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Dementia due to Parkinson's disease and Alzheimer's disease are associated with behavioural and psychological symptoms, including psychosis. Long-term management presents a challenge for health care providers and caregivers. Symptoms of psychosis include hallucinations and delusions; if untreated, these can lead to institutionalisation, decreased quality of life, and significant patient and caregiver distress. A critical step in the effective management of dementia-related psychosis (DRP) is the identification and diagnosis of affected patients. The lack of a standardised diagnostic approach presents a barrier to treatment and there are no consensus guidelines for DRP. Furthermore, there are no approved therapies for the treatment of DRP. Antipsychotic medications are often prescribed off-label, even though some are associated with an increased risk of adverse events or mortality. We present currently available screening tools and guidelines for the diagnosis and treatment of Parkinson's disease psychosis and DRP in the context of what is needed for effective management of psychosis.KEY POINTSWe present currently available screening tools and guidelines for Parkinson's disease psychosis and dementia-related psychosis, and discuss the unmet need for simple clinical diagnostic tools and treatment guidelines.The identification of psychosis is variable across different settings and specialties, without a unified approach to screening, definition, or diagnosis.Currently used tools for defining and assessing psychosis in a research setting are usually too cumbersome for everyday clinical practice.The development of a standardised set of diagnostic criteria would provide clinicians the opportunity to improve the detection, treatment, and quality of life of patients and their caregivers.

We hypothesized that Lomecel-B, an allogeneic medicinal signaling cell (MSC) therapeutic candidate for Alzheimer's disease (AD), is safe and potentially disease-modifying via pleiotropic mechanisms of action.We prospectively tested the predictions that Lomecel-B administration to mild AD patients is safe (primary endpoint) and would provide multiple exploratory indications of potential efficacy in clinical and biomarker domains (prespecified secondary/exploratory endpoints).Mild AD patient received a single infusion of low- or high-dose Lomecel-B, or placebo, in a double-blind, randomized, phase I trial. The primary safety endpoint was met. Fluid-based and imaging biomarkers indicated significant improvement in the Lomecel-B arms versus placebo. The low-dose Lomecel-B arm showed significant improvements versus placebo on neurocognitive and other assessments.Our results support the safety of Lomecel-B for AD, suggest clinical potential, and provide mechanistic insights. This early-stage study provides important exploratory information for larger efficacy-powered clinical trials.

Pattern recognition methodology was developed for the automated detection of marine oil spills in passive infrared multispectral remote sensing images. The images employed in this work were collected from the Deepwater Horizon oil spill accident in 2010. The imaging instrument for data collection was a downward-looking infrared line scanner equipped with eight optical bandpass filters in the spectral range of 8-12 μm on a fixed-wing aircraft. Oil slicks may show either positive or negative thermal contrast against the surrounding sea water, depending on the sun glint conditions or the oil thickness. Classifiers were developed separately to detect oil with different contrasts by the application of backpropagation neural networks to the preprocessed radiances. Preprocessing strategies included: (1) assembly of training data through

Several orthogonal signal correction (OSC) methods coupled with partial least-squares (PLS) were applied to near-infrared spectra in a longitudinal study for the prediction of glucose, urea, and tr...

At the end of the activity, participants will be able to:Implement evidence-based methods for cognitive impairment screening in primary care. Identify correct diagnostic criteria for mild cognitive impairment (MCI) and Alzheimer disease (AD) based on current guideline recommendations. Design appropriate and effective treatment plans for patients with MCI and AD and refer to a specialist when necessary. Describe advances in testing and treatment for AD that may impact dementia care.

The critical role of primary care clinicians (PCCs) in Alzheimer's disease (AD) prevention, diagnosis and management must evolve as new treatment paradigms and disease-modifying therapies (DMTs) emerge. Our understanding of AD has grown substantially: no longer conceptualized as a late-in-life syndrome of cognitive and functional impairments, we now recognize that AD pathology builds silently for decades before cognitive impairment is detectable. Clinically, AD first manifests subtly as mild cognitive impairment (MCI) due to AD before progressing to dementia. Emerging optimism for improved outcomes in AD stems from a focus on preventive interventions in midlife and timely, biomarker-confirmed diagnosis at early signs of cognitive deficits (i.e. MCI due to AD and mild AD dementia). A timely AD diagnosis is particularly important for optimizing patient care and enabling the appropriate use of anticipated DMTs. An accelerating challenge for PCCs and AD specialists will be to respond to innovations in diagnostics and therapy for AD in a system that is not currently well positioned to do so. To overcome these challenges, PCCs and AD specialists must collaborate closely to navigate and optimize dynamically evolving AD care in the face of new opportunities. In the spirit of this collaboration, we summarize here some prominent and influential models that inform our current understanding of AD. We also advocate for timely and accurate (i.e. biomarker-defined) diagnosis of early AD. In doing so, we consider evolving issues related to prevention, detecting emerging cognitive impairment and the role of biomarkers in the clinic.

Objective: To study whether memory control beliefs predict response to memory training, or change as a result of participating in memory training. Methods: Eighty community based participants with ...

Background: Alzheimer’s disease (AD) is increasingly prevalent and over 99% of drugs developed for AD have failed in clinical trials. A growing body of literature suggests that potent inhibitors of tumor necrosis factor-α (TNF-α) have potential to improve cognitive performance. Objective: In this review, we summarize the evidence regarding the potential for TNF-α inhibition to prevent AD and improve cognitive function in people at risk for dementia. Methods: We conducted a literature review in PubMed, screening all articles published before July 7, 2019 related to TNF blocking agents and curcumin (another TNF-α inhibitor) in the context of AD pathology. The keywords in the search included: AD, dementia, memory, cognition, TNF-α, TNF inhibitors, etanercept, infliximab, adalimumab, golimumab, and curcumin. Results: Three large epidemiology studies reported etanercept treated patients had 60 to 70% lower odds ratio (OR) of developing AD. Two small-randomized control trials (RCTs) demonstrated an improvement in cognitive performance for AD patients treated with etanercept. Studies using animal models of dementia also reported similar findings with TNF blocking agents (etanercept, infliximab, adalimumab, Theracurmin), which appeared to improve cognition. A small human RCT using Theracurmin, a well-absorbed form of curcumin that lowers TNF-α, showed enhanced cognitive performance and decreased brain levels of amyloid-β plaque and tau tangles. Conclusion: TNF-α targeted therapy is a biologically plausible approach to the preservation of cognition, and warrants larger prospective RCTs to further investigate potential benefits in populations at risk of developing AD.

