Potential for reducing dementia risk: association of the CAIDE score with additional lifestyle components from the LIBRA score in a population at high risk of dementia.

OBJECTIVES: Various dementia risk scores exist that assess different factors. We investigated the association between the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score and modifiable risk factors in the Lifestyle for Brain Health (LIBRA) score in a German population at high risk of Alzheimer's disease. METHOD: Baseline data of 807 participants of AgeWell.de (mean age: 68.8 years (SD = 4.9)) were analysed. Stepwise multivariable regression was used to examine the association between the CAIDE score and additional risk factors of the LIBRA score. Additionally, we examined the association between dementia risk models and cognitive performance, as measured by the Montreal Cognitive Assessment. RESULTS: High cognitive activity (ß = -0.016, p < 0.001) and high fruit and vegetable intake (ß = -0.032, p < 0.001) correlated with lower CAIDE scores, while diabetes was associated with higher CAIDE scores (ß = 0.191; p = 0.032). Although all were classified as high risk on CAIDE, 31.5% scored ≤0 points on LIBRA, indicating a lower risk of dementia. Higher CAIDE and LIBRA scores were associated with lower cognitive performance. CONCLUSION: Regular cognitive activities and increased fruit and vegetable intake were associated with lower CAIDE scores. Different participants are classified as being at-risk based on the dementia risk score used.

A multidomain intervention against cognitive decline in an at-risk-population in Germany: Results from the cluster-randomized AgeWell.de trial.

INTRODUCTION: We investigated the effectiveness of a multidomain intervention to preserve cognitive function in older adults at risk for dementia in Germany in a cluster-randomized trial. METHODS: Individuals with a Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score ≥ 9 aged 60 to 77 years were recruited. After randomization of their general practitioner (GP), patients received a multidomain intervention (including optimization of nutrition and medication, and physical, social, and cognitive activity) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance (composite z score, based on domain-specific neuropsychological tests). RESULTS: Of 1030 participants at baseline, n = 819 completed the 24-month follow-up assessment. No differences regarding global cognitive performance (average marginal effect = 0.010, 95% confidence interval: -0.113, 0.133) were found between groups at follow-up. Perceived restrictions in intervention conduct by the COVID-19 pandemic did not impact intervention effectiveness. DISCUSSION: The intervention did not improve global cognitive performance. HIGHLIGHTS: Overall, no intervention effects on global cognitive performance were detected. The multidomain intervention improved health-related quality of life in the total sample. In women, the multidomain intervention reduced depressive symptoms. The intervention was completed during the COVID-19 pandemic.

Types of leisure time physical activities (LTPA) of community-dwelling persons who have been screened positive for dementia.

BACKGROUND: To (a) describe the pattern of leisure time physical activities (LTPA) in community-dwelling persons who have been screened positive for dementia and (b) determine the health-related and sociodemographic factors associated with LTPA. METHODS: Data of the general practitioner-based, randomized, controlled intervention trial, DelpHi-MV (Dementia: life- and person-centered help in Mecklenburg-Western Pomerania) were used. Patients aged 70 years or older, who lived at home and had a DemTect< 9 were informed about the study by their General practitioners and invited to participate. Data from 436 participants with complete baseline data were used. Standardized, computer-assisted assessments were made during face-to-face interviews at the participants' homes. RESULTS: Two hundred thirty-eight patients (54.6%) carried out LTPA (men 58.4%, women 51.8%). Physically active patients mentioned one to two different activities; diversity of LTPA was higher for men than for women. The most-frequently mentioned types of activity were gardening (35.3%), cycling (24.1%) and mobility training (12.4%); there was only a statistically significant difference between men and women in cycling, χ2(1) = 21.47, p < .001. The odds of LTPA increased with increasing quality of life (OR = 2.41), lower impairments in activities of daily living (OR = 0.85), and living in a rural environment (OR = 2.02). CONCLUSIONS: Our findings suggest that people who have been screened positive for dementia living in a rural area are more likely to be active than people living in an urban area. Following studies should investigate whether this difference has an effect on the progression of dementia. TRIAL REGISTRATION: ClinicalTrial.gov Identifier NCT01401582 .

