating a meaning-based approach to well-being assessments that ensures holistic, personalised care by focusing on key indicators of life quality.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>We explored how adherence to the Mediterranean diet (MedDiet) and leisure-time physical activity (LTPA) impact psychoactive medication use in older adults.<div class="boxTitle">Methods</div>We assessed the cumulative MedDiet adherence and LTPA’s impact on mental health medication initiation in older individuals at high risk of chronic disease. Associations between the cumulative average of MedDiet adherence (per one-point increase in the adherence score) and LTPA (per increase in 20 metabolic equivalents of task-minute/day [METs-min/day]) with drug initiation were assessed by multivariable Cox regressions. We explored non-linear exposure-outcome associations using smoothed cubic splines and the multiplicative interaction between MedDiet and LTPA.<div class="boxTitle">Results</div>A total of 5940–6896 participants (mean age 67, 58% women) over 4.2–4.7 years, each point increase in MedDiet adherence decreased the initiation of antidepressants by 23–28% (HR 0.72, 95% CI 0.67–0.77), anxiolytics (HR 0.75, 0.70–0.81), antipsychotics (HR 0.77, 0.65–0.91), and antiseizures (HR 0.77, 0.69–0.85). Associations for anxiolytics and antiseizures were strong at low MedDiet adherence levels. Relationships between LTPA and initiation of antidepressants and anxiolytics were linear in the lowest LTPA values (0–150 METs-min/day); every 20 METs-min/day increases were associated with 20% lower risk of initiating antidepressants (HR 0.80, 0.75–0.86) and 15% less risk in anxiolytics (HR 0.85, 0.79–0.90). Association with antiseizures was linear (+20 METs-min/day: HR 0.96, 0.94–0.99), and no associations were found for antipsychotics. High MedDiet adherence (≥10) and LTPA (≥150 METs-min/day) reduced psychoactive drug initiation by 42%–59%. Combination was additive for antidepressants, antipsychotics and antiseizures and synergistic for anxiolytics.<div class="boxTitle">Conclusions</div>MedDiet and LTPA adherence reduced psychoactive drugs initiation in older adults.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Nature-based interventions (NBIs) may support older adults’ health and well-being, but it remains unclear which interventions are most effective, for whom and in which contexts. The existing Wilkie and Davinson framework explains the pathways between NBIs and health outcomes but underemphasises the effects of environmental qualities. Therefore, the study aims to critically examine existing NBIs and their associated health outcomes, with a focus on identifying the environmental qualities and pathways that are either facilitating or impeding.<div class="boxTitle">Methods</div>The review sought 16 databases for any nature-based interventions aimed at enhancing health outcomes where participants are older adults aged ≥65. The Mixed Methods Appraisal Tool assessed risk of bias. Narrative synthesis was used for result presentation.<div class="boxTitle">Results</div>Of 6143 articles retrieved, 84 studies were included. Participants were primarily community dwelling without specific conditions. Most studies were quantitative experiments. Interventions were predominantly multicomponent, with restoring psychological capacities as the most common pathway. Spiritual, behavioural and socioecological changes were identified. Some health mechanisms were specific to outdoor interventions, but indoor interventions showed comparable outcomes.<div class="boxTitle">Conclusions</div>The study predominantly included community-dwelling participants without specific health conditions, potentially limiting the generalisability of findings to older adults with multimorbidity or those in alternative living environments. Multicomponent interventions challenged direct associations between pathways and outcomes. Results extend existing frameworks by identifying spiritual, behavioural and socioecological benefits. Limited detailing of environmental qualities warrants further research to associate them with specific health outcomes.<div class="boxTitle">Registration</div>The protocol was registered on PROSPERO (CRD42024496114).</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>In older syncope patients, medical histories are often less reliable due to retrograde amnesia and cognitive impairment. Therefore, additional tests may be needed to reach a diagnosis. We conducted a systematic review to evaluate positivity rates and safety of head-up tilt testing (HUTT) in these patients.