Cardiac rehabilitation programs across Canada have suspended in-person services as a result of large-scale physical distancing recommendations designed to flatten the COVID-19 pandemic curve. Virtual cardiac rehabilitation (VCR) offers an alternate mechanism of care delivery, capable of providing similar patient outcomes and safety profiles compared to centre-based programs. In order to minimize care gaps, all centres should consider developing and implementing a VCR program. The process of this rapid implementation however can be daunting. Centres should initially focus on the collation, utilization and re-purposing of existing resources, equipment, and technology. Once established, programs should then focus on ensuring that quality indicators are met and care processes are protocolized. This should be followed by the development of sustainable VCR solutions to account for care gaps that existed prior to COVID-19, and to improve cardiac rehabilitation delivery moving forward. This article reviews the potential challenges and obstacles of this process and aims to provide pragmatic guidance to aid clinicians and administrators during this challenging time., Virtual cardiac rehabilitation offers an alternate mechanism of care delivery to ensure cardiovascular patients receive this guideline-based therapy during the COVID-19 pandemic. The challenges and obstacles associated with implementation of virtual cardiac rehabilitation program are reviewed and pragmatic guidance to aid clinicians and administrators is provided.

The COVID-19 pandemic has raised ethical questions for the cardiovascular leader and practitioner. Attention has been redirected from a system that focuses on individual patient benefit towards one that focuses on protecting society as a whole. Challenging resource allocation questions highlight the need for a clearly articulated ethics framework that integrates principled decision making into how different cardiovascular care services are prioritized. A practical application of the principles of minimizing harm, fairness, proportionality, respect, reciprocity, flexibility and procedural justice is provided, and a model for prioritization of the restoration of cardiovascular services is outlined. The prioritization model may be used to determine how and when cardiovascular services should be continued or restored. There should be a focus on an iterative and responsive approach to broader healthcare system needs, such as other disease groups and local outbreaks., for online listing: This paper provides an overview and application of relevant ethical principles in resource allocation decisions during the COVID-19 pandemic. A model for prioritization of cardiovascular services restoration is outlined. The model provides guidance on how and when cardiovascular services should be continued or restored, in an iterative and responsive fashion with the perspective of broader healthcare system needs.

Pattern recognition methodology was developed for the automated detection of methanol vapour plumes from passive multispectral infrared remote sensing data. The data employed in this work were coll...

Background While an assessment of the right ventricular (RV) size remains challenging, the entire RV is can be imaged on coronary computed tomography angiography (CCTA) studies. With prospective ECG-triggering, the RV end diastolic volume (RVEDV) cannot be measured; however, the RV mid-diastolic volume (RVMDV) can still be measured accurately from routine CCTA data sets. The objective of this study is to establish normal reference values for RVMDV. Methods Right ventricular mid-diastolic volumes were measured in 4855 consecutive patients undergoing prospectively ECG-triggered coronary CTA. All patients with known cardiac or pulmonary disease (coronary artery disease, myocardial infarction, revascularization, heart failure, pulmonary hypertension, congenital heart disease, valvular heart disease, atrial fibrillation, implantable cardiac defibrillator implantation, cardiac transplant, or cardiac surgery) or smoking history (3313 patients) were excluded. Results 1542 patients were analyzed (mean age 56.4 ± 11.1 years, mean BSA 1.96 ± 0.26 and 47% male). The mean RVMDV for men and women was 168.6 ± 37.6 mL and 117.6 ± 26.4 mL, respectively. Mean BSA-indexed RVMDV was 80.0 ± 15.3 mL/m2 and 64.1 ± 12.2 mL/m2 for men and women, respectively. The presence of hypertension and diabetes did not have an impact on these values. RVMDV and BSA-indexed RVMDV were lower in women and in older individuals. Conclusion Normal reference ranges for RVMDV were established using prospectively ECG-triggered coronary CTA studies. This data can be used to identify patients with abnormal RV volumes and potentially RV dysfunction, adding incremental diagnostic value to routine CCTA studies.

Purpose: The impact of cardiology fellows (CFs) and interventional cardiology fellows (ICFs) on patient radiation and contrast exposure during diagnostic coronary angiography and percutaneous coronary intervention is unknown. Methods: Between 2011 and 2014, 16,175 cases were retrospectively assessed involving 27 CFs, 22 ICFs and 24 staff as primary operators. Results: During diagnostic coronary angiography, ICFs administered the lowest radiation dose (5,648±5,523 cGy*cm2; 1.30 ± 1.27 mSv)—achieving 22% less radiation than the staff (6,889±4,294 cGy*cm2; 1.58 ± 0.99 mSv) and 36% less than CFs (7,700±6,751 cGy*cm2; 1.77 ± 1.55 mSv) (p

Concentration predictions from near-infrared spectra are used across a range of application areas. When aqueous samples are employed, the extreme temperature sensitivity of underlying water absorption bands can lead to significant errors in predicted analyte concentrations, even when efforts are made to control sample temperatures. To address this issue, a temperature-correction procedure was developed on the basis of modeling the systematic error that occurs in predicted concentrations as a function of variation in sample temperature. With this approach, a quantitative calibration model was developed for samples at a fixed temperature. This model was subsequently applied to the spectra of a second set of samples with known analyte concentrations collected under conditions of varying temperature. Using either measured temperatures or those estimated from a spectral temperature prediction model, a least-squares polynomial fit was performed between concentration residuals and temperature. Going forward, for a given sample temperature, the polynomial model was used to estimate the concentration residual at that temperature. The estimated residual was then used to correct the predicted concentration. For spectra collected in the 5000-4000 cm−1 near-infrared region, this methodology was tested for samples of glucose in buffer and mixture samples of glucose and lactate in buffer over the temperature range of 20.0–40.5 °C.