[Healthcare of the future-Insights and strategy for (dementia) health services research]. / Gesundheitsversorgung der Zukunft ­ Erkenntnisse und Strategie der (Demenz­)Versorgungsforschung.

BACKGROUND: Due to the demographic change healthcare for older people is becoming more important. A key strategic document for the near future is the national dementia strategy (NDS), which defines four fields of action including promoting excellent research on dementia. The NDS will guide and influence the further development of dementia healthcare research in the coming years. OBJECTIVE: The current research on specific NDS topics is presented and an outlook on expected developments is given. MATERIAL AND METHODS: This article provides a narrative review in which concepts and examples for selected sections of the NDS are presented: funding and promotion of healthcare research, development of evidence-based prevention and healthcare concepts and transfer into routine care, support for people with dementia (PwD) and their caregiver, cross-sectoral networking, participation in dementia research and networks in healthcare research. These were analyzed with respect to future developments and concretized based on current healthcare and promotion models. RESULTS: Insights are given into the healthcare concept of dementia care management, rethinking regional healthcare models such as medicine and e­health. The innovation fund and research practice networks are described as examples of current structural methods of evidence-based design of future healthcare. CONCLUSION: The NDS represents an ambitious agenda with very comprehensive goals and topics for the improvement of healthcare for PwD and will probably significantly influence healthcare research and thus healthcare in the future. Overarching, mutually influencing and strengthening components on the way to improvement of the situation for PwD and the healthcare system are translation, participation and networking in research.

Efficacy of cryotherapy for the treatment of cutaneous leishmaniasis: meta-analyses of clinical trials.

BACKGROUND: Cryotherapy is a local treatment for cutaneous leishmaniasis with variable efficacy and greater safety than conventional treatment. The objective of this study is to evaluate the efficacy and safety of cryotherapy for the treatment of cutaneous leishmaniasis and to compare it with pentavalent antimonials. METHODS: A meta-analysis based on a search of nine databases with eight strategies was conducted. Inclusion and exclusion criteria were applied, the methodological quality of each article was evaluated, and the reproducibility of the study selection and information extraction from each clinical trial was assured. The per lesion and per patient efficacy was calculated, and a meta-analysis of relative risks with the random effects model and the Dersimonian and Laird's, Begg, and Egger tests, along with a sensitivity analysis, were performed. A meta-regression based on the methodological quality of the trials included was also performed. RESULTS: Eight studies were included in which respective per lesion efficacies of 67.3 % and 67.7 % were reported for cryotherapy and pentavalent antimonials. In 271 patients treated with cryotherapy and in 199 with pentavalent antimonials, respective per protocol and intent to treat efficacies of 63.6 % and 54.2 % were found in the first group, and per protocol and intent to treat efficacies of 74.7 % and 68.3 % were found in the second group. The relative risk for the comparison of efficacy in the two groups was 0.73 (0.42-1.29). The results of the sensitivity analysis and the meta-regression analysis of relative risks were statistically equal to the overall results. CONCLUSION: This investigation provides evidence in favor of the use of cryotherapy given that its efficacy is similar to that of pentavalent antimonials.

Mediating Factors Associated With Physical Activity in Older Adults at Increased Dementia Risk.

While regular physical-activity (PA) is beneficial, multimorbid individuals at increased dementia risk may exhibit reduced PA levels. Thus, a more comprehensive understanding of mediating factors responsible for inactivity in this population is needed. This study investigated the impact of a multimodal intervention on PA changes at 24-month follow-up and associated mediating factors among community-dwelling patients aged 60-77, with increased dementia risk determined by the CAIDE Dementia Risk Score. Of 1030 participants recruited, 819 completed the assessment. Thus, a generalized estimating equations model initially assessed differences in PA over 24 months, followed by a tree analysis identifying mediating factors influencing PA changes post-intervention. While no significant effect on regular PA was found during the follow-up (P = .674), subgroup analysis revealed improved self-efficacy (P = .000) associated with increased engagement in PA. Incorporating self-efficacy elements into future strategies is crucial for promoting PA among individuals with multimorbidity and at increased dementia risk.

