Cost-effectiveness of the FindMyApps eHealth intervention vs. digital care as usual: results from a randomised controlled trial.

OBJECTIVES: Despite growing interest, the cost-effectiveness of eHealth interventions for supporting quality of life of people with dementia and their caregivers remains unclear. This study evaluated the cost-effectiveness of the FindMyApps intervention, compared to digital care-as-usual. FindMyApps aims to help people with dementia and their caregivers find and learn to use tablet apps that may support social participation and self-management of people with dementia and sense of competence of caregivers. METHOD: A randomised controlled trial (Netherlands Trial Register NL8157) was conducted, including people with mild cognitive impairment (MCI) or mild dementia and their informal caregivers (FindMyApps n = 76, digital care-as-usual n = 74). Outcomes for people with MCI/dementia were Quality-Adjusted Life-Years (QALYs), calculated from EQ-5D-5L data and the Dutch tariff for utility scores, social participation (Maastricht Social Participation Profile) and quality of life (Adult Social Care Outcomes Toolkit), and for caregivers, QALYs and sense of competence (Short Sense of Competence Questionnaire). Societal costs were calculated using data collected with the RUD-lite instrument and the Dutch costing guideline. Multiple imputation was employed to fill in missing cost and effect data. Bootstrapped multilevel models were used to estimate incremental total societal costs and incremental effects between groups which were then used to calculate Incremental Cost-Effectiveness Ratios (ICERs). Cost-effectiveness acceptability curves were estimated. RESULTS: In the FindMyApps group, caregiver SSCQ scores were significantly higher compared to care-as-usual, n = 150, mean difference = 0.75, 95% CI [0.14, 1.38]. Other outcomes did not significantly differ between groups. Total societal costs for people with dementia were not significantly different, n = 150, mean difference = €-774, 95%CI [-2.643, .,079]. Total societal costs for caregivers were significantly lower in the FindMyApps group compared to care-as-usual, n = 150, mean difference = € -392, 95% CI [-1.254, -26], largely due to lower supportive care costs, mean difference = €-252, 95% CI [-1.009, 42]. For all outcomes, the probability that FindMyApps was cost-effective at a willingness-to-pay threshold of €0 per point of improvement was 0.72 for people with dementia and 0.93 for caregivers. CONCLUSION: FindMyApps is a cost-effective intervention for supporting caregivers' sense of competence. Further implementation of FindMyApps is warranted.

Cognitive Impairment in Patients With Cardiac Disease: Implications for Clinical Practice.

Cognitive impairment is common in patients with cardiovascular disease. One in 3 patients presenting at cardiology clinics have some degree of cognitive impairment, depending on the cardiac condition, comorbidities, and age. In up to half of these cases cognitive impairment may go unrecognized; however, it may affect self-management and treatment adherence. The high prevalence of cognitive impairment in patients with cardiac disease is likely due to shared risk factors, as well as direct consequences of cardiac dysfunction on the brain. Moreover, cardiac interventions may have beneficial as well as adverse effects on cognitive functioning. In this review, we describe prevalence and risk factors for cognitive impairment in patients with several common cardiac conditions: heart failure, coronary artery disease, and aortic valve stenosis. We discuss the potential effects of guideline-based treatments on cognition and identify open questions and unmet needs. Given the high prevalence of unrecognized cognitive impairment in cardiac patients, we recommend a stepwise approach to improve detection and management of cognitive impairment.

Effectiveness of transmural team-based palliative care in prevention of hospitalizations in patients at the end of life: A systematic review and meta-analysis.

