Cognitive Dysfunction Research Articles

Association between a lower T-CD4+ /CD8+ lymphocyte ratio and cognitive impairment in older persons with HIV.

To ascertain the association between the LT-CD4 + /CD8 + ratio and cognitive impairment in older people living with HIV. A cross-sectional study was conducted, including 207 adults aged > 50years with HIV, receiving care at a tertiary-care hospital in Mexico City. Participants underwent a standardized geriatric and neuropsychological assessment to establish the presence of HIV-associated neurocognitive disorder according to the validated Antinori criteria. Multivariate logistic regression models were performed to determine the association between T-CD4 + /CD8 + lymphocyte ratio tercile values (0.57-0.91, and < 0.56; with > 0.91 being the reference category) and cognitive impairment. Participants' median age was 56 (IQR 53-62)years and 173 (83.6%) were men. The prevalence of any kind of cognitive impairment according to the Antinori criteria was 66.2% (n = 137), the highest proportion being asymptomatic neurocognitive impairment (n = 114, 83.2%). Adjusted logistic regression analyses showed that the lowest LT-CD4 + /CD8 + ratio tercile values (< 0.56) were independently associated with the presence of cognitive impairment (OR 3.16; 95% CI 1.22-8.16, p = 0.017). Lower LT-CD4 + /CD8 + ratios are independently associated with cognitively impaired older persons with HIV, which represents another factor that could be addressed to identify individuals at risk and focus on cognitive screening as well as correction of other modifiable risk factors.

Mitochondrial modulation treating postoperative cognitive dysfunction neuroprotection via DRP1 inhibition by Mdivi1

This study investigated the role of mitochondrial dynamics in postoperative cognitive dysfunction (POCD) and assessed the therapeutic potential of mitochondrial modulation, particularly through the inhibition of dynamin-related protein 1 (DRP1) with Mdivi-1. Our findings indicated that DRP1 inhibition substantially mitigated neuroinflammation mediated by microglial cells, contributing to improved cognitive function in POCD models. The administration of Mdivi-1 led to a notable decrease in mitochondrial fission, reduced reactive oxygen species (ROS) production, and stabilization of mitochondrial membrane potential, all of which correlate with diminished neuroinflammation, as evidenced by lower NOD-like receptor family pyrin domain containing 3 (NLRP3)/ interleukin-1β (IL-1β) expression in microglial cells. Importantly, Mdivi-1 treatment was also found to enhance synaptic plasticity, increasing synaptic spine density in the hippocampal region of POCD mice. This improvement in mitochondrial health and synaptic integrity was paralleled by enhanced cognitive performance, as demonstrated in Y-maze tests. These results underscored the critical role of mitochondrial dynamics in the pathophysiology of POCD and suggested that targeting mitochondrial dysfunction, specifically through DRP1 inhibition, could be an effective approach for POCD treatment.

Connecting the dots: A narrative review of the relationship between heart failure and cognitive impairment.

Large clinical data underscore that heart failure is independently associated to an increased risk of negative cognitive outcome and dementia. Emerging evidence suggests that cerebral hypoperfusion, stemming from reduced cardiac output and vascular pathology, may contribute to the largely overlapping vascular dementia and Alzheimer's disease. Despite these insights, cognitive outcomes remain largely overlooked in heart failure management. This narrative review outlines the prevalence and risk of cognitive impairment in heart failure patients, exploring potential shared pathophysiological mechanisms and examining the impact of heart failure therapy on cognitive deficits. Additionally, it discusses clinical implications and suggests future treatment approaches targeting therapeutic outcomes. Cognitive impairment is prevalent among individuals with heart failure, with reported rates varying widely depending on assessment methods. Shared pathological pathways and risk factors, including atrial fibrillation (AF), hypertension, obesity and type 2 diabetes mellitus, suggest a causal link. Mechanisms such as poor perfusion, microembolic events, ischaemic syndromes and cerebral inflammation contribute to this relationship. Moreover, heart failure itself may exacerbate cognitive dysfunction. This emerging understanding posits that vascular dementia and Alzheimer's disease may represent a pathophysiological continuum, driven by both the accumulation of misfolded proteins and cerebrovascular pathology due to cardiovascular dysfunction. Understanding these links is crucial for developing effective treatment strategies. The complex interplay between heart failure and cognitive impairment underscores the necessity for a holistic patient care approach. Both conditions share analogous disease processes, influencing self-management and independence in patients. Prioritizing brain health in heart failure management is essential to enhance patient prognosis and general well-being.