General practitioners' perspectives on lifestyle interventions for cognitive preservation in dementia prevention.

BACKGROUND: General practitioners (GPs) play a crucial role in identifying cognitive impairment and dementia and providing post-diagnostic care. This study investigates (1) how promising GP consider lifestyle changes to maintain cognitive performance in general, (2) GP beliefs about the power of modifiable health and lifestyle factors to maintain cognitive performance, and (3) whether those beliefs vary by GP age. METHODS: As part of the AgeWell.de trial, GPs (n = 72) completed a process evaluation questionnaire assessing their perspectives on lifestyle changes to preserve cognitive performance in elderly patients. In greater detail, their perceived efficacy of established risk and protective factors was investigated using a 5-point Likert scale. Descriptive statistical analyses were performed for research question (1) and (2). Spearman´s rank correlations and ordinal logistic regressions were used to answer research question (3). All results were interpreted exploratively. RESULTS: GPs rated the overall chance of lifestyle changes maintaining cognitive performance quite neutral with a median score of 3.0 (IQR = 2.0). They rated the efficacy of all the modifiable health and lifestyle factors high, with increase in physical and social activity ((Mdn = 5.0, IQR = 1.0) receiving the highest ratings with the narrowest range. Spearman's rank correlation indicated a significant positive relationship between age and the belief in "Optimization of nutrition" for preventing cognitive decline and dementia (ρ = .255, p = .041). However, ordinal logistic regressions showed no significant relationships between age and GP ratings of lifestyle change efficacy. CONCLUSION: These findings highlight the positive perception of GPs on the efficacy of modifiable health and lifestyle factors for preventing cognitive decline and dementia. TRIAL REGISTRATION: The AgeWell.de trial is registered in the German Clinical Trials Register (DRKS; trial identifier: DRKS00013555, Registration Date 07 December 2017).

Implementing a physical activity project for people with dementia in Germany-Identification of barriers and facilitator using consolidated framework for implementation research (CFIR): A qualitative study.

BACKGROUND: Despite physical activity (PA) health benefits, people with dementia (PwD) continue to report low levels of PA engagement compared with healthy older adults. Evidencing that PA initiatives still not reflect effective practice and outcomes. Previous studies have shown that several factors can mediate PA initiatives implementation in this population. However, most prior research have not use implementation science frameworks to outline in-depth barriers and facilitators that enables improved PA strategies in PwD. Therefore, a more holistic understanding of mediating factors is still needed. OBJECTIVE: To identify multilevel barriers and facilitator factors, applying the Consolidated Framework for Implementation Research (CFIR) to orient a systematic evaluation of one PA project in PwD and provide evidence-based evaluation results to enhance PA implementation efforts for PwD. METHOD: A qualitative study implemented in 4 German sports associations that applied a PA project for PwD. A total of 13 semi-structured interviews were conducted with 21 participants, project leaders (PLs) and sports trainers (STs). The Consolidated Framework for Implementation Research (CFIR) was used as an evaluation framework to orient both the data collection and analysis. RESULTS: A total of 13 interviews were conducted with 21 participants. The CFIR guided the identification of barriers and facilitating factors that need to be targeted at different levels for successful implementation. Barriers were identified, especially in the external level, as more solid networks and funding for sustainable proposals are still needed. Other barriers were low participation rates, stigma around the disease and the COVID 19 pandemic. On an individual and structural level facilitators were found like motivated appointed leaders, established planning process, and external organizations supporting sports associations in the implementation. CONCLUSION: Sports projects for PwD can benefit from structuring their interventions based on the CFIR framework as it helps identify multilevel factors that may influence their success and promote PA among PwD. Future efforts should continue working on implementing frameworks that facilitate and reduce the complexity of implementing sustainable PA projects for PwD.

