MyCOACH (COnnected Advice for Cognitive Health): a digitally delivered multidomain intervention for cognitive decline and risk of dementia in adults with mild cognitive impairment or subjective cognitive decline–study protocol for a randomised controlled trial

Introduction Digital health interventions are cost-effective and easily accessible, but there is currently a lack of effective online options for dementia prevention especially for people at risk due to mild cognitive impairment (MCI) or subjective cognitive decline (SCD). Methods and analysis MyCOACH (COnnected Advice for Cognitive Health) is a tailored online dementia risk reduction programme for adults aged ≥65 living with MCI or SCD. The MyCOACH trial aims to evaluate the programme’s effectiveness in reducing dementia risk compared with an active control over a 64-week period (N=326). Eligible participants are randomly allocated to one of two intervention arms for 12 weeks: (1) the MyCOACH intervention programme or (2) email bulletins with general healthy ageing information (active control). The MyCOACH intervention programme provides participants with information about memory impairments and dementia, memory strategies and different lifestyle factors associated with brain ageing as well as practical support including goal setting, motivational interviewing, brain training, dietary and exercise consultations, and a 26-week post-intervention booster session. Follow-up assessments are conducted for all participants at 13, 39 and 65 weeks from baseline, with the primary outcome being exposure to dementia risk factors measured using the Australian National University-Alzheimer’s Disease Risk Index. Secondary measures include cognitive function, quality of life, functional impairment, motivation to change behaviour, self-efficacy, morale and dementia literacy. Ethics and dissemination Ethical approval was obtained from the University of New South Wales Human Research Ethics Committee (HC210012, 19 February 2021). The results of the study will be disseminated in peer-reviewed journals and research conferences

A self-report risk index to predict occurrence of dementia in three independent cohorts of older adults: The ANU-ADRI

Background and Aims: The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer's disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts. Methods: This study included three validation cohorts, i.e., the Rush Memory and Aging Study (MAP) (n = 903, age ≥53 years), the Kungsholmen Project (KP) (n = 905, age ≥75 years), and the Cardiovascular Health Cognition Study (CVHS) (n = 2496, age ≥65 years) that were each followed for dementia. Baseline data were collected on exposure to the 15 risk factors included in the ANU-ADRI of which MAP had 10, KP had 8 and CVHS had 9. Risk scores and C-statistics were computed for individual participants for the ANU-ADRI and the CAIDE index. Results: For the ANU-ADRI using available data, the MAP study c-statistic was 0.637 (95% CI 0.596-0.678), for the KP study it was 0.740 (0.712-0.768) and for the CVHS it was 0.733 (0.691-0.776) for predicting AD. When a common set of risk and protective factors were used c-statistics were 0.689 (95% CI 0.650-0.727), 0.666 (0.628-0.704) and 0.734 (0.707-0.761) for MAP, KP and CVHS respectively. Results for CAIDE ranged from c-statistics of 0.488 (0.427-0.554) to 0.595 (0.565-0.625). Conclusion: A composite risk score derived from the ANU-ADRI weights including 8-10 risk or protective factors is a valid, self-report tool to identify those at risk of AD and dementia. The accuracy can be further improved in studies including more risk factors and younger cohorts with long-term follow-up. © 2014 Anstey et al

On the role of Rossby wave breaking in quasi‐biennial odulation of the stratospheric polar vortex

The boreal‐winter stratospheric polar vortex is more disturbed when the quasi‐biennial oscillation (QBO) in the lower stratosphere is in its easterly phase (eQBO), and more stable during the westerly phase (wQBO). This so‐called “Holton‐Tan effect” (HTE) is known to involve Rossby waves (RWs) but the details remain obscure. This tropical‐extratropical connection is re‐examined in an attempt to explain its intra‐seasonal variation and its relation to Rossby wave breaking (RWB). Reanalyses in isentropic coordinates from the National Center for Environmental Prediction Climate Forecast System for the 1979 – 2017 period are used to evaluate the relevant features of RWB in the context of waveguide, wave mean‐flow interaction, and the QBO‐induced meridional circulation. During eQBO, the net extratropical wave forcing is enhanced in early winter with ~25% increase in upward propagating PRWs of zonal wavenumber 1 (wave‐1). RWB is also enhanced in the lower stratosphere, characterized by convergent anomalies in the subtropics and at high‐latitudes and strengthened waveguide in between at 20‐40°N, 350‐650 K. In late winter, RWB leads to finite amplitude growth, which hinders upward propagating PRWs of zonal wavenumber 2 and 3 (wave‐2‐3). During wQBO, RWB in association with wave‐2‐3 is enhanced in the upper stratosphere. Wave absorption/mixing in the surf zone reinforces a stable polar vortex in early to middle winter. A poleward confinement of extratropical waveguide in the upper stratosphere forces RWB to extend downward around January. A strengthening of upward propagating wave‐2‐3 follows and the polar‐vortex response switches from reinforcement to disturbance around February, thus a sign reversal of the HTE in late winter