<div class="boxTitle">Methods</div>We searched Medline and Embase for HUTT positivity rates and diagnoses in older syncope patients (mean age ≥ 65 years) vs. younger patients. Secondary outcomes were time to syncope (TtS) and adverse events (AEs). Risk of bias was assessed with a modified version of the QUADAS-2.<div class="boxTitle">Results</div>In total, 42 studies were included, with 12 378 older participants in total. Positivity rates varied widely [passive HUTT 0.0%–90.0%; isoproterenol (IPR)-HUTT 18.3%–64.0%; nitroglycerin-HUTT 30.1%–90.5%]. The majority of studies found no differences between older and younger patients. Specificity was high for all HUTT-protocols (85.5%–100%). TtS did not differ between older and younger patients, but was significantly longer in control subjects. Nitroglycerin-HUTT yielded the most diagnoses (median 64.2% vs. 23.7% for passive, <span style="font-style:italic;">P</span> = .007, and 44.8% for IPR-HUTT, n.s.). Vasodepressive responses were more common than cardioinhibitory responses (median 54.9% vs. 9.1%) in older patients. AEs occurred in <6% of patients with passive/nitroglycerin-HUTT.<div class="boxTitle">Discussion/conclusion</div>There is no consistent evidence that HUTT results differ between older and younger syncope patients. Nitroglycerin-HUTT yields the most diagnoses, whilst retaining a high specificity, and is safe to perform in older patients. Future studies should focus on the additional value of HUTT on top of the initial evaluation in these patients.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>The occurrence of falls in adults 65+ years remains a common and costly issue worldwide. There is current evidence to suggest that falls can be prevented using evidence-based strength and balance interventions, such as the six-month Falls Management Exercise (FaME) programme. Perspectives of multiple key partners and providers of the FaME programme could inform future implementation and fall prevention strategies.<div class="boxTitle">Methods</div>Partners and providers involved in local community fall prevention pathways were purposefully recruited from three geographical areas across the UK. Semistructured interviews were conducted to gain a broad understanding of factors affecting the adoption, implementation and spread of FaME. Data were analysed using an inductive thematic approach and mapped to the Consolidated Framework for Implementation Research (CFIR).<div class="boxTitle">Results</div>Data from 25 participant interviews and document analysis revealed 11 themes organised within five CFIR domains—the innovation (3), outer setting (3), inner setting (1), characteristics of individuals (1) and process (2).<div class="boxTitle">Conclusion</div>The adoption, implementation and spread of FaME into community settings is complex and faces multiple health system challenges. For adoption and implementation to be facilitated, FaME programmes must demonstrate effectiveness and fit the local needs of those receiving the intervention. For spread to occur, influential decision-makers and funders must support wider programme rollout whilst also securing sufficient expert capacity to deliver the programme and ensure monitoring is in place to determine effectiveness of provision for older adults.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>The association between changes in physical functions and stroke incidence remains uncertain.<div class="boxTitle">Methods</div>A total of 7978 participants without stroke from the China Health and Retirement Longitudinal Study (CHARLS) were recruited in 2011–2012 and followed up until 2020. We assessed annual changes in physical functions from 2011 to 2015, including absolute grip strength, relative grip strength, walking speed, chair-rising time and standing balance. The Cox proportional hazards model was applied to assess the longitudinal associations between annual changes in physical functions and stroke. Restricted cubic spline analyses were used to explore the dose–response relationships.<div class="boxTitle">Results</div>During 71 714 person-years of follow-up, 549 incident stroke cases were reported. For each 1-kg absolute grip strength increment, 0.1-unit relative grip strength increment, or 1-point standing balance test score increment, the hazard of stroke was reduced by 12% [hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.84–0.93], 53% (HR: 0.47; 95% CI: 0.34–0.64), 55% (HR: 0.45; 95% CI: 0.30–0.67), respectively. We found a negative linear dose–response association of the annual change in absolute and relative grip strength with incident stroke, as well as a nonlinear association between the annual change in standing balance and incident stroke. However, neither the annual change in walking speed nor chair-rising time was related to the incident stroke.