The Hidden Dangers of Sedentary Living: Insights into Molecular, Cellular, and Systemic Mechanisms.

With the aging of the global population, neurodegenerative diseases are emerging as a major public health issue. The adoption of a less sedentary lifestyle has been shown to have a beneficial effect on cognitive decline, but the molecular mechanisms responsible are less clear. Here we provide a detailed analysis of the complex molecular, cellular, and systemic mechanisms underlying age-related cognitive decline and how lifestyle choices influence these processes. A review of the evidence from animal models, human studies, and postmortem analyses emphasizes the importance of integrating physical exercise with cognitive, multisensory, and motor stimulation as part of a multifaceted approach to mitigating cognitive decline. We highlight the potential of these non-pharmacological interventions to address key aging hallmarks, such as genomic instability, telomere attrition, and neuroinflammation, and underscore the need for comprehensive and personalized strategies to promote cognitive resilience and healthy aging.

Comparison of intensive treatment versus standard treatment in lowering blood pressure and its association with cognitive decline and dementia: a systematic review and meta-analysis

BACKGROUND: The ideal blood pressure target level for preventing cognitive decline or dementia in patients with systemic arterial hypertension (SAH) remains unclear. PURPOSE: This study aims to investigate whether intensive blood pressure reduction compared to standard treatment is associated with a reduced risk of cognitive decline or dementia in adults with SAH. METHODS: PubMed, Scopus and Cochrane databases were searched for randomized clinical trials (RCTs) comparing intensive treatment versus standard treatment for blood pressure reduction in patients with SAH. A random-effects model was used for analyzing the results, which were presented as relative risk (RR) with a 95% confidence interval (CI). Heterogeneity was examined using the I² statistic. Statistical analysis was performed using R software version 4.2.3. RESULTS: A total of 5 RCTs and 46,658 patients were included, of whom 23,726 (50,85%) underwent intensive therapy for SAH treatment. The mean age of participants ranged from 62.8 to 80.9 years in the intensive treatment group while it ranged from 63.3 to 80.3 years in the standard treatment group. Occurrence of dementia or probable dementia was significantly lower in the intensive treatment group (3.8% vs. 4,3%; RR 0.88; 95% CI: 0.80 - 0.96; p= 0.0049; I²=0%). Dementia or Cognitive decline (16.4% vs. 18.8%; RR 0.87; 95% CI 0.83 - 0.90; p < 0.000001; I²=0%), and cognitive decline (13.2% vs. 15.2%; RR 0.88; 95% CI 0.80 - 0.98; p= 0.014; I²=53%) also tended towards the intensive treatment group. Additionally, no significant association was found in mortality (6.4% vs. 7.3%; RR 0.87; 95% CI 0.75 - 1.02; p= 0.09; I²=28%) and serious adverse effects (34.4% vs. 35.5%; RR 0.99; 95% CI 0.92 - 1.06; p=0.73; I²=63%). CONCLUSION: Our study shows that intensive blood pressure treatment is associated with a fewer occurrence of dementia, probable dementia and cognitive decline in comparison to the standard blood pressure target.

Temporal bisection task as a predictor of cognitive deficits.

Evidence suggests that neuropsychiatric symptoms and deficits in attentional control and executive function can impair time discrimination, demonstrating the intricate link between cognitive processes, subjective well-being, and perception of time. However, the relationship between sleep quality and time discrimination remains elusive. This study aimed to understand differences in the temporal bisection task (TBT) performance. We expected that individuals with impaired cognition, executive function, quality of life, or sleep quality would have reduced time sensitivity. At the same time, those with stress, anxiety, or depression would show a shift in the point of subjective equality. Data were collected from 97 female participants (ranging from 20 to 72 years of age) in more than one moment, resulting in 163 measurements used for the analysis. Participants' neuropsychiatric status was assessed using a battery of tests and scales, including the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), the World Health Organization Quality of Life Questionnaire (WHOQOL), the Pittsburgh Sleep Quality Index (PSQI), and the Depression, Anxiety, and Stress Scale-21 items (DASS-21). The results showed that attention and executive control significantly affect time discrimination. In addition, the research indicated that better sleep quality is associated with improved time discrimination sensitivity.

