Psychometric properties of the Spanish version of the Chalder Fatigue Scale in clinical and general populations / Propiedades psicométricas de la versión española de la Escala de Fatiga de Chalder en población clínica y general

Objetivo: La Escala de Fatiga de Chalder (CFS) es una escala breve para evaluar fatiga que se utiliza en España, pero que no ha sido validada en su población. El objetivo del estudio fue adaptar y evaluar las propiedades psicométricas de la versión española de la CFS (Sp-CFS). Método: La muestra la conformaron 3,671 participantes (3.190 de la población general y 481 pacientes), con edades entre 18 y 86 años (M = 28.43; DT = 12.71), siendo el 67.6% mujeres. Las propiedades psicométricas de la escala se probaron en un diseño transversal utilizando validación cruzada (análisis factorial exploratorio y confirmatorio) y estimación de la invarianza (sexo y condición clínica). Resultados: Un modelo de cuatro factores (baja energía, problemas de sueño, problemas de concentración y disfunción cognitiva subjetiva) en lugar de un modelo original de dos factores (fatiga física y mental) proporcionó mejores índices de bondad de ajuste a los datos. La consistencia interna y la estabilidad de la escala fueron excelentes. Su validez convergente se apoyó en su asociación significativa con la ansiedad, la depresión, el estrés y los síntomas positivos y negativos del espectro de la psicosis. El instrumento no mostró diferencias significativas entre sexos ni condiciones clínicas, y discriminó entre la población general y los pacientes, obteniendo estos últimos puntajes significativamente mayores. Conclusiones: Sp-CFS es una escala fiable y válida para medir la fatiga en población general y clínica española.(AU)

Objective:The Chalder Fatigue Scale (CFS) is a brief self-report screening scale for fatigue that is used in Spain but has not been validated for the Spanish population. The aim of this study was to adapt and evalu-ate the psychometric properties of the Spanish version of the CFS (Sp-CFS). Method:The sample consisted of 3,671 participants (3,190 from the general population and 481 patients), aged 18 to 86 years (M=28.43; DT=12.71), 67.6% of whom were women. Psychometric properties of the scale were tested in a cross-sectional design using cross-validation (explora-tory and confirmatory factor analysis) and estimation of invariance (sex and clinical condition). Results:A four-factor model (low energy, sleep problems, concentration problems and subjective cognitive dysfunction) rather than an original two-factor model (physical and mental fatigue) pro-vided better indices of goodness of fit to the data. The internal consistencyand stability of the scale were excellent. Its convergent validity was sup-ported by its significant association with anxiety, depression, stress, and the positive and negative symptoms of the psychosis spectrum. The instru-ment did not show significant differences between sexes or clinical condi-tions, and it discriminated between the general population and the patients, with the latter obtaining significantly greater scores. Conclusions: Sp-CFS is a reliable and valid scale for measuring a transdiagnostic construct such as fatigue in Spanish general and clinical populations.(AU)

PPARγ activation ameliorates cognitive impairment and chronic microglial activation in the aftermath of r-mTBI.

Chronic neuroinflammation and microglial activation are key mediators of the secondary injury cascades and cognitive impairment that follow exposure to repetitive mild traumatic brain injury (r-mTBI). Peroxisome proliferator-activated receptor-γ (PPARγ) is expressed on microglia and brain resident myeloid cell types and their signaling plays a major anti-inflammatory role in modulating microglial responses. At chronic timepoints following injury, constitutive PPARγ signaling is thought to be dysregulated, thus releasing the inhibitory brakes on chronically activated microglia. Increasing evidence suggests that thiazolidinediones (TZDs), a class of compounds approved from the treatment of diabetes mellitus, effectively reduce neuroinflammation and chronic microglial activation by activating the peroxisome proliferator-activated receptor-γ (PPARγ). The present study used a closed-head r-mTBI model to investigate the influence of the TZD Pioglitazone on cognitive function and neuroinflammation in the aftermath of r-mTBI exposure. We revealed that Pioglitazone treatment attenuated spatial learning and memory impairments at 6 months post-injury and reduced the expression of reactive microglia and astrocyte markers in the cortex, hippocampus, and corpus callosum. We then examined whether Pioglitazone treatment altered inflammatory signaling mechanisms in isolated microglia and confirmed downregulation of proinflammatory transcription factors and cytokine levels. To further investigate microglial-specific mechanisms underlying PPARγ-mediated neuroprotection, we generated a novel tamoxifen-inducible microglial-specific PPARγ overexpression mouse line and examined its influence on microglial phenotype following injury. Using RNA sequencing, we revealed that PPARγ overexpression ameliorates microglial activation, promotes the activation of pathways associated with wound healing and tissue repair (such as: IL10, IL4 and NGF pathways), and inhibits the adoption of a disease-associated microglia-like (DAM-like) phenotype. This study provides insight into the role of PPARγ as a critical regulator of the neuroinflammatory cascade that follows r-mTBI in mice and demonstrates that the use of PPARγ agonists such as Pioglitazone and newer generation TZDs hold strong therapeutic potential to prevent the chronic neurodegenerative sequelae of r-mTBI.

