Latent profiles of modifiable dementia risk factors in later midlife: relationships with incident dementia, cognition, and neuroimaging outcomes.

In 2020, the Lancet Commission identified 12 modifiable factors that increase population-level dementia risk. It is unclear if these risk factors co-occur among individuals in a clinically meaningful way. Using latent class analysis, we identified profiles of modifiable dementia risk factors in dementia-free adults aged 60-64 years from the UK Biobank. We then estimated associations between these profiles with incident dementia, cognition, and neuroimaging outcomes, and explored the differences across profiles in the effects of a polygenic risk score for Alzheimer's disease on outcomes. In 55,333 males and 63,063 females, three sex-specific latent profiles were identified: cardiometabolic risk, substance use-related risk, and low risk. The cardiometabolic risk profile in both males and females was associated with greater incidence of all-cause dementia (male: OR [95% CI] = 2.33 [2.03, 2.66]; female: OR [95% CI] = 1.44 [1.24, 1.68]), poorer cognitive performance, greater brain atrophy, and greater white matter hyperintensity volume compared to the low risk profile. The substance use-related risk profile in males was associated with poorer cognitive performance and greater white matter hyperintensities compared to the low risk profile, but no difference in all-cause dementia incidence was observed (OR [95% CI] = 1.00 [0.95, 1.06]). In females, the substance use-related risk profile demonstrated increased dementia incidence (OR [95% CI] = 1.58 [1.57, 1.58]) and greater brain atrophy but smaller white matter hyperintensity volume compared to the low risk profile. The polygenic risk score had larger effects among females, and differentially influenced outcomes across profiles; for instance, there were larger effects of the polygenic risk score on atrophy in the cardiometabolic profile vs. the low risk profile among males, and larger effects of the polygenic risk score on loss of white matter integrity in the cardiometabolic profile vs. the low risk profile among females. These results reveal three modifiable dementia risk profiles, their unique cognitive/neuroimaging outcomes, and their interactions with genetic risk for Alzheimer's disease. These differences highlight the need to consider population heterogeneity in risk prediction tools and in planning personalized prevention strategies.

Relationship Between Direct Aggression and Prosocial Behavior: The Role of Attention and Intelligence Among Children at Risk for Behavioral Problems.

This study aimed to investigate the influence of attention and intelligence in the prediction of prosocial behavior by direct aggression (proactive or reactive) in school-aged children at risk for behavioral problems. The sample was composed of 64 children aged 6 to 8 years screened for risk of behavioral problems, who were enrolled in a clinical trial. Multiple regression models were tested to investigate the prediction of prosocial behavior by direct aggression (proactive or reactive), attention, and intelligence. Additive multiple moderation models were tested to analyze the conditional effect of attention and intelligence in the prediction of prosocial behavior by proactive and reactive aggression. Aggression (proactive or reactive), attention, and intelligence did not linearly predict prosocial behavior. Conditional effects were found only for the proactive aggression model. Negative impacts on prosocial behavior were observed among children with low attention and high intelligence performance, while medium and high levels of attention showed to be protective factors among low to medium intellectual ability children. Clinical impacts of the results are discussed.

Cytochrome P450-soluble epoxide hydrolase oxylipins, depression and cognition in type 2 diabetes.