Study protocol for development and validation of a single tool to assess risks of stroke, diabetes mellitus, myocardial infarction and dementia: DemNCD-Risk

Introduction Current efforts to reduce dementia focus on prevention and risk reduction by targeting modifiable risk factors. As dementia and cardiometabolic non-communicable diseases (NCDs) share risk factors, a single risk-estimating tool for dementia and multiple NCDs could be cost-effective and facilitate concurrent assessments as compared with a conventional single approach. The aim of this study is to develop and validate a new risk tool that estimates an individual's risk of developing dementia and other NCDs including diabetes mellitus, stroke and myocardial infarction. Once validated, it could be used by the public and general practitioners. Methods and analysis Ten high-quality cohort studies from multiple countries were identified, which met eligibility criteria, including large representative samples, long-term follow-up, data on clinical diagnoses of dementia and NCDs, recognised modifiable risk factors for the four NCDs and mortality data. Pooled harmonised data from the cohorts will be used, with 65% randomly allocated for development of the predictive model and 35% for testing. Predictors include sociodemographic characteristics, general health risk factors and lifestyle/behavioural risk factors. A subdistribution hazard model will assess the risk factors' contribution to the outcome, adjusting for competing mortality risks. Point-based scoring algorithms will be built using predictor weights, internally validated and the discriminative ability and calibration of the model will be assessed for the outcomes. Sensitivity analyses will include recalculating risk scores using logistic regression. Ethics and dissemination Ethics approval is provided by the University of New South Wales Human Research Ethics Committee (UNSW HREC; protocol numbers HC200515, HC3413). All data are deidentified and securely stored on servers at Neuroscience Research Australia. Study findings will be presented at conferences and published in peer-reviewed journals. The tool will be accessible as a public health resource. Knowledge translation and implementation work will explore strategies to apply the tool in clinical practice

P wave indices, heart rate variability and anthropometry in a healthy South Asian population

Background: South Asians have a low prevalence of atrial fibrillation (AF) in comparison with White Europeans despite a higher burden of hypertension, diabetes mellitus and coronary artery disease. The reason for this disparity is unclear but may relate to electrophysiological or structural differences within the atria or variations in autonomic function. We aimed to assess these areas using a range of non-invasive cardiac investigations. Methods: A prospective cohort study was performed on 200 South Asian and 200 Caucasian healthy volunteers aged 18–40 years. All subjects underwent electrocardiography (ECG), echocardiography and anthropometric measurements. Eighty subjects in each cohort underwent 24 hour ambulatory ECG and fifty subjects in each cohort underwent exercise testing. Results: Compared with White Europeans, South Asians were of a smaller height with lower lean body mass and smaller left atrial size. They had reduced P wave dispersion and P wave terminal force in lead V1. South Asians had a lower burden of supraventricular ectopy. They had a higher mean heart rate and South Asian males had lower heart rate variability, suggestive of sympathetic predominance. Exercise capacity was lower in South Asians. Conclusions: South Asians have differences in left atrial size, P wave indices, burden of supraventricular ectopy, heart rate, heart rate variability and anthropometric measurements. These differences may relate to variations in atrial morphology, atrial electrophysiology and autonomic function and might help to explain why South Asians are less susceptible to developing AF

Validation of the CogDrisk Instrument as Predictive of Dementia in Four General Community-Dwelling Populations

