The AUstralian multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention study (AU-ARROW): A study protocol for a single-blind, multi-site, randomized controlled trial.

INTRODUCTION: The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER. METHOD: AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55-79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a global composite cognitive score. Extra value will emanate from blood biomarker analysis, positron emission tomography (PET) imaging, brain magnetic resonance imaging (MRI), and retinal biomarker tests. DISCUSSION: The finalized AU-ARROW protocol is expected to allow development of an evidence-based innovative treatment plan to reduce cognitive decline and dementia risk, and effective transfer of research outcomes into Australian health policy. Highlights: Study protocol for a single-blind, randomized controlled trial, the AU-ARROW Study.The AU-ARROW Study is a member of the World-Wide FINGERS (WW-FINGERS) initiative.AU-ARROW's primary outcome measure is change in a global composite cognitive score.Extra significance from amyloid PET imaging, brain MRI, and retinal biomarker tests.Leading to development of an innovative treatment plan to reduce cognitive decline.

Implementation of a nurse-led, multidisciplinary model of care for older adults with cancer: a process evaluation protocol.

INTRODUCTION: Cancer is predominantly a disease of older adults, with an increasing number of cancer diagnoses in individuals aged 65 or older. Multiple geriatric factors have been shown to impact patient outcomes in cancer treatment. However, oncology specialists are not well adapted to incorporate geriatric assessment into practice due to a lack of resources and knowledge of the specialty.The primary aim of this study is to implement and evaluate a nurse-led, multidisciplinary model of care for older adults with cancer at two public tertiary hospitals in Melbourne, Australia. METHODS AND ANALYSIS: This study will aim to assess 200 patients across 2 sites. Both sites will assess individuals with lung cancer; the second site will also include individuals with genitourinary, upper gastrointestinal and colorectal cancers.This process evaluation will use quantitative and qualitative methods to explore the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) of the nurse-led, multidisciplinary model of care. ETHICS AND DISSEMINATION: Ethical approval and local governance approvals have been obtained by Austin Health and Monash Health Human Research Ethics committees. Dissemination will occur via publications, conferences, social medical and local engagement with clinicians, consumers and managers.

Examining emergency departments practices on advance care directives and medical treatment decision making using the victorian emergency minimum dataset.

INTRODUCTION: Existence of Advance Care Planning (ACP) documents including contact details of Medical Treatment Decision Makers (MTDM), are essential patient care records that support Emergency Department (ED) clinicians in implementing treatment concordant with patients' expressed wishes. Based upon previous findings, we conducted a statewide study to evaluate the performance of Victorian public hospital emergency departments on reporting of availability of records for ACP. METHOD: The study is a quantitative retrospective observational comparative design based upon ED tier levels as defined by the Australasian College for Emergency Medicine (ACEM) for the calendar year 2021. RESULTS: Of 1.8 million total Victorian ED attendances, 15,222 patients had an ACP alert status recorded. Of these, 7296 were aged ≥ 65 years (study group). Of the thirty-one public EDs that submitted data, 65 % were accredited and assigned a level of service tier. The presence of ACP alerts positively correlated to location, tier level, age and gender (MANOVA wilk's; p < 0.001, value=.981, F = (12, 15,300), partial ƞ2 = .006, observed power = 1.0 = 95.919). CONCLUSION: The identified rate of ACP reporting is low. Strategies to improve the result include synchronising ACP (generated at different points) electronically, staff education, training and further validation of the data at the sending and receiving agencies.

Vulnerability to environmental and climatic health provocations among women and men hospitalized with chronic heart disease: insights from the RESILIENCE TRIAL cohort.

