In humans, age-related accumulations of physical deficits are often characterized by frailty indices, which predict increased risk for neurodegeneration characteristic of Alzheimer's disease (AD). However, social capabilities also may diminish, with considerable variation in inter-individual trajectories of decline and AD risk. Social frailty has recently been proposed in humans and mice to characterize the severity of social impairments with age; however, no index of social frailty exists for nonhuman primates (NHPs). This represents a significant gap in the literature, as NHPs provide important translational opportunities to study brain-body relationships that promote healthy versus pathological aging. Here, we developed a novel index of social frailty in female vervet monkeys ( Chlorocebus aethiops sabaeus ) using six components of social behavior measuring positive interactions, agonistic interactions and social isolation. Members of this study comprise the Wake Forest Aging Vervet Cohort, which includes 30+ captive females ranging from middle- to very old age (8-29 years). Subjects live with their families in large, multi-matrilineal social groups. We first tested whether social frailty in vervets recapitulated age-related changes observed in humans. Next, we determined the cross-sectional relationships between social frailty and neuroanatomy derived from structural MRI. Finally, we tested whether social frailty predicted biomarkers associated with AD (MesoScale Discovery Platform: Ab40, Ab42, Ab42:40, ptau181, NfL, and GFAP) in CSF at approximately one year follow-up. The social frailty index increased with age (t= 3.695, p  <0.001). Social frailty was positively associated with CSF volumes (t= 2.163 p  = 0.035) and negatively associated with cortical gray matter (t=-4.261, p  <0.001), white matter (t=-2.591, p  = 0.013), and cerebellar (t=-3.716, p  <0.001) volumes. Social frailty also predicted several CSF biomarkers associated with AD. Higer social frailty predicted higher levels of phosphorylated tau (t=2.304, p  = 0.024) but lower Ab42 (t=-2.345 p  = 0.022) and Ab40 (t=-2.138, p  = 0.036). Social frailty was also associated with elevated NfL and GFAP in CSF; however, the associations did not reach statistical significance ( p 's <0.10). Like humans, some vervets may exhibit increasing socially frailty with age. These unhealthy aging trajectories - characterized by fewer positive interactions, social isolation, and agonistic interactions - are associated with AD neuroimaging and biofluid biomarkers.

Hip fracture is one of the most common admission diagnoses in the UK, accounting for >75,000 hospital admissions per year in England and Wales. Fractured neck of femur can be classified as a ‘frailty’ presentation because of an average age of >80 years, a clear association with ‘pathological falls’, including syncope, and a high number of co-morbidities. The combination of traumatic injury, frailty and surgery presents significant challenges to the managing team and requires a multidisciplinary approach to reduce the risk of perioperative complications, most commonly postoperative delirium, sepsis, cardiac complications, stroke and metabolic disturbance. Close monitoring with geriatric co-management has been shown to reduce complications and resultant morbidity, length of stay and mortality. Many lessons learnt from the experience of managing these very challenging patients has been transferred to other frail patients undergoing surgery in perioperative geriatric services and major trauma.

Animal models and human studies suggest that general anesthesia exposure during infancy results in long-lasting neurocognitive impairments. Because millions of children each year undergo procedures that require anesthesia, it is important to investigate the mechanism of anesthesia induced neurotoxicity to ultimately develop ways to protect the vulnerable developing brain. Animal models have played a key role in this investigation and have shown that neonatal general anesthesia exposure results in neuronal apoptosis, long-term mitochondrial dysfunction, and astrogliosis. The current study involved a rhesus macaque model of repeated sevoflurane exposure that has been shown to produce cognitive deficits, behavioral changes, and mitochondrial damage. This study sought to investigate whether prolonged sevoflurane exposure induced inflammation as measured in peripheral blood samples. Results found that sevoflurane exposure resulted in changing levels of inflammatory markers in the periphery. Specifically, interleukin 6 (IL-6) was increased immediately following sevoflurane exposure, but not at 24-h post-exposure. Plasma samples collected 24-h after exposure revealed increased granulocyte macrophage colony-stimulating factor (GM-CSF), but decreased monocyte chemoattractant protein-4 (MCP-4) and interferon gamma-induced protein 10 (IP-10) levels. Changes in these markers have been linked to cognitive impairment, and together these data suggest that plasma levels of cytokines and chemokines are a good potential medium to investigate anesthesia-induced inflammation in clinical populations.