A Multicenter Study of COPD and Cognitive Impairment: Unraveling the Interplay of Quantitative CT, Lung Function, HIF-1α, and Clinical Variables.

Purpose: The exact link between cognitive impairment (CI) and chronic obstructive pulmonary disease (COPD) is still limited. Thus, we aim to find the relationship and interaction of quantitative CT (QCT), lung function, HIF-1α, and clinical factors with the development of CI among COPD patients. Patients and Methods: A cross-sectional multicentre study was conducted from January 2022 to December 2023. We collected clinical data, spirometry, CT images, and venous blood samples from 114 COPD participants. Cognitive impairment assessment using the Montreal Cognitive Assessment Indonesian version (MoCA-Ina) with a cutoff value 26. The QCT analysis consists of lung density, airway wall thickness, pulmonary artery-to-aorta ratio (PA:A), and pectoralis muscles using 3D Slicer software. Serum HIF-1α analysis was performed using ELISA. Results: We found significant differences between %LAA-950, age, COPD duration, BMI, FEV1 pp, and FEV1/FVC among GOLD grades I-IV. Only education duration was found to correlate with CI (r = 0.40; p < 0.001). We found no significant difference in HIF-1α among GOLD grades (p = 0.149) and no correlation between HIF-1α and CI (p = 0.105). From multiple linear regression, we observed that the MoCA-Ina score was influenced mainly by %LAA-950 (p = 0.02) and education duration (p = 0.01). The path analysis model showed both %LAA and education duration directly and indirectly through FEV1 pp contributing to CI. Conclusion: We conclude that the utilization of QCT parameters is beneficial as it can identify abnormalities and contribute to the development of CI, indicating its potential utility in clinical decision-making. The MoCA-Ina score in COPD is mainly affected by %LAA-950 and education duration. Contrary to expectations, this study concludes that HIF-1α does not affect CI among COPD patients.

Neighborhood structure-guided brain functional networks estimation for mild cognitive impairment identification.

The adoption and growth of functional magnetic resonance imaging (fMRI) technology, especially through the use of Pearson's correlation (PC) for constructing brain functional networks (BFN), has significantly advanced brain disease diagnostics by uncovering the brain's operational mechanisms and offering biomarkers for early detection. However, the PC always tends to make for a dense BFN, which violates the biological prior. Therefore, in practice, researchers use hard-threshold to remove weak connection edges or introduce l 1-norm as a regularization term to obtain sparse BFNs. However, these approaches neglect the spatial neighborhood information between regions of interest (ROIs), and ROI with closer distances has higher connectivity prospects than ROI with farther distances due to the principle of simple wiring costs in resent studies. Thus, we propose a neighborhood structure-guided BFN estimation method in this article. In detail, we figure the ROIs' Euclidean distances and sort them. Then, we apply the K-nearest neighbor (KNN) to find out the top K neighbors closest to the current ROIs, where each ROI's K neighbors are independent of each other. We establish the connection relationship between the ROIs and these K neighbors and construct the global topology adjacency matrix according to the binary network. Connect ROI nodes with k nearest neighbors using edges to generate an adjacency graph, forming an adjacency matrix. Based on adjacency matrix, PC calculates the correlation coefficient between ROIs connected by edges, and generates the BFN. With the purpose of evaluating the performance of the introduced method, we utilize the estimated BFN for distinguishing individuals with mild cognitive impairment (MCI) from the healthy ones. Experimental outcomes imply this method attains better classification performance than the baselines. Additionally, we compared it with the most commonly used time series methods in deep learning. Results of the performance of K-nearest neighbor-Pearson's correlation (K-PC) has some advantage over deep learning.

