Factors associated with neurocognitive impairment in treatment experienced HIV+ Adults: A perspective from a Tertiary Care Center in Ethiopia: factors associated with HAND in Ethiopia

Background: Given the improvement in life expectancy of people living with HIV (PLWH) in sub-Saharan Africa, the risk of asymptomatic HIV-associated neurocognitive disorder (HAND) has increased. The study objectives were to investigate the prevalence of HAND and associated factors among treatment experienced adults in Ethiopia. Methods: A single-center observational cross-sectional study was conducted between December 2019 and June2020 to investigate HAND. International HIV dementia scale (IHDS) was used to screen for the disorder. Both descriptive and analytical statistics were used to analyze the data. Results: Total of 324 PLWH (63% females) who were on combination antiretroviral therapy for median of 144months (IQR: 108-168) were investigated. The mean age was 42.5 years (1SD=12.2). The prevalence of HAND was 75.3% and the difference was significantly more in those above 40 years of age (65.8% vs. 80.7%, p=0.003). Age is the only risk factor identified with multivariable logistic regression analysis. A linear decrement in the total score of cognitive performance was observed as the patient's age increase; age was responsible for 9.4% variation observed in IHDS score (r= -0.31, R2=0.094, p<0.0001). Although statistically not-significant, the trend for cardio-metabolic and behavioral risk factors (hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol and khat use) was higher in the group diagnosed with HAND. Conclusion: The occurrence of neurocognitive impairment was more pronounced in individuals aged 40 years and above who were HIV positive, compared to those below 40 years. Age was found to be an independent predictor of HAND. Cardiovascular and behavioral risk factors were observed more among patients with HAND compared to no-HAND

Enfermedad de pequeño vaso. Relación con deterioro funcional, cognitivo y afectivo en adultos mayores con enfermedad cerebrovascular / Small vessel disease. Relationship with functional, cognitive and affective impairment in elderly adults with cerebrovascular disease

INTRODUCCIÓN: La enfermedad cerebral de pequeño vaso es una causa principal de pérdida funcional, discapacidad y deterioro cognitivo. OBJETIVO: Determinar la prevalencia de la enfermedad de pequeño vaso y características clínicas que se asocian a mayor deterioro funcional, cognitivo y afectivo en adultos mayores con enfermedad cerebrovascular atendidos en el Servicio de Neurología del Hospital Carlos Andrade Marín en el período 2020 ­ 2021. METODOLOGÍA: Estudio observacional, analítico transversal con 80 pacientes mayores de 65 años con enfermedad cerebrovascular previamente diagnosticada. Se determinó cuáles presentaban enfermedad cerebral de pequeño vaso. Se compararon los dos grupos el de enfermedad cerebro vascular isquémico con y sin enfermedad cerebral de pequeño vaso. Se midió el grado de deterioro funcional con escala de Barthel; Lawton y Brody. El deterioro cognitivo con test de Montreal Cognitive Assessment ­Basic, estado afectivo con escala de Yesavage. Se utilizó razón de momios y se consideró significativo un valor p <0,05. Se utilizó el programa Statistical Package for Social Sciences versión 25. RESULTADOS: Los hombres representaron el 51,2%. La edad promedio fue 76,2 años. Prevalencia de enfermedad cerebral de pequeño vaso (87,5%). Escala de Fazekas grado 1 (46,3%), Factores asociados con enfermedad cerebral de pequeño vaso: tabaquismo [RR: 7,27; IC 95%: 1,69-31,3); enfermedad renal crónica [RR: 4,0; IC 95%: 1,01-15,7]. Dependencia moderada [RR: 6,42; IC 95%: 1,02-40,3]. Factores asociados con pérdida funcionalidad: gravedad del ictus. Factores asociados con deterioro cognitivo: infarto con doble territorio. Factores asociados con deterioro afectivo: infarto con doble territorio y síndrome metabólico (p<0,05). CONCLUSIÓN: La enfermedad cerebral de pequeño vaso tiene una elevada prevalencia entre los adultos mayores con enfermedad cerebrovascular y representó un deterioro cognitivo, funcional y afectivo considerable, en relación a los pacientes sin esta enfermedad.