BACKGROUND: Team-based palliative care interventions have shown positive results for patients at the end of life in both hospital and community settings. However, evidence on the effectiveness of transmural, that is, spanning hospital and home, team-based palliative care collaborations is limited. AIM: To systematically review whether transmural team-based palliative care interventions can prevent hospital admissions and increase death at home. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE (Ovid), Embase (Ovid), CINAHL (Ebsco), PsychINFO (Ovid), and Cochrane Library (Wiley) were systematically searched until January 2021. Studies incorporating teams in which hospital and community professionals co-managed patients, hospital-based teams with community follow-up, and case-management interventions led by palliative care teams were included. Data was extracted by two researchers independently. RESULTS: About 19 studies were included involving 6614 patients, of whom 2202 received an intervention. The overall pooled odds ratio of at least one hospital (re)admissions was 0.46 (95% confidence interval (CI) 0.34-0.68) in favor of the intervention group. The highest reduction in admission was in the hospital-based teams with community follow-up: OR 0.21 (95% CI 0.07-0.66). The pooled effect on home deaths was 2.19 (95% CI 1.26-3.79), favoring the intervention, with also the highest in the hospital-based teams: OR 4.77 (95% CI 1.23-18.47). However, studies had high heterogeneity regarding intervention, study population, and follow-up time. CONCLUSION: Transmural team-based palliative care interventions, especially hospital-based teams that follow-up patients at home, show an overall effect on lowering hospital admissions and increasing the number of patients dying at home. However, broad clinical and statistical heterogeneity of included studies results in uncertainty about the effect size.

Minding menopause in patients with cognitive impairment: a patient's perspective and reflections on clinical practice.

Many women experience impairment in cognitive function during perimenopause. These symptoms are often not attributed to perimenopause by women themselves, by family and friends, or by healthcare professionals. In this article, we present a case in which perimenopausal complaints were attributed to early dementia and discuss mechanisms contributing to the low level of awareness of perimenopausal symptoms amongst patients and clinicians. Stigma amongst women and healthcare professionals impairs the recognition of perimenopausal complaints, and consideration of treatment options by clinicians. We advocate raising awareness in patients and physicians with more education, and the incorporation of potential menopause-related symptoms in general clinical guidelines.

Is the association between blood pressure and cognition in the oldest-old modified by physical, vascular or brain pathology markers? The EMIF-AD 90 + Study.

BACKGROUND: Prior studies suggest a changing association between blood pressure (BP) and cognition with aging, however work in the oldest-old has yielded ambiguous results. Potentially, these mixed results can be explained by modifying factors. The aim of this study was to establish whether physical, vascular or brain pathology markers that describe a state of increased vulnerability, affect the association between BP and cognition in the oldest-old. Results may influence clinicians' decisions regarding the use of antihypertensives in this age group. METHODS: We included 122 individuals (84 without cognitive impairment and 38 with cognitive impairment) from the EMIF-AD 90 + Study (mean age 92.4 years). First, we tested cross-sectional associations of systolic and diastolic BP with a cognitive composite score. Second, we tested whether these associations were modified by physical markers (waist circumference, muscle mass, gait speed and handgrip strength), vascular markers (history of cardiac disease, carotid intima media thickness as a proxy for atherosclerosis and carotid distensibility coefficient as a proxy for arterial stiffness) or brain pathology markers (white matter hyperintensities and cortical thickness). RESULTS: In the total sample, there was no association between BP and cognition, however, waist circumference modified this association (p-value for interaction with systolic BP: 0.03, with diastolic BP: 0.01). In individuals with a high waist circumference, higher systolic and diastolic BP tended to be associated with worse cognition, while in individuals with a low waist circumference, higher systolic BP was associated with better cognition. The others physical, vascular and brain pathology markers did not modify the association between BP and cognition. CONCLUSIONS: When examining various markers for physical, vascular and brain vulnerability, only waist circumference affected the association between BP and cognition. This warrants further research to evaluate whether waist circumference may be a marker in clinical practice influencing the use of antihypertensives in the oldest-old.

[A survey study towards the opinions of clinicians, patients and care partners regarding computer tools in the memory clinic: sense or nonsense?] / Een vragenlijstonderzoek naar de mening van clinici, patiënten en naasten over computertools in de geheugenpolikliniek: zin of onzin?.