<div class="boxTitle">Conclusions</div>A greater improvement in absolute grip strength, relative grip strength or standing balance was suggested to be associated with a lower risk of stroke amongst middle-aged and older people. These objectively measured physical function changes are imperative for high-risk population classification and stroke prevention.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>The 2022 World Falls Guidelines recommend assessing concerns (or ‘fears’) about falling in multifactorial fall risk assessments. However, the evidence base for this recommendation is limited. This review evaluated the evidence for concerns about falling as an independent predictor of future falls, applying the Bradford Hill criteria for causality.<div class="boxTitle">Methods</div>Systematic review and meta-analyses were conducted (PROSPERO registration ID: CRD42023387212). MEDLINE, CINAHL Plus, Web of Science and PsycINFO were searched for studies examining associations between baseline concerns about falling and future falls in older adults (minimum 6-month follow-up). Meta-analyses examined associations between concerns about falling and future falls. Risk of bias was assessed using an adapted Newcastle Ottawa Scale for cohort studies, and evidence certainty was rated with GRADE.<div class="boxTitle">Results</div>About 53 studies, comprising 75,076 participants, were included. Meta-analysis showed significant independent association between baseline concerns and future falls when using the Falls Efficacy Scale-International to assess concerns (full scale version, pooled OR = 1.03 [95% CI = 1.02–1.05] per 1-point increase; short scale version, pooled OR = 1.08 [95% CI = 1.05–1.11]). Significant associations were also observed when using single-item measures of concerns (pooled OR = 1.60 [95% CI = 1.36–1.89] for high vs. low concerns). In contrast, balance confidence (Activities-Specific Balance Confidence Scale) did not predict future falls (pooled OR = 0.97 [95% CI = 0.93–1.01]). Despite 26 studies rated as poor quality, associations were consistent across studies of different quality. The overall certainty of the evidence was rated as moderate.<div class="boxTitle">Conclusions</div>Baseline concern about falling is a clear predictor of future falls in older adults, supporting its inclusion in fall risk assessments. Regular assessment of concerns about falling, along with targeted interventions, could help reduce the risk of falls in older adults.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Falls are a leading cause of morbidity and mortality among older adults, often linked to gait and balance impairments.<div class="boxTitle">Objective</div>To compare gait and balance metrics across fall risk levels in community-dwelling older adults and identify principal components predictive of fall risk.<div class="boxTitle">Design</div>Retrospective cohort study.<div class="boxTitle">Setting</div>General community.<div class="boxTitle">Subjects</div>Three hundred older adults were stratified into low, moderate and high fall risk groups using the STEADI toolkit.<div class="boxTitle">Methods</div>Gait and balance metrics were compared across groups. Principal component analysis (PCA) reduced dimensionality, and binary logistic regression assessed the predictive value of components.<div class="boxTitle">Results</div>High-risk individuals showed slower cadence, shorter step length, wider step width, greater gait variability and increased centre of pressure (CoP) and centre of mass (CoM) sway. PCA identified four gait and seven balance components, explaining 71.62% and 75.88% of variance, respectively. Logistic regression revealed Gait_principal component (PC)2 (instability) (OR = 2.545, <span style="font-style:italic;">P</span> < .001), Gait_PC3 (rhythm control) (OR = 1.659, <span style="font-style:italic;">P</span> = .006), Balance_PC1 (CoP sway during single-leg stance) (OR = 1.628, <span style="font-style:italic;">P</span> = .007), Balance_PC2 (CoM sway velocity variability) (OR = 1.450, <span style="font-style:italic;">P</span> = .032) and Balance_PC4 (CoP sway during double-leg stance, eyes closed) (OR = 1.616, <span style="font-style:italic;">P</span> = .004) as significant predictors. The model achieved 77.2% accuracy, with a sensitivity of 73.1% and a specificity of 79.4%.<div class="boxTitle">Conclusions</div>Gait instability, rhythm control and increased postural sway are key predictors of fall risk. Integrating gait and balance metrics enhances fall risk stratification, supporting clinical decision-making.