INTRODUCTION: Cerebral small vessel disease is a leading cause of functional loss, disability, and cognitive impairment. OBJECTIVE: To determine the prevalence of small vessel disease and clinical characteristics associated with greater functional, cognitive and affective impairment in older adults with cerebrovascular disease attended at the Neurology Service of the Carlos Andrade Marín Hospital in the period 2020 - 2021. METHODOLOGY: Observational, analytical cross-sectional study with 80 patients over 65 years of age with previously diagnosed cerebrovascular disease. It was determined which patients had cerebral small vessel disease. The two groups of ischemic cerebrovascular disease with and without cerebral small vessel disease were compared. The degree of functional impairment was measured with the Barthel, Lawton and Brody scales. Cognitive impairment was measured with the Montreal Cognitive Assessment-Basic test, and affective state with the Yesavage scale. Odds ratio was used and a p value <0,05 was considered significant. Statistical Package for Social Sciences version 25 was used. RESULTS: Males represented 51,2%. Mean age was 76,2 years. Prevalence of cerebral small vessel disease (87,5%). Fazekas scale grade 1 (46,3%), Factors associated with cerebral small vessel disease: smoking [RR: 7,27; 95% CI: 1,69-31,3); chronic kidney disease [RR: 4,0; 95% CI: 1,01-15,7]. Moderate dependence [RR: 6,42; 95% CI: 1,02-40,3]. Factors associated with loss of function: severity of stroke. Factors associated with cognitive impairment: infarction with double territory. Factors associated with affective impairment: dual territory infarction and metabolic syndrome (p<0.05). CONCLUSION: Cerebral small vessel disease has a high prevalence among older adults with cerebrovascular disease and represented a considerable cognitive, functional and affective deterioration, in relation to patients without this disease.

Las funciones ejecutivas: su significado y aplicación clínica / Executive functions: meaning and clinical application

Las funciones ejecutivas generalmente se conceptualizan como un conjunto de procesos generales de control de orden superior que trabajan juntos para dirigir y gestionar las funciones cognitivas, emocionales y conductuales, especialmente durante la resolución activa de problemas. Su disfunción es frecuente de ser detectada como comorbilidad de otros trastornos del neurodesarrollo, causa o efecto? La detección precoz de la disfunción ejecutiva y su abordaje terapéutico temprano, mejora el pronóstico global madurativo en el periodo infantojuvenil. Esta sucinta revisión de las funciones ejecutivas intenta resaltar su importancia para el pediatra y su mirada de los trastornos del neurodesarrollo (AU)

Executive functions are typically understood as a set of general higher-order control processes that collectively direct and manage cognitive, emotional, and behavioral functions, especially during active problem solving. Their dysfunction is often detected as a comorbidity of other neurodevelopmental disorders; cause or effect? Early detection of executive dysfunction and a prompt therapeutic approach improves the overall developmental prognosis in childhood and adolescence. This brief review of executive functions aims to highlight their importance for the pediatrician and his/her view of neurodevelopmental disorder (AU)

HDAC2 Inhibits Hippocampal Neurogenesis and Impairs the Cognitive Function in Prenatally Stressed Adult Offspring / HDAC2 Inhibe la Neurogénesis del Hipocampo y Afecta la Función Cognitiva en la Descendencia Adulta Estresada Prenatalmente

SUMMARY: The objective of this study was to investigate the mechanism of prenatal stress on the cognitive function of offspring, and clarify the change of histone deacetylase 2 (HDAC2) expression in hippocampal neurons of offspring. 16 pregnant SD rats were randomly divided into control group and stress group, with eight rats in each group. The stress group received restrained stress from 15 to 21 days of pregnancy, while the control group did not receive any treatment. Anxiety-like behavior and spatial memory, learning and memory ability were detected in open field, elevated plus maze, novel object recognition test, and Barnes maze. Nissl staining was used to detect the function of hippocampal neurons. Western blot was used to detect the expression of HDAC2 protein in hippocampal neurons of adult offspring. Immunofluorescence staining was used to detect the expression of HDAC2 protein and hippocampal neurogenesis. The learning and memory ability of adult offspring was decreased. The prenatal stress damaged the function of hippocampal neurons , the expression of HDAC2 was down-regulated, and the number of neurons was reduced. Maternal prenatal stress can down- regulate the expression of HDAC2 in the hippocampus of offspring, inhibits hippocampal neurogenesis and impairs the cognitive function.

