Characteristics of subjective cognitive decline associated with amyloid positivity.

INTRODUCTION: The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited. METHODS: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) ε4 carriership, and neuropsychiatric symptoms with amyloid positivity. RESULTS: Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE ε4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages. DISCUSSION: Next to age, setting, and APOE ε4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.

Addition of a non-immersive virtual reality component to treadmill training to reduce fall risk in older adults (V-TIME): a randomised controlled trial.

BACKGROUND: Age-associated motor and cognitive deficits increase the risk of falls, a major cause of morbidity and mortality. Because of the significant ramifications of falls, many interventions have been proposed, but few have aimed to prevent falls via an integrated approach targeting both motor and cognitive function. We aimed to test the hypothesis that an intervention combining treadmill training with non-immersive virtual reality (VR) to target both cognitive aspects of safe ambulation and mobility would lead to fewer falls than would treadmill training alone. METHODS: We carried out this randomised controlled trial at five clinical centres across five countries (Belgium, Israel, Italy, the Netherlands, and the UK). Adults aged 60-90 years with a high risk of falls based on a history of two or more falls in the 6 months before the study and with varied motor and cognitive deficits were randomly assigned by use of computer-based allocation to receive 6 weeks of either treadmill training plus VR or treadmill training alone. Randomisation was stratified by subgroups of patients (those with a history of idiopathic falls, those with mild cognitive impairment, and those with Parkinson's disease) and sex, with stratification per clinical site. Group allocation was done by a third party not involved in onsite study procedures. Both groups aimed to train three times per week for 6 weeks, with each session lasting about 45 min and structured training progression individualised to the participant's level of performance. The VR system consisted of a motion-capture camera and a computer-generated simulation projected on to a large screen, which was specifically designed to reduce fall risk in older adults by including real-life challenges such as obstacles, multiple pathways, and distracters that required continual adjustment of steps. The primary outcome was the incident rate of falls during the 6 months after the end of training, which was assessed in a modified intention-to-treat population. Safety was assessed in all patients who were assigned a treatment. This study is registered with ClinicalTrials.gov, NCT01732653. FINDINGS: Between Jan 6, 2013, and April 3, 2015, 302 adults were randomly assigned to either the treadmill training plus VR group (n=154) or treadmill training alone group (n=148). Data from 282 (93%) participants were included in the prespecified, modified intention-to-treat analysis. Before training, the incident rate of falls was similar in both groups (10·7 [SD 35·6] falls per 6 months for treadmill training alone vs 11·9 [39·5] falls per 6 months for treadmill training plus VR). In the 6 months after training, the incident rate was significantly lower in the treadmill training plus VR group than it had been before training (6·00 [95% CI 4·36-8·25] falls per 6 months; p<0·0001 vs before training), whereas the incident rate did not decrease significantly in the treadmill training alone group (8·27 [5·55-12·31] falls per 6 months; p=0·49). 6 months after the end of training, the incident rate of falls was also significantly lower in the treadmill training plus VR group than in the treadmill training group (incident rate ratio 0·58, 95% CI 0·36-0·96; p=0·033). No serious training-related adverse events occurred. INTERPRETATION: In a diverse group of older adults at high risk for falls, treadmill training plus VR led to reduced fall rates compared with treadmill training alone. FUNDING: European Commission.

The use of biomarkers for the etiologic diagnosis of MCI in Europe: an EADC survey.