AIMS: This study examined serum cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) oxylipins and depressive symptoms together in relation to cognitive performance in individuals with type 2 diabetes mellitus (T2DM). METHODS: Clinically cognitively normal T2DM individuals were recruited (NCT04455867). Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II; total scores ≤13 indicated minimal depressive symptoms and ≥ 14 indicated significant depressive symptoms). Executive function and verbal memory were assessed. Fasting serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass-spectrometry. RESULTS: The study included 85 participants with minimal depressive symptoms and 27 with significant symptoms (mean age: 63.3 ± 9.8 years, 49 % women). In all participants, higher concentrations of linoleic acid derived sEH (12,13-dihydroxyoctadecamonoenoic acid; DiHOME) and CYP450 (12(13)-epoxyoctadecamonoenoic acid; EpOME) metabolites were associated with poorer executive function (F1,101 = 6.094, p = 0.015 and F1,101 = 5.598, p = 0.020, respectively). Concentrations of multiple sEH substrates interacted with depressive symptoms to predict 1) poorer executive function, including 9(10)-EpOME (F1,100 = 12.137, p < 0.001), 5(6)-epoxyeicosatrienoic acid (5(6)-EpETrE; F1,100 = 6.481, p = 0.012) and 11(12)-EpETrE (F1,100 = 4.409, p = 0.038), and 2) verbal memory, including 9(10)-EpOME (F1,100 = 4.286, p = 0.041), 5(6)-EpETrE (F1,100 = 6.845, p = 0.010), 11(12)-EpETrE (F1,100 = 3.981, p = 0.049) and 14(15)-EpETrE (F1,100 = 5.019, p = 0.027). CONCLUSIONS: Associations of CYP450-sEH metabolites and depressive symptoms with cognition highlight the biomarker and therapeutic potential of the CYP450-sEH pathway in T2DM.

Longitudinal relationships between depressive symptoms, functional impairment, and physical activity in later late life.

The purpose of this study was to investigate relationships between depressive symptoms, functional disability, and physical activity over time in community-dwelling older adults. The Religious Order Study and Rush Memory and Aging Project are longitudinal cohort studies based in the United States which began recruitment in 1994 and 1997, respectively. This analysis included 1611 participants (27.4% male, 92.9% White, 74.7% cognitively normal) who were included at age 80 and followed until age 90. Depressive symptoms were assessed using the modified Center for Epidemiologic Studies Depression scale. Functional disability was assessed using the Instrumental Activities of Daily Living (IADL) scale. Physical activity was self-reported hours of weekly exercise. Reciprocal temporal relationships between these variables were investigated using a random intercept cross-lagged panel model, which decomposes observed variables into stable between-person ('trait') and variable within-person ('state') components to estimate the directional effects between variables over time. Traits for depressive symptoms, IADL disability, and physical activity were correlated. IADL disability showed autoregressive effects; disability starting at age 82 strongly predicted subsequent disability. Consistent autoregressive effects were not observed for depressive symptoms nor physical activity. Several small cross-lagged effects between states were observed for IADL disability and physical activity, as well as for IADL disability and depressive symptoms. There were no direct effects between depressive symptoms and physical activity, but several paths through IADL disability were observed between ages 82 and 88. Functional disability played an important role in octogenarians, highlighting the importance of maintaining functional independence later in life.

Reading instruction for students with intellectual disabilities who require augmentative and alternative communication: A multiple single case study with baseline, posttest, follow-up, and maintenance.

The purpose of the current study was to examine whether seven children, aged 6-10 years, with intellectual disabilities who require augmentative and alternative communication, could acquire phonological awareness and reading skills by using a reading material that is based on research on the evidence-based reading program Accessible literacy learning. The effect of the measures has been examined using a multiple single-case design with baseline, posttest, follow-up, and maintenance. All the teachers were trained to deliver the reading intervention in the students' familiar place at school. The results indicated that students with intellectual disabilities who require augmentative and alternative communication could acquire phonological awareness and decoding by working systematically with reading material based on evidence-based strategies.

Short-term effects of the strengthening families Program (SFP 10-14) in Brazil: a cluster randomized controlled trial.