El objetivo de este estudio fue investigar el mecanismo del estrés prenatal en la función cognitiva de la descendencia y aclarar el cambio de la expresión de la histona desacetilasa 2 (HDAC2) en las neuronas del hipocampo de la descendencia. 16 ratas SD preñadas se dividieron aleatoriamente en un grupo de control y un grupo de estrés, con ocho ratas en cada grupo. El grupo de estrés recibió estrés durante 15 a 21 días de pre, preñez, mientras que el grupo de control no recibió ningún tratamiento. El comportamiento similar a la ansiedad y la memoria espacial, el aprendizaje y la capacidad de memoria se detectaron en campo abierto, laberinto en cruz elevado, prueba de reconocimiento de objetos novedosos y laberinto de Barnes. La tinción de Nissl se utilizó para detectar la función de las neuronas del hipocampo. Se utilizó Western blot para detectar la expresión de la proteína HDAC2 en las neuronas del hipocampo de la descendencia adulta. La tinción de inmunofluorescencia se utilizó para detectar la expresión de la proteína HDAC2 y la neurogénesis del hipocampo. La capacidad de aprendizaje y memoria de la descendencia adulta se redujo. El estrés prenatal dañó la función de las neuronas del hipocampo, se reguló negativamente la expresión de HDAC2 y se redujo el número de neuronas. El estrés prenatal materno puede regular a la baja la expresión de HDAC2 en el hipocampo de la descendencia, inhibe la neurogénesis del hipocampo y deteriora la función cognitiva.

La atrofia cerebral como hallazgo o factor predictor del deterioro cognitivo en el envejecimiento normal / Cerebral Atrophy as a Finding of Predictive Factor for Cognitive Impairment in Normal Aging

Introducción: En el curso del envejecimiento es conocida la existencia de un patrón complejo de cambios estructurales cerebrales, conductuales y cognitivos, en ocasiones relacionados con enfermedades neurológicas y psiquiátricas. Objetivo: Determinar la posible relación de causalidad de la atrofia cerebral en la aparición del deterioro cognitivo en el curso del envejecimiento normal. Métodos: Se desarrolló un estudio retrospectivo, transversal, descriptivo y observacional. El universo estuvo conformado por el total de los pacientes de ambos sexos con edades comprendidas entre 35-74 años de edad, con indicaciones previas de tomografía computarizada de cráneo y cuyos resultados fueron informados con signos de atrofia cerebral, cuya cifra ascendió a 733. Resultados: El grupo de edad que predomino fue el de 45-54 años (35,3 por ciento), así como las pacientes del sexo femenino (66,3 por ciento). El 27,7 por ciento tenía como nivel de escolaridad el técnico medio superior y 36,2 por ciento fueron pacientes amas de casa. El 99,7 por ciento fueron diestros. Un total de 368 voluntarios presentaron deterioro cognitivo y 365 sujetos no evidenciaron declive en las funciones exploradas. Las funciones de atención y cálculo y retención verbal a corto plazo fueron las que se vieron más afectadas, seguidas de orientación espacial y memoria verbal de fijación. Conclusiones: No se logró establecer una relación de causalidad significativa entre el diagnóstico radiológico de atrofia cerebral y la presencia de deterioro cognitivo(AU)