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>To evaluate the effectiveness of digital technology-based serious games (DTBSGs) interventions in older adults with mild cognitive impairment (MCI).<div class="boxTitle">Methods</div>A librarian-designed search of eight databases was conducted to identify randomised controlled trials published in English or Chinese up to 10 August 2024. The primary and secondary outcomes were compared between the intervention and control groups. A fixed- or random-effects meta-analysis model was used to determine the mean difference, based on the results of the heterogeneity test. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.<div class="boxTitle">Results</div>A meta-analysis of 28 trials, including 1698 participants, showed greater improvements in favour of interventions using DTBSGs compared to the control group in global cognitive function, executive function, attention function, depression, and activities of daily living (ADL). However, there was no significant improvement in memory function, anxiety, apathy or quality of life (QOL) compared to the control group. Subgroup analysis showed that computer games, exergames and iPad tablet games were superior to immersive virtual reality (VR) games in terms of global cognitive and executive function. VR games were superior to computer games in terms of attention and ADL. The GRADE evidence quality assessment results showed that global cognitive function and ADL were of moderate quality; executive function, attention, depression and anxiety were of low quality; and memory, apathy and QOL were of very low quality.<div class="boxTitle">Conclusion</div>Patients with MCI benefited from DTBSGs. With the rapid development of information and communication technology, DTBSGs have great potential and may be used as adjuncts or substitutes in MCI rehabilitation.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Natural history of voiding parameters with age is poorly understood. We aim to understand both subjective and objective lower urinary tract parameters in older men over 5 years.<div class="boxTitle">Methods</div>The Concord Health and Ageing in Men Project is a prospective cohort study of older men, involving 1705 men aged 70 years and over living in Sydney, Australia. Men were assessed at 0, 2 and 5 years. Demographic information, medical history, International Prostate Symptom Score (IPSS), flow rate and post-void volume were collected at three timepoints.<div class="boxTitle">Results</div>A total of 1705 men aged 70–97 years participated. At 2 and 5 year follow-up, 1367 and 940 men presented for assessment. Mean IPSS was 7.35 at baseline, 6.96 at 2 years (<span style="font-style:italic;">P</span> = .9) and 7.18 at 5 years (<span style="font-style:italic;">P</span> = .30). Mean flow rate at baseline was 15.0 ml/s, 14.6 ml/s at 2 years (<span style="font-style:italic;">P</span> = .001) and 15.3 ml/s at 5 years (<span style="font-style:italic;">P</span> = .42). Adjusting for age at baseline, the change in flow over 5 years was not significant (<span style="font-style:italic;">P</span> = .93). Mean post-void residual was 72.4 ml at baseline, 84.0 ml at 2 years (<span style="font-style:italic;">P</span> = .003) and 93.2 ml at 5 years (<span style="font-style:italic;">P</span> = .001). Men with residual volume >200 ml at baseline had no significant change in residual over 5 years (<span style="font-style:italic;">P</span> = .51).<div class="boxTitle">Conclusions</div>Urinary symptoms and voiding parameters remain stable over 5 years. Men with elevated post-void volume did not deteriorate significantly. Conservative management of lower urinary tract symptoms appears a reasonable strategy in older men.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Antidepressants are used by 60% of residents of long-term care facilities (LTCFs). Mirtazapine and sertraline are the most commonly used antidepressants, despite little safety information for their use in LTCFs.<div class="boxTitle">Objective</div>To investigate risk of adverse outcomes (falls, fractures, cardiovascular-, dementia-, and delirium-related hospitalisations, all-cause mortality) associated with mirtazapine compared to sertraline use post-LTCF entry.<div class="boxTitle">Design</div>Active new user retrospective cohort study.<div class="boxTitle">Subjects</div>Individuals aged 65–105 years entering LTCFs in three Australian states during 1 January 2015 to 31 October 2018, who initiated mirtazapine or sertraline ≤60 days post-LTCF entry, with follow-up to 31 December 2019.