INTRODUCTION: Computer tools based on artificial intelligence could aid clinicians in memory clinics by supporting diagnostic decision-making and communicating diagnosis and prognosis. We aimed to identify preferences of end-users, and barriers and facilitators for using computer tools in memory clinics. METHODS: Between July and October 2020, we invited European clinicians (n=109, age 45±10y; 47% female) to participate in an online questionnaire. A second questionnaire was sent to patients (n=50, age 73±8y, 34% female) with subjective cognitive complaints (SCD, n=21), mild cognitive impairment (MCI, n=16) and dementia (n=13) and care partners (n=46, 65±12y, 54% female). RESULTS: The vast majority (75%) of all participants positively valued the use of computer tools in memory clinics. Facilitating factors included user-friendliness and increased diagnostic accuracy. Barriers included (doubts relating) reliability and validity of the tool and loss of clinical autonomy. The participants believe that tools should be used in addition to the current working method and not as a replacement. DISCUSSION: Our results provide an important step in the iterative process of developing computer tools for memory clinics in co-creation with end-users and could guide successful implementation.

The Prognostic Accuracy of Clinical Judgment Versus a Validated Frailty Screening Instrument in Older Patients at the Emergency Department: Findings of the AmsterGEM Study.

STUDY OBJECTIVE: To compare the prognostic accuracy of clinical judgment for frailty in older patients at the emergency department with a validated screening instrument and patient-perceived frailty. METHODS: A prospective cohort study in patients 70 years of age and older in 2 Dutch EDs with a follow-up of 3 months. A dichotomous question was asked to the physician and patient: "Do you consider the patient / yourself to be frail?" The Identification of Seniors At Risk-Hospitalized Patients (ISAR-HP) was used as a validated screening instrument. The primary composite outcome consisted of either functional decline, institutionalization, or mortality. RESULTS: A total of 736 patients were included. The physician identified 59% as frail, compared with 49% by ISAR-HP and 43% by patients themselves. The level of agreement was fair (Fleiss Kappa, 0.31). After 3 months, 31% of the patients experienced at least 1 adverse health outcome. The sensitivity was 79% for the physician, 72% for ISAR-HP, 61% for the patient, and 48% for all 3 combined. The specificity was 50% for the physician, 63% for ISAR-HP, 66% for the patient, and 85% for all 3 positive. The highest positive likelihood ratio was 3.03 (physician, ISAR-HP, patient combined), and the lowest negative likelihood ratio was 0.42 (physician). The areas under the receiver operating curves were all poor: 0.68 at best for ISAR-HP. CONCLUSION: Clinical judgment for frailty showed fair agreement with a validated screening instrument and patient-perceived frailty. All 3 instruments have poor prognostic accuracy, which does not improve when combined. These findings illustrate the limited prognostic value of clinical judgment as a frailty screener in older patients at the ED.

Prescribing errors in post - COVID-19 patients: prevalence, severity, and risk factors in patients visiting a post - COVID-19 outpatient clinic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has challenged healthcare globally. An acute increase in the number of hospitalized patients has necessitated a rigorous reorganization of hospital care, thereby creating circumstances that previously have been identified as facilitating prescribing errors (PEs), e.g. a demanding work environment, a high turnover of doctors, and prescribing beyond expertise. Hospitalized COVID-19 patients may be at risk of PEs, potentially resulting in patient harm. We determined the prevalence, severity, and risk factors for PEs in post-COVID-19 patients, hospitalized during the first wave of COVID-19 in the Netherlands, 3 months after discharge. METHODS: This prospective observational cohort study recruited patients who visited a post-COVID-19 outpatient clinic of an academic hospital in the Netherlands, 3 months after COVID-19 hospitalization, between June 1 and October 1 2020. All patients with appointments were eligible for inclusion. The prevalence and severity of PEs were assessed in a multidisciplinary consensus meeting. Odds ratios (ORs) were calculated by univariate and multivariate analysis to identify independent risk factors for PEs. RESULTS: Ninety-eight patients were included, of whom 92% had ≥1 PE and 8% experienced medication-related harm requiring an immediate change in medication therapy to prevent detoriation. Overall, 68% of all identified PEs were made during or after the COVID-19 related hospitalization. Multivariate analyses identified ICU admission (OR 6.08, 95% CI 2.16-17.09) and a medical history of COPD / asthma (OR 5.36, 95% CI 1.34-21.5) as independent risk factors for PEs. CONCLUSIONS: PEs occurred frequently during the SARS-CoV-2 pandemic. Patients admitted to an ICU during COVID-19 hospitalization or who had a medical history of COPD / asthma were at risk of PEs. These risk factors can be used to identify high-risk patients and to implement targeted interventions. Awareness of prescribing safely is crucial to prevent harm in this new patient population.