Introduction: In the course of aging, the existence of a complex pattern of behavioral, cognitive and cerebral structural changes is known, sometimes related to neurological and psychiatric diseases. Objective: To determine the possible causal relationship of cerebral atrophy with the onset of cognitive impairment in the course of normal aging. Methods: A retrospective, cross-sectional, descriptive and observational study was carried out. The study universe consisted of all patients of both sexes aged 35-74 years, with previous indications for cranial computed tomography and whose results were reported with signs of cerebral atrophy, which numbered 733. Results: The predominant age group was 45-54 years old (35.3percent), as well as female patients (66.3percent). The educational level of 27.7percent of the patients was technical high school and 36.2percent were housewife patients. A total of 99.7percent were right-handed. A total of 368 volunteers showed cognitive impairment and 365 subjects showed no decline in the tested functions. The functions of attention and calculation, as well as short-term verbal retention, were the most affected, followed by spatial orientation and speech retention memory. Conclusions: No significant causal relationship was established between the radiological diagnosis of cerebral atrophy and the presence of cognitive impairment(AU)

Evaluación de síntomas neuropsiquiátricos para la detección temprana de trastorno neurocognoscitivo / Evaluation of neuropsychiatry symptoms for the early detection of neurocognitive disorder

RESUMEN INTRODUCCIÓN: El diagnóstico oportuno del trastorno neurocognitivo es de los principales retos en la atención de los trastornos neurocognitivos. Por esto, se han generado estrategias para la detección preclínica de la enfermedad, entre ellas las destinadas a evaluar síntomas neuropsiquiátricos (NPS) como la escala Mild Behavior Impairment - Checklist (MBI-C). MÉTODOS: Inicialmente se realizó una búsqueda en BVSalud, Medline y PsycNet, luego se realizó una búsqueda en bola de nieve. Se incluyeron términos referentes a deterioro comportamental leve (abarcando los NPS en etapas tempranas), deterioro cognitivo leve y términos específicos del MBI-C. RESULTADOS: La presencia de NPS se asocia con un aumento en la incidencia anual de demencia. Al evaluarlos con MBI-C, su puntuación se correlaciona con biomarcadores como una mayor atrofia cortical, la presencia de la proteína β-amiloide, así como disminución en funciones ejecutivas como la capacidad de enfocar la atención y la memoria de trabajo. DISCUSIÓN: Los hallazgos en la literatura sugieren la utilidad de MBI-C como marcador de neurodegeneración en estadios previos a la demencia, esto mediante la evaluación de su capacidad predictiva de forma independiente y al compararla con otros biomarcadores. CONCLUSIONES: MBI-C supone ser un instrumento de fácil aplicabilidad e interpretación, sostenible e incluyente. Sin embargo, quedan vacíos sobre la pertinencia de esta escala, por lo que surge la necesidad de investigar este tema.

ABSTRACT INTRODUCTION: Early diagnosis of neurocognitive disorder is the main challenge of dementia health attention. Therefore, strategies for preclinical detection of the disease have been created, like those intended to evaluate neuropsychiatric symptoms (NPS), like the Mild Behavior Impairment - Checklist (MBI-C). METHODS: Research was performed in BVSalud, Medline, and Psynet. Then a snowball sampling was done. The terms included were mild behavioral impairment (included NPS in initial stages), mild cognitive impairment, and specific terms of MBI-C. RESULTS: The presence of NPS increase the incidence of dementia, with an annual conversion rate of 9%. About MBI-C, the score has been related to biomarkers like worse brain atrophy in patients with Parkinson's Disease and a positive relationship with the presence of B-amyloid protein. Also, Creese and cols. show that mild behavioral impairment (measured by MBI-C) is associated with a faster decrease in attention and working memory. DISCUSSION: MBI-C utility as a neurodegenerative marker has been demonstrated to detect cognitive, neuropsychiatry, and functional symptoms that may precede dementia by evaluating its predictive capacity alone and comparing it to other biomarkers. CONCLUSION: MBI-C is easy to apply and interpret, is sustainable and inclusive. However, there are still gaps in the relevance of the scale, so there is the need to continue investigating this topic.