Siniestralidad y apnea obstructiva del sueño. Revisión de la literatura y evaluación de la situación en 3 países latinoamericanos / Accident Rate and Obstructive Sleep Apnea: Literature Review and Assessment of the Situation in Three Latin American Countries

La apnea obstructiva del sueño (AOS) es una condición común en adultos en edad laboral. Incluso, en la actualidad, vemos cómo la edad de retiro se ha ido prolongando de tal manera que adultos mayores, quienes tienen mayor prevalencia de AOS, continúan trabajando incluso en situaciones de alto riesgo de siniestralidad. Uno de los principales síntomas de la AOS es la somnolencia diurna que puede contri- buir de manera directa al riesgo de accidentabilidad, compromiso cognitivo y desem- peño laboral. También se ha demostrado cómo la reducción de la materia gris a nivel cerebral y cerebelar provoca alteraciones en coordinación y capacidad de conducción. El tratamiento con dispositivos de presión positiva mejora el desempeño laboral y redu- ce la incidencia de accidentes de tránsito, pero algunos déficits cognitivos pueden per- sistir incluso después de meses de tratamiento. La evaluación del riesgo de accidentabilidad en conductores es un desafío y los cues- tionarios actuales no son adecuados para el cribado. Los simuladores de conducción y las pruebas de alerta son más prometedores. El futuro de la investigación se centra en estandarizar los resultados de los simulado- res, determinar los mejores predictores de eventos reales y utilizar la inteligencia arti- ficial y los automóviles autónomos para reducir los riesgos relacionados con la somno - lencia al volante. Es necesario que la posición de los entes gubernamentales de nuestros países latinoa- mericanos sea proactiva y orientada a la protección de la salud y la seguridad de la po- blación.

Obstructive sleep apnea (OSA) is a common condition among working-age adults. In today's context, we observe that the retirement age has been extended, with older adults, who have a higher prevalence of OSA, continuing to work even in high-risk situations. One of the main symptoms of OSA is daytime sleepiness, which can directly contribu- te to the risk of accidents, cognitive impairment and reduced work performance. It has also been demonstrated that the reduction of gray matter in the brain, especially in the cerebellum, can lead to coordination and driving capacity impairments. Treatment with positive pressure devices improves work performance and reduces the incidence of traffic accidents, but some cognitive deficits may persist even after months of treatment. Assessing the risk of accidents in drivers is a challenge, and current questionnaires are not suitable for screening. Driving simulators and alertness tests show more promise. The future of research is focused on standardizing simulator outcomes, identifying the best predictors of real-world events, and utilizing artificial intelligence and autonomous vehicles to mitigate risks associated with driver drowsiness. It is imperative that the stance of government entities in our Latin American countries is proactive and aimed at safeguarding the health and safety of the population.

Association between type of menopause and mild cognitive impairment: The REDLINC XII study.

OBJECTIVE: To evaluate the association between type of menopause (spontaneous or surgical) and mild cognitive impairment (MCI). STUDY DESIGN: This study was a cross-sectional, observational, and sub-analytical investigation conducted within gynecological consultations across nine Latin American countries. METHOD: We assessed sociodemographic, clinical, and anthropometric data, family history of dementia, and the presence of MCI using the Montreal Cognitive Assessment (MoCA) tool. RESULTS: The study involved 1185 postmenopausal women with a mean age of 55.3 years and a body mass index of 26.4 kg/m2. They had an average of 13.3 years of education, and 37 % were homemakers. Three hundred ninety-nine experienced menopause before 40, including 136 with surgical menopause (bilateral oophorectomy). Out of the 786 women who experienced menopause at 40 or more years, 110 did so due to bilateral oophorectomy. There were no differences in MoCA scores among women who experienced menopause before or after the age of 40. However, lower MoCA scores were observed in women with surgical menopause than in those with spontaneous menopause (23.8 ± 4.9 vs. 25.0 ± 4.3 points, respectively, p < 0.001). Our logistic regression model with clustering of patients within countries found a significant association between MCI and surgical menopause (OR 1.47, 95 % CI: 1.01-2.16), use (ever) of menopausal hormone therapy (OR 0.33, 95 % CI: 0.21-0.50), and having >12 years of education (OR 0.21, 95 % CI: 0.14-0.30). CONCLUSION: When comparing women who experience spontaneous menopause over the age of 40 with those who undergo it before this age, there was no observed increased risk of developing MCI, while those with surgical menopause, independent of age, are more prone to cognitive decline. Women who have ever used menopausal hormone therapy have a lower MCI risk. Further research is warranted to delve deeper into this topic.