The Accuracy of Four Frequently Used Frailty Instruments for the Prediction of Adverse Health Outcomes Among Older Adults at Two Dutch Emergency Departments: Findings of the AmsterGEM Study.

STUDY OBJECTIVE: Older adults presenting to the emergency department (ED) are at high risk of adverse health outcomes. This study aimed to evaluate the accuracy of 4 frequently used screening instruments for the prediction of adverse health outcomes among older adults in the ED. METHODS: This was a prospective cohort study in patients ≥70 years of age presenting to the ED in 2 hospitals in the Netherlands. Screening instruments included the acutely presenting older patient screening program (APOP) (providing 2 risk scores-functional decline [APOP1] and mortality [APOP2]), the International Resident Assessment Instrument Emergendy Department screener (InterRAI ED), the Identification of Seniors At Risk-Hospitalized Patients (ISAR-HP), and the safety management system (VMS). The primary outcome measure was a composite outcome encompassing functional decline, institutionalization, and mortality at 3 months after ED presentation. Other follow-up time points were 1 and 6 months. Analyses were performed to assess prognostic accuracy. RESULTS: In total, 889 patients were included. After 3 months, 267 (31%) patients experienced at least 1 adverse outcome. The positive likelihood ratio ranged from 1.67 (VMS) to 3.33 (APOP1), and the negative likelihood ratio ranged from 0.41 (ISAR-HP) to 0.88 (APOP2). Sensitivity ranged from 17% (APOP2) to 74% (ISAR-HP), and specificity ranged from 63% (ISAR-HP) to 94% (APOP2). The area under the curve ranged from 0.62 (APOP2) to 0.72 (APOP1 and ISAR-HP). Calibration was reasonable for APOP1 and VMS. The prognostic accuracy was comparable across all outcomes and at all follow-up time points. CONCLUSION: The frailty screening instruments assessed in this study showed poor to moderate prognostic accuracy, which brings into question their usability in the prediction of adverse health outcomes among older adults who present to the ED.

Are Apathy and Depressive Symptoms Related to Vascular White Matter Hyperintensities in Severe Late Life Depression?

OBJECTIVE: Apathy symptoms are defined as a lack of interest and motivation. Patients with late-life depression (LLD) also suffer from lack of interest and motivation and previous studies have linked apathy to vascular white matter hyperintensities (WMH) of the brain in depressed and nondepressed patients. The aim of this study was to investigate the relationship between apathy symptoms, depressive symptoms, and WMH in LLD. We hypothesize that late-onset depression (LOD; first episode of depression after 55 years of age) is associated with WMH and apathy symptoms. METHODS: Apathy scores were collected for 87 inpatients diagnosed with LLD. Eighty patients underwent brain magnetic resonance imaging. Associations between depressive and apathy symptoms and WMH were analyzed using linear regression. RESULTS: All 3 subdomains of the 10-item Montgomery-Åsberg Depression Rating Scale correlated significantly with the apathy scale score (all P < .05). In the total sample, apathy nor depressive symptoms were related to specific WMH. In LOD only, periventricular WMH were associated with depression severity (ß = 5.21, P = .04), while WMH in the left infratentorial region were associated with apathy symptoms (ß coefficient = 5.89, P = .03). CONCLUSION: Apathy and depressive symptoms are highly overlapping in the current cohort of older patients with severe LLD, leading to the hypothesis that apathy symptoms are part of depressive symptoms in the symptom profile of older patients with severe LLD. Neither apathy nor depressive symptoms were related to WMH, suggesting that radiological markers of cerebrovascular disease, such as WMH, may not be useful in predicting these symptoms in severe LLD.