AIMS: We aimed to recruit a representative cohort of women and men with multi-morbid chronic heart disease as part of a trial testing an innovative, nurse-co-ordinated, multi-faceted intervention to lower rehospitalization and death by addressing areas of vulnerability to external challenges to their health. METHODS AND RESULTS: The prospective, randomized open, blinded end-point RESILIENCE Trial recruited 203 hospital inpatients (mean age 75.7 ± 10.2 years) of whom 51% were women and 94% had combined coronary artery disease, heart failure, and/or atrial fibrillation. Levels of concurrent multi-morbidity were high (mean Charlson Index of Comorbidity Score 6.5 ± 2.7), and 8.9% had at least mild frailty according to the Rockwood Clinical Frailty Scale. Including the index admission, 19-20% of women and men had a pre-existing pattern of seasonally linked hospitalization (seasonality). Detailed phenotyping revealed that 48% of women and 40% of men had ≥3 physiological factors, and 15% of women and 16% of men had ≥3 behavioural factors likely to increase their vulnerability to external provocations to their health. Overall, 61-62% of women and men had ≥4 combined factors indicative of such vulnerability. Additional factors such as reliance on the public health system (63 vs. 49%), lower education (30 vs. 14%), and living alone (48 vs. 29%) were more prevalent in women. CONCLUSION: We successfully recruited women and men with multi-morbid chronic heart disease and bio-behavioural indicators of vulnerability to external provocations to their health. Once completed, the RESILIENCE TRIAL will provide important insights on the impact of addressing such vulnerability (promoting resilience) on subsequent health outcomes. REGISTRATION: ClinicalTrials.org: NCT04614428.

Adult Mental Health Presentations to Emergency Departments in Victoria, Australia between January 2018 and October 2020: Changes Associated with COVID-19 Pandemic Public Health Restrictions.

The COVID-19 pandemic and associated public health measures altered patterns of help-seeking for mental health, with increases in emergency department utilisation reported. We examined the association between COVID-19 restrictions and adult emergency department (ED) mental health presentations in Victoria, Australia, through secondary analysis of data from 39 public EDs across the state. Participants were all patients (18+ years) presenting between 1 January 2018 and 31 October 2020 with mental health or intentional self-harm. The main outcome was number of presentations for each mental health condition, by patient age, socioeconomic status (SES), location, and ED triage category. We used a Poisson regression model to compare predicted monthly ED presentations based on trends from 2018, 2019 and 2020 (up to 31 March), with observed presentations during the initial months of the COVID-19 pandemic (1 April to 31 October 2020). There was an average of 4,967 adult mental health presentations per month pre-COVID-19 (1 January-31 March 2020) and 5,054 per month during the COVID-19 period (1 April-31 October 2020). Compared to predicted incidence, eating disorder presentations increased 24.0% in the COVID-19 period, primarily among higher SES females aged 18-24 years. Developmental/behavioural disorder presentations decreased by 19.7% for all age groups. Pandemic restrictions were associated with overall increases in monthly adult ED presentations for mental health, with some disorders increasing and others decreasing. Accessibility of acute mental health services needs to be addressed to meet changing demand and ensure services are responsive to changes in presentations resulting from future public health challenges.

Facing uncertainty - Pilot testing of a palliative prognostic index training with hospital aged care assessment teams.

BACKGROUND: Prognostic avoidance can delay discussions about older hospital patients' life expectancy. This pilot study examined the effects of a prognostic training program on hospital clinicians' knowledge and confidence in identifying older patients at risk of dying. METHODS: Fifty-seven clinicians from aged care assessment teams at two Australian hospitals were introduced to the Palliative Prognostic Index, a 5-item checklist indicating prognoses between 3 and 6 weeks. Mixed-methods training evaluation included pre-post-training surveys and semi-structured interviews, conducted three months post-training. RESULTS: Clinicians used a combination of experience, knowledge, and intuition as strategies to generate prognoses. Allied health staff relied on intuition more often than medical and nursing staff. Prognostic tools were rarely used. Pre-post-training comparisons showed significant improvements in clinicians' knowledge and confidence in identifying signs of dying, particularly amongst allied health. Follow-up interviews highlighted advantages and challenges of using prognostic tools. Recommendations are made for addressing these.

IMpleMenting Effective infection prevention and control in ReSidential aged carE (IMMERSE): protocol for a multi-level mixed methods implementation study.