We investigated the use of Alzheimer's disease (AD) biomarkers in European Alzheimer's Disease Consortium centers and assessed their perceived usefulness for the etiologic diagnosis of mild cognitive impairment (MCI). We surveyed availability, frequency of use, and confidence in diagnostic usefulness of markers of brain amyloidosis (amyloid positron emission tomography [PET], cerebrospinal fluid [CSF] Aß42) and neurodegeneration (medial temporal atrophy [MTA] on MR, fluorodeoxyglucose positron emission tomography [FDG-PET], CSF tau). The most frequently used biomarker is visually rated MTA (75% of the 37 responders reported using it "always/frequently") followed by CSF markers (22%), FDG-PET (16%), and amyloid-PET (3%). Only 45% of responders perceive MTA as contributing to diagnostic confidence, where the contribution was rated as "moderate". Seventy-nine percent of responders felt "very/extremely" comfortable delivering a diagnosis of MCI due to AD when both amyloid and neuronal injury biomarkers were abnormal (P < .02 versus any individual biomarker). Responders largely agreed that a combination of amyloidosis and neuronal injury biomarkers was a strongly indicative AD signature.

Frailty in elderly people.

Frailty is the most problematic expression of population ageing. It is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. In landmark studies, investigators have developed valid models of frailty and these models have allowed epidemiological investigations that show the association between frailty and adverse health outcomes. We need to develop more efficient methods to detect frailty and measure its severity in routine clinical practice, especially methods that are useful for primary care. Such progress would greatly inform the appropriate selection of elderly people for invasive procedures or drug treatments and would be the basis for a shift in the care of frail elderly people towards more appropriate goal-directed care.

The cerebrospinal fluid "Alzheimer profile": easily said, but what does it mean?

BACKGROUND: We aimed to identify the most useful definition of the "cerebrospinal fluid Alzheimer profile," based on amyloid-ß1-42 (Aß42), total tau, and phosphorylated tau (p-tau), for diagnosis and prognosis of Alzheimer's disease (AD). METHODS: We constructed eight Alzheimer profiles with previously published combinations, including regression formulas and simple ratios. We compared their diagnostic accuracy and ability to predict dementia due to AD in 1385 patients from the Amsterdam Dementia Cohort. Results were validated in an independent cohort (n = 1442). RESULTS: Combinations outperformed individual biomarkers. Based on the sensitivity of the best performing regression formulas, cutoffs were chosen at 0.52 for the tau/Aß42 ratio and 0.08 for the p-tau/Aß42 ratio. Ratios performed similar to formulas (sensitivity, 91%-93%; specificity, 81%-84%). The same combinations best predicted cognitive decline in mild cognitive impairment patients. Validation confirmed these results, especially regarding the tau/Aß42 ratio. CONCLUSIONS: A tau/Aß42 ratio of >0.52 constitutes a robust cerebrospinal fluid Alzheimer profile. We recommend using this ratio to combine biomarkers.

Decision making under deep uncertainty for pandemic policy planning.

Policymakers around the world were generally unprepared for the global COVID-19 pandemic. As a result, the virus has led to millions of cases and hundreds of thousands of deaths. Theoretically, the number of cases and deaths did not have to happen (as demonstrated by the results in a few countries). In this pandemic, as in other great disasters, policymakers are confronted with what policy analysts call Decision Making under Deep Uncertainty (DMDU). Deep uncertainty requires policies that are not based on 'predict and act' but on 'prepare, monitor, and adapt', enabling policy adaptations over time as events occur and knowledge is gained. We discuss the potential of a DMDU-approach for pandemic decisionmaking.

Understanding multimorbidity requires sign-disease networks and higher-order interactions, a perspective.

Background: Count scores, disease clustering, and pairwise associations between diseases remain ubiquitous in multimorbidity research despite two major shortcomings: they yield no insight into plausible mechanisms underlying multimorbidity, and they ignore higher-order interactions such as effect modification. Objectives: We argue that two components are currently missing but vital to develop novel multimorbidity metrics. Firstly, networks should be constructed which consists simultaneously of signs, symptoms, and diseases, since only then could they yield insight into plausible shared biological mechanisms underlying diseases.Secondly, learning pairwise associations is insufficient to fully characterize the correlations in a system. That is, synergistic (e.g., cooperative or antagonistic) effects are widespread in complex systems, where two or more elements combined give a larger or smaller effect than the sum of their individual effects. It can even occur that pairs of symptoms have no pairwise associations whatsoever, but in combination have a significant association. Therefore, higher-order interactions should be included in networks used to study multimorbidity, resulting in so-called hypergraphs. Methods: We illustrate our argument using a synthetic Bayesian Network model of symptoms, signs and diseases, composed of pairwise and higher-order interactions. We simulate network interventions on both individual and population levels and compare the ground-truth outcomes with the predictions from pairwise associations. Conclusion: We find that, when judged purely from the pairwise associations, interventions can have unexpected 'side-effects' or the most opportune intervention could be missed. The hypergraph uncovers links missed in pairwise networks, giving a more complete overview of sign and disease associations.