INTRODUCTION: This study reports the evaluation of the short-term effects of the Strengthening Families Program (SFP 10-14), adapted as Famílias Fortes (Strong Families) in Brazil, on preventing adolescent drug use and improving parenting behaviors. METHODS: A two-arm, parallel cluster randomized controlled trial was conducted in 60 Social Assistance Reference Centers (SARC) from 12 Brazilian municipalities. In each city, the SARC were randomly assigned to the intervention or control group. A total of 805 families participated in the study, each contributing data from one parent or legal guardian and one adolescent totaling 1,610 participants. Data collection occurred before intervention implementation and 6 months after baseline collection. Data were analyzed using multilevel mixed-effects modeling with repeated measures in two different paradigms: Intention to Treat (ITT) and Per protocol (PP). The study was registered in the Brazilian Ministry of Health Register of Clinical Trials (REBEC), under protocol no. RBR-5hz9g6z. RESULTS: Considering the ITT paradigm, the program reduced the chance of parents and legal guardians being classified as negligent by 60% (95%CI 0.21; 0.78), increased the use of nonviolent discipline by caregivers (Coef 0.33, 95%CI 0.01; 0.64) and decreased the chance of adults exposing adolescents to their drunken episodes by 80% (95%CI 0.06; 0.54). No program effects were observed on outcomes related to adolescent drug use. Similar results were found for the PP paradigm. CONCLUSION: The positive effects on family outcomes suggest preventive potential of the program among the Brazilian population. Long-term evaluations are necessary to verify if the program can also achieve the drug use reduction goals not observed in the short term.

No association between metformin initiation and incident dementia in older adults newly diagnosed with diabetes.

BACKGROUND: Metformin has been suggested to reduce dementia risk; however, most epidemiologic studies have been limited by immortal time bias or confounding due to disease severity. OBJECTIVES: To investigate the association of metformin initiation with incident dementia using strategies that mitigate these important sources of bias. METHODS: Residents of Ontario, Canada ≥66 years newly diagnosed with diabetes from January 1, 2008 to December 31, 2017 entered this retrospective population-based cohort. To consider the indication for metformin monotherapy initiation, people with hemoglobin A1c of 6.5%-8.0% and estimated glomerular filtration rate ≥45 mL/min/1.73 m2 were selected. Using the landmark method to address immortal time bias, exposure was grouped into "metformin monotherapy initiation within 180 days after new diabetes diagnosis" or "no glucose-lowering medications within 180 days." To address disease latency, 1-year lag time was applied to the end of the 180-day landmark period. Incident dementia was defined using a validated algorithm for Alzheimer's disease and related dementias. Adjusted hazard ratios (aHR) and confidence intervals (CIs) were estimated from propensity-score weighted Cox proportional hazard models. RESULTS: Over mean follow-up of 6.77 years from cohort entry, metformin initiation within 180 days after new diabetes diagnosis (N = 12,331; 978 events; 65,762 person-years) showed no association with dementia risk (aHR [95% CI] = 1.05 [0.96-1.15]), compared to delayed or no glucose-lowering medication initiation (N = 22,369; 1768 events; 117,415 person-years). CONCLUSION: Early metformin initiation was not associated with incident dementia in older adults newly diagnosed with diabetes. The utility of metformin to prevent dementia was not supported.

Redefining effect size interpretations for psychotherapy RCTs in depression.

INTRODUCTION: Effect sizes are often used to interpret the magnitude of a result and in power calculations when planning research studies. However, as effect size interpretations are context-dependent, Jacob Cohen's suggested guidelines for what represents a small, medium, and large effect are unlikely to be suitable for a diverse range of research populations and interventions. Our objective here is to determine empirically-derived effect size thresholds associated with psychotherapy randomized controlled trials (RCTs) in depression by calculating the effect size distribution. METHODS: We extracted effect sizes from 366 RCTs provided by the systematic review of Cuijpers and colleagues (2020) on psychotherapy for depressive disorders across all age groups. The 50th percentile effect size, as this represents a medium effect size, and the 25th (small) and 75th (large) percentile effect sizes were calculated to determine empirically-derived effect size thresholds. RESULTS: After adjusting for publication bias, 0.27, 0.53, and 0.86 represent small, medium, and large effect sizes, respectively, for psychotherapy treatment for depressive disorders. DISCUSSION: The effect size distribution for psychotherapy treatment of depression indicates that observed effect size thresholds are larger than Cohen's suggested effect size thresholds (0.2, 0.5, and 0.8). These results have implications for the interpretation of study effects and the planning of future studies via power analyses, which often use effect size thresholds.