Background: Lack of external validation of dementia risk tools is a major limitation for generalizability and translatability of prediction scores in clinical practice and research. Objectives: We aimed to validate a new dementia prediction risk tool called CogDrisk and a version, CogDrisk-AD for predicting Alzheimer’s disease (AD) using cohort studies. Design, Setting, Participants and Measurements: Four cohort studies were identified that included majority of the dementia risk factors from the CogDrisk tool. Participants who were free of dementia at baseline were included. The predictors were component variables in the CogDrisk tool that include self-reported demographics, medical risk factors and lifestyle habits. Risk scores for Any Dementia and AD were computed and Area Under the Curve (AUC) was assessed. To examine modifiable risk factors for dementia, the CogDrisk tool was tested by excluding age and sex estimates from the model. Results: The performance of the tool varied between studies. The overall AUC and 95% CI for predicting dementia was 0.77 (0.57, 0.97) for the Swedish National study on Aging and Care in Kungsholmen, 0.76 (0.70, 0.83) for the Health and Retirement Study - Aging, Demographics and Memory Study, 0.70 (0.67,0.72) for the Cardiovascular Health Study Cognition Study, and 0.66 (0.62,0.70) for the Rush Memory and Aging Project. Conclusions: The CogDrisk and CogDrisk-AD performed well in the four studies. Overall, this tool can be used to assess individualized risk factors of dementia and AD in various population settings

Association of depression with newly diagnosed type 2 diabetes among adults aged between 25 to 60 years in Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>The combination of depression with type 2 diabetes is a public health problem. If diabetes is managed in its initial phase, the morbidity and mortality due to this combination may be prevented at an early stage. Therefore, we aimed to determine the association of depression with newly diagnosed type 2 diabetes among adults aged between 25 to 60 years in Karachi, Pakistan.</p> <p>Methods</p> <p>From July 2006 to September 2007, a matched case control study (n = 592) was conducted in Civil Hospital, Karachi. Incident cases of type 2 diabetes (n = 296) diagnosed within one month were recruited from diabetic Out Patient Department (OPD) of Civil Hospital, Karachi. They were matched on age and sex with controls (n = 296), who were attendants sitting in the medical out patient department of the same hospital, recruited on the basis of absence of classical symptoms of polyuria and polydispia along with random blood glucose level of <200 mg/dl measured by a glucometer. Depression was identified by the Siddiqui Shah Depression Scale. Conditional logistic regression was applied to examine the association of depression and other independent variables with newly diagnosed type 2 diabetes at 95% C.I. and P < 0.05.</p> <p>Results</p> <p>The study comprised of 592 subjects with 432(73%) males and 160(27%) females. Depression was significantly associated with newly diagnosed type 2 diabetes having mild level (mOR: 3.86; 95%CI: 2.22,6.71) and moderate to severe level (mOR: 3.41; 95%CI: 2.07,5.61). History of (h/o) gestational diabetes (mOR: 2.83; 95%CI: 1.05,7.64), family h/o diabetes (mOR: 1.59; 95%CI: 1.04,2.43), nuclear family (mOR: 1.75; 95%CI: 1.14,2.69), BMI (mOR: 1.62; 95%CI: 1.01,2.60 for obese and mOR: 2.12; 95%CI: 1.19,3.79 for overweight vs healthy to underweight) were also significantly associated with outcome, adjusting for age, sex, marital status, h/o smoking and h/o high BP.</p> <p>Conclusions</p> <p>Diabetics should be screened simultaneously for depression and concomitant preventive strategies for gestational diabetes, nuclear family and high BMI should also be used to prevent mortality/morbidity among patients between 25 to 60 years of age.</p

Changes in health risk behaviors of elementary school students in northern Taiwan from 2001 to 2003: results from the child and adolescent behaviors in long-term evolution study

