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Background: The Venablock© Venous Closure System (Invamed, Ankara, Turkey) is a novel cyanoacrylate-based non-thermal non-tumescent embolization device to block refluxing truncal veins for chronic venous insufficiency and varicose veins. The aim was to prospectively evaluate the safety and 6 months efficacy of Venablock© for the treatment of primary great saphenous vein (GSV) and small saphenous vein (SSV) incompetency in a multi-ethnic cohort from Singapore. Methods: This was a single arm, single investigator prospective study of 29 patients (39 limbs, 39 truncal veins) recruited over a 5-month period (August 2019 to February 2020), who were treated with the Venablock© device at a tertiary vascular unit in Singapore. Patients with symptomatic varicose veins (C2–6) and had truncal reflux > 0.5 second on venous Duplex ultrasound were included. Follow-up occurred at 2 weeks, 3 and 6 months with dedicated quality of life questionnaires and a targeted Duplex ultrasound performed to check for continued venous occlusion. Result: Mean age was 61.4 (±11.0) years and mean BMI was 26.2 (±5.7) kg/m2. 11/29 (37.9%) were males. Most common CEAP class treated was 2 (12/29, 41.3%). Mean diameter of treated GSV was 5.7 (±2.0) mm, 4.8 (±1.7) mm and 4.2 (±1.3) mm for the proximal, mid and distal above knee segments respectively. Mean time from access puncture to sheath removal was 23.4 (±10.0) mins. Vein occlusion at 2 weeks, 3 and 6 months was 39/39 (100%), 39/39 (100%) and 36/37 (97.2%) respectively. 5/29 (17.2%) developed puncture site infections, of which 3/29 (7.7%) required formal surgical drainage. 3/29 (7.7%) developed phlebitis. At 6 months, revised Venous Clinical Severity Score improved from 5.2 (±3.5) to 2.1 (±2.9; p <.001); EuroQol-5 Dimension score, from 7.4 (±2.1) to 5.7 (±1.4; p <.001); Aberdeen Varicose Vein Questionnaire score, from 18.1 (±15.5) to 7.9 (±8.9; p =.007); and Chronic Venous Insufficiency Questionnaire, from 18.6 (±16.2) to 4.5 (±6.3; p <.001). Conclusion: Venablock© is a safe and efficacious option of treating truncal venous insufficiency in a multi-ethnic Asian cohort from Singapore in the short term. There is a significant improvement in QoL. Longer follow-up is required to assess the durability of this technique, in particular the higher puncture site infection rates observed compared to other glue-based therapies. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to investigate whether there are differences between predominantly Caucasians and Asians from two disparate cohorts around the globe, with regard to their pre-operative venous reflux patterns and truncal vein characteristics, which could potentially help clinicians tailor venous treatment for chronic venous insufficiency on a more individualised basis in different parts of the world. Methods: A total of 200 lower limb chronic venous insufficiency duplex studies (127 Singaporean (predominantly Asian) patients) and 200 lower limb chronic venous insufficiency duplex scans (137 Americans predominantly Caucasians) were analysed and compared for differences in venous anatomy and reflux characteristics. Results: Asian patients from Singapore presented with higher CEAP scores compared to the predominantly Caucasian cohort from the US (30% CEAP 4a or greater vs. 17.5%; p < 0.01). Singaporeans had more great saphenous vein reflux starting at the sapheno-femoral junction (86% vs. 73%; p < 0.01) and ending at the ankle (93% vs. 46%; p < 0.01). Vein diameters were generally larger in the US cohort of patients (median 5.7 mm vs. 2.9 mm; p < 0.01). Conclusions: The predominantly Asian cohort from Singapore had smaller diameter truncal veins, longer segments of truncal vein reflux and present later with more advanced chronic venous insufficiency compared to their American counterparts. This information could help tailor endovenous ablation on a more individualised basis in the future. [ABSTRACT FROM AUTHOR]

Mindaugas Jurgelis,1,2 Johanna M Boardman,1,2 James P Coxon,1,2 Sean PA Drummond,1,2 Trevor TJ Chong1– 4 1Turner Institute for Brain and Mental Health, Monash University, Melbourne, Victoria, 3800, Australia; 2School of Psychological Sciences, Monash University, Melbourne, Victoria, 3800, Australia; 3Department of Neurology, Alfred Health, Melbourne, Victoria, 3004, Australia; 4Department of Clinical Neurosciences, St Vincent’s Hospital, Melbourne, Victoria, 3065, AustraliaCorrespondence: Mindaugas Jurgelis, Tel +61 491 020 830, Email m.k.jurgelis@gmail.com Trevor TJ Chong, Tel +61 3 9902 4222, Email trevor.chong@monash.eduPurpose: Motivation is an important driver of behaviour, and several frameworks distinguish the willingness of individuals to invest cognitive versus physical effort to achieve a goal. One outstanding question is whether sleep loss lowers motivation within specific domains of effort, or has a global effect on motivation across multiple domains. Here, we investigated the effects of sleep restriction on the motivation to invest cognitive or physical effort in return for reward.Materials and Methods: 24 healthy young adults (11 females) completed an effort-based decision-making task over two laboratory sessions – once while sleep restricted (three consecutive nights with a three-hour sleep opportunity), and the other while fully rested (nine-hour sleep opportunity on each night). In an initial reinforcement phase, participants were trained to ceiling performance across six levels of effort on separate cognitively and physically demanding tasks. Then, in the critical decision-making phase, participants revealed their preference for how much cognitive or physical effort they would be willing to invest for reward.Results: Sleep restriction reduced the willingness to exert cognitive effort, but spared motivation in the physical domain. Furthermore, the reduction in cognitive motivation appeared to be a primary motivational deficit, which could not be attributed to differences in reward-likelihood of different levels of effort or the temporal structure of the task.Conclusion: The results suggest that sleep restriction has a selective effect on cognitive over physical motivation, which has significant implications for real-world settings in which individuals must maintain high levels of cognitive motivation in the face of chronic sleep loss.Keywords: sleep loss, cognitive effort, physical effort, effort-based decision-making