Sexual dimorphism in anxiety is programmed in-utero by sex-steroids: Proof of concept using a disease-model and stress responses to COVID pandemic.

Sex differences in the psychological impact of the COVID-19 pandemic have been consistently reported, showing disproportionally high rates of anxiety/distress in women relative to men. The mechanisms underlying this sexual dimorphism remain unclear. The present study queries the potential protective role of early hyperandrogenism on brain development. A natural model of sex-steroids abnormality, classic congenital adrenal hyperplasia (CAH), was used to test this question. CAH is characterized by adrenal androgen overproduction in utero (prenatal) through the neonatal critical developmental period. An online survey collected information on subjective responses to the COVID-19 pandemic. Matched on demographic variables, 60 adults carrying a diagnosis of classic CAH and 240 adults from the general population (non-CAH) were compared on levels of anxiety/distress in the first year of the COVID-19 pandemic (May 2020-April 2021). Structural Equation Modeling was used to test the modulation by CAH status of Sex effects on anxiety/distress. Results revealed lower levels of anxiety/distress in the female CAH group compared to the other 3 groups (male CAH, female non-CAH, and male non-CAH). This finding suggests that pre-neonatal hyperandrogenism might impact the development of neural circuits underlying anxiety processes, in a way that enhances resilience to chronic stress.

A mixture model for differentiating longitudinal courses of multiple sclerosis.

BACKGROUND: Multiple sclerosis has a broad spectrum of clinical courses. Early identification of patients at greater risk of accumulating disability is essential. OBJECTIVES: Identify groups of patients with similar presentation through a mixture model and predict their trajectories over the years. METHODS: Retrospective study of patients from 1994 to 2019. We performed a latent profile analysis followed by a latent transition analysis based on eight parameters: age, disease duration, EDSS, number of relapses, multi-topographic symptoms, motor impairment, sphincter impairment, and infratentorial lesions. RESULTS: We included 629 patients, regardless of the phenotypical classification. We identified three distinct groups at the beginning and end of the follow-up. The three-classes model disclosed the "No disability regardless disease duration" (NDRDD) class with low EDSS and younger patients, the "Disability within a short disease duration" (DSDD) class with the worse disability besides short illness, and the "Disability within a long disease duration" (DLDD) class that achieved high EDSS over a long disease duration. EDSS, disease duration, and no sphincter impairment had the best entropy to distinguish classes at the initial presentation. Over time, the patients from NDRDD had a 52.1 % probability of changing to DLDD and 7.7 % of changing to DSDD. CONCLUSIONS: We identified three groups of clinical presentations and their evolution over time based on considered prognostic factors. The most likely transition is from NDRDD to DLDD.

High spatial resolution (10-50 µm) analysis of Sr isotopes in rock-forming apatite by LA-MC-ICP-MS.