<div class="boxTitle">Methods</div>The inverse probability of treatment weighting of individuals’ propensity scores was used to adjust Cox and Fine–Gray regression models to estimate the risk of outcomes of interest associated with mirtazapine compared to sertraline use in LTCFs. Weighted (adjusted) hazard ratios (aHRs), subdistribution hazard ratios and 95% confidence intervals (95% CIs) are presented.<div class="boxTitle">Results</div>A total of 5409 residents initiated mirtazapine (71%, <span style="font-style:italic;">n</span> = 3837) or sertraline (29%, <span style="font-style:italic;">n</span> = 1572) post-LTCF entry. After weighting, mirtazapine was associated with a higher risk of mortality (aHR 1.16, 95% CI 1.05–1.29) compared to sertraline. The risk of falls and fractures within 90 days was not statistically significantly different between the groups but was lower in mirtazapine users thereafter. No differences in risk of cardiovascular-, dementia- or delirium-related hospitalisations were observed.<div class="boxTitle">Conclusions</div>Compared to sertraline, mirtazapine use is associated with a higher risk of mortality and, after 90 days of use, a lower risk of falls and fractures. This risk of harm should be balanced with limited evidence for effectiveness when considering antidepressant therapy in LTCFs.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Hospitalisation often results in adverse effects in older adults, particularly an increased risk of functional and cognitive decline. Although in-hospital exercise interventions have shown benefits, their impact on intrinsic capacity (IC) remains unknown.<div class="boxTitle">Objective</div>To assess the effects of multicomponent exercise training on IC in acutely hospitalised older adults.<div class="boxTitle">Design</div>Pooled analysis of two randomised clinical trials.<div class="boxTitle">Setting</div>Three Acute Care for Elders units.<div class="boxTitle">Subjects</div>Hospitalised older adults (≥75 years).<div class="boxTitle">Methods</div>The control group received standard care, whereas the exercise group participated in an in-hospital multicomponent exercise program. The primary outcome was IC assessed using a composite score (0–100) across five domains: vitality (handgrip strength), cognition (Mini-Mental State Examination), psychological health (Yesavage Geriatric Depression Scale), locomotion (Short Physical Performance Battery) and sensory function (self-reported vision and hearing). Adverse outcomes were evaluated 1 year after discharge, including emergency visits, hospital re-admission and mortality.<div class="boxTitle">Results</div>A total of 570 patients (age 87.3 ± 4.8 years) were enrolled during acute hospitalisation [median duration 8 (interquartile range = 3) days] and randomised to the exercise (<span style="font-style:italic;">n</span> = 288) or control group (<span style="font-style:italic;">n</span> = 282). The exercise intervention significantly improved IC compared to the control group [7.74 points, 95% confidence interval (CI) 6.45–9.03, <span style="font-style:italic;">P</span> < .001], with benefits observed in all IC domains. IC score at discharge was inversely associated with mortality risk during follow-up (OR = 0.98 per each increase in IC score at discharge, 95% CI = 0.96, 0.99, <span style="font-style:italic;">P</span> = .010), although no association was found with emergency visits (<span style="font-style:italic;">P</span> = .866) or re-admissions (<span style="font-style:italic;">P</span> = .567).<div class="boxTitle">Conclusions</div>In-hospital exercise is an effective strategy to enhance IC in hospitalised older adults. Additionally, the IC score at discharge was inversely related to the mortality risk within 1 year of discharge.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>This cross-sectional study examined associations between 24-hour time-use composition (i.e. sleep, sedentary time, light physical activity and moderate-to-vigorous physical activity) and cognitive performance and explored whether demographic or genetic factors moderated these relationships.