Key event-related potentials (ERPs) of perceptual decision-making such as centroparietal positivity (CPP) elucidate how evidence is accumulated toward a given choice. Furthermore, this accumulation can be impacted by visual target selection signals such as the N2 contralateral (N2c). How these underlying neural mechanisms of perceptual decision-making are influenced by the spatial congruence of distractors relative to target stimuli remains unclear. Here, we used electroencephalography (EEG) in humans of both sexes to investigate the effect of distractor spatial congruency (same vs different hemifield relative to targets) on perceptual decision-making. We confirmed that responses for perceptual decisions were slower for spatially incongruent versus congruent distractors of high salience. Similarly, markers of target selection (N2c peak amplitude) and evidence accumulation (CPP slope) were found to be lower when distractors were spatially incongruent versus congruent. To evaluate the effects of congruency further, we applied drift diffusion modeling to participant responses, which showed that larger amplitudes of both ERPs were correlated with shorter nondecision times when considering the effect of congruency. The modeling also suggested that congruency's effect on behavior occurred prior to and during evidence accumulation when considering the effects of the N2c peak and CPP slope. These findings point to spatially incongruent distractors, relative to congruent distractors, influencing decisions as early as the initial sensory processing phase and then continuing to exert an effect as evidence is accumulated throughout the decision-making process. Overall, our findings highlight how key electrophysiological signals of perceptual decision-making are influenced by the spatial congruence of target and distractor., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Background: A multidisciplinary care model involving the interventional radiologist, vascular surgeon, interventional nephrologist, renal advanced nurse practitioner, and renal coordinators was implemented to improve the care for the patient admitted with dysfunctional hemodialysis access. This study aims to evaluate the effectiveness and sustainability of this multidisciplinary care model., Method: A dedicated interventional nephrology suite was established to perform endovascular procedures for patients admitted with hemodialysis access dysfunction via the emergency department of the hospital. We retrospectively collected data from electronic medical records 1-year before and after the implementation (April 2015). Outcome measures include waiting time for intervention, length of stays (LOS), number of dialysis catheter insertions before the intervention, number of inpatient dialysis required, and success rates of the interventions. The waiting time for intervention and LOS was tracked over the next 3 years to determine the sustainability of the care model., Results: Eight hundred eighty-one endovascular interventions (314 angioplasties, 567 thrombolysis) were performed on 554 patients. Post-implementation, a greater proportion of intervention was performed within 24 h (238 (50.2%) vs 70 (17.2%), p  < 0.001) with lesser proportion of patients requiring bridging hemodialysis via temporary catheter, 156 (32.9%) versus 215 (52.8%), p  < 0.001. A shorter median LOS and days-to-intervention were reported, 3 (IQR 2-6) versus 5 days (IQR 3-8), p  < 0.001 and 1 (IQR 1-2) versus 3 days (IQR 2-4), p  < 0.001 respectively. Less hemodialysis session/patient required, 2 (IQR 1-3) versus 3 (IQR 2-4), p  < 0.001. The procedural success rate was greater, 440 (92.8%) versus 355 (87.2%), p  = 0.020. Three years following implementation, the proportion of patients who received intervention within 24 h and were discharged within 48 h was reported to be persistently greater, 43% versus 13%, p  < 0.001, and 27% versus 6%, p  < 0.001 respectively., Discussion: This multi-disciplinary collaboration demonstrated a sustainable care model in improving the delivery of healthcare services for patients with dysfunctional hemodialysis access., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This study aims to evaluate the safety and efficacy of a short-term, low dose, weight-based subcutaneous enoxaparin protocol (SEP) in maintaining the patency of arteriovenous (AV) access with recurrent thrombosis., Methods: Prospective follow-up of 25 patients who presented to a tertiary institution with recurrent AV access thrombosis and treated with anticoagulation according to SEP following successful thrombectomy. Patency and safety outcomes of SEP were studied., Results: The participants were 66.4 ± 10.2 years old and predominantly male (60%) and of Chinese ethnicity (72%). The AV accesses had a median age of 1.4 (0.6, 5.6) years with 60% being non-autogenous arteriovenous access while 40% were autogenous arteriovenous access. Thrombolytic agents (urokinase (72%) or alteplase (28%)) were used in all procedures while adjunct thrombectomy device was used in only four procedures. The mean dose of enoxaparin was 36.0 ± 8.2 mg or 0.64 ± 0.1 mg/kg/day for a mean duration 30.0 days (Interquartile range: 27.5, 31.0). One patient developed minor bleeding episode. Kaplan-Meier analysis demonstrated that the mean thrombosis-free survival pre- versus post-SEP adoption was 27.3 (95% CI 17.9-36.7) versus 183.5 (95% CI 100.1-266.9) days ( p  < 0.001). After adjusting for the type of thrombolytic agent, use of adjunct thrombectomy device, cutting balloon, drug-coated balloon, and stent graft, SEP remained a significant factor associated with longer thrombosis-free patency (HR 0.166: 95% CI 0.070-0.392, p  < 0.001)., Discussion: SEP appears to be a feasible and safe thromboprophylaxis method to improve thrombosis-free patency for AV access with recurrent thrombosis., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Given the high risk of peri-operative morbidity and mortality associated with open repair, endovascular repair for thoraco-abdominal aneurysms is increasingly performed. This study aims to describe mid to long-term results for patients who were treated with COOK Custom-Made Endograft Device at a single Southeast Asian tertiary centre. Methods: Mid to long-term results of patients treated from 2012 to 2022 were retrospectively reviewed. Indications for treatment were aortic diameter > 5.5 cm, enlargement > 5 mm in 6 months or high-risk morphology. Clinical, operative, early to late complications and reintervention details were captured. The endpoints were technical success, primary patency and primary assisted patency. Results: Electronic medical records of 29 consecutive patients (64.4 ± 1.6 years old; 26/29 males 89.6%) were reviewed. 24/29 (83%) were hypertensive, and 20/29 (69%) were smokers. The mean diameter was 5.5 cm, and the majority were treated for Crawford type IV (19/29, 65.5%). Endograft deployment was 100%. Catheterisation of fenestration was successful in 109/116 (94%). 30-day mortality and morbidity were observed in 12/29 (41%), for which access site complications were most common. No significant haemorrhage or graft explant was recorded. The mean follow-up period was 32.4 months (range 1-108 months). Primary patency was 92.9% (95% CI: 83.8-100.0) at 6 months and decreased to 77.7% (95% CI: 63.4-95.2) at 24 months. Sac shrinkage or stability was noted in 17/29 (58.6%). Re-intervention was performed in 9/29 (31%) for limb occlusion (2/9, 22.2%), renal artery stent occlusion (1/9, 11.1%) and endoleaks (6/9, 66.6%). Assisted patency was maintained at 100% for 12 months before decreasing to 66.7% (95% CI: 37.9-100.0) at 24 months. Conclusions: The study reports the first mid-long-term result in this region, though limited by the sample size. Re-intervention at 30% suggests that disease and procedures remain challenging, emphasising the need to assimilate lessons and experience at high-volume centres.