Background: Better prognostic biomarkers are needed in older adults with cancer. There are established links between N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and sarcopenia, and sarcopenia is associated with poorer cancer survival. However, there are limited data regarding baseline NT-proBNP as a biomarker of cancer outcome. The GO2 trial recruited older and/or frail United Kingdom (UK) patients with advanced gastroesophageal cancer and investigated the role of chemotherapy dose de-escalation. Using the GO2 database, we sought to investigate the prognostic role of NT-proBNP as well as the interaction between NT-proBNP and frailty. Methods: This was a post-hoc analysis of a completed clinical trial. Frailty measures included ECOG performance status (PS) and GO2 frailty grouping (based on an assessment of nine geriatric domains). A corrected NT-proBNP (cBNP) was calculated for each patient, adjusting for the upper limit of normal (ULN) reference from each centre. Results: A total of 241 patients were eligible to be included in the analysis. The median age was 76 (range 52-89), 187 (77.6%) were male and 211 (87.6%) had adenocarcinoma. Eighty (33.2%) patients had a baseline NT-proBNP above the local ULN. There was no association between cBNP and ECOG PS (p = 0.36) or the GO2 frailty group (p = 0.58). Those with the highest cBNP (n = 59) had significantly inferior median overall survival: 5.3 months (mos.) vs. 6.8 mos. (medium, n = 120) vs. 8.2 mos. (low, n = 61); HR 1.57 (95% CI; 1.04-2.37), p = 0.031. This was maintained on a Cox regression analysis (HR 1.69, p = 0.01) accounting for the GO2 trial stratification factors. There was no clear association between frailty and NT-proBNP. Conclusions: In this study, NT-proBNP appeared to be prognostic-independent of other factors. Further investigation and validation are needed to confirm our findings and to determine the potential beneficial role of cardioprotective therapy in at-risk patients with cancer identified in this manner.

This study assessed relationships between age, glucose and insulin metabolism, and cognitive performance in vervet monkeys (Chlorocebus aethiops sabaeus) a valuable model for aging research. Executive function, working memory, body mass index (BMI), and glucose and insulin responses during intravenous glucose tolerance tests (IVGTTs) were assessed in 41 middle-aged to older (9.1–29.5 years), socially housed, female vervets. Cluster analyses yielded four distinct IVGTT response patterns relevant to type 2 diabetes development: (I) normal insulin response and euglycemia; (II) baseline euglycemia, hyperinsulinemic response, and adequate glucose clearance; (III) baseline euglycemia, impaired insulin response, and impaired glucose clearance; and (IV) baseline hyperglycemia, impaired insulin response, and hyperglycemia throughout the test. Age was associated with baseline glucose (β = 3.615; p < 0.001), glucose area under the curve (AUC) (β = 321.07; p = 0.002), glucose clearance (β = − 0.145; p < 0.001), and insulin AUC (β = − 40.603; p = 0.020). There was a main effect of aging over 1.5 years on insulin AUC (β = − 392.026, p = 0.023). Older animals tended to exhibit more rapid increases in fasting glucose over time (β = 0.986; p = 0.051). Higher BMI was associated with greater insulin resistance (HOMA-IR: β = 0.167; p = 0.004), fasting hyperglycemia (β = 1.120; p = 0.010), and impaired glucose regulation (glucose AUC: β = 136.59; p = 0.001). Worsening glycemic control was associated at follow-up with poorer executive function (χ2 = 8.134; p = 0.043) and tended to be associated with poorer working memory (χ2 = 6.363; p = 0.095). Aging vervets undergo a decline in glucose sensitivity, increasing insulin resistance, and impaired glucose handling. Metabolic perturbations characteristic of worsening prediabetes predicted worse cognition; however, future study is needed identify mechanisms underlying these relationships.