Objectives This study sought to: 1) determine if the current training volume guidelines are reasonable for attaining competence for interpreting myocardial perfusion imaging (MPI); and if not, 2) identify potential thresholds for training volumes and competence. Background There is a growing desire to adopt competency-based medical education (CBME). As such, the implementation of CBME will require new and novel methods of defining, measuring, and assessing clinical competence. The potential use of CBME in cardiac imaging has not been well studied. Methods Consecutive MPI studies were interpreted independently by trainees, and expert readers reviewed the same studies. Studies were quantified using summed scores and % left ventricular (LV) ischemia and the kappa agreement between trainee and expert were measured every 50 cases. Agreement for all MPI and abnormal MPI cases was calculated. Results A total of 24 trainees interpreted 9,668 MPI studies over 37 months. Agreement between trainees and expert readers increased with MPI case volumes but at different rates. The threshold for competence was set at 2 SDs below expert interobserver agreement. The average trainee surpassed this threshold for both summed stress score and %LV ischemia after 800 studies and after 400 abnormal MPI studies. Trainees learned at different rates and surpassed the competence threshold after different case volumes. Conclusions The use of CBME within nuclear cardiology appears to be feasible. Our results suggest that current guidelines may be insufficient to ensure competence and would support the need to increase the MPI case volumes. The use of CBME principles would suggest that trainees may achieve competence at different rates and our results suggest a shift in focus from volume-based learning toward target agreement thresholds.

Introduction Several case reports or small series have suggested a possible link between mRNA COVID vaccines and the subsequent development of myocarditis and pericarditis. This study is a prospective collection and review of all cases with a myocarditis/pericarditis diagnosis over a 2-month period at an academic medical center. Methods Prospective case series from 1st June 2021 until 31st July 2021. Patients were identified by admission and discharge diagnoses which included myocarditis or pericarditis. Inclusion criteria: in receipt of mRNA vaccine within one month prior to presentation; The CMR protocol included cine imaging, native T1 and T2 mapping, late gadolinium enhancement and post contrast T1 mapping. All CMR studies were read in consensus by two experienced readers. Diagnosis was based on clinical presentation, ECG/echo findings and serial troponins and was confirmed in each case by CMR. Incidence was estimated from total doses of mRNA vaccine administered in the Ottawa region for the matching time-period. This data was obtained from the Public Health Agency of Ottawa. Results 32 patients were identified over the period of interest. Eighteen patients were diagnosed with myocarditis; 12 with myopericarditis; and 2 with pericarditis alone. The median age was 33 years (18-65 years). The sex ratio was 2 females to 29 males. In 5 cases, symptoms developed after only a single dose of mRNA vaccine. In 27 patients, symptoms developed after their second dose of. Median time between vaccine dose and symptoms was 1.5 days (1-26 days). Chest pain was the commonest symptom, but many others were reported. Non-syncopal non-sustained ventricular tachycardia was seen in only a single case. Median LV ejection fraction (EF) was 57% (44-66%). Nine patients had an LVEF below the normal threshold of 55%. Incidence of myopericarditis overall was approximately 10 cases for every 10,000 inoculations. Summary and Conclusions This is the largest series in the literature to clearly relate the temporal relationship between mRNA COVID vaccination, symptoms and CMR findings. In most patients, symptom onset began within the first few days after vaccination with corresponding abnormalities in biomarkers and on ECG. Cardiac MRI confirmed acute myocardial and pericardial changes with the presence of edema demonstrated with both tissue mapping and late gadolinium enhancement. Symptoms settled quickly with standard therapy and patients were discharged within a few days. No major adverse cardiac events and no significant arrythmias were noted during inpatient stay. Further follow up will be required to ascertain the longer-term outcomes of this patient group.

OBJECTIVE: A rare variant in TREM2 (p.R47H, rs75932628) has been consistently reported to increase the risk for Alzheimer’s disease, while mixed evidence has been reported for association of the variant with other neurodegenerative diseases. Here, we investigated the frequency of the R47H variant in a diverse and well-characterized multicenter neurodegenerative disease cohort. METHODS: We examined the frequency of the R47H variant in a diverse neurodegenerative disease cohort, including a total of 3,058 patients clinically diagnosed with Alzheimer’s disease, frontotemporal dementia spectrum syndromes, mild cognitive impairment, progressive supranuclear palsy syndrome, corticobasal syndrome, or amyotrophic lateral sclerosis and 5,089 control subjects. RESULTS: We observed a significant association between the R47H variant and Alzheimer’s disease, while no association was observed with any other neurodegenerative disease included in this study. CONCLUSIONS: Our results support the consensus that the R47H variant is significantly associated with Alzheimer’s disease. However, we did not find evidence for association of the R47H variant with other neurodegenerative diseases.

Objectives:The goal of this study was to evaluate the ability of semantic (animal naming) and phonemic (FAS) fluency in their ability to discriminate between normal aging, amnestic-Mild Cognitive Impairment (a-MCI), and Alzheimer’s disease (AD).Design:We used binary logistic regressions, multinomial regressions, and discriminant analysis to evaluate the predictive value of semantic and phonemic fluency in regards to specific diagnostic classifications.Setting:Outpatient geriatric neuropsychology clinic.Participants:232 participants (normal aging = 99, a-MCI = 90, AD = 43; mean age = 65.75 years).Measurements:Mini-mental State Examination (MMSE), Controlled Oral Word Association TestResults:Results indicate that semantic and phonemic fluency were significant predictors of diagnostic classification, and semantic fluency explained a greater amount of the discriminant ability of the model.Conclusions:These results suggest that verbal fluency, particularly semantic fluency, may be an accurate and efficient tool in screening for early dementia in time-limited medical settings.