Objective: This study compares chronic limb-threatening ischemia disease characteristics and endovascular revascularization outcomes in a multi-ethnic Asian cohort vs their North American counterparts., Methods: The Society for Vascular Surgery Vascular Quality Initiative (VQI) registry database from the first and currently the only VQI center in Asia was reviewed to identify patients with chronic limb-threatening ischemia who underwent endovascular revascularization between July 2019 and April 2024. Standardized VQI reporting variables were compared against benchmarks derived from all participating centers in North America., Results: A total of 2862 endovascular revascularization procedures from our center were benchmarked against 129,347 procedures from 406 North American centers. Our cohort had a higher burden of comorbidities (diabetes mellitus, end-stage renal disease, cardiac disease) and presented with more advanced Wound, Ischemia, and foot Infection stages. Our patients had more heavily calcified and longer (14.8 cm vs 6.0 cm) diseased vessels with higher prevalence of multi-level (87% vs 54.6%), infrapopliteal (52.6% vs 38.9%), and inframalleolar (9.6% vs 2.4%) disease. Rates of technical success (92.7% vs 93%) and symptom improvement (39.1% vs 40.4%) were comparable between cohorts. However, 1-year mortality rates (28.9% vs 25.1%) and major amputation rates (13.3% vs 7.8%) were significantly higher., Conclusions: Short-term outcomes of technical success and symptom relief in our center were comparable to benchmarked North American outcomes despite having a cohort with more diseased vessels, higher Wound, Ischemia, and foot Infection stages, and more comorbidities. However, this cohort fared worse in longer term outcomes of 1-year mortality and major amputation rates. Further studies are required to elucidate the causes to improve these outcomes., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: This study investigated the association between gait speed, handgrip strength, and their combination, and the risk for developing clinically relevant depressive symptoms in community-dwelling older adults., Methods: A secondary analysis was conducted using data from the ASPirin in Reducing Events in the Elderly study. Participants were community-dwelling older adults in Australia and the United States of America followed for a median (interquartile range) of 3.97 (2.26) years. Baseline handgrip strength and gait speed were used as exposure variables, and their combination categories were also explored. Depression was measured using the modified Center for Epidemiological Studies Depression 10-item scale (CES-D 10). Cox regression was used to estimate Adjusted Hazard Ratios (AHR) with 95 % Confidence Intervals (CI) after adjusting for a range of potential confounders., Result: A total of 17,231 participants (55.3 % women) were included in the analysis. Slow gait and weak grip at baseline were associated with the risk of depression (AHR: 1.20; CI: 1.11-1.29 and 1.14; 1.06-1.23, respectively). The combination of the two physical performance measures was associated with a 31 % increase in the risk of depression (1.31; 1.16-1.47) and a significant dose-response association was observed for quintiles of gait and grip with depression., Limitations: Although the CES-D 10 is a validated scale, it is a self-reported tool rather than a clinical diagnosis of depression., Conclusion: Low physical function may be a risk factor for depression in older adults. This highlights the inextricable link between the physical and mental health of older adults, which can inform potential clinical and public health prevention strategies for depression in later life., Competing Interests: Declaration of competing interest TC has received honoraria for lectures from Roche. The authors declare no conflicts of interest., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Background: Percutaneous endovascular aneurysm repair (PEVAR) is the definitive therapy of choice for abdominal aortic aneurysms worldwide. However, current literature regarding the anatomic changes in the common femoral artery (CFA) post-PEVAR is sparse and contradictory, and a significant proportion of these studies did not control for the potential confounding effects of ethnicity. Thus, this study aims to investigate the anatomical effects of PEVAR on the CFA using an Asian study cohort., Methods: Between January 2019 and September 2023, the records of 113 patients who received PEVAR were reviewed. Groins with previous surgical interventions were excluded. The most proximate pre- and postoperative CT angiography of patients receiving PEVAR via the Perclose ProGlide™ Suture-Mediated Closure System were retrospectively analysed for changes in both the CFA inner luminal diameter (ID) and outer diameter (OD), the latter also encompassing the arterial walls. Access site complications within 3 months post-PEVAR were also recorded per patient., Results: One hundred seventeen groins from 60 patients were included in this study, with 1 report of pseudoaneurysm. The CFA ID exhibited a 0.167 mm decrease (p-value = 0.0403), while the OD decreased by 0.247 mm (p-value = 0.0107). This trend persisted when the data was separately analysed with the common cardiovascular risk factors of diabetes mellitus, hypertension and hyperlipidaemia., Conclusion: Our analysis demonstrated a statistically significant decrease in the CFA diameters post-PEVAR. However, the percentage changes were below established flow-limiting values, as reflected by the single access site complication reported. Hence, our findings give confidence in the safety profile of this procedure, even with the reported smaller baseline CFA lumen size in Asians. Moving forward, similar longer-term studies should be considered to characterise any late postoperative effects., (© 2024. The Author(s).)

Purpose: This is a prospective study to investigate the clinical outcomes of using noncompliant balloons in lower limb angioplasty for chronic limb threatening ischemia (CLTI)., Materials and Methods: This is a prospective single-center cohort study performed at a local tertiary hospital in Singapore. Consecutive patients who underwent lower limb angioplasty for CLTI using a noncompliant balloon catheter were enrolled if they were aged 40 years and above, presented with CLTI Rutherford grade 4 to 6, and had TASC C or D lesions in the lower limb vessels that were at least 100mm in length. Patient demographics, Rutherford grading, lesion characteristics, complications, and follow-up data were collected and analyzed. The primary outcomes were 30-day freedom from major adverse events, amputation-free survival (AFS) at 12 months, and freedom from clinically driven target lesion revascularization (cdTLR) at 12 months. Secondary outcomes included clinical success and target lesion primary patency (TLPP) at 12 months. Amputation-free survival, freedom from cdTLR, and TLPP were calculated by Kaplan-Meier analysis., Results: From May 2020 to December 2021, 50 patients (50 limbs) were enrolled. 43 (86%) patients had diabetes mellitus, while 12 patients (24%) had end-stage renal failure. 85 lesions were treated, including 59 (69.4%) below-the-knee (BTK) lesions. All the lesions were TASC C (n=45, 52.9%) or TASC D (n=40, 47.1%) lesions. Mean lesion length was 231.4±116.2mm. Technical success rate was 96.5%. No patients were lost to follow-up. Median follow-up duration was 282 days (IQR: 31-390 days). One patient died on day 26 due to an acute myocardial infarction. Two patients had groin hematomas postprocedure, both of which were treated conservatively. AFS, freedom from cdTLR, and TLPP at 12 months postprocedure was 70.0% (95% confidence interval [CI]: 58.4%-83.9%), 90.1% (95% CI: 83.4%-97.4%), and 61.1% (95% CI: 50.7%-73.6%), respectively., Conclusion: Early results have shown that the use of a high-pressure, noncompliant balloon is effective in lower limb angioplasty for CLTI in a highly challenging group of patients with a high prevalence of long BTK disease. Good vessel patency and limb salvage rates can be achieved, with a low complication rate. We await more long-term outcomes on vessel patency., Clinical Impact: There are many devices in the market for use in lower limb angioplasty. However, many of them come with an increased financial cost, procedural time and procedural difficulty. We report our prospective results with the exclusive use of a high pressure, non-compliant balloon, in a challening group of patients with a high prevalence of diabetes and end stage renal failure, achieving amputation free surival at 6 and 12 months post-procedure of 84.0% and 70.0% respectively. The use of non-compliant balloon is technically easy and does not add additional steps compared to a standard POBA procedure, thus limiting costs. We believe this article can be a push factor for clinicians to consider the use of these high pressure, non-compliant balloons in their patient care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To examine the healing outcomes of patients with venous leg ulcers requiring compression bandaging in community care versus tertiary care., Method: This was an analytical observational cohort study. Venous leg ulcer (VLU) patients who required compression bandaging were recruited from an outpatient vascular clinic between May 2021 and August 2022. Eligible patients received two-or four-layer compression bandaging and followed up with the community care or tertiary care centre nurses. The primary outcome was the difference in the total surface area of the VLU after 12 weeks, and the secondary outcome was the patient's quality of life, as measured by the Cardiff Wound Impact Schedule (CWIS)., Results: Forty-seven VLU patients were recruited; 27 received compression bandaging in the community care and 20 by the tertiary care centre. Mean age 70 years old (SD 11.04). The two most prevalent comorbidities were hypertension (51.06 %) and diabetes mellitus (38.29 %). Among those who completed follow-up (12 weeks), the median difference of the total surface area of the VLU between community-based care (p = 0.02) versus tertiary-based care (0.003) was significant. However, there was no difference in the healing status between community and tertiary-based care (p = 0.68). There was no difference in the quality of life of patients between groups., Conclusion: This first tropical study comparing VLU healing outcomes between community and tertiary care found no significant difference in healing with compression bandaging by nurses in either setting. However, the small sample size and high dropout rate limit the generalizability of the findings, necessitating a larger-scale study with longer follow-up. Despite these limitations, the study is a crucial step toward improving wound care services in Singapore, and highlights the need for further research to guide future community wound care implementation., Competing Interests: Declaration of competing interest Nil., (Copyright © 2024 Tissue Viability Society / Society of Tissue Viability. Published by Elsevier Ltd. All rights reserved.)