Time to move beyond surgical classification systems for endometriosis.

Endometriosis is a common condition associated with chronic pelvic pain and infertility. Its pathogenesis is poorly understood, diagnosis relies on laparoscopy, and staging is based on extent of disease. Unfortunately, the current staging systems do not correlate well with pain severity and impact, nor do they predict prognosis, i.e., treatment success and recurrence of disease. In this article, we discuss the strengths and limitations of current staging systems and propose modifications that will enable better classification systems to be developed in the future.

Physical Activity Determinants in Older German Adults at Increased Dementia Risk with Multimorbidity: Baseline Results of the AgeWell.de Study.

Background: Multimorbidity is a common issue in aging societies and is usually associated with dementia in older people. Physical activity (PA) may be a beneficial nonpharmacological strategy for patients with complex health needs. However, insufficient PA is predominant in this population. Thus, there is an evident need to expand the knowledge on potential determinants influencing PA engagement among elderly persons at risk of dementia and multimorbidity. Methods: We used baseline data from the multicenter, cluster-randomized controlled AgeWell.de study. The main aim was to describe PA engagement and identify potential PA determinants in a sample of community-dwelling Germans aged 60−77 years old with an increased risk of dementia and multimorbidity. Results: Of the 1030 included participants, approximately half (51.8%) engaged in PA ≥2 times/week for at least 30 min at baseline. We identified self-efficacy (beta = 0.202, (p < 0.001) and BMI (beta = −0.055, (p < 0.001) as potential PA determinants. Conclusions: The identified determinants, self-efficacy, and BMI are consistent with those reported in the literature. Specific knowledge on PA determinants and stages of change in persons with risk of dementia and multimorbidity might guide the development of effective future prevention measures and health services tailored to this population. Trial registration: German Clinical Trials Register (reference number: DRKS00013555).

Comparison among plaque assay, tissue culture infectious dose (TCID50) and real-time RT-PCR for SARS-CoV-2 variants quantification.

Background and Objectives: SARS-CoV-2 variants of concern (VOC) and interest (VOI) pose a significant threat to public health because the rapid change in the SARS-CoV-2 genome can alter viral phenotypes such as virulence, transmissibility and the ability to evade the host response. Hence, SARS-CoV-2 quantification techniques are essential for timely diagnosis and follow-up. Besides, they are vital to understanding viral pathogenesis, antiviral evaluation, and vaccine development. Materials and Methods: Five isolates of SARS-CoV-2: D614G strain (B.1), three VOC (Alpha, Gamma and Delta), and one VOI (Mu) were used to compare three techniques for viral quantification, plaque assay, median tissue culture infectious dose (TCID50) and real-time RT-PCR. Results: Plaque assay showed viral titers between 0.15 ± 0.01×107 and 1.95 ± 0.09×107 PFU/mL while viral titer by TCID50 assay was between 0.71 ± 0.01×106 to 4.94 ± 0.80×106 TCID50/mL for the five SARS-CoV-2 isolates. The PFU/mL titer obtained by plaque and the calculated from TCID50 assays differed by 0.61 log10, 0.59 log10, 0.59 log10 and 0.96 log10 for Alfa, Gamma, Delta, and Mu variants (p≤0.0007), respectively. No differences were observed for the D614G strain. Real-time PCR assay exhibited titers ranging from 0.39 ± 0.001×108 to 3.38 ± 0.04×108 RNA copies/µL for all variants. The relation between PFU/mL and RNA copies/mL was 1:29800 for D614G strain, 1:11700 for Alpha, 1:8930 for Gamma, 1:12500 for Delta, and 1:2950 for Mu. Conclusion: TCID50 assay was comparable to plaque assay for D614G but not for others SARS-CoV-2 variants. Our data demonstrated a correlation among PFU/mL and E gene RNA copies/µL, units of measure commonly used to quantify the viral load in diagnostic and research fields. The results suggest that the proportion of infectious virions in vitro changes depending on the SARS-CoV-2 variant, being Mu, the variant reaching a higher viral titer with fewer viral copies.