In situ Sr isotopes analysis of apatite by LA-(MC)-ICP-MS is challenged by the difficulty to monitor and correct isobaric interferences from atomic and polyatomic ions. We present a new routine procedure for analysing rock-forming apatites with a Thermo Scientific Neptune XT MC-ICP-MS coupled with a Teledyne Cetac Analyte Excite+ 193 nm laser ablation system. Five apatite standards that cover a large range of REE/Sr ratios were selected, and their 87Sr/86Sr ratios were measured in solution after dissolution and purification of Sr [Durango: 0.706321(5); Madagascar: 0.711814(5); Slyudyanka; 0.707705(4); Sumé: 0.707247(4); and Ipirá: 0.710487(4)]. The optimisation of both instrument setup and data reduction schemes was achieved through repeated measurements of calibration solutions and of apatite standards at four different rectangular-shaped laser ablation beam sizes (50 × 50, 25 × 25, 13 × 13 and 10 × 10 µm). Two complementary methods were developed for data reduction: Method 1, which corrects measured intensities for gas blank and instrumental mass bias only; and Method 2, which additionally corrects for isobaric interferences of 87Rb+, 166, 168 and 170Er++, 170, 172, 174 and 176Yb++, 40Ca44Ca+, 40Ca46Ca+, 44Ca43Ca+ and 40Ca48Ca+. A precision of ca. 100 ppm (2 s.e.) can be achieved on the 87Sr/86Sr ratio with a 50 µm laser ablation beam when using Method 2, and it remains better than 3000 ppm at 10 µm with Method 1. Method 1 gives precise and accurate 87Sr/86Sr ratios when 173Yb++ is below the global limit of detection (with LODglobal = 3 s.d. of the means of all gas blanks measurements). When 173Yb++ is above the LODglobal, Method 2 should be preferred as it provides more accurate 87Sr/86Sr ratios. Overall, this study offers a robust and reliable approach for LA-MC-ICP-MS analysis of Sr isotopes in rock-forming apatite at a high spatial resolution (i.e. down to 10 µm), overcoming previous limitations associated with instrumental set up and data reduction.

Perivascular spaces mediate a relationship between diabetes and other cerebral small vessel disease markers in cerebrovascular and neurodegenerative diseases.

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together. Counterfactual moderated mediation models found indirect effects of T2DM on volumes of other SVD and diffusion markers that were mediated by wmPVS: pWMH, dWMH, periventricular lacunes, and deep lacunes, and progression of deep lacunes over 1 year, in patients with hypertension, but not in patients without hypertension. Studying the regulation of cortical perivascular fluid dynamics may reveal mechanisms that mediate the impact of T2DM on cerebral small vessels.

Social jetlag is associated with adverse cardiometabolic latent traits in early adolescence: an observational study.

Introduction: Adolescence is marked by physiological and social changes, such as puberty, increased responsibilities and earlier school start times. This often leads to insufficient sleep on school nights and the need to compensate for lost sleep on weekends, causing a misalignment between biological and social times, which has been termed social jetlag (SJL). SJL triggers stress responses and is associated with several negative health outcomes, including higher cardiometabolic risk in adults. In adolescence, however, SJL has only been consistently related to increases in adiposity but its association with other cardiometabolic indicators are unclear. Method: In a sample of 278 healthy early adolescents (9-15 years of age; 168 girls) we investigated: 1) whether self-reported SJL is associated (using path analyses) with a cardiometabolic status latent factor obtained by testing the best fitting model via confirmatory factor analyses from an initial set of eight indicators [body mass index (BMI), waist/height ratio, triglyceride concentration, diastolic and systolic blood pressure, glycated hemoglobin, total cholesterol/high-density lipoprotein ratio (chol/HDL), and % body fat]; and 2) whether age and/or pubertal status influence the association between SJL and cardiometabolic status. Result: We found that, for girls, higher SJL was associated with more adverse cardiometabolic latent scores (the shared variance of BMI, waist/height ratio, chol/HDL and systolic blood pressure, which had acceptable model fit indices). However, the role of age and pubertal status in this association was unclear for both sexes. Discussion: SJL was associated with adverse cardiometabolic latent traits beyond increases in adiposity in this observational study in early female adolescents. Because disruptions of circadian rhythms are believed to lead to dysregulated energy homeostasis and not vice-versa, our findings highlight the need for sleep interventions in adolescence to help reduce the global burden of cardiometabolic ill health, especially in girls.

Structural integrity and skeletal trace elements in intertidal coralline algae across the Northeast Atlantic reveal a distinct separation of the leading and the trailing edge populations.