The development of quality indicators to improve psychosocial care in dementia.

BACKGROUND: The evidence for the effectiveness of psychosocial interventions in dementia care is growing but the implementation of available evidence is not automatic. Our objective was to develop valid quality indicators (QIs) for psychosocial dementia care that facilitate the implementation process in various countries and settings. METHODS: A RAND-modified Delphi technique was used to develop a potential set of QIs. Two multidisciplinary, international expert panels were involved in achieving content and face validity. Consensus on the final set was reached after a conference meeting where a third panel of dementia experts discussed measurability and applicability of the potential set. A retrospective cohort study was conducted to study the feasibility of using the final set in day care centers, hospitals, and nursing homes in Spain and The Netherlands. RESULTS: A total of 104 recommendations were selected from guidelines and systematic reviews and appraised for their contribution to improving the quality of dementia care by 49 dementia experts. Twenty-five experts attended the conference meeting and reached consensus on a set of 12 QIs representing the key elements of effective psychosocial care, such as shared decision-making and interventions tailored to needs and preferences. Data from 153 patient records showed that all but one QI subitem were applicable to all three settings in both countries. CONCLUSION: Our multidisciplinary and multinational strategy resulted in a set of unique QIs that aims exclusively at assessing the quality of psychosocial dementia care. Following implementation, these QIs will assist dementia care professionals to individualize and tailor psychosocial interventions.

Interview for Deterioration in Daily Living Activities in Dementia: construct and concurrent validity in patients with mild to moderate dementia.

BACKGROUND: The purpose of the study was to translate the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) into German and to evaluate the construct and concurrent validity in people with mild to moderate dementia. METHODS: IDDD data of two pooled samples (n = 301) were analyzed regarding ceiling and bottom effects, internal consistency, factor reliability and correlations with corresponding scales on cognition and activities of daily living. RESULTS: We found minimal bottom (< 5%) and ceiling (≤ 2%) effects, good internal consistency (Cronbach's α > 0.7) and moderate to good factor reliability (0.66-0.87). Low correlations with cognition (Pearson coefficient: < 0.17) confirmed the differences between cognitive testing and activities of daily living (ADL). Minor correlations with other ADL scores (r < 0.2) indicated that different scores cover a different range of ADLs. The original two factor model could not be confirmed. A suggested four factor model distinguishing initiative and performance of basic and instrumental ADL demonstrated better indices of fit and higher correlations with corresponding scales. CONCLUSION: A four factor model of the IDDD can be used in dementia research for assessing initiative in and performance of basic and household activities of daily living. The findings suggest that ADL scales correlate only poorly and that further development of the IDDD is needed to cover a broader range of ADLs.

The Impact of Payment Reforms on the Quality and Utilisation of Healthcare for Patients With Multimorbidity: A Systematic Review.