Physical Activity Interventions and Their Effects on Cognitive Function in People with Dementia: A Systematic Review and Meta-Analysis.

BACKGROUND: Physical activity (PA) has emerged as an alternative nonpharmacological approach to effectively address the effects of dementia. The primary aim was to identify and summarize PA interventions and their effects on cognitive function among persons with dementia (PwD). METHODS: A systematic review was conducted with a meta-analysis using different electronic databases, such as PubMed, Embase, APA PsycNET, and the Web of Science. The identified and selected studies were randomized controlled trials (RCTs) that were written in English, published between 2000 and 2020, and implemented among PwD who received a PA intervention and whose cognitive function was measured at baseline and during a follow-up. RESULTS: Twenty-two PA intervention studies met the eligibility criteria and showed a medium-size effect on the cognitive function of PwD, 0.4803 (95% CI = 0.1901-0.7704), with a high percentage of heterogeneity (I2 = 86%, p ≤ 0.0001). Moreover, this review complements other reviews by including eight studies that have not previously been considered. Overall, studies have methodological limitations. However, six studies implemented in the past five years have shown more robust methodological designs, including larger sample sizes and more comprehensive measurement tools. CONCLUSION: It is not yet possible to draw a conclusion on the ideal PA intervention for this population due to the high proportion of heterogeneity within the included studies. More emphasis is needed on the intensity of PA monitoring and adherence to such programs.

Matrix Effects of the Hydroethanolic Extract of Calyces of Physalis peruviana L. on Rutin Pharmacokinetics in Wistar Rats Using Population Modeling.

Rutin is the rutinose conjugate of quercetin. It presents several biological activities and is the major flavonoid in the hydroalcoholic extract of the calyces of Physalis peruviana L. It also shows hypoglycemic activity after oral administration. The aim of this work was to study the matrix effects of the extract from P. peruviana calyces on the pharmacokinetics of rutin and its metabolites in Wistar rats, using non-compartmental and population pharmacokinetic analyses. A pharmacokinetic study was performed after intravenous and oral administration of different doses of pure rutin and the extract. In the non-compartmental analysis, it was found that rutin from the extract exhibited higher distribution and clearance, as well as an 11-fold increase in the bioavailability of its active metabolites. A population pharmacokinetic model was also carried out with two compartments, double absorption and linear elimination, in which the extract and the doses were the covariates involved. This model correctly described the differences observed between rutin as a pure compound and rutin from the extract, including the dose dependency.

The Antiviral and Virucidal Activities of Voacangine and Structural Analogs Extracted from Tabernaemontana cymosa Depend on the Dengue Virus Strain.

Currently, no specific licensed antiviral exists for treating the illness caused by dengue virus (DENV). Therefore, the search for compounds of natural origin with antiviral activity is an important area of research. In the present study, three compounds were isolated and identified from seeds of Tabernaemontana cymosa plants. The in vitro antiviral effect of those compounds and voacangine against different DENV strains was assessed using different experimental approaches: compounds added before the infection (Pre), at the same time with the virus (Trans), after the infection (Post) or compounds present in all moments of the experiment (Pre-Trans-Post, Combined treatment). In silico studies (docking and molecular dynamics) were also performed to explain the possible antiviral mechanisms. The identified compounds were three structural analogs of voacangine (voacangine-7-hydroxyindolenine, rupicoline and 3-oxo-voacangine). In the Pre-treatment, only voacangine-7-hydroxyindolenine and rupicoline inhibited the infection caused by the DENV-2/NG strain (16.4% and 29.6% infection, respectively). In the Trans-treatment approach, voacangine, voacangine-7-hydroxyindolenine and rupicoline inhibited the infection in both DENV-2/NG (11.2%, 80.4% and 75.7% infection, respectively) and DENV-2/16681 infection models (73.7%, 74.0% and 75.3% infection, respectively). The latter strain was also inhibited by 3-oxo-voacangine (82.8% infection). Moreover, voacangine (most effective virucidal agent) was also effective against one strain of DENV-1 (DENV-1/WestPac/74) and against the third strain of DENV-2 (DENV-2/S16803) (48.5% and 32.4% infection, respectively). Conversely, no inhibition was observed in the post-treatment approach. The last approach (combined) showed that voacangine, voacangine-7-hydroxyindolenine and rupicoline inhibited over 90% of infections (3.5%, 6.9% and 3.5% infection, respectively) of both strains (DENV-2/NG and DENV-2/16681). The free energy of binding obtained with an in silico approach was favorable for the E protein and compounds, which ranged between -5.1 and -6.3 kcal/mol. Finally, the complex formed between DENV-2 E protein and the best virucidal compound was stable for 50 ns. Our results show that the antiviral effect of indole alkaloids derived from T. cymose depends on the serotype and the virus strain.