IL-12p70 Induces Neuroprotection via the PI3K-AKT-BCL2 Axis to Mediate the Therapeutic Effect of Electroacupuncture on Postoperative Cognitive Dysfunction.

Postoperative cognitive dysfunction (POCD), a postsurgical decline in cognitive function, primarily affects older adults and worsens their prognosis. Although elevated interleukin-12p70 (IL-12p70) is closely correlated with slower cognitive decline in older adults, its role in POCD remains unclear. Here, IL-12p70 is identified as a significant mediator of therapeutic effect of electroacupuncture (EA) on POCD. EA at acupoints ST36, GV20, and GV24 significantly enhanced cognitive behaviors of POCD mice. IL-12p70, downregulated in POCD mice but rescued by EA treatment, is the cytokine closely associated with EA's therapeutic effect. Clinically, IL-12p70 is downregulated in older adults' serum post-surgery. Furthermore, IL-12p70 exerts a potent neuroprotective effect in both neuronal cell lines and primary hippocampal neurons. The PI3K-AKT-BCL2 axis enriched by in silico analysis is validated as the signaling mechanism underlying IL-12p70-induced neuroprotection. In vivo, beneficial effects of EA treatment on the activation of PI3K-AKT-BCL2 axis and POCD are reproduced by IL-12p70 administration but attenuated by IL-12p70 knockdown. The findings reveal a novel mechanism underlying the therapeutic effect of EA on POCD, demonstrating that IL-12p70 exerts a neuroprotective effect by activating PI3K-AKT-BCL2 axis in hippocampal neurons. The newly-discovered function and mechanism of IL-12p70 highlight its potential in treating cognitive disorders.

Distinct Hippocampal Expression Profiles of lncRNAs in Obese Type 2 Diabetes Mice Exhibiting Cognitive Impairment.

Cognitive dysfunction has been accepted as a possible complication of type 2 diabetes (T2D), but few studies revealed the potential roles of Long non‑coding RNAs (lncRNAs) in cognitive dysfunction in T2D. The current research aims to demonstrate the specific expression patterns of lncRNA-mRNA in the hippocampi of T2D db/db mice exhibiting cognitive impairment. In this study, the results from behavioral tests showed that T2D db/db mice displayed short-term and spatial working memory deficits compared to db/m mice. Furthermore, western blot analysis demonstrated that compared with db/m mice, p-GSK3β (ser9) protein levels were markedly elevated in T2D db/db mice (P < 0.01). In addition, though not statistically significant, the ratio of p-Tau (Ser396) to Tau 46, α-Synuclein expression, and p-GSK3α (ser21) expression were also relatively higher in T2D db/db mice than in db/m mice. The microarray profiling revealed that 75 lncRNAs and 26 mRNAs were dysregulated in T2D db/db mice (> 2.0 fold change, P < 0.05). GO analysis demonstrated that the differentially expressed mRNAs participated in immune response, extracellular membrane-bounded organelle, and extracellular region. KEGG analysis revealed that the differentially expressed mRNAs were mainly involved in one carbon pool by folate, glyoxylate and dicarboxylate metabolism, autophagy, glycine, serine and threonine metabolism, and B cell receptor signaling pathway. A lncRNA‑mRNA coexpression network containing 71 lncRNAs and 26 mRNAs was built to investigate the interaction between lncRNA and mRNA. Collectively, these results revealed the differential hippocampal expression profiles of lncRNAs in T2D mice with cognitive dysfunction, and the findings from this study provide new clues for exploring the potential roles of lncRNAs in the pathogenesis of cognitive dysfunction in T2D.

Comparison of Serum and Cerebrospinal Fluid Neurofilament Light Chain Concentrations Measured by Ella™ and Lumipulse™ in Patients with Cognitive Impairment