The clinical and educational outcomes of an inter-professional student-led medication review team, a pilot study.

AIMS: The involvement of an inter-professional healthcare student team in the review of medications used by geriatric patients could not only provide patients with optimized therapy but also provide students with a valuable inter-professional learning experience. We describe and evaluate the clinical and learning outcomes of an inter-professional student-run mediation review program (ISP). SUBJECT AND METHOD: A variable team consisting of students in medicine, pharmacy, master advanced nursing practice, and master physician assistant reviewed the medication lists of patients attending a specialized geriatric outpatient clinic. RESULTS: During 32 outpatient visits, 188 medications were reviewed. The students identified 14 medication-related problems, of which 4 were not recognized by healthcare professionals. The ISP team advised 95 medication changes, of which 68 (71.6%) were directly implemented. Students evaluated this pilot program positively and considered it educational (median score 4 out of 5) and thought it would contribute to their future inter-professional relationships. CONCLUSION: An inter-professional team of healthcare students is an innovative healthcare improvement for (academic) hospitals to increase medication safety. Most formulated advices were directly incorporated in daily practice and could prevent future medication-related harm. The ISP also offers students a first opportunity to work in an inter-professional manner and get insight into the perspectives and qualities of their future colleagues.

The value of ambulatory blood pressure measurement to detect masked diastolic hypotension in older patients treated for hypertension.

OBJECTIVE: assess how many patients with low ambulatory diastolic blood pressure (DBP) are not identified when relying on office DBP alone, and thus have 'masked diastolic hypotension'. DESIGN: cross-sectional, retrospective cohort study. SETTING: academic hospital. SUBJECTS: 848 patients treated for hypertension who received ambulatory blood pressure monitoring (ABPM). METHODS: cut-off value between on- and off-target systolic blood pressure (SBP): 140 mmHg. Cut-off for low office and/or ambulatory DBP: DBP ≤ 70 mmHg. 'Masked diastolic hypotension' was defined as office DBP > 70 mmHg and mean ambulatory DBP ≤ 70 mmHg. RESULTS: mean age of the sample was 60 ± 13 years, 50% was female, 37% had diabetes, 42% preexisting cardiovascular disease (CVD), mean office blood pressure (BP) was 134/79 mmHg. In all patients (n = 848), low office DBP was present in n = 84(10%), while n = 183(22%) had low ambulatory DBP. In all patients with normal-to-high office DBP (n = 764), n = 122(16%) had 'masked diastolic hypotension'. In this group, ambulatory DBP was 14-19 mmHg lower than office DBP. Patients with low ambulatory DBP were older, had more (cardiovascular) comorbidities, and used more (antihypertensive) drugs. Antihypertensive drugs were lowered or discontinued in 30% of all patients with 'masked diastolic hypotension' due to side effects. CONCLUSIONS: 'masked diastolic hypotension' is common among patients treated for hypertension, particularly in older patients with CVD (e.g. coronary artery disease, diabetes), patient groups in which the European Society of Cardiology/Hypertension guideline advises to prevent low DBP. Although it remains to be examined at which BP levels the harms of low DBP outweigh the benefits of lowering SBP, our observations are aimed to increase awareness among physicians.