Spatial distribution of cognitive dysfunction and its risk factors in Chinese population aged 45 years and above / 南方医科大学学报

OBJECTIVE@#To analyze the spatial distribution of the prevalence of cognitive dysfunction and its risk factors in Chinese population aged 45 years and above to provide evidence for formulating regional prevention and control strategies.@*METHODS@#The study subjects with complete cognitive function data were selected from the follow-up data of the China Health and Retirement Longitudinal Study (CHARLS) Phase IV. ArcGis 10.4 software was used for spatial analysis of the prevalence of cognitive dysfunction in the population aged 45 years and above for each province based on the geographic information system (GIS) technology.@*RESULTS@#In 2018, the overall prevalence of cognitive dysfunction was 33.59% (5951/17716) in individuals aged 45 and above in China. Global spatial autocorrelation analysis indicated a spatial clustering and a positive autocorrelation (P < 0.001) of the prevalence of cognitive dysfunction in the study subjects, with a Moran's I value of 0.333085. The results of local spatial autocorrelation analysis showed that the southwestern region of China was the main aggregation area of patients with cognitive dysfunction. Geographically weighted regression analysis suggested that a male gender, an advanced age, and illiteracy were the major risk factors for cognitive dysfunction (P < 0.05). These 3 risk factors showed a spatial distribution heterogeneity with greater impact in the northern, western, and northwestern regions of China, respectively.@*CONCLUSION@#The prevalence of cognitive dysfunction is relatively high in individuals aged 45 years and above in China. A male gender, an advanced age, and illiteracy are the major risk factors for cognitive dysfunction and show different spatial distribution patterns, with the northern, western and northwestern regions of China as the key areas for prevention and control, where the prevention and control measures should be designed based on local conditions.

A study on factors associated with age of Alzheimer's disease onset / 中华流行病学杂志

Objective: To understand the distribution characteristics of age of Alzheimer's disease (AD) onset and influencing factors. Methods: Based on the follow-up data of Alzheimer's Disease Neuroimaging Initiative from 2005 to 2022, participants with normal cognition (CN) or mild cognitive impairment (MCI) at baseline survey, and those with progression to AD during follow-up period were selected as study subjects. Univariate analysis and multiple linear regression analysis were performed to explore the associations of gender, race, number of ApoE ε4 genes carried, family history, years of education and marital status with the age of AD onset. Results: A total of 405 participants, with an average age of (74.0±6.9) years at baseline survey, progressed to AD during follow up period. The age of AD onset was (76.6±7.5) years, and age of onset in men was about 1.9 years later than women. Multiple linear regression analysis showed that for each increase in ApoE ε4 gene number, the age of AD onset was about 0.344 years earlier. The age of AD onset was 4.007 years earlier for those with MCI at baseline survey compared with those with CN. Years of education were not significantly associated with the age of onset of AD (P>0.05). Conclusion: Those who carry ApoE ε4 gene, and have MCI at baseline survey might have earlier age of AD onset.

Association between cognitive impairment and main metals among oldest old aged 80 years and over in China / 中华预防医学杂志

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q1) of blood selenium, the ORs (95%CI) of Q3 and Q4 blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (Pnonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.

Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation / 中国中药杂志

Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.

Phosphate and tension homology-induced kinase 1/Parkin signaling mediates cognitive dysfunction in sepsis-associated encephalopathy through activation of hippocampal mitochondrial autophagy / 中华危重病急救医学