Objective: Neurofilament light chain proteins (NfLs) are considered a promising biomarker of neuroaxonal damage in several neurological diseases. Their measurement in the serum and cerebrospinal fluid (CSF) of patients with dementia may be especially useful. Our aim was to compare the NfL measurement performance of two advanced technologies, specifically the Ella™ microfluidic platform and the Lumipulse™ fully automated system, in patients with cognitive disorders. Methods: Thirty subjects with neurodegenerative cognitive disorders (10 with Alzheimer’s Disease, 10 with Frontotemporal Dementia, and 10 with non-progressive Mild Cognitive Impairment) seen at the Cognitive Neurology Clinic of Modena University Hospital (Italy) underwent CSF and serum NfL measurement with both the Ella™ microfluidic platform (Bio-Techne, Minneapolis, MN, USA)) and the Lumipulse™ fully automated system for the CLEIA (Fujirebio Inc., Ghent, Belgium). Correlation and regression analyses were applied to assess the association between NfL concentrations obtained with the two assays in CSF and serum. The Passing–Bablok regression method was employed to evaluate the agreement between the assays. Results: There were high correlations between the two assays (r = 0.976, 95% CI. 0.950–0.989 for CSF vs. r = 0.923, 95% CI 0.842–0.964 for serum). A Passing–Bablok regression model was estimated to explain the relationship between the two assays, allowing us to switch from one to the other when only one assay was available. Conclusions: We found a good degree of correlation between the two methods in patients with neurocognitive disorders. We also established a method that will allow comparisons between results obtained with either technique, allowing for meta-analyses and larger sample sizes.

The impact of neuroinflammation on neuronal integrity.

Neuroinflammation, characterized by a complex interplay among innate and adaptive immune responses within the central nervous system (CNS), is crucial in responding to infections, injuries, and disease pathologies. However, the dysregulation of the neuroinflammatory response could significantly affect neurons in terms of function and structure, leading to profound health implications. Although tremendous progress has been made in understanding the relationship between neuroinflammatory processes and alterations in neuronal integrity, the specific implications concerning both structure and function have not been extensively covered, with the exception of perspectives on glial activation and neurodegeneration. Thus, this review aims to provide a comprehensive overview of the multifaceted interactions among neurons and key inflammatory players, exploring mechanisms through which inflammation influences neuronal functionality and structural integrity in the CNS. Further, it will discuss how these inflammatory mechanisms lead to impairment in neuronal functions and architecture and highlight the consequences caused by dysregulated neuronal functions, such as cognitive dysfunction and mood disorders. By integrating insights from recent research findings, this review will enhance our understanding of the neuroinflammatory landscape and set the stage for future interventions that could transform current approaches to preserve neuronal integrity and function in CNS-related inflammatory conditions.

Mild cognitive impairment in amyotrophic lateral sclerosis: current view.

Amyotrophic lateral sclerosis (ALS) is a fatal multi-system neurodegenerative disorder with no effective treatment or cure. Although primarily characterized by motor degeneration, cognitive dysfunction is an important non-motor symptom that has a negative impact on patient and caregiver burden. Mild cognitive deficits are present in a subgroup of non-demented patients with ALS, often preceding motor symptoms. Detailed neuropsychological assessments reveal deficits in a variety of cognitive domains, including those of verbal fluency and retrieval, language, executive function, attention and verbal memory. Mild cognitive impairment (MCI), a risk factor for developing dementia, affects between 10% and over 50% of ALS patients. Neuroimaging revealed atrophy of frontal and temporal cortices, disordered white matter Integrity, volume reduction in amygdala and thalamus, hypometabolism in the frontal and superior temporal gyrus and anterior insula. Neuronal loss in non-motor brain areas, associated with TDP-43 deposition, one of the morphological hallmarks of ALS, is linked to functional disruption of frontostriatal and frontotemporo-limbic connectivities as markers for cognitive deficits in ALS, the pathogenesis of which is still poorly understood. Early diagnosis by increased cerebrospinal fluid or serum levels of neurofilament light/heavy chain or glial fibrillary acidic protein awaits confirmation for MCI in ALS. These fluid biomarkers and early detection of brain connectivity signatures before structural changes will be helpful not only in establishing early premature diagnosis but also in clarifying the pathophysiological mechanisms of MCI in ALS, which might serve as novel targets for prohibition/delay and future adequate treatment of this debilitating disorder.