Introduction: Poor social connection is considered a risk factor for dementia. Since socializing behaviors may cluster together or act compensatorily, we aimed to investigate social connection patterns and their association with dementia, for men and women separately., Methods: A total of 12,896 community-dwelling older adults (mean ± SD age: 75.2 ± 4.3 years, 54% women) without major cognitive impairment were included. Latent class analysis was conducted using 24 baseline social connection indicators. Cox proportional hazards regression was used to estimate the association between latent classes and incident dementia over 12 (median: 8.4) years follow-up., Results: Three distinct classes were identified in both genders: strong social connections with an intermediate friend-relative network (Class 1: men, 43.8%; women, 37.9%), weak social connections (Class 2: men, 29.6%; women, 27.4%), and strong social connections with a larger friend-relative network (Class 3: men, 26.6%; women, 34.7%). Compared to Class 1, men in Class 2 (HR: 1.38, 95% CI: 1.08-1.77) and women in Class 3 (HR: 1.27, 95% CI: 1.01-1.60) had an increased risk of dementia., Discussion: Dementia risk varies with different social connection patterns among older men and women., Highlights: Three distinct social connection patterns were identified based on 24 indicators. These patterns were related to dementia risk differently in men and women. In men, a weak social connection pattern was associated with a higher dementia risk. In women, a strong social connection with a relatively larger friend-relative network was associated with a greater dementia risk., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: The aim of PRISTINE was to evaluate the 6 and 12 months safety and efficacy of the Selution Sustained Limus Release (SLR)™ sirolimus-coated balloon for treatment of complex lower limb occlusive lesions (TASC II C & D) in patients with chronic limb threatening ischemia (CLTI) from Singapore., Methods: PRISTINE was a prospective, non-randomized, single arm, observational, multi-investigator, single-center clinical study. Complication-free survival at 30 days was the safety clinical endpoint. Immediate technical success (ability to cross and dilate the lesion and achieve residual angiographic stenosis < 30%), 6-month primary vessel patency, limb salvage, clinically driven target lesion revascularization (TLR) and amputation free survival (AFS) were the efficacy endpoints of interest., Results: Seventy five patients were included. There were 50 (68.0%) males; mean age, 69.0 ± 10.7 years. CLTI severity was based on the Rutherford Scale (R5 = 51; R6 = 17). Significant co-morbidities included diabetes mellitus (n = 68; 91.0%) and end-stage renal failure (n = 28; 37.0%). 112 atherosclerotic lesions were treated (TASC II D = 58 (52%); 76 (67%) de novo). There was 100% technical success. Mean lesion length treated was 22.4 ± 13.9 cm. Primary vessel patencies at 6 and 12 months were 64/86 (74%) and 43/74 (58%) and freedom from clinically driven TLR were 72/86 (84%) and 55/74 (74%) respectively. AFS was 61/73 (84.0%; five deaths and seven major lower extremity amputation) at 6-months. Mean Rutherford score improved from 5.1 ± 0.55 at baseline to 1.1 ± 2.05 (p < 0.05) at one year and there was a wound healing rate of 38/48 (79%) at the same timepoint., Conclusions: The Selution SLR™ drug eluting balloon is safe and efficacious in treating highly complex infra-inguinal atherosclerotic lesions in an otherwise challenging frail population of CLTI patients with a high incidence of diabetes and end-stage renal failure. It is associated with highly satisfactory acute technical and clinical success, 12-month target lesion patency and AFS., Level of Evidence: Level 2b, Individual Cohort Study., (© 2024. The Author(s).)

Regular exercise benefits learning and memory in older adults, but the neural mechanisms mediating these effects remain unclear. Evidence in young adults indicates that acute exercise creates a favourable environment for synaptic plasticity by enhancing cortical disinhibition. As such, we investigated whether plasticity-related disinhibition mediated the relationship between cardiorespiratory fitness and memory function in healthy older adults (n = 16, mean age = 66.06). Participants completed a graded maximal exercise test and assessments of visual and verbal memory, followed by two counterbalanced sessions involving 20 min of either high-intensity interval training exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. In line with our hypotheses, we observed a positive correlation between cardiorespiratory fitness and verbal memory, which was mediated by plasticity-related cortical disinhibition. Our novel finding implicates cortical disinhibition as a mechanism through which the effects of acute bouts of exercise may translate to improved memory in older adults. This finding extends current understanding of the physiological mechanisms underlying the positive influence of cardiorespiratory fitness for memory function in older adults, and further highlights the importance of promoting exercise engagement to maintain cognitive health in later life. KEY POINTS: There are well established benefits of regular exercise for memory function in older adults, but the mechanisms are unclear. Cortical disinhibition is important for laying down new memories, and is enhanced following acute exercise in young adults, suggesting it is a potential mechanism underlying these benefits in ageing. Older adults completed a fitness test and assessments of memory, followed by two sessions involving either 20 min of exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. Cardiorespiratory fitness was positively associated with memory performance. Higher fitness was associated with enhanced cortical disinhibition following acute exercise. Cortical disinhibition completely mediated the relationship between fitness and memory. This novel finding provides a mechanistic account for the positive influence of cardiorespiratory fitness on memory in later life, and emphasises the importance of regular exercise for cognitive health in older populations., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Cognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals., Methods: 19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke., Results: During a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants., Conclusions: These findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention., (© 2024. The Author(s).)