OBJECTIVE@#To investigate the effects of gene of phosphate and tension homology (PTEN)-induced putative kinase 1 (PINK1)/Parkin pathway on hippocampal mitophagy and cognitive function in mice with sepsis-associated encephalopathy (SAE) and its possible mechanism.@*METHODS@#A total of 80 male C57BL/6J mice were randomly divided into Sham group, cecal ligation puncture (CLP) group, PINK1 plasmid transfection pretreatment groups (p-PINK1+Sham group, p-PINK1+CLP group), empty vector plasmid transfection control group (p-vector+CLP group), with 16 mice in each group. The mice in CLP groups were treated with CLP to reproduce SAE models. The mice in the Sham groups were performed laparotomy only. Animals in the p-PINK1+Sham and p-PINK1+CLP groups were transfected with PINK1 plasmid through the lateral ventricle at 24 hours before surgery, while mice in the p-vector+CLP group were transfected with the empty plasmid. Morris water maze experiment was performed 7 days after CLP. The hippocampal tissues were collected, the pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and the mitochondrial autophagy was observed under a transmission electron microscopy after uranyl acetate and lead citrate staining. The expressions of PINK1, Parkin, Beclin1, interleukins (IL-6, IL-1β) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting.@*RESULTS@#Compared with the Sham group, CLP group mice in Morris water maze experiment had longer escape latency, shorter target quadrant residence time, and fewer times of crossing the platform at 1-4 days. Under the light microscope, the hippocampal structure of the mouse was injured, the neuronal cells were arranged in disorder, and the nuclei were pyknotic. Under the electron microscope, the mitochondria appeared swollen, round, and wrapped by bilayer or multilayer membrane structures. Compared with the Sham group, CLP group had higher expressions of PINK1, Parkin, Beclin1, LC3II/LC3I ratio, IL-6 and IL-1β in hippocampus, indicating that sepsis induced by CLP could activated inflammatory response and caused PINK1/Parkin-mediated mitophagy. Compared with the CLP group, p-PINK1+CLP group had shorter escape latencies, spent more time in the target quadrant and had more number of crossings in the target quadrant at 1-4 days. Under the light microscope, the hippocampal structures of mice was destroyed, the neurons were arranged disorderly, and the nuclei were pyknotic. Under transmission electron microscope, swollen and rounded mitochondria and mitochondrial structure wrapped by double membrane or multilayer membrane structure were observed. Compared with the CLP group, the levels of PINK1, Parkin, Beclin1 and LC3II/LC3 ratio in the p-PINK1+CLP group were significantly increased [PINK1 protein (PINK1/β-actin): 1.95±0.17 vs. 1.74±0.15, Parkin protein (Parkin/β-actin): 2.06±0.11 vs. 1.78±0.12, Beclin1 protein (Beclin1/β-actin): 2.11±0.12 vs. 1.67±0.10, LC3II/LC3I ratio: 3.63±0.12 vs. 2.27±0.10, all P < 0.05], while the levels of IL-6 and IL-1β were significantly decreased [IL-6 protein (IL-6/β-actin): 1.69±0.09 vs. 2.00±0.11, IL-1β protein (IL-1β/β-actin): 1.11±0.12 vs. 1.65±0.12, both P < 0.05], suggesting that overexpression of PINK1 protein could further activate mitophagy and reduce the inflammatory response caused by sepsis. There was no statistically significant difference in the above pathological changes and related indicators between Sham group and p-PINK1+Sham group, CLP group and p-vector+CLP group.@*CONCLUSIONS@#PINK1 overexpression can further activate CLP-induced mitophagy by upregulating Parkin, thereby inhibiting inflammation response and alleviate cognitive function impairment in SAE mice.

C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis / 神经科学通报·英文版

Alzheimer's disease (AD) is the most common type of dementia. Almost two-thirds of patients with AD are female. The reason for the higher susceptibility to AD onset in women is unclear. However, hormone changes during the menopausal transition are known to be associated with AD. Most recently, we reported that follicle-stimulating hormone (FSH) promotes AD pathology and enhances cognitive dysfunctions via activating the CCAAT-enhancer-binding protein (C/EBPβ)/asparagine endopeptidase (AEP) pathway. This review summarizes our current understanding of the crucial role of the C/EBPβ/AEP pathway in driving AD pathogenesis by cleaving multiple critical AD players, including APP and Tau, explaining the roles and the mechanisms of FSH in increasing the susceptibility to AD in postmenopausal females. The FSH-C/EBPβ/AEP pathway may serve as a novel therapeutic target for the treatment of AD.

Advances in the electrophysiological research on neurocognitive function in adolescents with non-suicidal self-injury / 中国当代儿科杂志

Non-suicidal self-injury (NSSI) is becoming increasingly common in adolescents and seriously affects their physical and mental health, and it is also a major risk factor for suicide among adolescents. NSSI has now become a public health issue of general concern; however, the identification of cognitive dysfunction in NSSI is still based on neuropsychological cognitive assessment and subjective questionnaire assessment, with a lack of objective evaluation indicators. As a method for studying the cognitive neural mechanism of NSSI, electroencephalography is a reliable tool for finding objective biomarkers of NSSI. This article reviews the recent research on electrophysiology associated with cognitive dysfunction in adolescents with NSSI.