Chronic Sleep Deprivation Altered the Expression of Memory-Related Genes and Caused Cognitive Memory Dysfunction in Mice

Lack of sleep, whether acute or chronic, is quite common and negatively affects an individual’s memory and cognitive function. The question of whether chronic sleep deprivation (CSD) causes cognitive impairment to arise and progress is not well studied. To investigate the effects of CSD on memory and cognition, this study began by establishing a CSD mouse model. Behavioral experiments on animals revealed that CSD induced cognitive behavioral abnormalities reminiscent of Alzheimer’s disease. Western blot experiments further demonstrated a considerable increase in amyloid-β (Aβ) expression in the mouse brain following CSD. Meanwhile, the hub gene Prkcg was searched for in the cerebellum using RNA-seq and bioinformatics analysis. PKCγ (Prkcg) expression was significantly reduced, as demonstrated by RT-qPCR and Western blot validations. Additionally, CSD was associated with downregulated CREB expression, decreased expression of the endothelin-converting enzyme (ECE1), and increased phosphorylation of ERK1/2 downstream of PKCγ. These findings suggested that CSD down-regulated PKCγ expression, decreased ECE1 expression, impaired Aβ degradation, and affected the PKCγ/ERK/CREB pathway and the synthesis of memory-related proteins. Overall, this study highlighted how CSD modulated PKCγ-related metabolism, impacting Aβ clearance and the production of memory-related proteins. Such insights are crucial for understanding and preventing sporadic Alzheimer’s disease (sAD) associated with CSD.

Tingkat Kemampuan Melempar Bola Pada Permainan Bocce Anak Tuna Grahita Ringan Peserta Didik Putri (SDLB) Negeri Wiradesa Kabupaten Pekalongan

Special Education is intended for students who experience difficulties in the learning process due to physical, emotional, mental, intellectual, or social disorders, or have extraordinary intelligence and talent potential (National Education System Law of 2003). Children with physical, cognitive, and behavioural disorders generally receive educational services at Special Schools (SLB), which are special schools for children with special needs. This study used a "One Group Pretest - Posttest" design with a sample size of 10 female students in elementary school. Before being given treatment, an initial measurement of gross motor skills was carried out on moderately mentally retarded students at SLB Negeri Wiradesa with light warm-ups. Furthermore, bocce games were given as a treatment to train gross motor skills. After that, re-measurements were carried out to see changes in gross motor skills, referred to as final tests. The results of the study showed that bocce games could improve the gross motor skills of moderately mentally retarded students in Physical Education subjects at SLB Negeri Wiradesa, especially for female students.

The THINC-it tool: temporal sensitivity to change over time

IntroductionCognitive dysfunction is believed to be among the core features of Bipolar Depression(BD-D). However, its evaluation and available treatments are limited. Here, we conducted a longitudinal follow-up clinical trial using the THINC-it tool to evaluate temporal sensitivity to change over time in cognitive function among patients with bipolar depression from a Chinese cohort. It is helpful to verify whether the scale can continuously and reliably measure cognitive function in different time points and reduce the measurement error caused by time factors. Hope our findings could provide insights into the significance of the THINC-it tool as an iterative clinical cognitive evaluation tool.MethodsA total of 120 patients with bipolar depression(40 males and 80 females, respectively) alongside 100 healthy controls(23 males and 77 females, respectively) were recruited in the study. All participants were interviewed for 8 weeks, using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale(YMRS). The primary dependent measure was the previously validated THINC-it tool, followed by psychometric analysis.ResultsRepeated measures of the THINC-it tool at baseline, one-week, and eight-week periods were conducted after controlling for age, gender, and education effects. Results from the general linear model revealed no significant time differences in variances(P > 0.05). Similarly, adjusting for confounding factors (age, gender, education, and HAMD-17 scores), results from the longitudinal analysis showed that there were no significant differences in cognitive impairment over time(P > 0.05). However, we found significant differences between BD-D and Healthy Control(HC) groups with regards to Spotter, Codebreaker, Trails, Perceived Deficits Questionnaire for Depression-5-items(PDQ-5-D), and THINC-it Total composite(P < 0.05), but not in Symbol Check (p = 0.191).ConclusionThese findings indicate that the THINC-it tool effectively detects sensitivity to change in groups and maintains stability at times, indicating that it is a feasible and reliable instrument for evaluating cognitive dysfunction in Chinese patients with bipolar depression.