<div class="boxTitle">Methods</div>This analysis included baseline data from cognitively unimpaired older adults (<span style="font-style:italic;">n</span> = 648) enrolled in the Investigating Gains in Neurocognition in an Intervention Trial of Exercise study. Time use was measured using wrist-worn triaxial accelerometers. Cognitive domains were determined using a confirmatory factor analysis from a comprehensive neuropsychological battery. Linear regression models tested associations between time-use composition and cognitive factors, adjusting for age, sex, education, body mass index, apolipoprotein E4 (<span style="font-style:italic;">APOE4</span>) allele carriage and study site. Interaction terms evaluated moderation of time use by age, sex, education and <span style="font-style:italic;">APOE4</span> status. We also examined the theoretical impact of reallocating time between time-use behaviours on cognitive performance using compositional isotemporal substitution methods.<div class="boxTitle">Results</div>Time-use composition was associated with processing speed (<span style="font-style:italic;">F</span> = 5.16, <span style="font-style:italic;">P</span> = .002), working memory (<span style="font-style:italic;">F</span> = 4.81, <span style="font-style:italic;">P</span> = .003) and executive function/attentional control (<span style="font-style:italic;">F</span> = 7.09, <span style="font-style:italic;">P</span> < .001) but not episodic memory (<span style="font-style:italic;">F</span> = 2.28, <span style="font-style:italic;">P</span> = .078) or visuospatial function (<span style="font-style:italic;">F</span> = 2.26, <span style="font-style:italic;">P</span> = .081). <span style="font-style:italic;">Post hoc</span> isotemporal substitution analyses found that significant associations were driven by time spent in moderate-to-vigorous physical activity (MVPA), with lesser amounts of MVPA associated with poorer cognitive performance. There was no evidence of moderation by any tested factors.<div class="boxTitle">Conclusions</div>Increasing or decreasing MVPA, at the expense of time spent in sleep, sedentary behaviour or light physical activity, may be related to individual variation in processing speed, executive function/attentional control and working memory in older adulthood.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background and Objective</div>Previous research assessing whether biological ageing (BA) indicators can enhance the risk assessment of cardiovascular disease (CVD) outcomes beyond established CVD risk indicators, such as Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE2)/SCORE2-Older Persons (OP), is scarce. We explored whether BA indicators, namely the Rockwood Frailty Index (FI) and leukocyte telomere length (TL), improve predictive accuracy of CVD outcomes beyond the traditional CVD risk indicators in general population of middle-aged and older CVD-free individuals.<div class="boxTitle">Methods</div>Data included 14 118 individuals from three population-based cohorts: TwinGene, Health 2000 (H2000), and the Helsinki Birth Cohort Study, grouped by baseline age (<70, 70+). The outcomes were incident CVD and CVD mortality with 10-year follow-up. Risk estimations were assessed using Cox regression and predictive accuracies with Harrell’s C-index.<div class="boxTitle">Results</div>Across the three study cohorts and age groups: (i) a higher FI, but not TL, was associated with a higher occurrence of incident CVD (<span style="font-style:italic;">P</span> < .05), (ii) also when considering simultaneously the baseline CVD risk according to FRS or SCORE2/SCORE2-OP (<span style="font-style:italic;">P</span> < .05) (iii) adding FI to the FRS or SCORE2/SCORE2-OP model improved the predictive accuracy of incident CVD. Similar findings were seen for CVD mortality, but less consistently across the cohorts.<div class="boxTitle">Conclusions</div>We show robust evidence that a higher FI value at baseline is associated with an increased risk of incident CVD in middle-aged and older CVD-free individuals, also when simultaneously considering the risk according to the FRS or SCORE2/SCORE2-OP. The FI improved the predictive accuracy of CVD outcomes beyond the traditional CVD risk indicators and demonstrated satisfactory predictive accuracy even when used independently.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Within a week of his 20 January 2025 inauguration, US President Donald J. Trump issued an order that froze all federal grants and loans, creating confusion and anxiety about the future of research and development in US biomedical science. The politicisation of science creates significant challenges not only for the researchers who depend on public funding to undertake their research, but also for the public understanding of why basic research is so important to the health and economic prosperity of the world’s ageing populations. In 1944 US President Franklin D. Roosevelt wrote a letter to the director of the Office of Scientific Research and Development, Dr. Vannevar