Cognitive impairment in a Colombian cohort of patients with systemic lupus erythematosus: A cross-sectional study.

CONTEXT: Cognitive deficits are neuropsychiatric syndromes associated with systemic lupus erythematosus. In our context, there are no data on the frequency of cognitive deficit as a manifestation of neuropsychiatric SLE or the associated conditions. OBJECTIVE: To define determinants of cognitive deficit in a cohort of Colombian patients with SLE attending a third-level hospital. METHODS AND PATIENTS: This descriptive cross-sectional study included patients with SLE, explored the presence of cognitive impairment through screening testing using the Montreal Cognitive Assessment (MoCA test), and diagnostic confirmation with a specific neuropsychological test battery recommended by the American College of Rheumatology. Quality of life was assessed using the LupusCol questionnaire and depression using the Beck Depression Inventory. RESULTS: Most patients were women, with a median age of 37 years (IQR, 28.0 - 46.7). Most patients had a level of higher education or technical education. Fifty-nine (62.9%) patients presented with a normal MoCA test result ≥26 points, and 35 (37.1%) patients with a score <26 points that were considered abnormal. The comprehensive neuropsychological test battery was applied to 31 patients (33.0%) with an abnormal MoCA test. Forty-one patients (48.8%) had some degree of depression. The median loss of quality of life was 21.03% (IQR 10.2 - 40.3). 19 patients (20%) presented some degree of cognitive deficit, 15 (15.95% of the total sample) had cognitive impairment, and 4 (4.25%) had cognitive decline. In a logistic regression analysis using data from patients undergoing specific tests, variables related to cognitive deterioration were found to be associated with a lower quality of life, showing an adjusted odds ratio of 1.05 (CI 1.01-0.09). No association was demonstrated with SLEDAI, prednisolone use, cyclophosphamide use, and the presence of depression. CONCLUSION: In this study, it was found in 16% of patients evaluated with the complete neuropsychological test battery and in 37% with the MoCA screening test. Our results suggest that it is crucial to implement strategies to assess cognitive deficit, depression, and quality of life in the consultation of patients with SLE and to raise awareness among health providers who care for patients with lupus about their presence and impact.

Impaired exploration induced by type 1 diabetes is related to locomotor activity rather than a reduction in motivation.

Type 1 diabetes mellitus (T1D) is associated with cognitive impairments in humans. A well-established animal model of T1D is induced through the administration of streptozotocin (STZ), a glucose analog that induces pancreatic ß-cell death, resulting in hyperglycemia and cognitive impairment linked to neuroinflammation and oxidative stress. Tumor necrosis factor (TNF)-α, a key inflammatory mediator, is elevated in the central nervous system (CNS) of diabetic animals. In this study, we utilized TNFR1 knockout mice to investigate the role of TNFR1 signaling in short-term T1D-related cognitive impairment. Our findings showed that diabetic animals did not develop cognitive damage within the first 2 weeks of T1D but exhibited reduced exploration in all behavioral tests. Our findings suggest that this reduction in exploration was attributable to motor impairment, as there was no reduction in motivated novelty-seeking behavior. Additionally, deletion of TNFR1 signaling attenuated gait speed impairment in diabetic mice, but did not affect other motor-related or exploratory behaviors.