Inadequate treatment of multimorbidity is recognised as a major determinant of the effectiveness of healthcare and also of its inappropriate expenditures. However, current payment systems target, primarily, the treatment of single diseases, thus hindering integrated delivery of care for patients with multimorbidity (PwM). This review aims to assess the effects of targeted reforms of payment systems which could help attain a higher quality of care and reduce unnecessary healthcare utilisation. In June 2020, a search of Medline and EMBASE revealed 13 relevant articles. The most common payment models were the use of bundled payments (n = 4) and diagnosis-related group payments (n = 4). Except for an increase in hospital admissions (n = 3), no outcome showed unambiguous significant effects across more than one study. The two studies which focused explicitly on PwM showed a significant decrease in 30-day hospital readmissions. This, however, was not maintained after 60 days in one study. No general conclusion could be drawn on the effects of targeted payment reforms for PwM. Our findings suggest that reforms should be combined with more multifaceted healthcare delivery to address the complex patterns of healthcare use effectively. Thorough evaluations of targeted payment reforms are needed urgently to contribute to the body of evidence required.

Study protocol of the multi-site randomised controlled REDALI-DEM trial--the effects of structured relearning methods on daily living task performance of persons with dementia.

BACKGROUND: Evidence from pilot trials suggests that structured learning techniques may have positive effects on the performance of cognitive tasks, movement sequences or skills in patients with Alzheimer's disease. The purpose of this trial is to evaluate whether the usual method of learning by trial and error or the method of errorless learning demonstrate better effects on the performance of two selected daily living tasks six weeks after the intervention in people with mild to moderate dementia. METHODS/DESIGN: A seven-centre single-blind, active-controlled design with a 1:1 randomisation for two parallel groups will include 175 persons diagnosed with Alzheimer's disease or mixed type dementia (MMSE 14-24), living at home, showing at least moderate need for assistance in instrumental activities of daily living; primary carer available and informed consent of patient and primary carer. Patients of both study arms will receive 15 one-hour-sessions at home by trained interventionists practising two daily living tasks individually selected. In one group the trial and error technique and in the other group the errorless learning method will be applied. Primary outcome is the task performance measured with the Task Performance Scale six weeks post treatment. DISCUSSION: The trial results will inform us to improve guidelines for instructing individuals with memory impairments. A user-friendly practice guideline will allow an efficient implementation of structured relearning techniques for a wide range of service providers in dementia care. TRIAL REGISTRATION: DRKS00003117.

Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy is caused by deposition of the amyloid beta protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid beta(40) and beta(42) proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid beta(40) (p < 0.01 vs controls or Alzheimer disease) and amyloid beta(42) concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid beta(42) and total tau discriminated cerebral amyloid angiopathy from controls, with an area under the receiver operator curve of 0.98. Our data are consistent with neuropathological evidence that amyloid beta(40) as well as amyloid beta(42) protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid beta proteins toward the cerebrospinal fluid.

A systematic review of communication strategies for people with dementia in residential and nursing homes.

BACKGROUND: The impairment of verbal skills of people with dementia challenges communication. The aim of this review was to study the effects of nonpharmacological interventions in residential and nursing homes on (1) communication between residents with dementia and care staff, and (2) the neuropsychiatric symptoms of residents with dementia. METHOD: Pubmed, PsychInfo, Web of Science, the Cochrane Library, and reference lists from relevant publications were systematically searched to find articles about controlled interventions with communication strategies. The data collected were pooled and subjected to a meta-analysis. RESULTS: Nineteen intervention studies were selected for this review. They included structured and communicative "sessions at set times" for residents (e.g. life review) and communication techniques in activities of "daily care" applied by care staff (e.g. sensitivity to nonverbal communication). A meta-analysis of five set-time interventions (communication) and another meta-analysis of four set-time interventions (neuropsychiatric outcomes) found no significant overall effects. Individual set-time intervention studies report positive effects on communication when interventions are single-task sessions, like life review or one-on-one conversation. Interventions around daily care activities had positive effects on communication outcomes. Effects of both types of interventions on neuropsychiatric symptoms were divergent. CONCLUSION: This review indicates that care staff can improve their communication with residents with dementia when strategies are embedded in daily care activities or interventions are single-task sessions at set times. These results offer the possibility of improving the quality of care, but not of directly reducing neuropsychiatric symptoms. More research is needed to study the effect of communication interventions on neuropsychiatric symptoms.