[Neuprotection of post-acute COVID-19 cognitive impairment]. / Neiroprotektsiya pri postkovidnykh kognitivnykh narusheniyakh.

OBJECTIVE: To evaluate the efficacy of Cortexin in the treatment of patients with post-Covid impairment. MATERIAL AND METHODS: Treatment results of 109 patients with post-Covid cognitive impairment aged from 42 to 65 years were analyzed. The main group (MG, n=52), 29 (55.8%) men and 23 (44.2%) women, average age 58.1±4.9 years, who received Cortexin continuously for 20 days at a dose of 10 mg i.m., after 3, 6 months. The comparison group included 57 people, 31 (54.4%) men and 26 (45.6%) women (average age 59.3±3.8 years). The effectiveness of therapy was assessed using neuropsychological testing with international scales. RESULTS: During treatment, statistically significant differences were obtained in MG patients in the form of improved concentration (p<0.05), increased control of exutative functions (p<0.05), and auditory-verbal memory (p=0.002). There were no adverse events in the MG. CONCLUSION: Cortexin is highly effective and safe, and can be recommended as part of a combined staged therapy for post-Covid cognitive impairment. Thus, the study confirms the feasibility of using Cortexin, which has a neurocytoprotective effect.

[Multidisciplinary consensus on the use of Cereton drug in treatment of central nervous system diseases with cognitive impairments of congenital and acquired origin in children. Resolution of the multidisciplinary panel of experts]. / Mezhdistsiplinarnyi konsensus po primeneniyu preparata Tsereton v terapii zabolevanii tsentral'noi nervnoi sistemy s kognitivnymi narusheniyami vrozhdennogo i priobretennogo geneza u detei. Rezolyutsiya mezhdistsiplinarnogo soveta ekspertov.

Interdisciplinary consensus on the use of Cereton in the treatment of central nervous system diseases with cognitive impairment of congenital and acquired genesis in children. Resolution of the interdisciplinary council of expertsXXIII All-Russian Forum "Zdravnitsa-2024".

Markerless Motion Capture to Quantify Functional Performance in Neurodegeneration: Systematic Review.

BACKGROUND: Markerless motion capture (MMC) uses video cameras or depth sensors for full body tracking and presents a promising approach for objectively and unobtrusively monitoring functional performance within community settings, to aid clinical decision-making in neurodegenerative diseases such as dementia. OBJECTIVE: The primary objective of this systematic review was to investigate the application of MMC using full-body tracking, to quantify functional performance in people with dementia, mild cognitive impairment, and Parkinson disease. METHODS: A systematic search of the Embase, MEDLINE, CINAHL, and Scopus databases was conducted between November 2022 and February 2023, which yielded a total of 1595 results. The inclusion criteria were MMC and full-body tracking. A total of 157 studies were included for full-text screening, out of which 26 eligible studies that met the selection criteria were included in the review. . RESULTS: Primarily, the selected studies focused on gait analysis (n=24), while other functional tasks, such as sit to stand (n=5) and stepping in place (n=1), were also explored. However, activities of daily living were not evaluated in any of the included studies. MMC models varied across the studies, encompassing depth cameras (n=18) versus standard video cameras (n=5) or mobile phone cameras (n=2) with postprocessing using deep learning models. However, only 6 studies conducted rigorous comparisons with established gold-standard motion capture models. CONCLUSIONS: Despite its potential as an effective tool for analyzing movement and posture in individuals with dementia, mild cognitive impairment, and Parkinson disease, further research is required to establish the clinical usefulness of MMC in quantifying mobility and functional performance in the real world.

Stakeholder-informed pragmatic trial protocol of the TabCAT-BHA for the detection of cognitive impairment in primary care.