Association between cognitive performance and manual dexterity in patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a progressive neurological condition resulting from the degeneration of dopaminergic neurons in the substantia nigra. Impaired manual dexterity and cognitive impairment are common symptoms and are often associated with recurrent adverse events in this population. OBJECTIVE: To verify the association between cognitive performance and manual dexterity in people with PD. METHODS: This is a cross-sectional observational study, with 29 participants, who underwent cognitive and manual dexterity assessments, and the following tools were used: Trail Making Test, box and block test (BBT), Learning Test of Rey and Nine Hole Peg Test. Descriptive statistics for clinical and demographic data were performed using mean and standard deviation, and data normality was assessed using the Shapiro-Wilk test. Spearman's nonparametric test was used to determine the correlation between variables. RESULTS: Our findings revealed significant associations between cognitive performance and manual dexterity. The nine-hole peg test positively correlated with TMT-Part A and Part B, establishing a relationship between manual dexterity and cognitive functions such as attention and mental flexibility. On the other hand, BBT showed an inverse relationship with TMT-Part B, indicating that longer time on this task was associated with lower manual dexterity. CONCLUSION: Fine manual dexterity had a significant correlation with visual search skills and motor speed, while gross motor dexterity had a negative correlation with cognitive skills. No significant results were demonstrated regarding the interaction between manual dexterity and memory.

Cognitive Impairment in Liver Tranplant Recipients: A Cross-Sectional Study.

OBJECTIVES: The proportion of older transplant recipients has increased. Cognitive impairment is not rare after kidney transplant, but data on this issue in liver transplant recipients are scarse. MATERIALS AND METHODS: In this cross-sectional study, we evaluated all liver transplant recipients from a single center in Brazil from July 2018 to June 2020 in terms of cognitive performance to determine the prevalence of neurocognitive disorder. We compared liver transplant recipients with neurocognitive disorder with liver transplant recipients without neurocognitive disorder. We also compared those with an alcoholic cause of liver transplant with other patients. The presence of depressive symptoms was assessed. We performed correlations of clinical data with cognitive scores. RESULTS: In a sample of 100 recipients with median age of 62 years (interquartile range, 56.2-69 y), neurocognitive disorder was present in 21% of the group. Patients with cognitive impairment were older (68 y [61-72] vs 61 y [52-68]; P = .019) and had a trend to higher proportion of persistent kidney injury (33.3% vs 13.9%; P = .055) versus patients without cognitive impairment. Recipients with alcoholic cause of liver transplant exhibited worse cognitive performance in the Mini-Mental State Examination (score of 26 [23.7-28.2] vs 28 [26-29]; P = .024) and the Alzheimer Disease Assessment Scale-cognitive (score of 10.4 [8.6-14.2] vs 8 [6.3-10]; P = .008) than other patients. Weak negative correlations were shown in cognitive performance scores versus recipient age (Semantic Verbal Fluency test, r = -0.334 [P = .001]; Clock Drawing test, r = -0.209 [P = .037]; Alzheimer Disease Assessment Scale-cognitive, r = -0.323 [P = .001]). CONCLUSIONS: Neurocognitive disorder was common in liver transplant recipients, in part due to increased age. This study also suggested a role for alcoholic cause of liver transplant and persistent kidney injury in the development of cognitive impairment.

[Construction and validation of a test for verbal auditory screening of cognitive alterations (CAVAC)]. / Construcción y validación de un test para el cribado auditivo verbal de alteraciones cognitivas (CAVAC).

INTRODUCTION: The global burden of dementia will continue to increase and Latin America will be one of the most affected regions. It is urgent to have new and better cognitive screening tools. There are few screenings composed entirely of auditory-verbal items and even more so for Argentine culture. The objective was to build and validate a test for verbal auditory screening of cognitive alterations (CAVAC) in Argentina. SUBJECTS AND METHODS: Evidence based in test content was analyzed through 16 experts collaborated. In addition, evidence based on relationships to other variables, internal consistency and the ability to discriminate between cognitively healthy subjects, Mild Cognitive Impairment (MCI) and dementia were investigated. The CAVAC was applied to 316 Argentines (M age = 68,5). Volunteers from the general population and patients from neurology services from two Argentine hospitals participated. RESULTS: The CAVAC test explores orientation/attention, memory/learning, language and executive functions, and is administered in 10 minutes with a score of 0 to 30. Aiken's V coefficient was satisfactory for all items. The CAVAC achieved a high correlation with the Mini Mental (0.762) and an acceptable Cronbach's alpha (0.746). The CAVAC score differs between controls, mild cognitive impairment (MCI) and dementia, and the ROC curves reveal adequate area values ??to discriminate MCI and dementia (>0.7), and cut-off points with good sensitivity-specificity. CONCLUSIONS: A new auditory-verbal test is made available for the screening of cognitive alterations with acceptable evidence of validity, good reliability, with the capacity to identify MCI and dementia, and free of charge for use.