Intertidal macroalgae, such as coralline algae, represent an essential structural element and substrate in rocky coastal zones. They have a high degree of flexibility allowing their survival in environments with severe mechanical stress during tidal cycles. This study characterised the genicula and intergenicula of the calcifying red algae Corallina officinalis across its geographic distribution in the Northeast Atlantic. Poleward populations have constructed more sturdy cell walls compared to equatorward populations, potentially due to greater local adaptations to higher frequency and intensity of environmental factors like storms and wave action. Southern populations showed a lack of local adaptation culminating in survival rather than thriving within their current environment, hence, they are located at the margin of this species' favourable conditions. Results clarify significant differences between latitudes and indicate a north-to-south gradient in this species' skeletal elemental composition. Northern populations were dominated by cadmium, whereas chromium was the major trace element found in southern populations. In the future, these characteristics could lead to a permanent decline and a decrease in the ecosystem functions of C. officinalis in the southern locations in the Northeast Atlantic, which may be accelerated by predicted future climatic changes.

Reading intervention for students with intellectual disabilities without functional speech who require augmentative and alternative communication: a multiple single-case design with four randomized baselines.

BACKGROUND: Literacy is one of the most important skills a students can achieve, as it provides access to information and communication. Unfortunately, literacy skills are not easily acquired, especially for students with intellectual disabilities who require augmentative and alternative communication (AAC). There are many barriers to literacy acquisition, some due to low expectations from parents and teachers and lack of evidence-based reading programs and reading materials adapted for AAC. Barriers as a result of extensive support needs is also a real factor. This trial aims to deliver reading instructions to 40 students with intellectual disabilities who require AAC and contribute in the debate on how to best support this population through reading instructions to maximizes their reading skills. METHODOLOGY: Forty non-verbal or minimally verbal students (age 6-14) with intellectual disabilities who require AAC will be part of a reading intervention with a multiple single-case design with four randomized baselines. The intervention period will last for 18 months and will commence in March 2023. The students will receive the intervention in a one-to-one format, working systematically with a reading material that contains phonological awareness and decoding tasks based on the Accessible Literacy Learning (ALL) developed by Janice Light and David McNaughton. All the teachers will be trained to deliver the reading intervention. DISCUSSION: The reading material "Lesing for alle" (Reading for all) is based on and follow the strategies behind the research of ALL. The current trial will through a reading intervention contribute to move beyond only teaching sight words and combine several reading components such as sound blending, letter-sound correspondence, phoneme segmentation, shared reading, recognition of sight words, and decoding. The strategies and methods in use is built on the existing science of reading, especially what has been effective in teaching reading for students with intellectual disabilities who require AAC. There is limited generalizability of prior findings in reading-related phonological processing interventions to different populations of them who use AAC specially outside of the USA. More research is needed to understand how programs designed to improve reading skills across other settings understand the program's long-term effects and to study the effectiveness when delivered by educators who are not speech language therapists or researchers. TRIAL REGISTRATION: NCT05709405 . Registered 23 January 2023.

Cut-off point, sensitivity and specificity for screening the reading fluency in children. / Pontos de corte, sensibilidade e especificidade para rastreamento da fluência leitora em crianças.

PURPOSE: to establish cut-off point for reading speed and accuracy, to obtain minimum values for comprehending texts, and allow classifying students from 2nd to 5th grade of elementary school according to good or poor reading performance. METHODS: 147 assessment protocols for oral reading and text comprehension of students from 3rd to 5th grade of Elementary School with and without reading difficulties were analyzed. The oral text reading rate and accuracy values were analyzed. ROC curves were constructed, and sensitivity and specificity calculated for each reading fluency parameter, and each school grade. RESULTS: Sensitivity and specificity for measures of rate and accuracy in text reading were calculated for the 3rd, 4th, and 5th grades. Rate and precision under the ROC curve did not differ statistically. The values for the 2nd grade were mathematically estimated. CONCLUSION: The cutoff values expected for students from 2nd to 3rd grade were identified, with recommendations for using the oral text reading rate for reading comprehension screening procedures.