Mortality Risk and Its Association with Geriatric Domain Deficits in Older Outpatients: The Amsterdam Ageing Cohort.

INTRODUCTION: In older patients, life expectancy is determined by a complex interaction of multiple geriatric domains. A comprehensive geriatric assessment (CGA) captures different geriatric domains. Yet, if and how components of the CGA are related to mortality in an outpatient geriatric setting is unknown. In the Amsterdam Ageing Cohort, we therefore studied distribution and accumulation of geriatric domain deficits in relation to mortality. METHODS: All patients received a CGA as part of standard care, independent of referral reason. We summarized deficits on the CGA, using predefined cutoffs, in 5 geriatric domains: somatic, mental, nutritional, physical, and social domain. Information on mortality was obtained from the Dutch municipal register. We used age- and sex-adjusted Cox proportional hazards analyses to relate the separate domains and accumulation of impaired domains to overall mortality. RESULTS: From the 1,055 geriatric outpatients (53% female; age 79 ± 7 years), 172 patients (16%) had died after 1.7 ± 1.1 years. In 626 patients (59%), 3 or more domains were impaired. All domains were independently associated with mortality, with the highest hazard for the somatic domain (HR 3.7 [1.7-8.0]) and the lowest hazard for the mental domain (HR 1.5 [1.1-12.0]). In addition, accumulation of impaired domains showed a gradually increased mortality risk, ranging from HR 2.2 (0.8-6.1) for 2 domains to HR 9.6 (3.7-24.7) for all 5 domains impaired. CONCLUSIONS: This study provides evidence that impairment in multiple geriatric domains is highly prevalent and independently and cumulatively associated with mortality in an outpatient geriatric setting.

Evaluation of FindMyApps: protocol for a randomized controlled trial of the effectiveness and cost-effectiveness of a tablet-based intervention to improve self-management and social participation of community-dwelling people with mild dementia, compared to usual tablet use.

BACKGROUND: For the rising number of people living with dementia, cost-effective community-based interventions to support psychosocial care are needed. The FindMyApps intervention has been developed with and for people with dementia and their caregivers, to help them use tablets to facilitate self-management and engagement in meaningful social activities. A feasibility study and exploratory pilot trial evaluating FindMyApps have been carried out. This definitive trial further evaluates the effectiveness of the intervention and, for the first time, the cost-effectiveness. METHODS: A randomized controlled non-blinded single-center two-arm superiority trial will be conducted. Community-dwelling people with Mild Cognitive Impairment (MCI), or dementia with a Mini Mental-State Examination (MMSE) of > 17 and < 26, or Global Deterioration Scale 3 or 4, with an informal caregiver and access to a wireless internet connection will be included. In total, 150 patient-caregiver dyads will be randomly allocated to receive either usual care (control arm - tablet computer; n = 75 dyads) or usual care and the FindMyApps intervention (experimental arm - tablet computer and FindMyApps; n = 75 dyads). The primary outcomes are: for people with dementia, self-management and social participation; for caregivers, sense of competence. In addition to a main effect analysis, a cost-effectiveness analysis will be performed. In line with MRC guidance for evaluation of complex interventions a process evaluation will also be undertaken. DISCUSSION: Results of the trial are expected to be available in 2023 and will be submitted for publication in international peer-reviewed scientific journals, in addition to conference presentations and reporting via the EU Marie Sklodowska-Curie DISTINCT ITN network. By providing evidence for or against the effectiveness and cost-effectiveness of the FindMyApps intervention, the results of the trial will influence national implementation of FindMyApps. We hope that the results of the trial will further stimulate research and development at the intersection of technology and psycho-social care in dementia. We hope to further demonstrate that the randomized controlled trial is a valuable and feasible means of evaluating new digital technologies, to stimulate further high-quality research in this growing field. TRIAL REGISTRATION NUMBER: Netherlands Trial Register: NL8157 ; registered 15th November 2019.