Wavelet analysis was evaluated as a data preprocessing tool in the construction of automated classifiers for the detection of volatile organic compounds from passive Fourier transform infrared remote sensing data collected in a downward-looking mode from an aircraft platform. The discrete wavelet transform was applied to single-beam spectra and patterns were formed with either the wavelet coefficients directly or with spectra reconstructed with selected resolution levels of the wavelet decomposition. Automated classifiers were constructed with support vector machines (SVM) and used to detect releases of methanol from an industrial site. A key issue in this work was the desire to use data collected during controlled experiments on the ground to train the SVM classifiers. Spectral backgrounds in these ground-collected data are different than those encountered as the aircraft flies, however, and the development of successful classification models requires spectral preprocessing to suppress background...

As the world's population ages and people live longer, the changes in the aging brain present substantial challenges to our health and society. With greater longevity come age-related diseases, many of which have direct and indirect influences on the health of the brain. Although there is some degree of predictable decline in brain functioning with aging, meaningful cognitive decline is not inevitable and is perhaps preventable. In this review, we present the case that the course of aging-related brain disease and dysfunction can be modified. We present the evidence for conditions and risk factors that may contribute to cognitive decline and dementia and for interventions that may mitigate their impact on cognitive functioning later in life, or even prevent them and their cognitive sequelae from developing. Although much work remains to be done to meet the challenges of the aging brain, strategies to promote its health have been demonstrated and offer much promise, which can only be realized if we mount a vigorous public health effort to implement these strategies.

An altitude-based background correction strategy was developed for use in the application of pattern recognition methods to the classification of gamma-ray spectra collected during airborne surveys. Application of this methodology helped to suppress the background spectral variation that serves to obscure the photopeaks associated with low levels of gamma-ray emission. The correction method was implemented by optimizing a database of background gamma-ray spectra collected at various locations and altitudes. Given this background database, a field-collected spectrum was corrected by performing linear regression onto a background spectrum from the database at a matching altitude. The residuals about the regression fit were then digitally filtered and submitted to nonparametric linear discriminant analysis for the purpose of computing classification models for targeted radioisotopes. The resulting classifiers were applied to predict the presence or absence of specific radioisotope signatures in data acquired during airborne surveys. Employing data provided by the U.S Environmental Protection Agency Airborne Spectral Photometric Environmental Collection Technology (ASPECT) program, classification models were computed to detect the presence of cesium-137 (137Cs) and cobalt-60 (60Co). The optimized classifiers were tested over 12 diverse locations, with nine of these data sets containing the target radioisotopes. Correct classification percentages of 99.4% and 99.8% were obtained for the 137Cs and 60Co classifiers, respectively, on the basis of comparisons to visual inspections of the corresponding spectra.

Objective While behavioral risk factors for depression have been assessed in select samples, previous research is limited in addressing such correlates across the lifespan. To this end, we assessed the relationship between self-reported depression and four behavioral risk factors (smoking, obesity, limited physical activity, and less healthy diet) in a representative United States adult sample. Methods Data were drawn from 30,116 Gallup-Healthways survey respondents, and stratified according to younger (18–39), middle-aged (40–59), and older (60–99) adults. The survey included demographic information, questions relating to the four risk factors, and an item on self-reported depression. Weighted multivariable logistic regressions, controlling for sex, ethnicity, and socioeconomic variables, were used to calculate odds ratios (OR) and confidence intervals (CI) for each correlate. Results Sixteen percent of respondents endorsed a prior diagnosis of depression; 17% smoked; 26% were obese; 50% engaged in limited physical activity; and 41% had a less healthy diet. Smoking was most strongly associated with risk for depression (OR: 2.71, 95% CI [2.41–3.04], 1.81 [1.62–2.02] and 1.82 [1.55–2.15] for younger, middle-aged and older age groups, respectively), followed by obesity (OR = 1.65 [1.45-1.86], 1.54 [1.39–1.71], 1.67 [1.46–1.90]), limited physical activity (OR = 1.32 [1.18–1.48], 1.48 [1.35–1.66], 1.61 [1.41–1.82]), and a less healthy diet (OR = 1.20 [1.08–1.32], 1.21 [1.06–1.37] for middle-aged and older groups). Depression rates increased with the number of risk factors. Conclusion Behavioral risk factors are associated with an increased risk for depression across the lifespan with some variability according to age groups.

A generalized methodology was developed for automating the detection of radioisotopes from gamma-ray spectra collected from an aircraft platform using sodium-iodide detectors. Employing data provided by the U.S Environmental Protection Agency Airborne Spectral Photometric Environmental Collection Technology (ASPECT) program, multivariate classification models based on nonparametric linear discriminant analysis were developed for application to spectra that were preprocessed through a combination of altitude-based scaling and digital filtering. Training sets of spectra for use in building classification models were assembled from a combination of background spectra collected in the field and synthesized spectra obtained by superimposing laboratory-collected spectra of target radioisotopes onto field backgrounds. This approach eliminated the need for field experimentation with radioactive sources for use in building classification models. Through a bi-Gaussian modeling procedure, the discriminant scores that served as the outputs from the classification models were related to associated confidence levels. This provided an easily interpreted result regarding the presence or absence of the signature of a specific radioisotope in each collected spectrum. Through the use of this approach, classifiers were built for cesium-137 ((137)Cs) and cobalt-60 ((60)Co), two radioisotopes that are of interest in airborne radiological monitoring applications. The optimized classifiers were tested with field data collected from a set of six geographically diverse sites, three of which contained either (137)Cs, (60)Co, or both. When the optimized classification models were applied, the overall percentages of correct classifications for spectra collected at these sites were 99.9 and 97.9 % for the (60)Co and (137)Cs classifiers, respectively.