Alzheimer's disease (AD) is the primary cause of dementia worldwide and is increasing in incidence. In humans, impaired glucose handling characteristic of pre‐ and type 2 diabetes (T2D) is associated with cognitive dysfunction and AD risk. Vervet monkeys ( Cholorocebus aethiops sabaeus ) have emerged as a nonhuman primate model of early AD due to similarities to humans in phylogeny, endocrine, sociality, cognition, brain structure and function, AD‐like neuropathology, and response to risk factor modification. Thus, these NHPs provide important opportunities to determine relationships between age, glucose handling, and cognitive performance. We determined glucose and insulin levels in 101 ivGTTs, conducted over 4 yrs (∼16 human years), in 41 middle‐ to very old‐aged female vervets (9‐30 years), living in long term, stable social groups. We determined temporal relationships between glucose handling and age, and cognitive performance (executive function and working memory), and examined BMI as a modifier of these relationships. Cluster analyses yielded four distinct patterns of glucose handling and insulin responsivity relevant to the development of T2D: 1) normal insulin response and euglycemia, 2) hyperinsulinemia with baseline euglycemia, 3) lack of insulin response and euglycemia, and 4) lack of insulin response and hyperglycemic. Age was associated with baseline glucose ( r (51)=0.57, p <0.001), insulin area under the curve (AUC) from 0‐60 minutes ( r (35)=‐0.27, p = 0.017), insulin AUC from time 10‐40 minutes ( r (31)=‐0.23, p = 0.031), glucose AUC from time 10‐40 minutes ( r (48)=0.43, p = 0.030), and glucose clearance from time 10‐40 minutes ( r (42)=‐0.48, p <0.001). Older age plus higher BMI predicted poorer glucose handling (r(69)=0.96, p = 0.055). Glucose handling was associated with subsequent cognitive performance. Executive function declined with decreasing insulin production (F(1,9)=7.61, p = 0.022) in middle‐age, whereas working memory declined with increasing glucose levels at older ages (glucose baseline: F(1,10)=21.13, p <0.001; AUC F(1,10)=12.72, p = 0.005). Older vervets with better glycemic control had better cognitive function than their same aged counterparts with poorer glycemic control. Vervets exhibit biological subtypes of glucose and insulin physiology like humans, and develop age‐related impaired metabolic functioning. Glucose handling predicts cognitive performance; these relationships may manifest in older age and vary with obesity. Funding: R24AG073199, Harry O. Parker Neuroscience Research Fund, P30AG072947

INTRODUCTION:Adults aged 70 years and over account for almost 60% of colorectal cancer (CRC) diagnoses in the United Kingdom. Whilst emergency presentation of CRC is known to be associated with poorer outcomes across all ages, older adults are less likely to be treated with curative intent and have poorer overall survival (OS). We aimed to investigate whether presentation, management, or outcome differed in older (≥70 years) versus younger (<70 years) adults in our population. MATERIALS AND METHODS:The electronic records of patients diagnosed with CRC within the period 2016 to 2019 in National Health Service (NHS) Tayside, Scotland were retrospectively analysed. Patients were grouped by age (<70 years and ≥70 years). Demographics were compared by Chi-squared or t-test, and Kaplan-Meier and Cox proportional hazard regression were used for survival analyses. RESULTS:In total, 1245 patients were diagnosed with CRC (median age 71 years, range 20-98). Of these, 215 patients (17.3%) presented emergently and were included in the analysis. Older adults accounted for 65.1% (n = 140) of emergency presentations. Older adults were less likely to present with classical symptoms of CRC (80.0% vs 90.7%, p = 0.04) and more likely to present via the medical assessment unit (46.4% vs 30.7%, p = 0.03). Additionally, older adults were less likely to receive a histological diagnosis of CRC (71.4% vs 97.3%, p < 0.001) or have complete staging investigations performed (78.6% vs 96.0%, p < 0.001). Fewer older adults underwent surgical management (55.0% vs 86.7%, p < 0.001) and fewer were treated with chemotherapy (14.3% vs 69.3%, p < 0.001). Whilst older adults had poorer median OS than those aged <70 years (12.0 vs 34.4 months, p < 0.001), multivariate Cox proportional hazards regression demonstrated that higher stage (stage III hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.7, stage IV HR 16.7, 95% CI 9.7-28.8, incomplete HR 8.2, 95% CI 4.6-14.7) and not receiving chemotherapy (HR 2.6, 95% CI 1.7-4.0) were associated with poorer survival, whereas age and sex were not. DISCUSSION:Emergency presentation of colorectal cancer was more common in older adults. Older adults were more likely to present atypically, less likely to have completed staging, and had lower rates of intervention, which were associated with poorer survival outcome.