The application scenarios study on the intervention of cognitive decline in elderly population using metaverse technology / 生物医学工程学杂志

China is facing the peak of an ageing population, and there is an increase in demand for intelligent healthcare services for the elderly. The metaverse, as a new internet social communication space, has shown infinite potential for application. This paper focuses on the application of the metaverse in medicine in the intervention of cognitive decline in the elderly population. The problems in assessment and intervention of cognitive decline in the elderly group were analyzed. The basic data required to construct the metaverse in medicine was introduced. Moreover, it is demonstrated that the elderly users can conduct self-monitoring, experience immersive self-healing and health-care through the metaverse in medicine technology. Furthermore, we proposed that it is feasible that the metaverse in medicine has obvious advantages in prediction and diagnosis, prevention and rehabilitation, as well as assisting patients with cognitive decline. Risks for its application were pointed out as well. The metaverse in medicine technology solves the problem of non-face-to-face social communication for elderly users, which may help to reconstruct the social medical system and service mode for the elderly population.

Research on mild cognitive impairment diagnosis based on Bayesian optimized long-short-term neural network model / 生物医学工程学杂志

The recurrent neural network architecture improves the processing ability of time-series data. However, issues such as exploding gradients and poor feature extraction limit its application in the automatic diagnosis of mild cognitive impairment (MCI). This paper proposed a research approach for building an MCI diagnostic model using a Bayesian-optimized bidirectional long short-term memory network (BO-BiLSTM) to address this problem. The diagnostic model was based on a Bayesian algorithm and combined prior distribution and posterior probability results to optimize the BO-BiLSTM network hyperparameters. It also used multiple feature quantities that fully reflected the cognitive state of the MCI brain, such as power spectral density, fuzzy entropy, and multifractal spectrum, as the input of the diagnostic model to achieve automatic MCI diagnosis. The results showed that the feature-fused Bayesian-optimized BiLSTM network model achieved an MCI diagnostic accuracy of 98.64% and effectively completed the diagnostic assessment of MCI. In conclusion, based on this optimization, the long short-term neural network model has achieved automatic diagnostic assessment of MCI, providing a new diagnostic model for intelligent diagnosis of MCI.

Research on classification method of multimodal magnetic resonance images of Alzheimer's disease based on generalized convolutional neural networks / 生物医学工程学杂志

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Neuroimaging based on magnetic resonance imaging (MRI) is one of the most intuitive and reliable methods to perform AD screening and diagnosis. Clinical head MRI detection generates multimodal image data, and to solve the problem of multimodal MRI processing and information fusion, this paper proposes a structural and functional MRI feature extraction and fusion method based on generalized convolutional neural networks (gCNN). The method includes a three-dimensional residual U-shaped network based on hybrid attention mechanism (3D HA-ResUNet) for feature representation and classification for structural MRI, and a U-shaped graph convolutional neural network (U-GCN) for node feature representation and classification of brain functional networks for functional MRI. Based on the fusion of the two types of image features, the optimal feature subset is selected based on discrete binary particle swarm optimization, and the prediction results are output by a machine learning classifier. The validation results of multimodal dataset from the AD Neuroimaging Initiative (ADNI) open-source database show that the proposed models have superior performance in their respective data domains. The gCNN framework combines the advantages of these two models and further improves the performance of the methods using single-modal MRI, improving the classification accuracy and sensitivity by 5.56% and 11.11%, respectively. In conclusion, the gCNN-based multimodal MRI classification method proposed in this paper can provide a technical basis for the auxiliary diagnosis of Alzheimer's disease.

Progress on Prevention and Treatment of Cerebral Small Vascular Disease Using Integrative Medicine / 中国结合医学杂志

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.

Recent research on cognitive impairment in children with acute lymphoblastic leukemia / 中国当代儿科杂志

Acute lymphoblastic leukemia (ALL) is the most common malignant neoplastic disease in children. With the continuous improvement in diagnosis and treatment, there has been an increasing number of ALL children who achieve long-term survival after complete remission; however, a considerable proportion of these children have cognitive impairment, which has a serious adverse impact on their learning, employment, and social life. This article reviews the latest research on cognitive impairment in children with ALL from the aspects of the influencing factors, detection techniques, and prevention/treatment methods for cognitive impairment.