Background and Aims: Legalization of cannabis (CB) for both medicinal and, in some states, recreational use, has given rise to increasing usage rates across the country. Of particular concern are indications that frequent CB use may be selectively harmful to the developing adolescent brain compared with adult-onset usage. However, the long-term effects of heavy, adolescent CB use on brain structure and cognitive performance in late-life remain unknown. A critical brain region is the hippocampus (HC), where there is a striking intersection between high concentrations of cannabinoid 1 (CB1) receptors and age-related pathology. Design: We investigated whether older adults (average age=66.6+7.2 years old) with a history of early life CB use show morphological differences in hippocampal subregions compared with older, nonusers. Methods: We performed high-resolution magnetic resonance imaging combined with computational techniques to assess cortical thickness of the medial temporal lobe, neuropsychological testing, and extensive drug use histories on 50 subjects (24 formerly heavy cannabis users [CB+ group] abstinent for an average of 28.7 years, 26 nonusers [CB− group]). We investigated group differences in hippocampal subregions, controlling for age, sex, and intelligence (as measured by the Wechsler Test of Adult Reading), years of education, and cigarette use. Results: The CB+ subjects exhibited thinner cortices in subfields cornu ammonis 1 [CA1; F(1,42)=9.96, p=0.0003], and CA2, 3, and the dentate gyrus [CA23DG; F(1,42)=23.17, p

Coronary revascularization in ischemic heart failure patients carries an increased risk of mortality and morbidity. The clinical concept of viability (and hence the role of viability imaging) is relevant when one considers dysfunctional myocardium which occurs after an ischemic injury. A myocardial viability study is targeted to patients who are at high risk for cardiac death or other cardiac events and where it is uncertain if they will benefit from revascularization. Different techniques such as SPECT, PET, STRESS-ECHO, and CMR can be used to assess myocardial viability. Several observational studies have suggested that the presence of viable myocardium can predict recovery in LV function and improved survival after revascularization. While PARR-2 do not demonstrate a significant outcome benefit for patients undergoing FDG PET, there was a trend, and post-hoc analyses showed outcome benefit when there was adherence to recommendations and at experienced centers with a team based approach. STICH viability did not show that viability predicted outcome benefit with revascularization raising questions and controversy about the role of viability imaging. Ongoing studies such as IMAGE-HF, evaluation of the role of neurohormonal imaging, the PAREPET study, and current application in chronic total occlusion are seeking to answer some of the questions that remain regarding the role of viability imaging in patient with IHD and HF.

Hospitals and ambulatory facilities significantly reduced cardiac care delivery in response to the first wave of the COVID-19 pandemic. The deferral of elective cardiovascular procedures led to a marked reduction in healthcare delivery with a significant impact on optimal cardiovascular care. International and Canadian data have reported dramatically increased wait-times for diagnostic tests and cardiovascular procedures, as well as associated increased cardiovascular morbidity and mortality. In the wake of the demonstrated ability to rapidly create critical care and hospital ward capacity, we advocate a different approach during the second and possible subsequent COVID-19 pandemic waves. We suggest an approach, informed by local data and experience, which balances the need for an expected rise in demand for healthcare resources to ensure appropriate COVID-19 surge capacity, with continued delivery of essential cardiovascular care. Incorporating cardiovascular care leaders into pandemic planning and operations will help healthcare systems minimize cardiac care delivery disruptions, while maintaining critical care and hospital ward surge capacity and continuing measures to reduce transmission risk in healthcare settings. Specific recommendations targeting the main pillars of cardiovascular care are presented: ambulatory, inpatient, procedural, diagnostic, surgical and rehabilitation., Cardiovascular care delivery was significantly reduced during the first wave of the COVID-19 pandemic, leading to reports of increased wait-times, with associated cardiovascular morbidity and mortality. Recommendations are presented advocating for a different approach in the second and subsequent waves of COVID-19 to balance surge capacity while preserving delivery of essential cardiovascular care.

Identify the burden experienced by patients with dementia-related delusions and hallucinations. Assess patients with dementia for the presence of delusions and hallucinations. Individualize treatment in patients with dementia-related delusions and hallucinations. Align treatment of patients with Parkinson's psychosis with current recommendations.

Objective:Because of inconsistent findings regarding the relationship between sleep quality and cognitive function in people with age-related memory complaints, we examined how self-reports of sleep quality were related to multiple domains of both objective and subjective cognitive function in middle-aged and older adults.Design:A cross-sectional study involving analysis of baseline data, collected as part of a clinical trial.Measurements:Two hundred and three participants (mean age = 60.4 [6.5] years, 69.0% female) with mild memory complaints were asked to rate their sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and their memory performance using the Memory Functioning Questionnaire (MFQ), which measures self-awareness of memory ability. Neurocognitive performance was evaluated using the Continuous Performance Test (CPT), Trail Making Test, Buschke Selective Reminding Test, and the Brief Visuospatial Test – Revised (BVMT-R).Results:Total PSQI scores were significantly associated with objective measures of sustained attention (CPT hit reaction time by block and standard error by block) and subjective memory loss (MFQ frequency and seriousness of forgetting). The PSQI components of (poorer) sleep quality and (greater) sleep disturbance were related to (worse) sustained attention scores while increased sleep latency and daytime sleepiness were associated with greater frequency and seriousness of forgetting.Conclusions:Sleep quality is related to both objective measures of sustained attention and self-awareness of memory decline. These findings suggest that interventions for improving sleep quality may contribute not only to improving the ability to focus on a particular task but also in reducing memory complaints in middle-aged and older adults.

Objective We sought to determine the prognostic value of coronary computed tomography angiography (CCTA) in patients with a history of percutaneous coronary intervention (PCI). Background Although the prognostic value of CCTA has been well studied, its incremental value in patients with previous PCI has not been robustly investigated. Methods Consecutive patients with previous PCI were prospectively enrolled and CCTA images were evaluated for coronary artery disease (CAD) severity. Patients were followed for major adverse cardiovascular events (MACE) which was a composite of cardiac death and non-fatal myocardial infarction. All-cause death was assessed as a secondary endpoint. Results A total of 501 patients were analyzed with a mean follow-up time of 59.5 ± 32.0 months and 52 patients (10.4%) experienced MACE. Multivariable Cox regression analysis showed that CAD severity was a predictor of MACE with 0, 1, 2, and 3 vessel disease having annual rates of 1.3%, 2.2%, 2.2%, and 5.3%, respectively. All-cause death was similar in all categories of CAD. Conclusions In patients with previous PCI, CAD severity as measured with CCTA has independent and incremental prognostic value.