Exercise is known to benefit motor skill learning in health and neurological disease. Evidence from brain stimulation, genotyping, and Parkinson's disease studies converge to suggest that the dopamine D2 receptor, and shifts in the cortical excitation and inhibition (E:I) balance, are prime candidates for the drivers of exercise-enhanced motor learning. However, causal evidence using experimental pharmacological challenge is lacking. We hypothesized that the modulatory effect of the dopamine D2 receptor on exercise-induced changes in the E:I balance would determine the magnitude of motor skill acquisition. To test this, we measured exercise-induced changes in excitation and inhibition using paired-pulse transcranial magnetic stimulation (TMS) in 22 healthy female and male humans, and then had participants learn a novel motor skill-the sequential visual isometric pinch task (SVIPT). We examined the effect of D2 receptor blockade (800 mg sulpiride) on these measures within a randomized, double-blind, placebo-controlled design. Our key result was that motor skill acquisition was driven by an interaction between the D2 receptor and E:I balance. Specifically, poorer skill learning was related to an attenuated shift in the E:I balance in the sulpiride condition, whereas this interaction was not evident in placebo. Our results demonstrate that exercise-primed motor skill acquisition is causally influenced by D2 receptor activity on motor cortical circuits., Competing Interests: T.T.-J.C. has received honoraria for lectures from Roche. The remaining authors declare no competing financial interests., (Copyright © 2024 the authors.)

Objectives: This study examines the gender-specific associations between a wide range of social activities and dementia risk., Methods: A prospective cohort study was conducted involving community-dwelling older Australians (≥70 years) without significant cognitive impairment at enrolment. During the first year of enrolment, we assessed 25 self-reported social activities covering various aspects, including support from relatives and friends, community participation, social interactions with surroundings, and loneliness. Dementia diagnosis followed DSM-IV criteria, adjudicated by an international expert panel. To estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between social activities and dementia, we performed Cox proportional hazards models, adjusting for age, educational attainment, baseline global cognition, and depressive symptoms., Results: Among 9,936 participants who completed all social activity questionnaires (median [IQR] age: 73.4 [71.6-77.1] years; 47.4% men), dementia was diagnosed in 3.8% of men (n = 181/4,705) and 2.6% of women (n = 138/5,231) over a median 6.4 years (IQR: 5.3-7.6, range: 0.2-10.1) follow-up. Gender-specific relationships emerged: caregiving for a person with illness/disability in women (HR: 0.65, 95% CI: 0.42-0.99), and having ≥9 relatives feeling close to call for help in men (HR: 0.56, 95% CI: 0.33-0.96; reference <9 relatives) were associated with reduced dementia risk. Unexpectedly, in women, having ≥5 friends with whom they felt comfortable discussing private matters were associated with a greater dementia risk (HR: 1.69, 95% CI: 1.10-2.59; reference ≤2 friends). Imputed models further identified that babysitting/childminding was associated with lower dementia risk in men (HR: 0.75, 95% CI: 0.56-0.99). No other social activities showed significant associations with dementia., Discussion: This study provides evidence of social activities influencing dementia risk. Further investigations are required to uncover the mechanisms driving these observed relationships., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Introduction: Medium-term clinical outcome data are lacking for cyanoacrylate glue (CAG) ablation for symptomatic varicose veins, especially from the Asian population., Objectives: Aim was to determine the 3-year symptomatic relief gained from using the VenaSeal™ device to close refluxing truncal veins from the Singaporean ASVS prospective registry., Methods: The revised Venous Clinical Severity Score (rVCSS) and three quality of life (QoL) questionnaires were completed to assess clinical improvement in venous disease symptoms along with a dedicated patient satisfaction survey. 70 patients (107 limbs; 40 females; mean age of 60.9 ± 13.6 years) were included at 3 years., Results: At 3 years, rVCSS showed sustained improvement from baseline (5.00 to 0.00; p < 0.001) and 51/70 (72.9%) had improvement by at least 2 or more CEAP categories. Freedom from reintervention was 90% and 85.7% patients were extremely satisfied with the treatment outcome. No further reports of further hypersensitivity reactions after one year., Conclusion: The 3-year follow-up results of the ASVS registry demonstrated continued and sustained clinical efficacy with few reinterventions following CAG embolization in Asian patients with chronic venous insufficiency., Trial Registration: ClinicalTrials.gov Registration: NCT03893201., (© 2024. The Author(s).)

Background: This study examined the associations of body mass index (BMI) and waist circumference (WC), as well as their short- and long-term changes over time, with incident dementia in older individuals., Methods: Data came from 18,837 community-dwelling individuals aged 65+ years from Australia and the United States, who were relatively healthy without major cognitive impairment at enrolment. Anthropometric measures were prospectively assessed at baseline, as well as change and variability from baseline to year two (three time-points). In a subgroup (n = 11,176), self-reported weight at age 18 and 70+ years was investigated. Dementia cases satisfied DSM-IV criteria. Cox regression was used to examine the associations between anthropometric measures and incident risk of dementia., Results: Compared to normal weight, an overweight (HR: 0.67, 95%CI: 0.57-0.79, p < 0.001) or obese BMI (HR: 0.73, 95%CI: 0.60-0.89, p = 0.002), or a larger WC (elevated, HR: 0.71, 95%CI: 0.58-0.86, p < 0.001; highly elevated, HR: 0.65, 95%CI: 0.55-0.78, p < 0.001; relative to low) at baseline was associated with lower dementia risk. In contrast, substantial increases in BMI (>5%) over 2 years after baseline were associated with higher dementia risk (HR: 1.49, 95% CI: 1.17-1.91, p = 0.001). Increased dementia risk was also seen with an underweight BMI at baseline and a 2-year BMI decrease (>5%), but these associations appeared only in the first 4 years of follow-up. Compared to normal weight at both age 18 and 70+ years, being obese at both times was associated with increased dementia risk (HR: 2.27, 95%CI: 1.22-4.24, p = 0.01), while obesity only at age 70+ years was associated with decreased risk (HR: 0.70, 95%CI: 0.51-0.95, p = 0.02)., Conclusions: Our findings suggest that long-term obesity and weight gain in later life may be risk factors for dementia. Being underweight or having substantial weight loss in old age may be early markers of pre-clinical dementia., (© 2024 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Aim: To compare the effectiveness and safety of pharmacological thrombolysis and mechanical thrombectomy., Material and Methods: This review was conducted in accordance with the PRISMA guidelines. Pooled proportions and subgroup analysis were calculated for primary and secondary patency rates, technical success, clinical success, major and minor complications rates., Results: This systematic review identified a total of 6,492 studies of which 17 studies were included for analysis. A total of 1,089 patients comprising 451 (41.4 %) and 638 (58.6 %) patients who underwent thrombolysis and mechanical thrombectomy procedures, respectively, were analysed. No significant differences were observed between thrombolysis and mechanical thrombectomy procedures in terms of technical success, clinical success, major and minor complications rates, primary and secondary patency rates; however, subgroup analysis of overall arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs) demonstrated a significantly higher rate of major complications within the AVF group (p=0.0248)., Conclusion: The present meta-analysis suggests that pharmacological thrombolysis and mechanical thrombectomy procedures are similarly effective and safe; however, AVFs are subject to