BACKGROUND: Older people living in residential aged care facilities are at high risk of acquiring infections such as influenza, gastroenteritis, and more recently COVID-19. These infections are a major cause of morbidity and mortality among this cohort. Quality infection prevention and control practice in residential aged care is therefore imperative. Although appointment of a dedicated infection prevention and control (IPC) lead in every Australian residential aged care facility is now mandated, all people working in this setting have a role to play in IPC. The COVID-19 pandemic revealed inadequacies in IPC in this sector and highlighted the need for interventions to improve implementation of best practice. METHODS: Using mixed methods, this four-phase implementation study will use theory-informed approaches to: (1) assess residential aged care facilities' readiness for IPC practice change, (2) explore current practice using scenario-based assessments, (3) investigate barriers to best practice IPC, and (4) determine and evaluate feasible and locally tailored solutions to overcome the identified barriers. IPC leads will be upskilled and supported to operationalise the selected solutions. Staff working in residential aged care facilities, residents and their families will be recruited for participation in surveys and semi-structured interviews. Data will be analysed and triangulated at each phase, with findings informing the subsequent phases. Stakeholder groups at each facility and the IMMERSE project's Reference Group will contribute to the interpretation of findings at each phase of the project. DISCUSSION: This multi-site study will comprehensively explore infection prevention and control practices in residential aged care. It will inform and support locally appropriate evidence-based strategies for enhancing infection prevention and control practice.

Site of care and factors associated with mortality in unvaccinated Australian aged care residents during COVID-19 outbreaks.

BACKGROUND: Residential InReach presents an alternative to hospital admission for aged care residents swabbed for coronavirus disease 2019 (COVID-19), although relative outcomes remain unknown. AIMS: To compare rates and predictors of 28-day mortality for aged care residents seen by InReach with COVID-19, or 'suspected COVID-19' (sCOVID), including hospital versus InReach-based care. METHODS: Prospective observational study of consecutive patients referred to a Victorian InReach service meeting COVID-19 testing criteria between April and October 2020 (prevaccine availability). COVID-19 was determined by positive polymerase chain reaction testing on nasopharyngeal swab. sCOVID-19 was defined as meeting symptomatic Victorian Government testing criteria but persistently swab negative. RESULTS: There were no significant differences in age, sex, Clinical Frailty Score (CFS) or Charlson Comorbidity Index (CCI) between 152 patients with COVID-19 and 118 patients with sCOVID. Similar results were found for 28-day mortality between patients with COVID-19 (35/152, 23%) and sCOVID (32/118, 27%) (P = 0.4). For the combined cohort, 28-day mortality was associated with initial oxygen saturation (P < 0.001), delirium (P < 0.001), hospital transfer for acuity (P = 0.02; but not public health/facility reasons), CFS (P = 0.04), prior ischaemic heart disease (P = 0.01) and dementia (P = 0.02). For patients with COVID-19, 28-day mortality was associated with initial oxygen saturation (P = 0.02), delirium (P < 0.001) and hospital transfer for acuity (P = 0.01), but not public health/facility reasons. CONCLUSION: Unvaccinated aged care residents meeting COVID-19 testing criteria seen by InReach during a pandemic experience high mortality rates, including with negative swab result. Residents remaining within-facility (with InReach) experienced similar adjusted mortality odds to residents transferred to hospital for public health/facility-based reasons, and lower than those transferred for clinical acuity.

Healthcare providers' experiences with advance care planning and goals of patient care medical treatment orders in residential aged care facilities: an explanatory descriptive study.

BACKGROUND: Advance care planning (ACP) is a process by which people communicate their healthcare preferences and values, planning for a time when they are unable to voice them. Within residential aged care facilities (RACF), both the completion and the clarity of ACP documents are varied and, internationally, medical treatment orders have been used to address these issues. AIMS: In this study, goals of patient care (GOPC) medical treatment orders were introduced alongside usual ACP in three RACF to improve healthcare decision-making for residents. This study explored the experiences of RACF healthcare providers with ACP and GOPC medical treatment orders. METHODS: The study used an explanatory descriptive approach. Within three RACF where the GOPC medical treatment orders had been introduced, focus groups and interviews with healthcare providers were performed. The transcribed interviews were analysed thematically. RESULTS: Healthcare providers not only reported support for ACP and GOPC but also discussed many problematic issues. Analysis of the data identified four main themes: enablers, barriers, resident autonomy and advance documentation (ACP and GOPC). CONCLUSION: Healthcare providers identified ACP and GOPC as positive tools for assisting with medical decision-making for residents. Although barriers exist in completion and activation of plans, healthcare providers described them as progressing resident-centred care. Willingness to follow ACP instructions was reported to be reduced by lack of trust by clinicians. Families were also reported to change their views from those documented in family-completed ACP, attributed to poor understanding of their purpose. Participants reported that GOPC led to clearer documentation of residents' medical treatment plans rather than relying on ACP documents alone.