BACKGROUND: Cognitive impairment and dementia are frequently under-recognized. Health system strategies anchored in primary care are essential to address gaps in timely, comprehensive diagnosis. The goal of this paper is to describe the adaptation of a tablet-based brain health assessment (TabCAT-BHA) intervention and the study protocol to test its effectiveness in improving the detection of cognitive impairment, including dementia. METHODS: This mixed-methods, pragmatic, cluster randomized, hybrid effectiveness-implementation trial is being conducted in two 18-month waves with 26 Kaiser Permanente Southern California primary care clinics, with 13 serving as intervention clinics and 13 as usual care clinics. Patients 65 years and older with memory concerns (n ~ 180,000) receiving care at the 26 clinics will be included in the analyses. Primary care clinics are provided the following practice supports as part of the TabCAT-BHA intervention: brief education and training on neurocognitive disorders and study workflows; digital tools to assess cognitive function and support clinician decision making and documentation; and registered nurse support during the work-up and post-diagnosis periods for primary care providers, patients, and families. The intervention was adapted based on engagement with multiple levels of clinical and operational leaders in the healthcare system. Effectiveness outcomes include rates of cognitive impairment diagnosis in primary care and rates of completed standardized cognitive assessments and specialist referrals with incident diagnoses. Implementation outcomes include acceptability-appropriateness-feasibility, adoption, and fidelity. RESULTS: We identified seven themes organized by system-, provider-, and patient-level domains that were used to adapt the TabCAT-BHA intervention. Accordingly, changes were made to the provider education, diagnostic work-up, and post-diagnostic support. Results will be reported in fall of 2027. CONCLUSIONS: Our engagement with multiple primary and specialty care clinical and operational leaders to adapt the TabCAT-BHA intervention to these primary care clinics has informed the protocol to evaluate the intervention's effectiveness for improving the detection of cognitive impairment, including dementia, in an integrated healthcare system. TRIAL REGISTATION: Clinicaltrials.gov: NCT06090578 (registered 10/24/23).

Characterizing white matter connectome abnormalities in patients with temporal lobe epilepsy using threshold-free network-based statistics.

INTRODUCTION: Emerging evidence illustrates that temporal lobe epilepsy (TLE) involves network disruptions represented by hyperexcitability and other seizure-related neural plasticity. However, these associations are not well-characterized. Our study characterizes the whole brain white matter connectome abnormalities in TLE patients compared to healthy controls (HCs) from the prospective Epilepsy Connectome Project study. Furthermore, we assessed whether aberrant white matter connections are differentially related to cognitive impairment and a history of focal-to-bilateral tonic-clonic (FBTC) seizures. METHODS: Multi-shell connectome MRI data were preprocessed using the DESIGNER guidelines. The IIT Destrieux gray matter atlas was used to derive the 162 × 162 structural connectivity matrices (SCMs) using MRTrix3. ComBat data harmonization was applied to harmonize the SCMs from pre- and post-scanner upgrade acquisitions. Threshold-free network-based statistics were used for statistical analysis of the harmonized SCMs. Cognitive impairment status and FBTC seizure status were then correlated with these findings. RESULTS: We employed connectome measurements from 142 subjects, including 92 patients with TLE (36 males, mean age = 40.1 ± 11.7 years) and 50 HCs (25 males, mean age = 32.6 ± 10.2 years). Our analysis revealed overall significant decreases in cross-sectional area (CSA) of the white matter tract in TLE group compared to controls, indicating decreased white matter tract integrity and connectivity abnormalities in addition to apparent differences in graph theoretic measures of connectivity and network-based statistics. Focal and generalized cognitive impaired TLE patients showcased higher trend-level abnormalities in the white matter connectome via decreased CSA than those with no cognitive impairment. Patients with a positive FBTC seizure history also showed trend-level findings of association via decreased CSA. CONCLUSIONS: Widespread global aberrant white matter connectome changes were observed in TLE patients and characterized by seizure history and cognitive impairment, laying a foundation for future studies to expand on and validate the novel biomarkers and further elucidate TLE's impact on brain plasticity.

Compound impact of cognitive and physical decline: A qualitative interview study of people with Parkinson's and cognitive impairment, caregivers and professionals.