Matrix effects of the hydroethanolic extract and the butanol fraction of calyces from Physalis peruviana L. on the biopharmaceutics classification of rutin.

OBJECTIVES: The Biopharmaceutics Classification System (BCS) categorizes active pharmaceutical ingredients according to their solubility and permeability properties, which are susceptible to matrix or formulation effects. The aim of this research was to evaluate the matrix effects of a hydroethanolic extract of calyces from Physalis peruviana L. (HEE) and its butanol fraction (BF), on the biopharmaceutics classification of their major compound, quercetin-3-O-rutinoside (rutin, RU). METHODS: Rutin was quantified by HPLC-UV, and Caco-2 cell monolayer transport studies were performed to obtain the apparent permeability values (Papp ). Aqueous solubility was determined at pH 6.8 and 7.4. KEY FINDINGS: The Papp values followed this order: BF > HEE > RU (1.77 ± 0.02 > 1.53 ± 0.07 > 0.90 ± 0.03 × 10-5  cm/s). The lowest solubility values followed this order: HEE > RU > BF (2.988 ± 0.07 > 0.205 ± 0.002 > 0.189 ± 0.005 mg/ml). CONCLUSIONS: According to these results, rutin could be classified as BCS classes III (high solubility/low permeability) and IV (low solubility/low permeability), depending on the plant matrix. Further work needs to be done in order to establish how apply the BCS for research and development of new botanical drugs or for bioequivalence purposes.

Perfil lector de niños con y sin retraso lector en la ciudad de cali (colombia) / Reading performance of children with and without reading delay in Cali (Colombia)

Resumen El presente estudio piloto tiene por objetivo identificar diferencias en el perfil lector de una muestra de niños con y sin retraso lector. Para ello se evaluaron cuarenta niños de ocho y nueve años de edad, de estrato socioeconómico bajo, que cursan entre segundo y cuarto de primaria en un colegio privado, sin ánimo de lucro, en la ciudad de Cali (Colombia). La mitad de los estudiantes conformó el grupo experimental, al ser diagnosticados con retraso lector. La otra mitad fue el grupo control. Todos los niños fueron evaluados con los subdominios de habilidades metalingüísticas y de lectura de la batería Evaluación Neuropsicológica Infantil (ENI). Los principales resultados del estudio demuestran que los niños con retraso lector presentan dificultades en sus habilidades del lenguaje oral, como conciencia fonológica y comprensión, que son esenciales para una correcta adquisición del proceso lector.

Abstract This pilot study aims to identify differences in the reading profile of a sample of children with and without reading delay. 40 children aged eight and nine years old, of low socioeconomic status, from second to fourth grade that assist to a private non-profit school of Cali (Colombia) participated in the study. Half of the children formed the experimental group, since they were diagnosed with reading delay. The other half formed the control group. All children were assessed with the subdo-mains of Habilidades Metalingüísticas and Lectura of the Evaluación Neuropsicológica Infantil battery (ENI). The main results of the study showed that children with reading delay presented difficulties in some of their oral language skills that are needed to acquire reading, such as phonological awareness and comprehension.