Background Although rare, uterine sarcomas account for a high proportion of uterine cancer mortality. Treatment options and robust trial data are limited.Objectives The TOURISM study (Treatment Outcomes in UteRIne SarcoMa) is a UK-wide study by the National Oncology Trainees Collaborative for Healthcare Research which aimed to characterise this patient cohort.Design A retrospective descriptive cohort study. Patients with carcinosarcomas/mixed Mullerian tumours, non-uterine gynaecological sarcomas and uterine metastases were excluded. Routine clinical data, including general patient demographics, diagnosis, treatment and outcomes, were collated and pseudonymised.Setting Patients diagnosed with uterine sarcoma in the UK National Health Service between 1 January 2008 and 31 December 2017 were identified from electronic records.Participants A total of 406 patients from eight centres were eligible for inclusion.Results The median age at diagnosis was 56 years, with leiomyosarcoma the most common diagnosis (54.4%). The majority (57.9%) were diagnosed at the International Federation of Gynecology and Obstetrics stage I, with 19.7% diagnosed at stage IV. Nearly half (45.2%) of the patients received at least one line of chemotherapy, of which most (81.0%) received doxorubicin first-line. In the stage I group 7.4% received adjuvant chemotherapy and 15.0% received adjuvant radiotherapy. Median overall survival was 37 months; however, survival varied significantly by stage at diagnosis (stage I: 105 months; stage II: 33 months; stage III: 19 months; stage IV: 14 months).Conclusions Our data highlight the diversity in patient management in uterine sarcoma and a marked survival advantage for patients diagnosed with stage I disease. These data highlight the importance of a multidisciplinary approach and describe real-world trends in systemic therapies, radiotherapy and surgical treatment in this rare cancer type.

1521 Background: Older adults have a higher risk of developing chemotherapy (CTx) related toxicity. The Cancer Aging Research Group (CARG) score was developed and validated in the USA to predict risk of severe CTx induced toxicity in older adults; subsequent validation studies have had varying results. The TOASTIE study sought to evaluate the CARG score prospectively in a United Kingdom (UK) population. Methods: This multicentre, prospective, observational study recruited patients aged ≥65 years commencing first-line neo-adjuvant, adjuvant or palliative CTx for any solid organ malignancy. Those receiving non-CTx agents were excluded. Baseline demographics and established frailty measures were recorded, including Eastern Cooperative Oncology Group performance status (ECOG PS), Rockwood Clinical Frailty Scale (CFS), Geriatric-8 (G8) score and Charlson Co-morbidity Index (CCI). CARG score was calculated after initial Oncology consultation. Follow-up data including CTCAEv5 toxicity and hospital admissions were collected retrospectively. Results: 19 centres recruited 330 patients between Nov 2019 - Dec 2022. Median age was 73 years (range 65-92) and 51.9% were male. 54.9% had a primary tumour of gastrointestinal origin, 48.7% received CTx with palliative intent and 70.8% received doublet therapy. At baseline, 85% patients had an ECOG PS 0 or 1, with median CFS 3 (range 0-8), G8 score 12 (range 6-16) and CCI 6 (range 2-12). Follow-up data was available for 314 (92.6%) patients; the median CTx cycles received was 4 (range 1-16) with 124 (39%) patients dose reduced at cycle one. Treatment delays occurred in 83 (26.4%) patients and 123 (39.2%) stopped treatment early, with 60 (48.8%) cases due to treatment-related toxicity. 69(22.3%) patients experienced a CTCAE grade ≥3 toxicity and 84 (27%) requiring hospital admission. CARG score was available for 313 patients; 107 (34.2%) low risk, 167 (53.4%) medium risk and 39 (12.5%) high risk. Increasing CARG risk groups had increased toxicity rates (low 19.6%, medium 22.2%, high 28.2%) however this was non-significant with no evidence of robust predictive performance (Table). The performance of CFS and ECOG PS was superior to CARG. Conclusions: In this UK older patient population, baseline frailty was prevalent. CARG score was unable to robustly discriminate or predict risk of high-grade toxicity. ECOG showed superior, albeit limited, ability to predict and discriminate toxicity risk. This study highlights the need for development of further tools predictive of toxicity in this population. [Table: see text]