BACKGROUND: Cognitive impairment is common in Parkinson's disease and is associated with poorer quality of life and increased caregiver distress, but little qualitative information is available on lived experiences of people with Parkinson's who also have cognitive impairment. OBJECTIVES: The aim of this study was to explore the challenges of cognitive impairment in Parkinson's, triangulating the perspectives of people with Parkinson's, caregivers and healthcare professionals. METHODS: Semistructured interviews were conducted with 11 people with Parkinson's and cognitive impairment, 10 family caregivers and 27 healthcare professionals, using purposive sampling in the United Kingdom (2019-2021). Cognitive impairment was identified by healthcare professionals and required subjective symptoms. Relevant cognitive diagnoses were recorded. Interviews were audio-recorded, transcribed and analysed using reflexive thematic analysis. RESULTS: An overarching concept of the compound impact of cognitive and physical decline was developed, with six themes. Four themes describe the experience of living with cognitive impairment in Parkinson's: (1) Challenges in Daily Activities, (2) Psychological Impact and (3) Evolving Communication Difficulties together contributing to (4) Social Shift, encompassing a reduction in wider social activities but intensification of close relationships with increased dependence. A fifth theme (5) Living Well describes positive influences on these experiences, encompassing intrinsic motivation, self-management strategies and supportive relationships. Furthermore, underlying and shaping the whole experience was the sixth theme: (6) Preconceptions about Cognitive Impairment, describing fear and denial of symptoms and poor understanding of the nature of cognitive impairment in Parkinson's, with differences to other dementia pathologies. CONCLUSIONS: Cognitive impairment superimposed on the existing challenges of Parkinson's has a multifaceted impact and makes living with the condition arduous. Increased understanding of the experiences of this group and employing the identified facilitators for living well may be able to improve patient and caregiver experiences. PATIENT OR PUBLIC CONTRIBUTION: Two people with Parkinson's and cognitive impairment and three caregivers contributed to the study. Between them they contributed throughout the entirety of the project, giving input at conceptualisation as well as advice and review of interview questions, participant information leaflets, recruitment, interpretation of findings and summaries of the project.

Comparative effectiveness of interventions for cancer treatment-related cognitive impairment in adult cancer survivors: protocol for a systematic review.

BACKGROUND: Cancer treatment-related cognitive impairment (CTRCI) can substantially reduce the quality of life of cancer survivors. Many treatments of CTRCI have been evaluated in randomized controlled trials (RCTs), including psychological interventions, pharmacologic interventions, and other therapies. There is a pressing need to establish the benefits and harms of previously studied CTRCI treatments. The proposed systematic review and network meta-analyses will assess the relative efficacy and safety of competing interventions for the management of CTRCI. METHODS: In consultation with the review team, an experienced medical information specialist will draft electronic search strategies for MEDLINE®, Embase, CINAHL, PsycINFO, and the Cochrane Trials Registry. We will seek RCTs of interventions for the treatment of CTRCI in adults with any cancer, except cancers/metastases of the central nervous system. Due to the anticipated high search yields, dual independent screening of citations will be expedited by use of an artificial intelligence/machine learning tool. The co-primary outcomes of interest will be subjective and objective cognitive function. Secondary outcomes of interest will include measures of quality of life, mental and physical health symptoms, adherence to treatment, and harms (overall and treatment-related harms and harms associated with study withdrawal), where feasible, random-effects meta-analyses and network meta-analyses will be pursued. We will address the anticipated high clinical and methodological heterogeneity through meta-regressions, subgroup analyses, and/or sensitivity analyses. DISCUSSION: The proposed systematic review will deliver a robust comparative evaluation of the efficacy and safety of existing therapies for the management of CTRCI. These findings will inform clinical decisions, identify evidence gaps, and identify promising therapies for future evaluation in RCTs.

Potential association between obstructive lung diseases and cognitive decline.

Introduction: Chronic obstructive lung diseases, such as asthma and COPD, appear to have a more extensive impact on overall functioning than previously believed. The latest data from clinical trials suggests a potential link between cognitive deterioration and chronic obstructive inflammatory lung disease. This raises the question of whether these diseases affect cognitive functions and whether any relevant biomarker may be identified. Methods: This prospective observational study included 78 patients divided equally into asthma, COPD, and control groups (n=26, 27 and 25 respectively). The participants underwent identical examinations at the beginning of the study and after at least 12 months. The test battery comprised 16 questionnaires (11 self-rated, 5 observer-rated, assessing cognition and mental state), spirometry, and blood samples taken for PKA and CREB mRNA evaluation. Results: A 2.3-fold increase in CREB mRNA was observed between examinations (p=0.014) for all participants; no distinctions were observed between the asthma, COPD, and control groups. Pooled, adjusted data revealed a borderline interaction between diagnosis and CREB expression in predicting MMSE (p=0.055) in COPD, CREB expression is also associated with MMSE (ß=0.273, p=0.034) like with the other conducted tests (ß=0.327, p=0.024) from COPD patients. No correlations were generally found for PKA, although one significant negative correlation was found between the first and second time points in the COPD group (ß=-0.4157, p=0.049),. Discussion: Chronic obstructive lung diseases, such as asthma and COPD, may have some linkage to impairment of cognitive functions. However, the noted rise in CREB mRNA expression might suggest a potential avenue for assessing possible changes in cognition, especially in COPD; such findings may reveal additional transcription factors linked to cognitive decline.