higher major complications compared to AVGs., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Treatment of cephalic arch stenosis (CAS) is associated with high risk of failure and complications. Although stent-graft (SG) placement has improved patency rates, stent edge restenosis has been raised as a potential limiting factor for SG usage in CAS. This study aims to evaluate the safety and efficacy of combining stent graft placement with paclitaxel-coated balloon (PCB) angioplasty versus PCB alone in the treatment of CAS., Methods: This is an investigator-initiated, prospective, international, multicenter, open-label, randomized control clinical trial that plans to recruit 80 patients, who require fistuloplasty from dysfunctional arteriovenous fistula (AVF) from CAS. Eligible participants are randomly assigned to receive treatment with SG and PCB or PCB alone in a 1:1 ratio post-angioplasty ( n  = 40 in each arm). Randomization is stratified by de novo or recurrent lesion, and the participants are followed up for 1 year. The primary endpoints of the study are target lesion primary patency (TLPP) and access circuit primary patency (ACPP) rates at 6-months. The secondary endpoints are TLPP and ACPP at 3- and 12-month; target lesion and access circuit assisted primary and secondary patency rates at 3, 6, and 12-months and the total number of interventions; complication rate; and cost-effectiveness., Discussion: This study will evaluate the clinical efficacy and safety of combination SG and PCB implantation compared to PCB alone in the treatment of CAS for hemodialysis patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Healthy aging is associated with changes in motor sequence learning, with some studies indicating decline in motor skill learning in older age. Acute cardiorespiratory exercise has emerged as a potential intervention to improve motor learning, however research in healthy older adults is limited. The current study investigated the impact of high-intensity interval exercise (HIIT) on a subsequent sequential motor learning task. Twenty-four older adults (aged 55-75 years) completed either 20-minutes of cycling, or an equivalent period of active rest before practicing a sequential force grip task. Skill learning was assessed during acquisition and at a 6-hour retention test. In contrast to expectation, exercise was associated with reduced accuracy during skill acquisition compared to rest, particularly for the oldest participants. However, improvements in motor skill were retained in the exercise condition, while a reduction in skill was observed following rest. Our findings indicate that high-intensity exercise conducted immediately prior to learning a novel motor skill may have a negative impact on motor performance during learning in older adults. We also demonstrated that exercise may facilitate early offline consolidation of a motor skill within this population, which has implications for motor rehabilitation., (© 2024. The Author(s).)

Identification of high-risk carotid plaques in asymptomatic patients remains a challenging but crucial step in stroke prevention. The challenge is to accurately monitor the development of high-risk carotid plaques and promptly identify patients, who are unresponsive to best medical therapy, and hence targeted for carotid surgical interventions to prevent stroke. Inflammation is a key operator in destabilisation of plaques prior to clinical sequelae. Currently, there is a lack of imaging tool in routine clinical practice, which allows assessment of inflammatory activity within the atherosclerotic plaque. Herein, we have used a periarterial cuff to generate a progressive carotid atherosclerosis model in apolipoprotein E-deficient mice. This model produced clinically relevant plaques with different levels of risk, fulfilling American Heart Association (AHA) classification, at specific timepoints and locations, along the same carotid artery. Exploiting this platform, we have developed smart molecular magnetic resonance imaging (MRI) probes consisting of dual-targeted microparticles of iron oxide (DT-MPIO) against VCAM-1 and P-selectin, to evaluate the anti-inflammatory effect of statin therapy on progressive carotid atherosclerosis. We demonstrated that in vivo DT-MPIO-enhanced MRI can (i) quantitatively track plaque inflammation from early to advanced stage; (ii) identify and characterise high-risk inflamed, vulnerable plaques; and (iii) monitor the response to statin therapy longitudinally. Moreover, this molecular imaging-defined therapeutic response was validated using AHA classification of human plaques, a clinically relevant parameter, approximating the clinical translation of this tool. Further development and translation of this molecular imaging tool into the clinical arena may potentially facilitate more accurate risk stratification, permitting timely identification of the high-risk patients for prophylactic carotid intervention, affording early opportunities for stroke prevention in the future., (© 2022. The Author(s).)

People with methamphetamine use disorder (MUD) struggle to shift their behaviour from methamphetamine-orientated habits to goal-oriented choices. The model-based/model-free framework is well suited to understand this difficulty by unpacking the computational mechanisms that support experienced-based (model-free) and goal-directed (model-based) choices. We aimed to examine whether 1) participants with MUD differed from controls on behavioural proxies and/or computational mechanisms of model-based/model-free choices; 2) model-based/model-free decision-making correlated with MUD symptoms; and 3) model-based/model-free deficits improved over six weeks in the group with MUD. Participants with MUD and controls with similar age, IQ and socioeconomic status completed the Two-Step Task at treatment commencement (MUD n = 30, Controls n = 31) and six weeks later (MUD n = 23, Controls n = 26). We examined behavioural proxies of model-based/model-free decisions using mixed logistic regression, and their underlying mechanisms using computational modelling. At a behavioural level, participants with MUD were more likely to switch their choices following rewarded actions, although this pattern improved at follow up. At a computational level, groups were similar in their use of model-based mechanisms, but participants with MUD were less likely to apply model-free mechanisms and less likely to repeat rewarded actions. We did not find evidence that individual differences in model-based or model-free parameters were associated with greater severity of methamphetamine dependence, nor did we find that group differences in computational parameters changed between baseline and follow-up assessment. Decision-making challenges in people with MUD are likely related to difficulties in pursuing choices previously associated with positive outcomes., (© 2023 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: A prospective, pilot study was designed to test the feasibility of using sirolimus-coated balloon (SCB) to treat graft vein junction of thrombosed arteriovenous graft (AVG) following successful pharmacomechanical thrombectomy. The present report provides the 1-year results of this study., Methods: This is a 1-year follow-up of a single, prospective, single-arm study that was conducted from 2018 to 2019 in 20 patients who presented to a tertiary institution with thrombosed AVG. The recruited patients received SCB angioplasty at the graft-vein junction following successful endovascular thrombectomy of a thrombosed AVG. One year after recruitment, there were three deaths, one AVG revision, and one AVG explantation among the participants recruited. The outcomes of 15 subjects at 1-year following the index procedure obtained from electronic medical records were re-examined., Results: The 1-year access circuit primary patency rate was 40%, while assisted primary and secondary patency rates were 46.7% and 73.3%, respectively. A total of 16 interventions (4 angioplasties, 12 thrombectomies) were performed in 9 patients over the 12 months. Four AVGs were abandoned. The median number of interventions per patient was 1 (0-3) per year. Using Kaplan-Meier analysis, the mean estimated post-intervention access circuit primary patency was 230 (95% CI: 162-300) days, while access circuit assisted primary patency was 253 (95% CI: 187-320) days, and access circuit secondary patency was 292 (95% CI: 230-356) days. Sub-group analysis did not show a significant difference in the mean estimated primary patency between AVG with de novo and recurrent stenosis (245 days, 95% CI: 151-339 vs 210 days, 95% CI: 113-307; p  = 0.29)., Conclusions: SCB may help sustain the patency of thrombosed AVG following successful thrombectomy., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CS Tan and TY Tang received grant support from Concept Medical, during the conduct of the study