COVID-19 pandemic: end-of-life experience in Australian residential aged care facilities.

BACKGROUND: The COVID-19 pandemic has significantly impacted those in residential aged care facilities (RACF). This research was undertaken to explore and better understand the effects of the pandemic on the experience of next-of-kin and carers who encountered the death of a loved one who resided within a RACF during the pandemic. AIMS: To explore end-of-life experiences for residents who die in RACF and their next-of-kin/carers during the COVID-19 pandemic, to identify areas of concern and areas for improvement. METHODS: Prospective single-centre mixed methods research was undertaken involving telephone interview with next-of-kin or carers of residents who died within 30 days of being referred to Austin Health Residential InReach Service during the 'second wave' of COVID-19 in Melbourne, Australia, in 2020. Qualitative and quantitative data were collected. Qualitative description and aspects of grounded theory were used for analysing qualitative data. Thematic analysis of the interview transcripts used open and axial coding to identify initial themes and then to group these under major themes. RESULTS: Forty-one telephone interviews were analysed. Major themes identified included: COVID-19 pandemic, communication and technology, death and dying experience, bereavement and grief, and social supports and external systems. CONCLUSIONS: Findings identify the many COVID-19 pandemic-related challenges faced by participants and their dying loved one in RACF. Access to palliative care and bereavement support is crucial for dying residents and for grieving that has been made more difficult by the pandemic.

Synthetic microbleeds generation for classifier training without ground truth.

BACKGROUND AND OBJECTIVE: Cerebral microbleeds (CMB) are important biomarkers of cerebrovascular diseases and cognitive dysfunctions. Susceptibility weighted imaging (SWI) is a common MRI sequence where CMB appear as small hypointense blobs. The prevalence of CMB in the population and in each scan is low, resulting in tedious and time-consuming visual assessment. Automated detection methods would be of value but are challenged by the CMB low prevalence, the presence of mimics such as blood vessels, and the difficulty to obtain sufficient ground truth for training and testing. In this paper, synthetic CMB (sCMB) generation using an analytical model is proposed for training and testing machine learning methods. The main aim is creating perfect synthetic ground truth as similar as reals, in high number, with a high diversity of shape, volume, intensity, and location to improve training of supervised methods. METHOD: sCMB were modelled with a random Gaussian shape and added to healthy brain locations. We compared training on our synthetic data to standard augmentation techniques. We performed a validation experiment using sCMB and report result for whole brain detection using a 10-fold cross validation design with an ensemble of 10 neural networks. RESULTS: Performance was close to state of the art (~9 false positives per scan), when random forest was trained on synthetic only and tested on real lesion. Other experiments showed that top detection performance could be achieved when training on synthetic CMB only. Our dataset is made available, including a version with 37,000 synthetic lesions, that could be used for benchmarking and training. CONCLUSION: Our proposed synthetic microbleeds model is a powerful data augmentation approach for CMB classification with and should be considered for training automated lesion detection system from MRI SWI.

Generative Model of Brain Microbleeds for MRI Detection of Vascular Marker of Neurodegenerative Diseases.

Cerebral microbleeds (CMB) are increasingly present with aging and can reveal vascular pathologies associated with neurodegeneration. Deep learning-based classifiers can detect and quantify CMB from MRI, such as susceptibility imaging, but are challenging to train because of the limited availability of ground truth and many confounding imaging features, such as vessels or infarcts. In this study, we present a novel generative adversarial network (GAN) that has been trained to generate three-dimensional lesions, conditioned by volume and location. This allows one to investigate CMB characteristics and create large training datasets for deep learning-based detectors. We demonstrate the benefit of this approach by achieving state-of-the-art CMB detection of real CMB using a convolutional neural network classifier trained on synthetic CMB. Moreover, we showed that our proposed 3D lesion GAN model can be applied on unseen dataset, with different MRI parameters and diseases, to generate synthetic lesions with high diversity and without needing laboriously marked ground truth.