OBJETIVO: estabelecer pontos de corte para valores de velocidade e acurácia de leitura, a fim de obter valores mínimos para compreensão de textos, e permitir classificar alunos de 2º a 5º ano do Ensino Fundamental, de acordo com bom ou pobre desempenho em leitura. MÉTODO: foram analisados ​​147 protocolos de avaliação de leitura oral e compreensão textual de escolares de 3º a 5º ano com e sem dificuldades de leitura. A taxa de leitura oral de texto e os valores de acurácia foram analisados. Curvas ROC foram construídas e a sensibilidade e a especificidade, calculadas para cada parâmetro de fluência de leitura por ano escolar. RESULTADOS: A sensibilidade e a especificidade para medidas de taxa e acurácia na leitura de texto foram calculadas para o 3º, 4º e 5º anos. A taxa e a precisão sob a curva ROC não diferiram estatisticamente. Os valores do 2º ano foram estimados matematicamente. CONCLUSÃO: Foram identificados os valores de corte esperados para escolares do 2º ao 5º ano, com recomendações de utilização da taxa de leitura de texto oral para procedimentos de rastreamento da compreensão leitora.

Association of sulfonylureas with the risk of dementia: A population-based cohort study.

BACKGROUND: Sulfonylureas are oral glucose-lowering medications positioned as a second-line therapy for type 2 diabetes. Evidence relating them to cognitive decline has been mixed. The objective was to determine whether sulfonylurea use was associated with a differential risk of dementia compared with dipeptidyl peptidase-4 (DPP4) inhibitor use. METHODS: Using administrative data from residents in Ontario, Canada, adults aged ≥66 years who were new users of a sulfonylurea or a DPP4 inhibitor from June 14, 2011, to March 31, 2021 entered this population-based retrospective cohort study. Dementia was ascertained using a validated algorithm for Alzheimer's disease and related dementias. Propensity-score weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and confidence intervals (CI) for time to incident dementia. The observation window started at 1 year after cohort entry to mitigate protopathic bias due to delayed diagnosis. The primary analysis used an intention-to-treat exposure definition. A separate propensity-score weighted analysis was conducted to explore within-class differences in dementia risk among sulfonylurea new users selected from the primary cohort. RESULTS: Among 107,806 DPP4 inhibitor new users and 37,030 sulfonylurea new users, sulfonylureas compared with DPP4 inhibitors were associated with a higher risk of dementia (18.4/1000 person-years; aHR [95% CI] = 1.09 [1.04-1.15]) over a mean follow-up of 4.82 years from cohort entry. Glyburide compared to gliclazide exhibited a higher dementia risk (aHR [95% CI] = 1.17 [1.03-1.32]). CONCLUSION: New use of a sulfonylurea especially glyburide was associated with a higher dementia risk compared with new use of a DPP4 inhibitor in older adults with diabetes.

Establishing new cutoffs for Cohen's d: An application using known effect sizes from trials for improving sleep quality on composite mental health.

OBJECTIVE: Cohen's d conventional effect size cutoffs [small (0.2), medium (0.5), and large (0.8)] might not be representative of the reported distribution of effect sizes across the different areas of health. Effect size cutoffs might vary not only depending on the area of research, but also on the type of intervention and population. That is, they are context dependent. Therefore, we present strategies to redefine small, medium, and large effect size based on 25, 50, and 75th percentile, respectively. METHODS: We illustrate these techniques applying them to 72 effect sizes, derived from 65 randomized controlled trials described in a recent meta-analysis (10.1016/j.smrv.2021.101556) of improving sleep quality on composite mental health. Such percentiles are equally distanced from the average effect size as suggested by Jacob Cohen and checked for potential attenuation effects (via weight selection model) and outliers (via OutRules). RESULTS: new cutoffs for effect size distribution of -0.177, -0.329, and -0.557, for small, medium, and large effect size were found, respectively. applying Cohen's effect size thresholds (0.2, 0.5, and 0.8) for trials of improving sleep quality on composite mental health might over-estimate effect sizes compared to the real-world context, especially around medium and large effect sizes.