Plasma trimethylamine-n-oxide associates with reduced hippocampal volume and cognitive impairment in atrial fibrillation

Abstract Background/Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia in modern society and affected patients appear particularly vulnerable to cognitive dysfunction. Yet, the pathomechanism of this association other than thromboembolism (TE) is not fully understood. We have shown earlier an association of cognitive dysfunction with the gut microbiome derivate trimethylamine-N-oxide (TMAO), which predominantly results from the consumption of red meat. We therefore hypothesized that TMAO may affect hippocampal volume (HV) as a brain structure relevant for cognition. Purpose To demonstrate the structure-function correlation of high TMAO levels with reduced cognitive function and lower HV in a large cohort of patients with atrial fibrillation. Methods We included 1’736 patients with confirmed AF from the Swiss-AF-cohort with both, available blood samples for TMAO measurement and with brain magnetic resonance imaging (bMRI) for the determination of HV at baseline. TMAO levels were measured by liquid chromatography-mass spectrometry (LC-MS). bMRI were obtained by 1.5 or 3 Tesla scanners. HV was assessed by the FreeSurfer software (v 7.4.0) subregion segmentation module and normalized by using Sequence Adaptive Multimodal SEGmentation (SAMSEG) to determine the segmentation based intracranial volume. Patients were divided into TMAO quartiles (Q1: 0.6-3.8, Q2: 3.8-5.5, Q3: 5.5-8.5, Q4: 8.5-164.3μmol/l). Their TMAO levels were compared with their HV (unit = mm3) in linear mixed effect models adjusted for multiple covariates (model 1: age, sex, total intracranial volume (ICV), education level; model 2 = model 1 + smoking status, body mass index (BMI), alcohol consumption, physical activity; model 3 = model 2 + hypertension, coronary artery disease, previous stroke, geriatric depression scale). We assessed both unilateral HV (right = RHV, left = LHV) and bilateral HV standardized by the individual total ICV. Results Overall mean age was 72.5 years (+/-8.4 SD), 27.2% were female. Most of the patients were well educated (39.4% advanced, 48.8% middle education) and 44% never smoked. After multivariable adjustments, patients in the highest TMAO quartile showed a significant reduction of bilateral HV volume of 93.4mm3 (95% CI -179.0 to -7.8, p = 0.03). The RHV appeared more affected and was significantly reduced by 48.2mm3 (CI -93.4, -3.0, p=0.04), whereas LHV was decreased by 44.2mm3 (-89.4, 1.0, p=0.06) in the highest TMAO quartile. Conclusion(s) TMAO negatively associates with bilateral HV in patients with AF. Our results suggest a structure-function-correlation between high TMAO levels and cognitive dysfunction. The findings may be relevant for the high TMAO-exposed patients and advocates for the importance of (possible dietary) prevention in AF.

Real-life data on the tolerability of SGLT2 inhibitors in elderly patients with heart failure

Abstract Introduction Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated their effectiveness in improving the prognosis of heart failure. However, there is some hesitation in clinical practice to prescribe them to elderly patients due to a lack of long-term safety data. The SafeGLT2 study aims to evaluate the tolerance of SGLT2i in elderly patients with heart failure in real-life settings. Methods This is a prospective study conducted in acute geriatric units in the Île-de-France region between February 2020 and May 2023. All patients admitted for acute heart failure (AHF), aged 75 years and older, were included. The diagnosis was confirmed by an expert committee, and patients were followed for one year. Treatments were recorded upon admission and discharge, along with demographic characteristics and medical history. SGLT2i tolerance data were collected and analyzed, including renal insufficiency, hypovolemia, genital infections, urinary infections, hypoglycemia, diabetic ketoacidosis, fractures, amputations, etc. A comparison of tolerance data between heart failure patients treated with SGLT2i and those not receiving SGLT2i was performed. Results 288 patients were included in the study with a mean age of 88 years, 53% (n=153) were female, and a median Charlson Comorbidity Index (CCI) of 8.77 [2.71]. 44.1% (n=127) of patients had neurocognitive disorders, 39.6% (n=114) were malnourished, 32.6% (n=94) were fallers, 53.8% (n=155) had renal insufficiency (eGFR &amp;lt; 60 ml/min), and 11.5% (n=33) lived in institutions. A total of 33% (n=95) were treated with SGLT2i upon discharge. No serious adverse effects were found in this very frail population receiving SGLT2i compared to the group not receiving SGLT2i (severe hypotension, hypovolemia, ketoacidosis, hypoglycemia, fracture, amputation). Beneficial effects on renal function (improvement of renal function at 6 months) were observed in the SGLT2i group despite a temporary decrease in glomerular filtration rate of less than 30% after SGLT2i initiation. However, a statistically significant increase in urinary tract infections (16.8% vs 4.15%), genital infections (12.6% vs 1.5%), and constipation (10% vs 1%) was found in the SGLT2i group compared to the group without SGLT2i. Conclusion These data indicate that SGLT2i are well tolerated in very elderly frail heart failure patients. However, the occurrence of urogenital infections appears to be more frequent in this population and requires particular surveillance.