Integration of Inpatient and Residential Care In-Reach Service Model and Hospital Resource Utilization: A Retrospective Audit.

OBJECTIVE: In parts of Australia, Residential In-Reach (RIR) services have been implemented to treat residential aged care (RAC) residents for acute conditions in their place of residence to avoid preventable hospital presentation. Our service was initiated in 2009 and restructured in 2014. We compared acute healthcare resource utilization (RIR activity and emergency hospital presentations) by RAC residents under 2 RIR models of care. DESIGN: Acute RAC RIR service model of care was changed from existing nurse/emergency physician-led service to nurse/geriatrician-led service and incorporate inpatient liaison nurse consultant into the team. SETTING: RAC episodes and hospital presentations from a single tertiary referral hospital and its associated RAC RIR service. METHODS: Retrospective audit comparing RIR activity, hospital presentations, and associated costs from 2 12-month periods, prior to and postimplementation. Data were expressed as a proportion of the total number of RAC beds in the hospital RIR catchment. RESULTS: After implementation of the new model of care, RIR episodes of care increased from 589 to 985 (15.3 vs 24.7 episodes/100 RAC beds, P < .001). Emergency department (ED) presentations fell from 1616 to 1478 (41.9 vs 37.2 presentations/100 RAC beds, P < .001). There were fewer unplanned ED presentations by RIR patients (2.4% vs 0.8%, = 0.03) and fewer 28-day ED re-presentations (16.8% vs 13.7%, P = .01) under the new model of care. ED cost [$AUD 30,830 vs $28,030/100 RAC beds ($USD 21,344 vs $19,407), P < .001] and inpatient admission costs [$145,607 vs $117,531/100 RAC beds ($USD 100,814 vs $81,380), P < .001] were each lower in the second period. CONCLUSIONS AND IMPLICATIONS: In the 12 months following implementation of the new model of care, an increase in RIR activity, and a decrease in ED presentations was observed. Further research is necessary to validate these retrospective findings and better evaluate clinical outcomes and consumer satisfaction of the service.

Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease.

Infection with novel SARS-CoV-2 carries significant morbidity and mortality in patients with pulmonary compromise, such as lung cancer, autoimmune disease, and pneumonia. For early stages of mild to moderate disease, care is entirely supportive.Antiviral drugs such as remdesivir may be of some benefit but are reserved for severe cases given limited availability and potential toxicity. Repurposing of safer, established medications that may have antiviral activity is a possible approach for treatment of earlier-stage disease. Tetracycline and its derivatives (e.g. doxycycline and minocycline) are nontraditional antibiotics with a well-established safety profile, potential efficacy against viral pathogens such as dengue fever and chikungunya, and may regulate pathways important in initial infection, replication, and systemic response to SARS-CoV-2. We present a series of four high-risk, symptomatic, COVID-19+ patients, with known pulmonary disease, treated with doxycycline with subsequent rapid clinical improvement. No safety issues were noted with use of doxycycline.Doxycycline is an attractive candidate as a repurposed drug in the treatment of COVID-19 infection, with an established safety profile, strong preclinical rationale, and compelling initial clinical experience described here.The reviews of this paper are available via the supplemental material section.

Myh11+ microvascular mural cells and derived mesenchymal stem cells promote retinal fibrosis.