Bush, asking Bush how science and medicine could be best harnessed to win the war of science against disease. Bush’s response, in his acclaimed 1945 book entitled <span style="font-style:italic;">Science, The Endless Frontier</span>, detailed how ‘scientific capital’ determines the pace and shape of technological progress. The war against disease approach to public health and medicine has helped increase life expectancy, by reducing the prevalence of premature death, but it has also contributed to the increasing global healthspan-lifespan gap, which is nearly 10 years. Translational gerontology, and in particular the goal of developing geroprotective drugs that may help fortify the ‘biological resilience’ needed to increase healthy life expectancy, must become an integral part of a ‘wisdom-inquiry’ approach to public health and medicine if the aspiration of healthy longevity is to be realised this century.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>The electronic frailty index (eFI) is nationally implemented into UK primary care electronic health record systems to support routine identification of frailty. The original eFI has some limitations such as equal weighting of deficit variables, lack of time constraints on variables known to resolve and definition of frailty category cut-points. We have developed and externally validated the eFI2 prediction model to predict the composite risk of home care package; hospital admission for fall/fracture; care home admission; or mortality within one year, addressing the limitations of the original eFI.<div class="boxTitle">Methods</div>Linked primary, secondary and social care data from two independent retrospective cohorts of adults aged ≥65 in 2018 was used; the population of Bradford using the Connected Bradford dataset (development cohort, 78 760 patients) and the population of Wales, from the Secure Anonymised Information Linkage databank (external validation cohort, 660 417 patients). Candidate predictors included the original eFI variables, supplemented with variables informed by literature reviews and clinical expertise. The composite outcome was modelled using Cox regression.<div class="boxTitle">Results</div>In internal validation the model had excellent discrimination (C-index = 0.803, Nagelkerke’s <span style="font-style:italic;">R</span><sup>2</sup> = 0.0971) with good calibration (Calibration slope = 1.00). In external validation, the model had good discrimination (C-index = 0.723, Nagelkerke’s <span style="font-style:italic;">R</span><sup>2</sup> = 0.064), with some evidence of miscalibration (Calibration slope = 1.104).<div class="boxTitle">Conclusions</div>The eFI2 demonstrates robust prediction for key frailty-related outcomes, improving on the original eFI. Our use of novel methodology to develop and validate the eFI2 will advance the field of frailty-related research internationally, setting a new methodological standard.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Recognizing perceived stress as a modifiable risk factor, mindfulness-based programs show promise for stress mitigation in older adults with mild cognitive impairment (MCI).<div class="boxTitle">Objective</div>To assess the efficacy of a mindfulness-based contextual cognitive defusion training (M-bCCDT) program on perceived stress and other health outcomes, and to examine the reliable and clinically significance of these improvements at individual-level among older adults with MCI.<div class="boxTitle">Design</div>A two-arm, assessor-blinded randomized controlled trial.<div class="boxTitle">Settings and participants</div>102 community-dwelling older adults with MCI.<div class="boxTitle">Methods</div>Participants were randomly allocated to either a M-bCCDT program (weekly 60-minute sessions for 8 weeks, followed by 12 weeks of unsupervised practice) or health promotion classes. Measures of perceived stress, memory function, global cognitive function, psychomotor speed and mindfulness awareness were collected at baseline (T0), 8-week (T1) and 20-week (T2). Intervention effects were assessed at a group level (Generalized Estimating Equation, GEE) and individual level (Reliable and Clinically Significant Changes, RCSC).<div class="boxTitle">Results</div>The M-bCCDT program demonstrated significant interaction effects in perceived stress compared to the wait-list control group by GEE analysis (β<sub>T1</sub> = −3.686, 95% CI [−5.397, −1.976]; β<sub>T2</sub> = −7.608, 95% CI [−9.387, −5.829]). Furthermore, this program also showed significant efficacy in memory function, psychomotor speed and mindfulness awareness. RCSC indicated that 30 participants (59%) in the intervention group showed statistically significant improvement in perceived stress at 8-week, with 7 (14%) clinically significant. This increased to 38 (75%) with 20 (39%) clinically significant at 20-week. Secondary outcomes also showed statistically and clinically significant improvements over time, but no improvement in global cognitive function at the individual level.