Introduction: Risk factors for cardiovascular disease (CVD) also increase the risk of dementia. However, whether commonly used CVD risk scores are associated with dementia risk in older adults who do not have a history of CVD, and potential gender differences in this association, remains unclear. The aim of this study was to determine whether CVD risk scores are prospectively associated with cognitive decline and dementia in initially healthy older men and women., Methods: A total of19,114 participants from a prospective cohort of individuals aged 65+ years without known CVD or dementia were recruited. The atherosclerotic cardiovascular disease risk score (ASCVDRS), Systematic Coronary Risk Evaluation 2-Older Persons (SCORE2-OP), and the Framingham risk score (FRS) were calculated at baseline. Risk of dementia (according to DSM-IV criteria) and cognitive decline (defined as a &gt;1.5 standard deviation decline in global cognition, episodic memory, psychomotor speed, or verbal fluency from the previous year) were assessed using hazard ratio., Results: Over a median follow-up of 6.4 years, 850 individuals developed dementia and 4,352 cognitive decline. Men and women in the highest ASCVDRS tertile had a 41% (95% CI 1.08, 1.85) and 45% (1.11, 1.89) increased risk of dementia compared to the lowest tertile, respectively. Likewise, men and women in the highest SCORE2-OP tertile had a 64% (1.24, 2.16) and 60% (1.22, 2.11) increased risk of dementia compared to the lowest tertile, respectively. Findings were similar, but the risk was slightly lesser when examining risk of cognitive decline for both ASCVDRS and SCORE2-OP. However, FRS was only associated with the risk of cognitive decline among women (highest vs. lowest tertiles: 1.13 [1.01-1.26])., Conclusion: These findings suggest the utility of the ASCVDRS and SCORE2-OP in clinical practice, to not only assess future risk of CVD, but also as potential early indicators of cognitive impairment, even in relatively healthy older men and women., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: The global burden of peripheral artery disease (PAD) has been increasing. Guidelines for PAD recommend evidence-based medical therapy (EBMT) to reduce the risks of cardiovascular events and death but the implementation of this is highly variable. This study aimed to understand the current practices regarding EBMT prescription in PAD patients and the key barriers and facilitators for implementing PAD guidelines., Method: A qualitative study was conducted in the largest tertiary hospital in Singapore from December 2021 to March 2023. The participants included healthcare professionals and in-patient pharmacists involved in the care of PAD patients, as well as patients with PAD who had undergone a lower limb angioplasty revascularisation procedure. Data were collected through in-depth, individual semi-structured interviews conducted face-to-face or remotely by a trained research assistant. Interviews were audio-recorded, transcribed and systematically coded using data management software NVivo 12.0. The Tailored Implementation for Chronic Diseases (TICD) framework was used to guide the interviews and analysis., Results: Twelve healthcare professionals (4 junior consultants, 7 senior consultants, and 1 senior in-patient pharmacist) and 4 patients were recruited. Nine themes in 7 domains emerged. Only a small proportion of doctors were aware of the relevant guidelines, and the generalisability of guidelines to patients with complicated conditions was the doctors' main concern. Other barriers included cost, frequent referrals, lack of interprofessional collaboration, not being the patients' long-term care providers, short consultation time and patients' limited medication knowledge., Conclusion: Findings from this study may inform strategies for improving healthcare professionals' adherence to guidelines and patients' medication adherence., Competing Interests: The authors declared no conflicts of interest.

Objectives: Psychological stress has been proposed as a risk factor for cognitive impairment and dementia. However, it remains unclear how an individual's stress-coping ability (i.e., psychological resilience) is related to cognition. This cross-sectional study investigated whether perceived stress and psychological resilience were associated with cognition and a modifiable dementia risk score in a large community-based sample of cognitively normal adults. The moderating effect of psychological resilience was also examined., Methods: Participants (mean age = 57 ± 7 years) enrolled in the web-based Healthy Brain Project completed the Perceived Stress Scale and the Connor-Davidson Resilience Scale. Domains of attention and working memory were assessed using the Cogstate Brief Battery (n = 1,709), and associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery (n = 1,522). Dementia risk was estimated for 1,913 participants using a modified version of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia dementia risk score, calculated using only readily modifiable dementia risk factors., Results: In separate linear regression analyses adjusted for age, sex, education, and race, greater levels of perceived stress and lower levels of psychological resilience were associated with poorer performance across all cognitive domains, as well as a higher modifiable dementia risk score. Psychological resilience did not moderate the effect of perceived stress on cognition or the dementia risk score., Discussion: Higher perceived stress and lower resilience were associated with poorer cognition and a greater burden of modifiable dementia risk factors. Intervention studies are required to determine if lowering stress and building resilience can mitigate cognitive deficits and reduce dementia risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical plasticity in young and older adults. We acquired measures of cortical excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 20 young (mean ± SD = 25.30 ± 4.00 years, 14 females) and 20 older (mean ± SD = 64.10 ± 6.50 years, 11 females) healthy adults. Single- and paired-pulse TMS measurements were collected before and after a 20 min bout of high-intensity interval cycling exercise or an equivalent period of rest, and again after intermittent theta burst stimulation (iTBS). In both young (P = 0.027, Cohen's d = 0.87) and older adults (P = 0.006, Cohen's d = 0.85), there was an increase in glutamatergic excitation and a reduction in GABAergic inhibition from pre- to postexercise. However, in contrast to younger adults, older adults showed an attenuated plasticity response to iTBS following exercise (P = 0.011, Cohen's d = 0.85). These results demonstrate an age-dependent decline in cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults. Our findings align with the hypothesis that the capacity for cortical plasticity is altered in older age. KEY POINTS: Exercise enhances motor cortical plasticity in young adults, but how ageing influences this effect is unknown. Here, we compared primary motor cortical plasticity responses in young and older adults before and after a bout of high-intensity interval exercise and again after a plasticity-inducing protocol, intermittent theta burst stimulation. In both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in GABAergic inhibition. Our key result was that older adults showed an attenuated plasticity response to theta burst stimulation following exercise, relative to younger adults. Our findings demonstrate an age-dependent decline in exercise-enhanced cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Psychological stress is a potential modifiable risk factor for cognitive decline. However, the extent to which self-reported psychological stress is