Evaluating the Feasibility of Emotion Expressions in Avatars Created From Real Person Photos: Pilot Web-Based Survey of Virtual Reality Software.

BACKGROUND: The availability and potential of virtual reality (VR) has led to an increase of its application. VR is suggested to be helpful in training elements of social competence but with an emphasis on interventions being tailored. Recognizing facial expressions is an important social skill and thus a target for training. Using VR in training these skills could have advantages over desktop alternatives. Children with autism, for instance, appear to prefer avatars over real images when assessing facial expressions. Available software provides the opportunity to transform profile pictures into avatars, thereby giving the possibility of tailoring according to an individual's own environment. However, the emotions provided by such software should be validated before application. OBJECTIVE: Our aim was to investigate whether available software is a quick, easy, and viable way of providing emotion expressions in avatars transformed from real images. METHODS: A total of 401 participants from a general population completed a survey on the web containing 27 different images of avatars transformed, using a software, from real images. We calculated the reliability of each image and their level of difficulty using a structural equation modeling approach. We used Bayesian confirmatory factor analysis testing under a multidimensional first-order correlated factor structure where faces showing the same emotions represented a latent variable. RESULTS: Few emotions were correctly perceived and rated as higher than other emotions. The factor loadings indicating the discrimination of the image were around 0.7, which means 49% shared variance with the latent factor that the face is linked with. The standardized thresholds indicating the difficulty level of the images are mostly around average, and the highest correlation is between faces showing happiness and anger. CONCLUSIONS: Only using a software to transform profile pictures to avatars is not sufficient to provide valid emotion expressions. Adjustments are needed to increase faces' discrimination (eg, increasing reliabilities). The faces showed average levels of difficulty, meaning that they are neither very difficult nor very easy to perceive, which fits a general population. Adjustments should be made for specific populations and when applying this technology in clinical practice.

State, trait, and accumulated features of the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) in mild Alzheimer's disease.

Background: The Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) is used to assess decline in memory, language, and praxis in Alzheimer's disease (AD). Methods: A latent state-trait model with autoregressive effects was used to determine how much of the ADAS-Cog item measurement was reliable, and of that, how much of the information was occasion specific (state) versus consistent (trait or accumulated from one visit to the next). Results: Participants with mild AD (n = 341) were assessed four times over 24 months. Praxis items were generally unreliable as were some memory items. Language items were generally the most reliable, and this increased over time. Only two ADAS-Cog items showed reliability >0.70 at all four assessments, word recall (memory) and naming (language). Of the reliable information, language items exhibited greater consistency (63.4% to 88.2%) than occasion specificity, and of the consistent information, language items tended to reflect effects of AD progression that accumulated from one visit to the next (35.5% to 45.3%). In contrast, reliable information from praxis items tended to come from trait information. The reliable information in the memory items reflected more consistent than occasion-specific information, but they varied between items in the relative amounts of trait versus accumulated effects. Conclusions: Although the ADAS-Cog was designed to track cognitive decline, most items were unreliable, and each item captured different amounts of information related to occasion-specific, trait, and accumulated effects of AD over time. These latent properties complicate the interpretation of trends seen in ordinary statistical analyses of trials and other clinical studies with repeated ADAS-Cog item measures. Highlights: Studies have described unfavorable psychometric properties of the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog), bringing into question its ability to track changes in cognition uniformly over time. There remains a need to estimate how much of the ADAS-Cog measurement is reliable, of that how much is occasion specific versus consistent, and of the consistent information, how much represents enduring traits versus autoregressive effects (i.e., effects of Alzheimer's disease [AD] progression carried over from one assessment to the next).A latent state-trait model with autoregressive effects in mild AD found most items to be unreliable, and each item to capture different amounts of occasion-specific, trait, and autoregressive information. Language items, specifically, naming and the memory item word recall, were the most reliable.Psychometric idiosyncrasies of individual items complicate the interpretation of their summed score, biasing ordinary statistical analyses of repeated measures in mild AD. Future studies should consider item trajectories individually.