Aims: WHO Grade 3 (G3) meningiomas are rare tumours with limited data to guide management. This retrospective study documents UK management approaches across 14 centres over 11 years. Materials and methods: Patients with WHO G3 meningioma between 01/01/2008 and 31/12/2018 were identified. Data were collected on demographics, management strategy, adjuvant radiotherapy, approach in recurrence setting and survival. Results: 84 patients were identified. 21.4% transformed from lower-grade disease. 96.4% underwent primary surgical resection, with 20.8% having evidence of residual disease on their post-op MRI. 59.3% of patients underwent adjuvant radiotherapy (RT) following surgical resection. Overall median PFS and OS were 12.6 months and 28.2 months, respectively. Median OS in the group who underwent complete surgical resection was 34.9 months, compared to 27.5 months for those who had incomplete resection (HR 0.58, 95% CI 0.27-1.23, p = 0.15). Median OS was 33.1 months for those who underwent adjuvant RT and 14.0 months for those who did not (HR 0.48, 95% CI 0.27-0.84, p = 0.004). Median adjuvant RT dose delivered was 60Gy (range 12Gy-60Gy), 45.8% of adjuvant RT was delivered using IMRT. At disease relapse, 31% underwent salvage surgery and 29.3% underwent salvage RT. Of those treated with salvage RT, 64.7% were re-treats and all were treated with hypofractionated RT. Conclusion: Surgery continues to be the preferred primary management strategy. Post-operative MRI within 48 hours is indicated to assess presence of residual disease and guide further surgical options. Adjuvant radiotherapy plays an important part of the management paradigm in these patients with the data supporting an attached survival advantage. Further surgery and re-irradiation is an option in the disease recurrence setting with radiosurgery frequently utilised in this context. Crown Copyright (c) 2024 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Our brain adeptly navigates goals across time frames, distinguishing between urgent needs and those of the past or future. The hippocampus is a region known for supporting mental time travel and organizing information along its longitudinal axis, transitioning from detailed posterior representations to generalized anterior ones. This study investigates the role of the hippocampus in distinguishing goals over time: whether the hippocampus encodes time regardless of detail or abstraction, and whether the hippocampus preferentially activates its anterior region for temporally distant goals (past and future) and its posterior region for immediate goals. We use a space-themed experiment with 7T functional MRI on 31 participants to examine how the hippocampus encodes the temporal distance of goals. During a simulated Mars mission, we find that the hippocampus tracks goals solely by temporal proximity. We show that past and future goals activate the left anterior hippocampus, while current goals engage the left posterior hippocampus. This suggests that the hippocampus maps goals using timestamps, extending its long axis system to include temporal goal organization. It is unclear how the brain prioritizes goals. Here, the authors show that the mental timestamps assigned to goals guide their dissociation along the anterior-posterior parts of the hippocampus, extending its long axis system to include temporal goal organization.

Major trauma is defined as ‘an injury or a combination of injuries that are life-threatening and could be life changing because it may result in long-term disability’. It accounts for around 22,000 admissions per year across the UK. Since 2012, the UK trauma system has been delivered using a hub and spoke ‘network’ of regional major trauma centres, with surrounding trauma units. This has enabled access to timely, coordinated and highly specialist trauma care, resulting in significantly reduced mortality rates. Trauma remains the leading cause of death in children and young adults in the UK; however, in recent years there has been recognition of an increasing incidence in major trauma in older people. The combination of severe, multisystem injury and a background of co-morbidity and frailty adds an extra dimension to the coordination and management of trauma care in this complex population. The changing demographics of major trauma have meant there is a growing recognition that physicians should be aware of trauma management as patients may end up under their care, and should also take an active role in the continuing care of major trauma patients from admission to definitive care through to rehabilitation and discharge. This has led to the development of physicians in trauma care, usually in the form of ‘major trauma geriatrics’ to help facilitate this and work alongside colleagues in surgery, anaesthetics and specialist rehabilitation to optimize the outcomes for these complex patients.