Retinal diseases are frequently characterized by the accumulation of excessive scar tissue found throughout the neural retina. However, the pathophysiology of retinal fibrosis remains poorly understood, and the cell types that contribute to the fibrotic response are incompletely defined. Here, we show that myofibroblast differentiation of mural cells contributes directly to retinal fibrosis. Using lineage tracing technology, we demonstrate that after chemical ocular injury, Myh11+ mural cells detach from the retinal microvasculature and differentiate into myofibroblasts to form an epiretinal membrane. Inhibition of TGFßR attenuates Myh11+ retinal mural cell myofibroblast differentiation, and diminishes the subsequent formation of scar tissue on the surface of the retina. We demonstrate retinal fibrosis within a murine model of oxygen-induced retinopathy resulting from the intravitreal injection of adipose Myh11-derived mesenchymal stem cells, with ensuing myofibroblast differentiation. In this model, inhibiting TGFßR signaling does not significantly alter myofibroblast differentiation and collagen secretion within the retina. This work shows the complexity of retinal fibrosis, where scar formation is regulated both by TGFßR and non-TGFßR dependent processes involving mural cells and derived mesenchymal stem cells. It also offers a cautionary note on the potential deleterious, pro-fibrotic effects of exogenous MSCs once intravitreally injected into clinical patients.

Restricted Effect of Cerebral Microbleeds on Regional Magnetic Susceptibility.

BACKGROUND: Cortical iron accumulation has been reported as a pathological feature of Alzheimer's disease (AD). The cause of cortical iron elevation in AD is unknown but may be contributed by hemosiderin deposits in cerebral microbleeds that frequently occur in this disease. OBJECTIVE: To investigate the impact of cerebral microbleeds (which are more frequent in AD) on the magnetic susceptibility of the surrounding brain tissue. METHODS: 32 MRI scans from the Australian Imaging, Biomarker and Lifestyle (AIBL) study were found to have cerebral microbleeds by manual assessment of susceptibility weighted images. Quantitative susceptibility mapping (QSM; an MRI technique that is sensitive to iron) was used to estimate iron content in the tissue surrounding the microbleed in four concentric radii. Furthermore, the mirror regions on the contralateral hemisphere were also demarcated. A simulation analysis was conducted to investigate the effect of QSM imaging on cerebral microbleeds with varying sizes. RESULTS: 77 microbleeds were identified from the available scans. The immediate proximal region to the cerebral microbleeds had enhanced tissue susceptibility (∼0.02 PPM), but importantly, this did not extend beyond one voxel radius. This finding with in vivo data was also replicated in a simulation study. However, the presence of microbleeds could lead to over-estimation of tissue QSM in unsupervised quantification, therefore processing methods to avoid this artefact without the need for their manual identification are proposed. CONCLUSION: The local changes in susceptibility due to microbleeds outside the focal lesion are restricted to 1 voxel and may be explained by partial voluming artefacts caused by limited imaging resolution. The susceptibly change induced by the microbleed is a relatively small proportion of tissue and could not account for regional iron changes observed in AD cortex.

Pericyte Bridges in Homeostasis and Hyperglycemia.

Diabetic retinopathy is a potentially blinding eye disease that threatens the vision of one-ninth of patients with diabetes. Progression of the disease has long been attributed to an initial dropout of pericytes that enwrap the retinal microvasculature. Revealed through retinal vascular digests, a subsequent increase in basement membrane bridges was also observed. Using cell-specific markers, we demonstrate that pericytes rather than endothelial cells colocalize with these bridges. We show that the density of bridges transiently increases with elevation of Ang-2, PDGF-BB, and blood glucose; is rapidly reversed on a timescale of days; and is often associated with a pericyte cell body located off vessel. Cell-specific knockout of KLF4 in pericytes fully replicates this phenotype. In vivo imaging of limbal vessels demonstrates pericyte migration off vessel, with rapid pericyte filopodial-like process formation between adjacent vessels. Accounting for off-vessel and on-vessel pericytes, we observed no pericyte loss relative to nondiabetic control retina. These findings reveal the possibility that pericyte perturbations in location and process formation may play a role in the development of pathological vascular remodeling in diabetic retinopathy.

REAVER: A program for improved analysis of high-resolution vascular network images.