differentially associated with decline in specific cognitive domains remains unclear. Differences may be due to heterogeneity in the aspects of psychological stress investigated, for example, neuroticism (which is linked to vulnerability to stress), perceived stress, or exposure to stressful life events. This review aims to establish the associations between these aspects of self-reported psychological stress and cognitive decline. PsychINFO, Embase and MEDLINE were searched from database inception to September 2021. Studies were included if they were observational, prospective, and if they investigated the association between self-reported psychological stress and cognitive decline in adults with a minimum mean age of 40 years at baseline. Thirty studies satisfied the inclusion criteria, with most examining neuroticism (n = 17) as a predictor of cognitive decline. Fewer examined perceived stress (n = 7) or stressful life events (n = 6). There was evidence of an association between neuroticism and cognitive decline, particularly in the domain of memory. Similarly, across studies, perceived stress was also associated with memory decline. Research investigating the relationship between stressful life events and cognitive decline had fewer outcomes to interpret. Overall, the findings highlight that memory may be particularly susceptible to high levels of neuroticism and perceived stress. We identified a lack of research into some cognitive domains, such as executive function, which should be addressed by future studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Recent genome-wide association studies identified new dementia-associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort., Methods: We used Cox models and area under the curve (AUC) to validate new PRSs (PRS-83SNP, PRS-SBayesR, and PRS-CS) compared with an older PRS-23SNP in 12,031 initially-healthy participants ≥70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria., Results: PRS-83SNP, PRS-SBayesR, and PRS-CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [APOE] ε4) hazard ratios per standard deviation (SD) of 1.35 (1.23-1.47), 1.37 (1.25-1.50), and 1.42 (1.30-1.56), respectively. The AUC of a model containing conventional/non-genetic factors and APOE was 74.7%. This was improved to 75.7% (p = 0.007), 76% (p = 0.004), and 76.1% (p = 0.003) with addition of PRS-83SNP, PRS-SBayesR, and PRS-CS, respectively. The PRS-23SNP did not improve AUC (74.7%, p = 0.95)., Conclusion: New PRSs for dementia significantly improve risk-prediction performance, but still account for less risk than APOE genotype overall., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Recent studies have reported associations between high plasma high-density lipoprotein cholesterol (HDL-C) levels and risk of all-cause mortality, age-related macular degeneration, sepsis and fractures, but associations with dementia risk remain unclear. To determine whether high plasma HDL-C levels are associated with increased incident dementia risk in initially-healthy older people., Methods: We conducted a post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial; a double-blind, randomized, placebo-controlled trial of daily low-dose aspirin in healthy older people. ASPREE recruited 16,703 participants aged ≥70 years (from Australia) and 2411 participants aged ≥65 years (from the US) between 2010 and 2014. Participants had no diagnosed cardiovascular disease, dementia, physical disability, or life-threatening illness at enrolment and were cognitively healthy (3MS score ≥78). All-cause dementia was a primary trial endpoint, and determined by DSM-IV criteria. Cox regression was used to examine hazard ratios between HDL-C categories <40 mg/dL, 40-60 mg/dL (reference category), 60-80 mg/dL, and >80 mg/dL and dementia. Restricted cubic spline curves were used to determine nonlinear associations. Data analysis was performed from October 2022 to January 2023., Findings: Of the 18,668 participants, 850 (4.6%) cases of incident dementia were recorded over 6.3 (SD 1.8) years. Participants with high HDL-C (>80 mg/dL) had a 27% higher risk of dementia (HR 1.27, 95% CI 1.03, 1.58). Age stratified analyses demonstrated that the risk of incident dementia was higher in participants ≥75 years compared to participants <75 years (HR 1.42, 95% CI 1.10, 1.83 vs HR 1.02, 95% CI 0.68, 1.51). Associations remained significant after adjusting for covariates including age, sex, country of enrolment, daily exercise, education, alcohol consumption, weight change over time, non-HDL-C, HDL-C-PRS, and APOE genotype., Interpretation: In a population of initially-healthy older adults aged ≥75 years, high HDL-C levels were associated with increased risk of all-cause dementia., Funding: National Institutes of Health, USA; National Health and Medical Research Council Australia; Monash University (Melbourne, VIC, Australia); and the Victorian Cancer Agency (Australia)., Competing Interests: SMH is the recipient of National Health and Medical Research Council (NHMRC) Early Career Fellowship (APP1142198), JMCN is supported through an NHMRC Leadership Fellowship (IG 1173690). PL is supported by a National Heart Foundation Future Leader Fellowship (102604). JR is supported by an NHMRC Leadership Investigator Grant (2016438). TC is supported by an Australian Research Council Future Fellowship (FT220100294), and has received honoraria from Roche for lectures. GFW received grants from Arrowhead Pharma, Amgen, Novartis, Silence Therapeutics; consulting fee from Amgen, Novartis, Sanofi, Esperion; honoraria from Amgen, Novartis, Sanofi; support for attending meetings from Novartis, Silence Therapeutics. No other disclosures are reported by the other authors., (© 2023 The Author(s).)

Background and Objectives: It has been suggested that higher triglyceride levels were associated with a lower risk of Alzheimer disease. This study aimed to examine the association of triglycerides with dementia and cognition change in community-dwelling older adults., Methods: This prospective longitudinal study used data from the Aspirin in Reducing Events in the Elderly (ASPREE) randomized trial of adults aged 65 years or older without dementia or previous cardiovascular events at enrollment. The main outcome was incident dementia. Other outcomes included changes in composite cognition and domain-specific cognition (global cognition, memory, language and executive function, and psychomotor speed). The association between baseline triglycerides and dementia risk was estimated using Cox proportional hazard models adjusting for relevant risk factors. Linear mixed models were used to investigate cognitive change. The analysis was repeated in a subcohort of participants with available APOE -ε4 genetic data with additional adjustment for APOE -ε4 carrier status and an external cohort (UK Biobank) with similar selection criteria applied., Results: This study included 18,294 ASPREE participants and 68,200 UK Biobank participants (mean age: 75.1 and 66.9 years; female: 56.3% and 52.7%; median [interquartile range] triglyceride: 106 [80-142] mg/dL and 139 [101-193] mg/dL), with dementia recorded in 823 and 2,778 individuals over a median follow-up of 6.4 and 12.5 years, respectively. Higher triglyceride levels were associated with lower dementia risk in the entire ASPREE cohort (hazard ratio [HR] with doubling of triglyceride: 0.82, 95% CI 0.72-0.94). Findings were similar in the subcohort of participants with APOE-ε4 genetic data (n = 13,976) and in the UK Biobank cohort (HR was 0.82 and 0.83, respectively, all p ≤ 0.01). Higher triglycerides were also associated with slower decline in composite cognition and memory over time ( p ≤ 0.05)., Discussion: Older adults with higher triglyceride levels within the normal to high-normal range had a lower dementia risk and slower cognitive decline over time compared with individuals with lower triglyceride levels. Higher triglyceride levels may be reflective of better overall health and/or lifestyle behaviors that would protect against dementia development. Future studies are warranted to investigate whether specific components within the total circulating pool of plasma triglycerides may promote better cognitive function, with the hope of informing the development of new preventive strategies., (© 2023 American Academy of Neurology.)