[[abstract]]Background: Previous research has indicated that children's behaviors have long-term effects on later life. Hence it is important to monitor the development of health risk behaviors in childhood. This study examined the changes in health risk behaviors in fourth- to sixth-grade students in northern Taiwan from 2001 to 2003. Methods: The Child and Adolescent Behaviors in Long-Term Evolution (CABLE) study collected data from 1,820 students from 2001 to 2003 (students were 9 or 10 years old in 2001). Exploratory factor analysis was used to determine the aggregation of health risk behaviors. A linear growth curve model was used to determine whether health risk behaviors changed over time. Results: Of the 13 behaviors, staying up late and eating snacks late at night were the most prevalent (82.3% of subjects in 2001, 81.8% in 2002, 88.5% in 2003) and second most prevalent (68.7%, 67.4%, 71.6%) behaviors, respectively, from 2001 to 2003. The three least prevalent health risk behaviors were chewing betel nut (1.0%, 0.4%, 0.2%), smoking (1.4%, 1.0%, 0.8%), and drinking alcohol (8.5%, 6.0%, 5.2%). The frequencies of swearing and staying up late showed the greatest significant increases with time. On the other hand, suppressing urination and drinking alcohol decreased over time. Using exploratory factor analysis, we aggregated the health risk behaviors into three categories: unhealthy habits, aggressive behaviors, and substance use. Although students did not display high levels of aggressive behavior or experimentation with substances, the development of these behaviors in a small proportion of students should not be ignored. The results of the linear growth curve model indicated that unhealthy habits and aggressive behaviors increased over time. However, substance use slightly decreased over time. Conclusion: We found that some health risk behaviors increased with time while others did not. Unhealthy habits and aggressive behaviors increased, whereas substance use slightly decreased during this period. Educational professionals should pay attention to the different patterns of change in these behaviors in elementary school students

Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock

Background Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process. Methods Endotoxemic shock was induced in sheep by administration of an escalating dose of lipopolysaccharide, after which they subsequently received either no fluid bolus resuscitation or a 0.9% saline bolus. Lung tissue, bronchoalveolar fluid (BAL) and plasma were analysed by real-time PCR, ELISA, flow cytometry and immunohistochemical staining to assess inflammatory cells, cytokines, hyaluronan and matrix metalloproteinases. Results Endotoxemia was associated with decreased serum albumin and total protein levels, with activated neutrophils, while the glycocalyx glycosaminoglycan hyaluronan was significantly increased in BAL. Quantitative real-time PCR studies showed higher expression of IL-6 and IL-8 with saline resuscitation but no difference in matrix metalloproteinase expression. BAL and tissue homogenate levels of IL-6, IL-8 and IL-1β were elevated. Conclusions This data shows that the inflammatory response is enhanced when a host with endotoxemia is resuscitated with saline, with a comparatively higher release of inflammatory cytokines and endothelial/glycocalyx damage, but no change in matrix metalloproteinase levels

Immunoglobulin GM 3 23 5,13,14 phenotype is strongly associated with IgG1 antibody responses to Plasmodium vivax vaccine candidate antigens PvMSP1-19 and PvAMA-1

<p>Abstract</p> <p>Background</p> <p>Humoral immune responses play a key role in the development of immunity to malaria, but the host genetic factors that contribute to the naturally occurring immune responses to malarial antigens are not completely understood. The aim of the present investigation was to determine whether, in subjects exposed to malaria, GM and KM allotypes--genetic markers of immunoglobulin γ and κ-type light chains, respectively--contribute to the magnitude of natural antibody responses to target antigens that are leading vaccine candidates for protection against <it>Plasmodium vivax</it>.</p> <p>Methods</p> <p>Sera from 210 adults, who had been exposed to malaria transmission in the Brazilian Amazon endemic area, were allotyped for several GM and KM determinants by a standard hemagglutination-inhibition method. IgG subclass antibodies to <it>P. vivax </it>apical membrane antigen 1 (PvAMA-1) and merozoite surface protein 1 (PvMSP1-19) were determined by an enzyme-linked immunosorbent assay. Multiple linear regression models and the non-parametric Mann-Whitney test were used for data analyses.</p> <p>Results</p> <p>IgG1 antibody levels to both PvMSP1-19 and PvAMA-1 antigens were significantly higher (<it>P </it>= 0.004, <it>P </it>= 0.002, respectively) in subjects with the GM 3 23 5,13,14 phenotype than in those who lacked this phenotype.</p> <p>Conclusions</p> <p>Results presented here show that immunoglobulin GM allotypes contribute to the natural antibody responses to <it>P. vivax </it>malaria antigens. These findings have important implications for the effectiveness of vaccines containing PvAMA-1 or PvMSP1-19 antigens. They also shed light on the possible role of malaria as one of the evolutionary selective forces that may have contributed to the maintenance of the extensive polymorphism at the GM loci.</p