Emerging scientific evidence indicates that frequent digital technology use has a significant impact-both negative and positive-on brain function and behavior. Potential harmful effects of extensive screen time and technology use include heightened attention-deficit symptoms, impaired emotional and social intelligence, technology addiction, social isolation, impaired brain development, and disrupted sleep. However, various apps, videogames, and other online tools may benefit brain health. Functional imaging scans show that internet-naive older adults who learn to search online show significant increases in brain neural activity during simulated internet searches. Certain computer programs and videogames may improve memory, multitasking skills, fluid intelligence, and other cognitive abilities. Some apps and digital tools offer mental health interventions providing self-management, monitoring, skills training, and other interventions that may improve mood and behavior. Additional research on the positive and negative brain health effects of technology is needed to elucidate mechanisms and underlying causal relationships. .La evidencia científica que está surgiendo muestra que el empleo frecuente de la tecnología digital tiene un impacto significativo, tanto negativo como positivo, en la función cerebral y en el comportamiento. Los posibles efectos nocivos del tiempo prolongado frente a la pantalla y del empleo de la tecnología incluyen síntomas como marcado déficit de atención, deterioro de la inteligencia emocional y social, adicción a la tecnología, aislamiento social, deterioro del desarrollo cerebral y alteraciones del sueño. Sin embargo, hay varias aplicaciones, videojuegos y otras herramientas en línea que pueden beneficiar la salud del cerebro. En las imágenes cerebrales funcionales se ha observado que los adultos mayores vírgenes a internet que aprenden a buscar en línea, muestran aumentos significativos en la actividad neuronal cerebral durante las búsquedas simuladas en internet. Ciertos programas computacionales y videojuegos pueden mejorar la memoria, las destrezas en tareas múltiples, la fluidez de la inteligencia y otras habilidades cognitivas. Hay varias aplicaciones y herramientas digitales que ofrecen intervenciones en salud mental y que proporcionan automanejo, monitoreo, capacitación junto a otras intervenciones que pueden mejorar el estado de ánimo y el comportamiento. Se require de investigación adicional acerca de los efectos positivos y negativos de la tecnología sobre la salud del cerebro para dilucidar los mecanismos y las relaciones causales subyacentes.D’après de nouvelles données scientifiques, l’usage fréquent des technologies numériques influe significativement sur le comportement et le fonctionnement cérébral, de façon aussi bien négative que positive. Une pratique excessive des écrans et des technologies numériques peut avoir des effets néfastes comme des symptômes de déficit d'attention, une intelligence émotionnelle et sociale altérée, une dépendance à la technologie, un isolement social, un développement cérébral dégradé et des troubles du sommeil. Cependant, certaines applications, jeux vidéo et autres outils en ligne peuvent avoir des effets bénéfiques sur le cerveau. L'imagerie fonctionnelle montre une activité neuronale significativement augmentée chez des personnes âgées jamais exposées à Internet et qui apprennent à faire des recherches en ligne. Certains programmes informatiques et jeux vidéo peuvent améliorer la mémoire, les compétences multitâches, l'agilité de l’intelligence et d'autres capacités cognitives. Dans le domaine de la santé mentale, différents outils et applications numériques permettant l'autogestion, le suivi, l'acquisition de compétences et d'autres techniques sont susceptibles d'améliorer l'humeur et le comportement du patient. Les effets positifs et négatifs de la technologie sur la santé cérébrale nécessitent d’être encore étudiés afin d’en mieux comprendre les mécanismes et les relations de cause à effet.

Objectives:Geriatric depression often presents with memory and cognitive complaints that are associated with increased risk for Alzheimer’s disease (AD). In a parent clinical trial of escitalopram combined with memantine or placebo for geriatric depression and subjective memory complaints, we found that memantine improved executive function and delayed recall performance at 12 months (NCT01902004). In this report, we used positron emission tomography (PET) to assess the relationship between in-vivo amyloid and tau brain biomarkers and clinical and cognitive treatment response.Design:In a randomized double-blind placebo-controlled trial, we measured 2-(1-{6-[(2-[F18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile ([18F]FDDNP) binding at baseline and assessed mood and cognitive performance at baseline, posttreatment (6 months), and naturalistic follow-up (12 months).Participants:Twenty-two older adults with major depressive disorder and subjective memory complaints completed PET scans and were included in this report.Results:Across both treatment groups, higher frontal lobe [18F]FDDNP binding at baseline was associated with improvement in executive function at 6 months (corrected p = .045). This effect was no longer significant at 12 months (corrected p = .12). There was no association of regional [18F]FDDNP binding with change in mood symptoms (corrected p = .2).Conclusions:[18F]FDDNP binding may predict cognitive response to antidepressant treatment. Larger trials are required to further test the value of [18F]FDDNP binding as a biomarker for cognitive improvement with antidepressant treatment in geriatric depression.

The life expectancy of people infected with human immunodeficiency virus (HIV) is rising due to better access to combination anti-retroviral therapy (ART). Although ART has reduced acquired immune deficiency syndrome (AIDS) related mortality and morbidity, there has been an increase in non-AIDS defining illnesses such as diabetes mellitus, hypercholesterolemia and coronary artery disease (CAD). HIV is a disease marked by inflammation which has been associated with specific biological vascular processes increasing the risk of premature atherosclerosis. The combination of pre-existing risk factors, atherosclerosis, ART, opportunistic infections and coagulopathy contributes to rising CAD incidence. The prevalence of CAD has emerged as a major contributor of morbidity in these patients due to longer life expectancy. However, ART has been associated with lipodystrophy, dyslipidemia, insulin resistance, diabetes mellitus and CAD. These adverse effects, along with drug-drug interactions when ART is combined with cardiovascular drugs, result in significant challenges in the care of this group of patients. Exercise tolerance testing, echocardiography, myocardial perfusion imaging, coronary computed tomography angiography and magnetic resonance imaging help in the diagnosis of CAD and heart failure and help predict cardiovascular outcomes in a manner similar to non-infected individuals. This review will highlight the pathogenesis and factors that link HIV to CAD, presentation and treatment of HIV-patients presenting with CAD and review briefly the cardiac imaging modalities used to identify this entity and help prognosticate future outcomes.