Associations between gut microbiota, faecal short-chain fatty acids, and blood pressure across ethnic groups: the HELIUS study.

AIMS: Preliminary evidence from animal and human studies shows that gut microbiota composition and levels of microbiota-derived metabolites, including short-chain fatty acids (SCFAs), are associated with blood pressure (BP). We hypothesized that faecal microbiota composition and derived metabolites may be differently associated with BP across ethnic groups. METHODS AND RESULTS: We included 4672 subjects (mean age 49.8 ± 11.7 years, 52% women) from six different ethnic groups participating in the HEalthy Life In an Urban Setting (HELIUS) study. The gut microbiota was profiled using 16S rRNA gene amplicon sequencing. Associations between microbiota composition and office BP were assessed using machine learning prediction models. In the subgroups with the largest associations, faecal SCFA levels were compared in 200 subjects with lower or higher systolic BP. Faecal microbiota composition explained 4.4% of the total systolic BP variance. Best predictors for systolic BP included Roseburia spp., Clostridium spp., Romboutsia spp., and Ruminococcaceae spp. Explained variance of the microbiota composition was highest in Dutch subjects (4.8%), but very low in South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan and Turkish descent groups (explained variance <0.8%). Faecal SCFA levels, including acetate (P < 0.05) and propionate (P < 0.01), were lower in young Dutch participants with low systolic BP. CONCLUSIONS: Faecal microbiota composition is associated with BP, but with strongly divergent associations between ethnic groups. Intriguingly, while Dutch participants with lower BP had higher abundances of several SCFA-producing microbes, they had lower faecal SCFA levels. Intervention studies with SCFAs could provide more insight in the effects of these metabolites on BP.

Comparative analysis of the association between 35 frailty scores and cardiovascular events, cancer, and total mortality in an elderly general population in England: An observational study.

BACKGROUND: Frail elderly people experience elevated mortality. However, no consensus exists on the definition of frailty, and many frailty scores have been developed. The main aim of this study was to compare the association between 35 frailty scores and incident cardiovascular disease (CVD), incident cancer, and all-cause mortality. Also, we aimed to assess whether frailty scores added predictive value to basic and adjusted models for these outcomes. METHODS AND FINDINGS: Through a structured literature search, we identified 35 frailty scores that could be calculated at wave 2 of the English Longitudinal Study of Ageing (ELSA), an observational cohort study. We analysed data from 5,294 participants, 44.9% men, aged 60 years and over. We studied the association between each of the scores and the incidence of CVD, cancer, and all-cause mortality during a 7-year follow-up using Cox proportional hazard models at progressive levels of adjustment. We also examined the added predictive performance of each score on top of basic models using Harrell's C statistic. Using age of the participant as a timescale, in sex-adjusted models, hazard ratios (HRs) (95% confidence intervals) for all-cause mortality ranged from 2.4 (95% CI: 1.7-3.3) to 26.2 (95% CI: 15.4-44.5). In further adjusted models including smoking status and alcohol consumption, HR ranged from 2.3 (95% CI: 1.6-3.1) to 20.2 (95% CI: 11.8-34.5). In fully adjusted models including lifestyle and comorbidity, HR ranged from 0.9 (95% CI: 0.5-1.7) to 8.4 (95% CI: 4.9-14.4). HRs for CVD and cancer incidence in sex-adjusted models ranged from 1.2 (95% CI: 0.5-3.2) to 16.5 (95% CI: 7.8-35.0) and from 0.7 (95% CI: 0.4-1.2) to 2.4 (95% CI: 1.0-5.7), respectively. In sex- and age-adjusted models, all frailty scores showed significant added predictive performance for all-cause mortality, increasing the C statistic by up to 3%. None of the scores significantly improved basic prediction models for CVD or cancer. A source of bias could be the differences in mortality follow-up time compared to CVD/cancer, because the existence of informative censoring cannot be excluded. CONCLUSION: There is high variability in the strength of the association between frailty scores and 7-year all-cause mortality, incident CVD, and cancer. With regard to all-cause mortality, some scores give a modest improvement to the predictive ability. Our results show that certain scores clearly outperform others with regard to three important health outcomes in later life. Finally, we think that despite their limitations, the use of frailty scores to identify the elderly population at risk is still a useful measure, and the choice of a frailty score should balance feasibility with performance.