The conundrum of human immune system "senescence".

There is a great deal of debate on the question of whether or not we know what ageing is (Ref. Cohen et al., 2020). Here, we consider what we believe to be the especially confused and confusing case of the ageing of the human immune system, commonly referred to as "immunosenescence". But what exactly is meant by this term? It has been used loosely in the literature, resulting in a certain degree of confusion as to its definition and implications. Here, we argue that only those differences in immune parameters between younger and older adults that are associated in some definitive manner with detrimental health outcomes and/or impaired survival prospects should be classed as indicators of immunosenescence in the strictest sense of the word, and that in humans we know remarkably little about their identity. Such biomarkers of immunosenescence may nonetheless indicate beneficial effects in other contexts, consistent with the notion of antagonistic pleiotropy. Identifying what could be true immunosenescence in this respect requires examining: (1) what appears to correlate with age, though generality across human populations is not yet confirmed; (2) what clearly is part of a suite of canonical changes in the immune system that happen with age; (3) which subset of those changes accelerates rather than slows aging; and (4) all changes, potentially population-specific, that accelerate agig. This remains an immense challenge. These questions acquire an added urgency in the current SARS-CoV-2 pandemic, given the clearly greater susceptibility of older adults to COVID-19.

Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study.

BACKGROUND: Alzheimer's disease (AD) pathology is common in patients with amnestic mild cognitive impairment (aMCI) without dementia, but the prevalence of AD pathology in patients with subjective cognitive impairment (SCI) and non-amnestic mild cognitive impairment (naMCI) is unknown. AD is characterised by decreased CSF concentrations of Abeta(42) and increased concentrations of tau. We investigated the prevalence of a CSF AD profile in patients with SCI, naMCI, or aMCI and the association of this profile with cognitive outcome in each group. METHODS: Patients with SCI, naMCI, aMCI, and neurologically healthy controls were recruited from 20 memory clinics across Europe, between January, 2003, and June, 2005, into this prospective cohort study. A CSF AD profile was defined as an abnormal ratio of Abeta(42):tau. Patients were assessed annually up to 3 years. Outcome measures were changes in memory, overall cognition, mini-mental state examination (MMSE) score, daily function, and progression to AD-type dementia. FINDINGS: The CSF AD profile was more common in patients with SCI (31 of 60 [52%]), naMCI (25 of 37 [68%]), and aMCI (56 of 71 [79%]) than in healthy controls (28 of 89 [31%]). The profile was associated with cognitive decline in patients with naMCI (memory, MMSE, and daily function) and in patients with aMCI (MMSE and daily function). In patients with aMCI, a CSF AD profile was predictive of AD-type dementia (OR 26.8, 95% CI 1.6-456.4). INTERPRETATION: AD is a common cause of SCI, naMCI, and aMCI and is associated with cognitive decline in patients with naMCI or aMCI. Patients with SCI might be in the early stages of AD, and cognitive decline might become apparent only after longer follow-up. FUNDING: European Commission; Ana Aslan International Foundation.

Geriatric Education Programs for Emergency Department Professionals: A Systematic Review.