Alterations in vascular networks, including angiogenesis and capillary regression, play key roles in disease, wound healing, and development. The spatial structures of blood vessels can be captured through imaging, but effective characterization of network architecture requires both metrics for quantification and software to carry out the analysis in a high-throughput and unbiased fashion. We present Rapid Editable Analysis of Vessel Elements Routine (REAVER), an open-source tool that researchers can use to analyze high-resolution 2D fluorescent images of blood vessel networks, and assess its performance compared to alternative image analysis programs. Using a dataset of manually analyzed images from a variety of murine tissues as a ground-truth, REAVER exhibited high accuracy and precision for all vessel architecture metrics quantified, including vessel length density, vessel area fraction, mean vessel diameter, and branchpoint count, along with the highest pixel-by-pixel accuracy for the segmentation of the blood vessel network. In instances where REAVER's automated segmentation is inaccurate, we show that combining manual curation with automated analysis improves the accuracy of vessel architecture metrics. REAVER can be used to quantify differences in blood vessel architectures, making it useful in experiments designed to evaluate the effects of different external perturbations (eg, drugs or disease states).

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer's disease.

BACKGROUND: The Centiloid scale was developed to standardise the results of beta-amyloid (Aß) PET. We aimed to determine the Centiloid unit (CL) thresholds for CERAD sparse and moderate-density neuritic plaques, Alzheimer's disease neuropathologic change (ADNC) score of intermediate or high probability of Alzheimer's Disease (AD), final clinicopathological diagnosis of AD, and expert visual read of a positive Aß PET scan. METHODS: Aß PET results in CL for 49 subjects were compared with post-mortem findings, visual read, and final clinicopathological diagnosis. The Youden Index was used to determine the optimal CL thresholds from receiver operator characteristic (ROC) curves. RESULTS: A threshold of 20.1 CL (21.3 CL when corrected for time to death, AUC 0.97) yielded highest accuracy in detecting moderate or frequent plaque density while < 10 CL was optimal for excluding neuritic plaque. The threshold for ADNC intermediate or high likelihood AD was 49.4 CL (AUC 0.98). Those cases with a final clinicopathological diagnosis of AD yielded a median CL result of 87.7 (IQR ± 42.2) with 94% > 45 CL. Positive visual read agreed highly with results > 26 CL. CONCLUSIONS: Centiloid values < 10 accurately reflected the absence of any neuritic plaque and > 20 CL indicated the presence of at least moderate plaque density, but approximately 50 CL or more best confirmed both neuropathological and clinicopathological diagnosis of Alzheimer's disease.

Frailty, MRI, and FDG-PET Measures in an Australian Memory Clinic Cohort.

Given that the global population is aging, the number of age-related syndromes, such as frailty, is expected to rise in conjunction. Frailty is characterized by the loss of homeostatic reserve, rendering the individual vulnerable to poor health outcomes. Many biological mechanisms have been proposed to contribute to frailty. However, few studies have assessed the associations between frailty and brain diseases or neuroimaging biomarkers. Aims: The aims of this study were to measure the prevalence of frailty in a memory clinic and to examine associations between frailty and brain changes found on magnetic resonance imaging (MRI) and 18-F deoxyglucose (FDG) positron emission tomography (PET) in memory clinic attendees. Methods: A 54-items Frailty Index was retrospectively assessed for all clinic attendees from 2014. Frailty was defined as FI > 0.25. MR images were analyzed for stroke, cerebral small vessel disease [CSVD, including cerebral microbleeds (CMBs), cortical superficial siderosis (CSS), and white matter hyperintensity (WMH)], and neurodegenerative changes [MRI: mesial temporal atrophy (MTA), FDG-PET: regional hypometabolism], blind to clinical findings. Results: There were 209 clinic attendees in 2014, of whom 121 had MRI performed. The prevalence of frailty (using FI) in the memory clinic in 2014 was 38.3% overall (patients without MRI: 43.2%, patients with MRI 34.7%, p = 0.25). Frailty was associated with presence of deep WMH, increased severity of periventricular WMH, and presence of CSS, but not neurodegeneration markers (MTA atrophy/FDG-PET hypometabolism). Conclusion: The findings support the idea that previously reported associations between frailty and imaging evidence of CSVD in other cohorts are also relevant to the Australian clinic setting. Given that a large proportion of memory clinic attendees are frail, there may be opportunities for interventions to reduce preventable adverse health outcomes, such as falls and fractures, and reduce the prevalence and impact of frailty in this cohort.