Effects of repetitive transcranial magnetic stimulation on neuronal excitability and ion channels in hindlimb unloading mice / 生物医学工程学杂志

Weightlessness in the space environment affects astronauts' learning memory and cognitive function. Repetitive transcranial magnetic stimulation has been shown to be effective in improving cognitive dysfunction. In this study, we investigated the effects of repetitive transcranial magnetic stimulation on neural excitability and ion channels in simulated weightlessness mice from a neurophysiological perspective. Young C57 mice were divided into control, hindlimb unloading and magnetic stimulation groups. The mice in the hindlimb unloading and magnetic stimulation groups were treated with hindlimb unloading for 14 days to establish a simulated weightlessness model, while the mice in the magnetic stimulation group were subjected to 14 days of repetitive transcranial magnetic stimulation. Using isolated brain slice patch clamp experiments, the relevant indexes of action potential and the kinetic property changes of voltage-gated sodium and potassium channels were detected to analyze the excitability of neurons and their ion channel mechanisms. The results showed that the behavioral cognitive ability and neuronal excitability of the mice decreased significantly with hindlimb unloading. Repetitive transcranial magnetic stimulation could significantly improve the cognitive impairment and neuroelectrophysiological indexes of the hindlimb unloading mice. Repetitive transcranial magnetic stimulation may change the activation, inactivation and reactivation process of sodium and potassium ion channels by promoting sodium ion outflow and inhibiting potassium ion, and affect the dynamic characteristics of ion channels, so as to enhance the excitability of single neurons and improve the cognitive damage and spatial memory ability of hindlimb unloading mice.

Relationship between nutrient-related dietary pattern and mild cognitive impairment in middle-aged and elderly people in 15 provinces of China / 中华流行病学杂志

Objective: To explore the relationship between nutrient-related dietary pattern and mild cognitive impairment (MCI) in middle-aged and elderly people. Methods: A total of 6 444 middle-aged and elderly people aged ≥55 years were selected in 2018 China Health and Nutrition Survey. MCI was evaluated by Mini-Mental State Examination, and the intakes of various foods were obtained by consecutive 3-day 24-hour dietary survey and weighing method. The intakes of various nutrients and total dietary energy were calculated based on the food composition table. Demographic and social information, lifestyle and health status of the respondents were obtained through questionnaire survey and physical measurements. In this study, vitamin C, vitamin E, zinc, iron, copper and selenium were selected as dependent variables. Nutrient-related dietary patterns were extracted by reduced rank regression method, and the relationship between dietary patterns and MCI was analyzed by multivariate logistic regression model. Results: Six dietary patterns were extracted in this study, and dietary pattern 1 with the highest explanatory degree was selected for subsequent analysis. Dietary pattern 1 was characterized by higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products and plant oil. Multivariate logistic regression analysis showed that the risk of MCI was lower in Q4 dietary score group than in Q1 dietary score group (OR=0.69, 95%CI: 0.49-0.98) in the 55-64 age group. In people with sleep duration of 8 hours per day, the risk of MCI was reduced in Q2, Q3 and Q4 dietary score groups compared with the Q1 dietary score group, with OR values of 0.68 (95%CI: 0.51-0.92), 0.67 (95%CI: 0.49-0.92) and 0.65 (95%CI: 0.45-0.92), respectively. Interaction analysis showed that the risk for MCI increased in those aged 65-74 years and ≥75 years compared with those aged 55-64 years in Q1 dietary score group. However, the risk for MCI decreased in both age groups as dietary pattern scores increased. Compared with those with sleep duration less or more than 8 hours per day in Q1 dietary score group, those with sleep duration of 8 hours per day in Q2 and Q3 dietary score groups had a reduced risk for MCI. Conclusion: Dietary patterns with higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products, and plant oil are negatively associated with MCI in people aged 55-64 years and those who slept 8 hours per day, and may reduce the risk of MCI with aging.