Aims This large prospective cohort study sought to confirm the incremental prognostic value of coronary computed tomographic angiography (CCTA) measured over a prolonged follow-up duration. CCTA has diagnostic and prognostic value but data supporting its long-term prognostic value in a large prospectively recruited cohort with suspected coronary artery disease (CAD) has been limited. Methods and results Consecutive patients (without history of myocardial infarction, revascularization, cardiac transplantation, and congenital heart disease) were prospectively enrolled. CCTA was evaluated for CAD severity, total plaque score (TPS), and left ventricular ejection fraction. Patients were followed for major adverse events (MAE) and major adverse cardiac events (MACE). Over a total of 99 months, 8667 consecutive CCTA patients (mean age = 57.1 ± 11.1 years, 52.9% men) were prospectively enrolled and followed for a mean duration of 7.0 ± 2.6 years. At follow-up, there were a total of 723 MAE, 278 MACE, 547 all-cause deaths, 110 cardiac deaths, and 104 non-fatal myocardial infarction. Patients without coronary atherosclerosis at the time of CCTA had a very low annual event rate for both MAE and MACE (0.45%/year and 0.19%/year, respectively). Both MAE and MACE increased with increasing TPS and severity of CAD. In patients with non-obstructive CAD and who were statin-naive, TPS ≥5 had MACE rates >0.75%/year. Patients with high-risk CAD had an annual MAE and MACE rates of 3.52%/year and 2.58%/year, respectively. Adjusted hazard ratio of the severity of CAD based on multivariable analyses indicated that the prognostic values were incremental. Conclusion CCTA has independent and incremental prognostic value that is durable over time. The absence of coronary atherosclerosis portends an excellent prognosis. Patients with increasing non-obstructive plaque burden have worse prognosis and a TPS threshold ≥5 may identify a population that may benefit from statin therapy.

Caution is warranted when in vitro results of biomarkers labeled with tritium were perfunctorily used to criticize in vivo data and conclusions derived with the same tracers labeled with positron emitters and positron emission tomography (PET). This concept is illustrated herein with the PET utilization of [18F]FDDNP, a biomarker used for in vivo visualization of β-amyloid and tau protein neuroaggregates in humans, later contradicted by in vitro data reported with [3H]FDDNP. In this investigation, we analyze the multiple factors involved in the experimental design of the [3H]FDDNP in vitro study that led to the erroneous interpretation of results. The present work describes full details on the synthesis, characterization, purity, and kinetics of radiolytic stability of [3H]FDDNP. The optimal in vitro conditions for detecting tau and β-amyloid protein aggregates using macroscopic and microscopic autoradiography with both [18F]FDDNP and [3H]FDDNP are also presented. Macroscopic autoradiography determinations were performed with [3H]FDDNP of verified purity using established methods described previously in the literature. The autoradiographic results using phosphate buffered saline (PBS) with less than 1 % EtOH and pure, freshly prepared [3H]FDDNP compared with the earlier reported data using [3H]FDDNP of undetermined purity and PBS in 10 % EtOH demonstrate the critical importance of rigorous experimental design for meaningful in vitro determinations. [18F]FDDNP binding to both amyloid plaques and neurofibrillary tangles was confirmed by amyloid and tau immunohistochemical stains of adjacent tissues. This work illustrates the sensitivity of in vitro techniques to various experimental conditions and underscores that conclusions obtained from translational in vitro to in vivo determinations must always be performed with extreme care to avoid wrong interpretations that can be perpetuated and assumed without further analysis.

Author(s): Siddarth, Prabha; Rahi, Berna; Emerson, Natacha D; Burggren, Alison C; Miller, Karen J; Bookheimer, Susan; Lavretsky, Helen; Dobkin, Bruce; Small, Gary; Merrill, David A | Abstract: BackgroundPhysical activity (PA) plays a major role in maintaining cognition in older adults. PA has been shown to be correlated with total hippocampal volume, a memory-critical region within the medial temporal lobe (MTL). However, research on associations between PA and MTL sub-region integrity is limited.ObjectiveTo examine the relationship between PA, MTL thickness, and its sub-regions, and cognitive function in non-demented older adults with memory complaints.MethodsTwenty-nine subjects aged ≥60 years, with memory complaints were recruited for this cross-sectional study. PA was tracked for 7 days using accelerometers, and average number of steps/day determined. Subjects were categorized into two groups: those who walked ≤4000 steps/day (lower PA) and those with g4000 steps/day (higher PA). Subjects received neuropsychological testing and 3T MRI scans. Nonparametric ANCOVAs controlling for age examined differences between the two groups.ResultsTwenty-six subjects aged 72.7(8.1) years completed the study. The higher PA group (n = 13) had thicker fusiform gyrus (median difference = 0.11 mm, effect size (ES) = 1.43, p = 0.001) and parahippocampal cortex (median difference = 0.12 mm, ES = 0.93, p = 0.04) compared to the lower PA group. The higher PA group also exhibited superior performance in attention and information-processing speed (median difference = 0.90, ES = 1.61, p = 0.003) and executive functioning (median difference = 0.97, ES = 1.24, p = 0.05). Memory recall was not significantly different between the two groups.ConclusionOlder non-demented individuals complaining of memory loss who walked g4000 steps each day had thicker MTL sub-regions and better cognitive functioning than those who walked ≤4000 steps. Future studies should include longitudinal analyses and explore mechanisms mediating hippocampal related atrophy.