Towers of Kuwait Arabic Neurocognitive Assessment: A novel executive and visuospatial functions assessment tool added to the CERAD neuropsychological battery-Arabic version (CERAD-ArNB)

Assessment of executive and visuospatial neurocognitive domains is lacking in the Omani population, especially for elderly individuals with low educational levels. Therefore, the Towers of Kuwait-Arabic Neurocognitive Assessment (ToK-ArNA) was developed using similar psychometric features of Tower of London (ToL) test, and the unique architecture of Towers of Kuwait, with the potential to overcome the limitation of ToL color perception difficulties that might be encountered in subjects with hereditary or acquired color vision disorders. We enrolled 120 older Arabic-speaking Omanis from January 2022 to November 2022 and all participants underwent screening to ensure normal cognitive function before performing the ToL and ToK-ArNA tests. Validity, reliability, and non-parametric statistical tests were used for data analysis. A total of 85 participants, 51 men (60%) and 34 women (40%) met the inclusion criteria and completed the testing. Statistical analyses confirmed the validity and reliability of ToK-ArNA compared to ToL, with comparable total Time and Accuracy scores and more preference towered the ToK-ArNA among the participants. Despite the study limitations, these results indicate that the ToK-ArNA is a reliable and applicable executive and visuospatial function assessment tool and further studies are warranted to establish its validity in patients with various neurocognitive disorders

Cognitive profile and behavioral problems in cohort of Egyptian children with cystic fibrosis: a single-center study

BackgroundCystic fibrosis (CF) is a debilitating and time-consuming disease that can interfere with or impair typical daily life activities and social interactions. This study aims to identify and evaluate behavioral problems and cognitive dysfunction in children with CF.Methods and proceduresThis study was carried out on a cohort of 40 children diagnosed with CF. Patients were assessed using a child behavior checklist (CBCL) and intelligence quotient (IQ) photograph test. The obtained results were compared with 40 matched controls.ResultsThe male population accounted for 62.5% of the patients included in the study. Patients with CF exhibited elevated somatic, anxious and aggressive behaviors relative to the control group with p values < 0.012, < 0.025, < 0.027 respectively. In addition; there was a statistically significant positive correlation between somatic problems with both age of the patients and disease duration (r value for age = 0.368; r value for duration = 0.468). Furthermore; there was positive correlation between anxious behavior with age of patients and disease duration ( r value for age = 0.358; r value for duration = 0.351). Otherwise, patients had comparable IQs (median of 107.5) with those of the control group (median of 105) with p value = 0.544.ConclusionOur findings indicate that CF has a substantial negative impact on the behavior of affected patients. However, it did not have an impact on the individual’s level of intelligence. There is evidence indicating a connection between patients’ age and disease duration with behavioral problems.

Characterising Long COVID in an Irish cohort: a study of symptom type, severity and determinants

Abstract Long COVID (LC) is a multisystem disorder impacting 65 million people globally. This secondary analysis of data from the Follow-up After Disease Acquisition (FADA) retrospective cohort study of COVID-19 recovery, aimed to characterise the nature and severity of LC in an Irish sample. The Modified COVID-19 Yorkshire Rehabilitation Scale categorised symptoms. Data analysis employed descriptive statistics and logistic regression. Of 4,671 respondents, 2,338 (50.1%) self-reported LC. LC participants were predominantly female (1,543, 66%), White Irish (1,512, 84.9%), and highly-educated (1,174, 65.8%). 907 (51.5%), had ≥one baseline co-morbidity. Most (1,076, 59.1%) had never smoked. Only 6.9% (162) of LC cases were ever hospitalised with acute COVID-19. Recovery was reported by 979 (41.9%). Of those with persistent symptoms 306 (31.6%) were classified as “moderate/severe.” Fatigue was predominant, (1,021, 75.1%) accompanied by cognitive dysfunction (932, 68.5%) and breathlessness (870, 64.0%). Functional impairment, assessed by the EQ-5D-5L score, was evident. Factors associated with LC persistence and severity included baseline co-morbidities (aOR persistent LC 1.44 [95% CI 1.12-1.85], p = 0.005; aOR moderate/severe LC 2.90 [1.92-4.37] p &amp;lt; 0.001)), smoking (aOR persistent LC 1.59 [1.11-2.28] p = 0.01, aOR moderate/severe=1.65 [1.0-2.71] p = 0.05), and meeting/exceeding WHO’s physical activity guidelines (aOR persistent LC 1.49 [1.16-1.92], p = 0.002, aOR moderate/severe=1.69 [1.12-2.54], p = 0.01). LC’s diverse symptomatology and functional impairment serve as a call to action to the health service to equip itself to address this complexity. This study offers insights into LC symptom type, duration, and determinants, emphasising the need for Public Health to traverse domains, to improve all facets of population health. These findings add to the current understanding of LC, providing a foundation for the development of tailored LC services. Key messages • Long COVID causes a constellation of diverse symptoms. • The Irish Health service needs to be equipped to manage the diverse symptomatologu.