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

Breast cancer remains the most prevalent cancer worldwide, necessitating advancements in its management. Surgery remains the recommended primary treatment although neoadjuvant or adjuvant treatments, such as chemotherapy, may also be indicated. However, such medications confer a risk of toxicity, often resulting in dose reductions and hospitalisations. This morbidity is particularly pertinent within older patients, for whom their experience of breast cancer is already faced through the lens of unique challenges often including comorbidity, socioeconomic decline and limited support networks. Quality of life (QoL) assessments acknowledge the impact of diagnosis and treatment on patients' psychological, emotional and physical well-being. Multiple tools exist (each with their own strengths and weaknesses) ranging from the more comprehensive [such as the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)] to the more broadly focused [including the General Functional Assessment of Cancer Therapy (FACT-G)]. However, while such tools have existed for some time, there remains a gap in clinical guidance as to their integration, particularly within older patient cohorts. This article seeks to address these complexities in breast cancer decision-making by exploring how QoL assessment can best be utilised inform efficacy-tolerability trade-offs, and subsequently facilitate optimal patient-centred care.

The worldwide population is ageing, alongside an increase in cancer incidence rates. Over the past 10 years, there has been huge progress in the field of oncology with earlier diagnosis and an expansion of treatment options, leading to a growing number of older people living with cancer. That has meant that caring for older patients with cancer is now part of day-to-day oncology practices. This cohort often has geriatric syndromes and a higher prevalence of frailty and complex needs and preparing our clinical services to optimise care for these patients is essential. Whilst it is widely accepted that comprehensive geriatric assessments are of benefit to patients, only a small proportion of patients can access these through specialised teams during their cancer care. In the past few years there has been significant progress in this field throughout the United Kingdom (UK). The goal of this review is to inform other health care systems how to learn from what has been done in the UK. This paper provides an update from our previous review in 2020, detailing the new services being implemented and made available to patients and an expansion in the number of new pilot teams and research projects/trials throughout the four nations of the UK.

Abstract Background Frailty is associated with adverse in-hospital outcomes after major trauma in older people, but the association with longer term survival and recovery is unclear. We aimed to investigate post discharge survival and health-related quality of life (HRQoL) in older patients at six months after major trauma centre (MTC) admission. Methods This was a multi-centre study of patients aged ≥65 years admitted to five MTCs. Data were collected via questionnaire at hospital discharge and six months later. The primary outcome was patient-reported HRQoL at follow up using Euroqol EQ5D-5L visual analogue scale (VAS). Secondary outcomes included health status according to EQ5D dimensions and care requirements at follow up. Multivariable linear regression analysis was conducted to evaluate the association between predictor variables and EQ-5D-5L VAS at follow up. Results Fifty-four patients died in the follow up period, of which two-third (64%) had been categorised as frail pre-injury, compared to 21 (16%) of the 133 survivors. There was no difference in self-reported HRQoL between frail and not-frail patients at discharge (Mean EQ-VAS: Frail 55.8 vs. Not-frail 64.1, p=0.137) however at follow-up HRQoL had improved for the not-frail group but deteriorated for frail patients (Mean EQ-VAS: Frail: 50.0 vs. Not-frail: 65.8, p=0.009). There was a two-fold increase in poor quality of life at six months (VAS ≤50) for frail patients (Frail: 65% vs. Not-frail: 30% p<0.009). Frailty (β-13.741 [95% CI -25.377, 2.105], p=0.02), increased age (β -1.064 [95% CI [-1.705, -0.423] p=0.00) and non-home discharge (β -12.017 [95% CI [118.403, 207.203], p=0.04) were associated with worse HRQoL at follow up. Requirements for professional carers increased five-fold in frail patients at follow-up (Frail: 25% vs. Not-frail: 4%, p=0.01). Conclusions Frailty is associated with increased mortality post trauma discharge and frail older trauma survivors had worse HRQoL and increased care needs at six months post-discharge. For older trauma patients frailty is a predictor of poor longer-term HRQoL after injury should enable early specialist review and discharge planning.

The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.

Cognitive dysfunction in aging is a major biomedical challenge. Whether treatment with klotho, a longevity factor, could enhance cognition in human-relevant models such as in nonhuman primates is unknown and represents a major knowledge gap in the path to therapeutics. We validated the rhesus form of the klotho protein in mice showing it increased synaptic plasticity and cognition. We then found that a single administration of low-dose, but not high-dose, klotho enhanced memory in aged nonhuman primates. Systemic low-dose klotho treatment may prove therapeutic in aging humans.