Relationship between triglyceride-glucose index and cognitive function among community-dwelling older adults: a population-based cohort study.

Background: The global increase in the aging population presents considerable challenges, particularly regarding cognitive impairment, a major concern for public health. This study investigates the association between the triglyceride-glucose (TyG) index, a measure of insulin resistance, and the risk of cognitive impairment in the elderly. Methods: This prospective cohort study enrolled 2,959 participants aged 65 and above from the 2015 and 2020 waves of the China Health and Retirement Longitudinal Study (CHARLS). The analysis employed a logistic regression model to assess the correlation between the TyG index and cognitive impairment. Results: The study included 2,959 participants, with a mean age of 71.2 ± 5.4 years, 49.8% of whom were female. The follow-up in 2020 showed a decrease in average cognitive function scores from 8.63 ± 4.61 in 2015 to 6.86 ± 5.45. After adjusting for confounding factors, a significant association was observed between TyG index quartiles and cognitive impairment. Participants in the highest quartile (Q4) of baseline TyG had a higher risk of cognitive impairment compared to those in the lowest quartile (Q1) (odds ratio [OR]: 1.97, 95% confidence intervals [CI]: 1.28-2.62, P<0.001). Conclusion: The study highlights a significant connection between elevated TyG index levels and cognitive impairment among older adults in China. These findings suggest that targeted interventions to reduce the TyG index could mitigate cognitive impairment and potentially lower the incidence of dementia.

Astragalin improves cognitive disorder in Alzheimer's disease: Based on network pharmacology and molecular docking simulation.

We investigate the mechanism of action of astragalin (AST) in the treatment of Alzheimer's disease (AD). Network pharmacology was conducted to analyze the relationships among AST, AD, and neuroinflammation, The APP/PS1 transgenic mice with AD were used in the experiments; to be specific, the influence of AST on the behavior of mice was analyzed by Morris water maze and eight-arm radial maze tests, the tissue inflammatory factor levels were detected by ELISA, and pathological changes were analyzed by H&E and immunohistochemical staining. Analysis results of network pharmacology suggested that AST exerted the multi-target effect on neuroinflammation in AD. Through molecular docking and dynamics analyses, COX2 might be the target of AST. Moreover, animal experimental results demonstrated that AST improved the behavior of AD mice, and enhanced the motor and memory abilities, meanwhile, it suppressed the expression of inflammatory factors in tissues and the activation of microglial cells. this study discovers that AST can suppress microglial cell activation via COX2 to improve neuroinflammation in AD.

Blood-brain barrier disruption: a culprit of cognitive decline?

Cognitive decline covers a broad spectrum of disorders, not only resulting from brain diseases but also from systemic diseases, which seriously influence the quality of life and life expectancy of patients. As a highly selective anatomical and functional interface between the brain and systemic circulation, the blood-brain barrier (BBB) plays a pivotal role in maintaining brain homeostasis and normal function. The pathogenesis underlying cognitive decline may vary, nevertheless, accumulating evidences support the role of BBB disruption as the most prevalent contributing factor. This may mainly be attributed to inflammation, metabolic dysfunction, cell senescence, oxidative/nitrosative stress and excitotoxicity. However, direct evidence showing that BBB disruption causes cognitive decline is scarce, and interestingly, manipulation of the BBB opening alone may exert beneficial or detrimental neurological effects. A broad overview of the present literature shows a close relationship between BBB disruption and cognitive decline, the risk factors of BBB disruption, as well as the cellular and molecular mechanisms underlying BBB disruption. Additionally, we discussed the possible causes leading to cognitive decline by BBB disruption and potential therapeutic strategies to prevent BBB disruption or enhance BBB repair. This review aims to foster more investigations on early diagnosis, effective therapeutics, and rapid restoration against BBB disruption, which would yield better cognitive outcomes in patients with dysregulated BBB function, although their causative relationship has not yet been completely established.

Development of the Brazilian version of the Mini-Addenbrooke Cognitive Examination (M-ACE BR) to screen for cognitive impairment in older adults.