Association between silent cerebral embolism and cognitive alterations following transcatheter aortic valve replacement in bicuspid versus tricuspid aortic valve patients

Abstract Background Silent cerebral ischemic lesions (SCILs) is a common magnetic resonance imaging (MRI) finding in severe aortic stenosis patients post - transcatheter aortic valve replacement (TAVR). We evaluated the association between SCILs and cognitive alterations in patients with bicuspid aortic valve (BAV) versus tricuspid aortic valve (TAV) post-TAVR. Methods This study enrolled 100 consecutive TAVR (45 with BAV and 55 TAV). DW-MRI and neurocognitive evaluation (MoCA score) were performed at baseline, discharge, and 1- and 12-month post-discharge. Results Ninety-two out of the 100 patients (92%) exhibited cognitive dysfunction at baseline. Post-TAVR, overall cognitive function significantly improved, the average MOCA score increased from 18.69±6.74 to 22.18±6.30. During the 1-year follow-up, 54 patients demonstrated improved cognitive function, and the number of patients with moderate-to-severe cognitive dysfunction (MoCA score &amp;lt; 18) significantly decreased from 32 to 16. Prevalence of SCILs was 14% and 72% at baseline and discharge, respectively. New SCILs were observed in 60 patients at discharge, distributed across all vascular territories, averaging 4 lesions with a total volume of 215.4±195.4mm3. Although no significant correlation existed between total volume of new SCILs and cognitive changes post-TAVR (R=-0.133, p=0.206), patients with SCILs still displayed significant cognitive improvement (MoCA score from 18.4±6.6 to 22.0±7.1), whereas patients who developed large SCILs (lesion diameter &amp;gt;9) showed less improvement compared to those with small or median SCILs (number of patients who had cognitive improvement: 32 vs. 52, p&amp;lt;0.05). Cognitive function improvement post-TAVR did not significantly differ between BAV and TAV patients, MoCA scores were comparable (BAV group, n=45, from 18.63±6.68 to 21.88±6.80 vs. TAV group, n=55, from 18.73±6.81 to 22.42±5.80; p&amp;gt;0.05). DW-MRI revealed more new SCILs in BAV patients post-TAVR compare to TAV patients (235 lesions vs. 150 lesions, respectively). In BAV patients, SCILs primarily manifested in small and medium sizes (224 lesions), despite more severe calcification (valvular calcium volume 956.5±644.0 mm vs. 634.4±508.0 mm3; p=0.028). The number of large lesions was similar in the two groups (11 in BAV group and 10 in TAV group). Conclusion TAVR demonstrates positive effects on improving cognitive function in aortic stenosis patients, despite common occurrence of SCILs in both BAV and TAV patients. Cognitive function post-TAVR was comparable between BAV and TAV patients. The cognitive improvement from TAVR may be less impacted by small- and medium-sized SCILs, while severe SCILs might impede or diminish the cognitive benefits of TAVR.table

Silent cerebral microvascular disease and longitudinal risk of cognitive decline in atrial fibrillation