OBJECTIVES: To evaluate geriatric education programs for emergency department (ED) professionals based on: content and teaching methods and learning outcome effects and factors promoting or hindering program implementation. DESIGN: Systematic review. SETTING: ED. PARTICIPANTS: Physicians, nurses, and medical residents working in the ED. METHODS AND MEASUREMENT: Five major biomedical databases were searched for (quasi) experimental studies, published between 1990 and April 2018, evaluating geriatric education programs for ED professionals. Data were synthesized around study quality, learning participants, teaching content and methods, and Kirkpatrick learning outcomes. RESULTS: Nine before-after studies were included. Learners were mostly ED residents and, to a smaller extent, ED nurses and physicians. Study quality was moderate, with the lowest scores on sampling and instrument validity. Programs varied from a 1-day workshop to a 2-year curriculum, mostly combining didactic lectures with active and experiential learning formats. Topics commonly addressed included managing: geriatric syndromes, trauma and falls, medication, atypical presentations, and care transitions. Statistically significant improvements were mostly found in learners' knowledge acquisition (six studies). Significant improvements were also found in single studies on: self-reported geriatric screening, documentation of geriatric care, and appropriate urinary catheter placement. Factors promoting program implementation included: solving competing educational demands and busy work schedules, embedding the program in preexisting curricula, and close collaboration between emergency and geriatric medicine faculties. CONCLUSIONS: Various geriatric education programs improve the geriatric knowledge of ED professionals and seem to positively impact their clinical practice. However, more program evaluations with larger study samples, and use of valid and reliable outcome measures, are needed to provide robust evidence on the effectiveness of such programs. J Am Geriatr Soc, 1-8, 2019. J Am Geriatr Soc 67:2402-2409, 2019.

Is every-day walking in older adults more analogous to dual-task walking or to usual walking? Elucidating the gaps between gait performance in the lab and during 24/7 monitoring.

BACKGROUND: The traditional evaluation of gait in the laboratory during structured testing has provided important insights, but is limited by its "snapshot" character and observation in an unnatural environment. Wearables enable monitoring of gait in real-world environments over a week. Initial findings show that in-lab and real-world measures differ. As a step towards better understanding these gaps, we directly compared in-lab usual-walking (UW) and dual-task walking (DTW) to daily-living measures of gait. METHODS: In-lab gait features (e.g., gait speed, step regularity, and stride regularity) derived from UW and DTW were compared to the same gait features during daily-living in 150 elderly fallers (age: 76.5 ± 6.3 years, 37.6% men). In both settings, features were extracted from a lower-back accelerometer. In the real-world setting, subjects were asked to wear the device for 1 week and pre-processing detected 30-s daily-living walking bouts. A histogram of all walking bouts was determined for each walking feature for each subject and then each subject's typical (percentile 50, median), worst (percentile 10) and the best (percentile 90) values over the week were determined for each feature. Statistics of reliability were assessed using Intra-Class correlations and Bland-Altman plots. RESULTS: As expected, in-lab gait speed, step regularity, and stride regularity were worse during DTW, compared to UW. In-lab gait speed, step regularity, and stride regularity during UW were significantly higher (i.e., better) than the typical daily-living values (p < 0.001) and different (p < 0.001) from the worst and best values. DTW values tended to be similar to typical daily-living values (p = 0.205, p = 0.053, p = 0.013 respectively). ICC assessment and Bland-Altman plots indicated that in-lab values do not reliably reflect the daily-walking values. CONCLUSIONS: Gait values measured during relatively long (30-s) daily-living walking bouts are more similar to the corresponding values obtained in the lab during dual-task walking, as compared to usual walking. Still, gait performance during most daily-living walking bouts is worse than that measured during usual and dual-tasking in the lab. The values measured in the lab do not reliably reflect daily-living measures. That is, an older adult's typical daily-living gait cannot be estimated by simply measuring walking in a structured, laboratory setting.

Delirium After Transcatheter Aortic Valve Implantation Under General Anesthesia: Incidence, Predictors, and Relation to Long-Term Survival.