<div class="boxTitle">Conclusions</div>The M-bCCDT program positively impacted perceived stress and mindfulness awareness in older adults with MCI, facilitating the improvements in memory and psychomotor speed, with these benefits sustained for 20 weeks. It offers a systematic approach for community healthcare providers in MCI stress management.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background</div>Physiological age (PA) derived from clinical indicators including blood-based biomarkers and tests of physiological function can be compared with chronological age to examine disparities in health between older adults of the same age. Though education interacts with sex to lead to inequalities in healthy ageing, their combined influence on longitudinally measured PA has not been explored. We derived PA based on longitudinally measured clinical indicators and examined how sex and education interact to inform PA trajectories.<div class="boxTitle">Methods</div>Three waves of clinical indicators (2004/05–2012/13) drawn from the English Longitudinal Study of Ageing (ages 50–100 years) were used to estimate PA, which was internally validated by confirming associations with incident chronic conditions, functional limitations and memory impairment after adjustment for chronological age and sex. Joint models were used to construct PA trajectories in 8891 English Longitudinal Study of Ageing participants to examine sex and educational disparities in PA.<div class="boxTitle">Findings</div>Amongst the least educated participants, there were negligible sex differences in PA until age 60 (sex difference [men–women] age 50 = −0.6 years [95% confidence interval = −2.2 to 0.6]; age 60 = 0.4 [−0.6 to 1.4]); at age 70, women were 1.5 years (0.7–2.2) older than men. Amongst the most educated participants, women were 3.8 years (1.6–6.0) younger than men at age 50 and 2.7 years (0.4–5.0) younger at age 60, with a nonsignificant sex difference at age 70.<div class="boxTitle">Interpretation</div>Higher education provides a larger midlife buffer to physiological ageing for women than men. Policies to promote gender equity in higher education may contribute to improving women’s health across a range of ageing-related outcomes.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div>Personality disorders, characterised by enduring and maladaptive patterns of behaviour, cognition and emotional regulation, affect 1 in 10 older adults. Personality disorders are frequently encountered in geriatric care considering their association with multimorbidity and increased health care utilisation. Patients with personality disorders often receive inadequate somatic health care due to (i) difficulties in expressing their actual symptoms and needs, (ii) challenging interactions with professionals, and (iii) non-compliance with medical treatment and lifestyle advice. Acknowledging personality disorders in geriatric care may improve treatment outcomes of somatic diseases. Since empirical evidence on personality diagnosis and treatment in older adults is scarce, we summarise future endeavours. First, the development of age-inclusive diagnostic tools should be prioritised to ensure comparability across age groups and facilitate longitudinal research over the lifespan. Second, evidence-based treatment approaches should be tailored to older people. Insight-oriented psychotherapies remain effective in later life considering sufficient level of introspection. Supportive and mediative therapies may better suit those with significant cognitive or physical impairments. Geriatric care models should be ideal for managing the complex needs of these patients when a consistent approach can be assured within the geriatric team as well as within the network considering the high level of interdisciplinary exchange needed. Third, considering the dynamic nature of personality disorders older adults should not be excluded from studies using novel technologies for real-time monitoring and personalised care. By addressing these gaps, the field can improve somatic treatment outcomes and uphold the dignity and well-being of older adults with personality disorders.</span>
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