Abstract Background A relationship between silent stroke and cognitive disorder has recently been suggested in patients with nonvalvular atrial fibrillation (NVAF). This research is an exploratory research study to investigate the occurrence of asymptomatic cerebrovascular disorders with NVAF. Methods The SKAF (Silent cerebral microvascular disease and longitudinal risK of cognitive decline in Atrial Fibrillation) study is a prospective, investigator-initiated, multicenter, observational study of Japanese patients with NVAF aged 60 years or older. We had planned to enroll two hundred NVAF patients with no history of symptomatic stroke or dementia, and an anticoagulant therapy with edoxaban is being performed or an anticoagulant therapy is not being performed, and one hundred patients with sinus rhythm, for comparison. We collected patient characteristics, clinical course, the data of head MRI test and cognitive function test (Montreal Cognitive Assessment (MoCA)) at the baseline and the 24 months follow-up. The primary endpoint was the composite of silent ischemic stroke and micro-bleeding over a 24-month follow-up period. The secondary endpoint was cognitive decline over a 24-month follow-up period. Results The study was started in October 2016, with a planned 2-year recruitment period. As of January 31, 2018, a total of 326 patients were enrolled. Of those, 99 patients with sinus rhythm (SR group) and 214 patients with NVAF (NVAF group) were analyzed (male, 193 (62%) patients; age, 72.2±6.5 years). 156 of 195 (80%) patients with NVAF received the anticoagulant therapy with edoxaban. There was no significant difference of the primary composite for the endpoints between two groups (17.4% versus 17.4%; p=1.00). The incidences of silent ischemic stroke and micro-bleeding in SR and NVAF groups over a 24-month follow-up period were 9.3% and 10.8% (p= 0.833), and 8.1% and 9.2% (p=1.00), respectively. The NVAF group exhibited a significantly larger decline in cognition changes in MoCA score than SR group (-0.830 versus 0,000; p=0.0131). Notably, NVAF was found to be associated with cognitive decline. Conclusion The SKAF registry provided an equivalent risk of silent cerebral microvascular disease in patients with SR and NVAF. Clinically, NVAF had an impact on cognitive decline.

Lyotropic Liquid Crystalline Based Nasal Spray for Improved Parkinson's Treatment: Enhanced Superior Nasal Tract Deposition and Antioxidation Strategy

AbstractThe blood–brain barrier is one of the serious challenges in the treatment of Parkinson's disease (PD), which severely hinders the drug's brain bioavailability. In this study, a lyotropic liquid crystalline (LLC) based in situ gel nasal spray loaded with the first‐line drug Levodopa (LDA) for PD is developed to resolve this issue based on a nose‐to‐brain drug delivery approach. Specifically, the two key stages of LLC‐based in situ gel nasal spray, droplet deposition, and drug retention are tailored. By adjusting LLC's precursor solution's viscosity, the droplet deposition on the superior nasal tract can be increased by 18 times. Through nasal mucus‐triggered sol–gel transition, the LDA nasal cavity retention is prolonged by three times. The epigallocatechin gallate is incorporated into the LLC‐based in situ gel nasal spray to inhibit the autoxidation of LDA and alleviate the oxidative stress response in PD. The results show that the LLC‐based in situ gel nasal spray has a 26‐fold higher brain bioavailability of LDA compared to oral administration. The PD rats show a significant improvement in behavioral and cognitive disorders after administration. The LLC‐based in situ gel nasal spray is proved to work by reducing oxidative damage. This study is anticipated to offer a promising strategy for the clinical application of LDA.

Brain-Derived Neurotrophic Factor (BDNF) is Associated with Self-Reported Cognitive Function in Adults with HIV.

Background: People with HIV (PWH) are at risk of developing HIV-associated neurocognitive disorder (HAND) despite receiving combination antiretroviral therapy. Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive function and neuroplasticity, but its role in HIV-related neuroinflammation remains understudied. Methods: This study analyzed data from the CHAMPS study, assessing BDNF serum levels and cognitive function in 140 adults with HIV at baseline. Cognitive function was evaluated using the PROMIS Applied Cognition-Abilities 8-item questionnaire. BDNF levels (pg/ml) were measured using high sensitivity Enzyme-Linked Immunoassay (ELISA) kits. Linear regression analyses were conducted to explore the associations between BDNF levels, cognitive function, and AIDS diagnosis, adjusting for demographic variables. Results: A significant positive association was found between BDNF levels and cognitive function scores in PWH (p = .03). Additionally, PWH with a history of AIDS diagnosis showed significantly lower BDNF levels (p = .02). Other demographic factors did not significantly impact cognitive function or BDNF levels in this cohort. Conclusions: Our results highlight the potential of BDNF as a biomarker for cognitive decline in PWH and suggest its relevance in understanding HAND pathophysiology. Further research is warranted to explore the multifaceted interactions influencing cognitive outcomes in this population and to develop targeted interventions for improving cognitive health in PWH.