BACKGROUND/OBJECTIVES: Prospectively collected data on postoperative delirium (POD) after transcatheter aortic valve implantation (TAVI) are scarce. The aim of this study was to report the incidence and risk factors of delirium after TAVI under general anesthesia and to assess the association of POD with clinical outcome and short- and long-term survival. DESIGN: Prospective cohort study. SETTING: Academic medical center. PARTICIPANTS: A total of 703 subsequent patients undergoing TAVI under general anesthesia between 2008 and 2017. MEASUREMENTS: Delirium was assessed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria. Outcomes were postprocedural clinical outcome and short- and long-term survival (30 days and 5 years, respectively). RESULTS: POD was observed in 16.5% (116/703), was the strongest independent predictor of long-term mortality (hazard ratio = 1.91; 95% confidence interval [CI] = 1.36-2.70), and was associated with impaired 30-day and 5-year survival (92.2% vs 96.8% [P = .025] and 40.0% vs 50.0% [P = .007], respectively). Stroke and new onset of atrial fibrillation were more often observed in delirious patients (6.9% vs 1.9% and 12.1% vs 5.1%, respectively). Strongest independent predictors of POD were prior delirium (odds ratio [OR] = 2.56; 95% CI = 1.52-4.31) and aortic valve area less than 0.75 cm2 (OR = 2.39; 95% CI = 1.53-3.74). CONCLUSION: One in six patients experienced POD after TAVI under general anesthesia. POD was the strongest predictor of long-term mortality and was associated with impaired short- and long-term survival. Prior delirium and a more calcified aortic valve were the strongest independent predictors of POD. J Am Geriatr Soc 67:2325-2330, 2019.

Immunocapture-based fluorometric assay for the measurement of neprilysin-specific enzyme activity in brain tissue homogenates and cerebrospinal fluid.

Neprilysin, a zinc-metalloendopeptidase, has important roles in the physiology and pathology of many diseases such as hypertension, cancer and Alzheimer's disease. We have developed an immunocapture assay to measure the specific enzyme activity of neprilysin in brain tissue homogenates and cerebrospinal fluid (CSF). The assay uses a neprilysin-specific antibody, previously used in a commercially available ELISA kit, to isolate and immobilise NEP from brain homogenates and CSF, prior to the addition of a fluorogenic peptide substrate (Mca-RPPGFSAFK(Dnp)). This fluorogenic substrate is ordinarily cleaved by multiple enzymes. We have shown that without the immunocapture phase, even under reaction conditions reported to be specific for neprilysin - i.e. in the presence of thiorphan, at pH above 7 - the fluorogenic peptide substrate does not allow neprilysin activity in brain homogenates and CSF to be discriminated from that of other closely related enzymes. The specificity of the immunocapture enzyme activity assay was confirmed by >80% inhibition of substrate cleavage in brain homogenates and CSF in the presence of thiorphan. The assay allows high-throughput analysis and, critically, also ensures a high level of enzyme specificity even when assaying crude tissue homogenates or CSF.

Feasibility of a new community-based geriatric intervention programme: an exploration of experiences of GPs, nurses, geriatricians, patients and caregivers.

PURPOSE: To determine the feasibility of the Dutch Geriatric Intervention Programme (DGIP) in primary care. Within the DGIP, a nurse cooperates with a General Practitioner (GP) and a clinical geriatrician to assess and manage care for community-living older patients. The aim of this study was to describe both views of care receivers and those of professionals in order to identify facilitating factors and barriers for implementation of the DGIP. METHOD: Combined quantitative and qualitative data collection methods were used. Pre- and post-questionnaires were taken from GPs (n= 15), nurses (n = 6) and geriatricians (n = 2). These professionals were also interviewed. In addition patients (n = 11 out of total n = 54) and their carers (n = 37) were interviewed. RESULTS: GPs appreciated the support by the DGIP for problems in cognition, mood and mobility. Lack of knowledge and time restriction was the cause of their incapability at that point. In the cooperation between professionals, nurses felt that they had to initiate the contact. Personal contact helped the mutual communication. Involving the carer of the patient proved very important. All disciplines found this of crucial importance in order to deliver a tailored intervention and create conditions for optimal care. Barriers, for which the programme was tailored during the implementation, were: resistance in referrals of patients to the programme, nurses' and GPs' knowledge of diagnostic tests, communication problems and insufficient involvement of caregivers. CONCLUSIONS: The implementation of the DGIP was feasible, but several barriers need ongoing attention by implementation, like communication between disciplines.