BACKGROUND: Age is the most important risk factor for develop dementia, and the recommendation is that older adults are cognitively tested to detect impairment in the initial stage for adequate treatment. The demand for the care of these older adults is great, drawing attention to the need for rapid tests, with good accuracy and simple application to identify cognitive impairment. OBJECTIVE: To develop and validate the Brazilian Mini-Addenbrooke Cognitive Examination (M-ACE BR) as a short screening test for cognitive impairment in older adults. METHODS: The M-ACE BR was developed using the Mokken scaling analysis in 352 participants (cognitively unimpaired [CU] = 232, cognitive impairment no dementia [CIND] = 82; and dementia = 38) and validated in an independent sample of 117 participants (CU = 25; CIND = 88; and dementia = 4). RESULTS: The Mokken scaling analysis derived 9 items (spatial orientation, anterograde memory, retrograde memory, delayed recall, recognition [name and address], letter verbal fluency, repetition of 4 words, naming of 10 items, and comprehension) with a maximum score of 51 points and an average duration time of 7 minutes. The cut-off score ≤ 43/51 for CIND had a sensitivity of 59.09% and a specificity of 80%. For a screening test in which sensitivity is prioritized for further investigation, we suggest using a cutoff of ≤ 47 (sensitivity 85.23% and specificity 24%), maintaining a good positive predictive value (79.8%). CONCLUSION: The M-ACE BR is a brief and adequate instrument to detect cognitive impairment in older Brazilian adults. However, screening for CIND and for different educational levels should be further explored.

ANTECEDENTES: A idade é o fator de risco mais importante para o desenvolvimento de demência, e a recomendação é que os idosos sejam testados cognitivamente para detectar comprometimento na fase inicial para o tratamento adequado. A demanda pelo atendimento desses idosos é grande, chamando atenção para a necessidade de testes rápidos, com boa acurácia e de simples aplicação para identificar o comprometimento cognitivo. OBJETIVO: Desenvolver e validar a versão brasileira do Mini-Addenbrooke's Cognitive Examination (M-ACE BR) como um teste rápido para rastreio de comprometimento cognitivo em idosos. MéTODOS: A M-ACE BR foi desenvolvida usando análise da escala de Mokken em 352 participantes (cognitivamente saudáveis [CS] = 232, comprometimento cognitivo sem demência [CCSD] = 82; e demência = 38) e validado em uma amostra independente de 117 participantes (CS = 25; CCSD = 88; e demência = 4). RESULTADOS: A análise de escala de Mokken derivou 9 itens (orientação espacial, memória anterógrada, memória retrógrada, evocação tardia, reconhecimento [nome e endereço], fluência verbal de letras, repetição de 4 palavras, nomeação de 10 itens e compreensão) com pontuação máxima de 51 pontos e tempo médio de duração de 7 minutos. O escore de corte ≤ 43/51 para CCSD teve sensibilidade de 59,09% e especificidade de 80%. Para um teste de rastreio, em que a sensibilidade é priorizada para investigação posterior, sugerimos utilizar um ponto de corte ≤ 47 (sensibilidade 85,23% e especificidade 24%), mantendo um bom valor preditivo positivo (79,8%). CONCLUSãO: A M-ACE BR é um instrumento breve e adequado para detectar comprometimento cognitivo em idosos brasileiros. No entanto, o rastreio para a identificação de CCSD e para diferentes níveis de escolaridade deve ser melhor explorado.

Molecular signatures of normal pressure hydrocephalus: a large-scale proteomic analysis of cerebrospinal fluid.

Given the persistent challenge of differentiating idiopathic Normal Pressure Hydrocephalus (iNPH) from similar clinical entities, we conducted an in-depth proteomic study of cerebrospinal fluid (CSF) in 28 shunt-responsive iNPH patients, 38 Mild Cognitive Impairment (MCI) due to Alzheimer's disease, and 49 healthy controls. Utilizing the Olink Explore 3072 panel, we identified distinct proteomic profiles in iNPH that highlight significant downregulation of synaptic markers and cell-cell adhesion proteins. Alongside vimentin and inflammatory markers upregulation, these results suggest ependymal layer and transependymal flow dysfunction. Moreover, downregulation of multiple proteins associated with congenital hydrocephalus (e.g., L1CAM, PCDH9, ISLR2, ADAMTSL2, and B4GAT1) points to a possible shared molecular foundation between congenital hydrocephalus and iNPH. Through orthogonal partial least squares discriminant analysis (OPLS-DA), a panel comprising 13 proteins has been identified as potential diagnostic biomarkers of iNPH, pending external validation. These findings offer novel insights into the pathophysiology of iNPH, with implications for improved diagnosis.