Objective Growing evidence supports an association between increased blood pressure and: (a) poor cognitive performance in older adults, and (b) various biomarkers of increased Alzheimer's disease (AD) neuropathology. The objective of this study was to determine whether systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly associated with cognitive functioning in non-demented adults, and to examine in vivo AD pathology as a possible mediator of this association. Methods Positron emission tomography (PET) scans with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) provide in vivo measurements of plaque and tangle burden. A total of 101 non-demented older subjects with blood pressure data and FDDNP-PET scans were drawn from a larger study of predictors of cognitive decline. A neuropsychological test battery was used to compute "global cognitive scores" (averaged across five key domains), which served as an index of general cognitive functioning. Results Higher DBP (but not SBP) was significantly associated with lower cognitive scores, controlling for age, sex, antihypertensive medication use, and ApoE genotype (η 2 = 0.06). However, this relationship was no longer significant after introducing FDDNP-PET binding as an additional covariate in the statistical models. In vivo plaque and tangle burden accounted for over 30% of the observed association between higher DBP and poorer cognitive performance. Conclusions By suggesting a mediation of the relationship between DBP and cognitive functioning by FDDNP-PET binding, this study advances our understanding of some potential predictors of cognitive decline in non-demented adults, and underscores the importance of devising early multimodal interventions to more effectively combat degenerative brain disorders.

The temperature sensitivity of underlying water absorption bands can lead to baseline artifacts or apparent spectral band shifts in near infrared spectra and can negatively impact multivariate calibration models used in quantitative analyses. To address this issue, efforts can be made to suppress the temperature-induced spectral variation or knowledge of the temperature can be used to adjust the calibration. To facilitate the latter approach, we explored the ability to estimate the aqueous temperature of the sample directly from the combination region of the near infrared spectrum. This temperature modeling strategy addresses applications in which it is difficult to obtain an accurate sample temperature with a conventional measurement probe. Temperature models were developed by use of partial least-squares regression combined with the discrete wavelet transform. Models were constructed from the 5000 to 4000 cm−1 region of near infrared spectra for pH 7.4 buffer solutions over the temperature range of 20.0–40.5℃. The long-term predictive ability of the models was assessed by use of 13 sets of prediction spectra collected over the course of 13 months, yielding values of the root mean square error of prediction ranging from 0.19 to 0.36℃. In addition, laboratory-prepared solutions of glucose, mixture solutions of glucose, lactate, urea in buffer, and bovine plasma were used to assess the predictive ability of the temperature models in increasingly complex matrixes. The effects of pH and buffer molarity were also studied. While increasing the complexity of the spectral background resulted in increases in root mean square error of prediction (0.33–1.01℃), retuning the models to incorporate the modified spectral backgrounds lowered the resulting root mean square error of prediction values to the range of 0.3℃. This work demonstrates the practical utility of spectral-based temperature measurements that employ the absorbance of the water baseline rather than the peak absorbance.

An alarm algorithm for detecting episodes of nocturnal hypoglycemia is demonstrated in simulation studies that incorporate the use of a tissue phantom. Based on transmission spectra collected in the near-infrared combination region of 4000–5000 cm −1 , pattern recognition methods are used to classify spectra into alarm and non-alarm data classes on the basis of whether or not they signify a glucose excursion below a user-defined hypoglycemic alarm threshold. A reference spectrum and corresponding glucose concentration are acquired at the start of the monitoring period, and absorbance values of subsequent spectra are computed relative to this reference. The resulting differential spectra reflect differential glucose concentrations that correspond to the differences in concentration between each spectrum and the reference. Given the alarm threshold, a database of calibration differential spectra are partitioned into those above and below the threshold. Piecewise linear discriminant analysis is then used to compute a classification model that can be applied to differential spectra collected during the monitoring period in order to identify spectra that signal glucose concentrations in the hypoglycemic range. This alarm algorithm is demonstrated in two multiple-day dynamic studies that incorporate a tissue phantom composed of films of keratin and collagen that approximate the thicknesses of the corresponding proteins found in human tissue.

Background The C677T functional variant in the methylenetetrahydrofolate reductase ( MTHFR ) gene leads to reduced enzymatic activity and elevated blood homocysteine levels. Hyperhomocysteinemia has been linked with higher rates of cardiovascular diseases, cognitive decline, and late-life depression. Methods Three-dimensional magnetic resonance imaging data were analyzed from 738 individuals (aged 75.5 ± 6.8 years; 438 men, 300 women), including 173 patients with Alzheimer's disease, 359 subjects with mild cognitive impairment, and 206 healthy older adults, scanned as part of the Alzheimer's Disease Neuroimaging Initiative. Results We found that this variant associates with localized brain atrophy, after controlling for age, sex, and dementia status, in brain regions implicated in both intellectual and emotional functioning, notably the medial orbitofrontal cortices. The medial orbitofrontal cortex is involved in the cognitive modulation of emotional processes, and localized atrophy in this region was previously linked with both cognitive impairment and depressive symptoms. Here, we report that increased plasma homocysteine level mediates the association between MTHFR genotype and lower medial orbitofrontal volumes and that these volumes mediate the association between cognitive decline and depressed mood in this elderly cohort. We additionally show that vitamin B 12 deficiency interacts with the C677T variant in the etiology of hyperhomocysteinemia. Conclusions This study sheds light on important relationships between vascular risk factors, age-related cognitive decline, and late-life depression, and it represents a significant advance in our understanding of clinically relevant associations relating to MTHFR genotype.

Introduction The translocase of outer mitochondrial membrane 40 ( TOMM40 ), which lies in linkage disequilibrium with apolipoprotein E ( APOE ), has received attention more recently as a promising gene in Alzheimer's disease (AD) risk. TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. Methods In this study, we examined the effects of TOMM40 using high-resolution magnetic resonance imaging in 65 healthy, older subjects with and without the APOE e4 AD-risk variant. Results Examining individual subregions within the MTL, we found a significant relationship between increasing poly-T lengths of the TOMM40 variant and thickness of the entorhinal cortex only in subjects who did not carry the APOE e4 allele. Discussion Our data provide support for TOMM40 variant repeat length as an important contributor to AD-like MTL pathology in the absence of APOE e4.