Resilience to cognitive impairment in the oldest-old: design of the EMIF-AD 90+ study.

BACKGROUND: The oldest-old (subjects aged 90 years and older) population represents the fastest growing segment of society and shows a high dementia prevalence rate of up to 40%. Only a few studies have investigated protective factors for cognitive impairment in the oldest-old. The EMIF-AD 90+ Study aims to identify factors associated with resilience to cognitive impairment in the oldest-old. In this paper we reviewed previous studies on cognitive resilience in the oldest-old and described the design of the EMIF-AD 90+ Study. METHODS: The EMIF-AD 90+ Study aimed to enroll 80 cognitively normal subjects and 40 subjects with cognitive impairment aged 90 years or older. Cognitive impairment was operationalized as amnestic mild cognitive impairment (aMCI), or possible or probable Alzheimer's Disease (AD). The study was part of the European Medical Information Framework for AD (EMIF-AD) and was conducted at the Amsterdam University Medical Centers (UMC) and at the University of Manchester. We will test whether cognitive resilience is associated with cognitive reserve, vascular comorbidities, mood, sleep, sensory system capacity, physical performance and capacity, genetic risk factors, hallmarks of ageing, and markers of neurodegeneration. Markers of neurodegeneration included an amyloid positron emission tomography, amyloid ß and tau in cerebrospinal fluid/blood and neurophysiological measures. DISCUSSION: The EMIF-AD 90+ Study will extend our knowledge on resilience to cognitive impairment in the oldest-old by extensive phenotyping of the subjects and the measurement of a wide range of potential protective factors, hallmarks of aging and markers of neurodegeneration. TRIAL REGISTRATION: Nederlands Trial Register NTR5867 . Registered 20 May 2016.

Association of early left ventricular dysfunction with advanced magnetic resonance white matter and gray matter brain measures: The CARDIA study.

INTRODUCTION: Relations between heart failure and clinically manifested stroke are well known, but the associations between heart and brain early abnormalities are not totally clear. AIMS: We explore relations of subclinical brain abnormalities with early cardiac dysfunction in a large healthy middle-aged biracial cohort. METHODS: The CARDIA study enrolled 5115 young adults aged 18-30 years at baseline (1985-1986). We assessed 719 Caucasian and African American participants of the CARDIA study, with echocardiograms and brain MRI at follow-up year 25 (2010-2011). Echocardiography assessed aortic root diameter; LVEF; circumferential, longitudinal, and radial deformation. Cerebral MRI DTI, and, on a subset, ASL perfusion sequences were used to assess white matter fractional anisotropy and gray matter cerebral blood flow (CBF). Linear regression explored relations between cardiac parameters and cerebral measures, adjusting for anthropometrics, risk factors, and brain constitutional variation. RESULTS: Mean age 50 ± 4 years, SBP 118 ± 15 mm Hg; 60% white, and 48% men. Mean CBF was 46 ± 9 mL/100 g/min, and white matter fractional anisotropy was 0.31 ± 0.02. Worse circumferential deformation and larger aortic root were related to worse white matter fractional anisotropy. Worse radial systolic deformation was related to worse CBF in multivariable models. LVEF did not relate to early brain abnormalities. CONCLUSIONS: In spite of no apparent effect of LV ejection fraction, early subclinical cardiac dysfunction and brain abnormalities are present and associated in middle-aged generally healthy individuals.

Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease.

Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia. ©RSNA, 2016 Online supplemental material is available for this article.