TITLE: Construcción y validación de un test para el cribado auditivo verbal de alteraciones cognitivas (CAVAC).Introducción. La carga mundial de demencia continuará en aumento y Latinoamérica será una de las regiones más afectadas. Urge contar con nuevas y mejores herramientas de cribado cognitivo. Son pocos los cribados compuestos íntegramente por ítems auditivos-verbales, y más aún para cultura argentina. El objetivo fue construir y validar un test para el cribado auditivo verbal de alteraciones cognitivas (CAVAC) en Argentina. Sujetos y métodos. Se analizó la evidencia basada en el contenido de la prueba mediante colaboración de 16 jueces. Se investigó, además, la evidencia basada en relaciones con otras variables, la consistencia interna y la capacidad para discriminar entre sujetos cognitivamente sanos, con deterioro cognitivo leve (DCL) y con demencia. Se aplicó el CAVAC a 316 argentinos (media de edad = 68,5). Participaron voluntarios de población general y pacientes de servicios de neurología de dos hospitales argentinos. Resultados. El CAVAC explora la orientación/atención, la memoria/aprendizaje, el lenguaje y las funciones ejecutivas, y se administra en 10 minutos, con una puntuación de 0 a 30. El coeficiente V de Aiken fue satisfactorio para todos los ítems. El CAVAC alcanzó correlación fuerte con el Minimental State Examination (0,762) y un alfa de Cronbach aceptable (0,746). La puntuación del CAVAC difirió entre controles, pacientes con DCL y con demencia, y las curvas ROC revelaron valores de área adecuados para identificar el DCL y la demencia (>0,7), con puntos de corte con buena sensibilidad-especificidad. Conclusiones. Se deja a disposición un nuevo test auditivo-verbal para el cribado de alteraciones cognitivas con aceptables evidencias de validez, buena fiabilidad, capacidad para identificar el DCL y la demencia, y de uso libre y gratuito.

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.

What is the most appropriate handgrip strength testing protocol for sarcopenia screening in older adults with cognitive impairment?

BACKGROUND: Handgrip strength (HGS) testing is a highly recommended method for screening for sarcopenia in older adults. However, there is no consensus on the optimal protocol and number of trials for screening sarcopenia in older adults with cognitive impairment. OBJECTIVE: To investigate the use of the first trial (FT), the mean of three trials (MT), and the highest value (HT) from three trials of the HGS test to screen for sarcopenia in older adults with cognitive impairment. Additionally, to analyze the consistency, agreement, and measurement error in the diagnosis of muscle weakness. METHODS: 176 older adults with cognitive impairment were evaluated. The HGS test was repeated three times. Analyses were performed using the Friedman repeated measures test with Wilcoxon post-hoc, intraclass correlation coefficient (ICC), Standard Error of Measurement (SEM), Minimal Detectable Change (MDC95), and Kappa index tests. RESULTS: There was no significant difference between the first trial (FT) and the mean of three trials (MT) (d = 0.17 [95 % CI: -0.08, 0.42]), but both differed significantly from the highest value (HT) (p < 0.001). The ICC indicated a reliability of 0.97 (95 % CI: 0.95, 0.98) across all participants, while the kappa index demonstrated over 80 % agreement. The SEM for the first measure of HGS ranged from 0.59 to 2.12 kgf. The MDC95 ranged from 1.64 to 5.87 kgf. CONCLUSION: For HGS testing, there was excellent consistency between the FM and MT. All three testing methods demonstrated excellent agreement in diagnosing muscle weakness. The measurement errors confirm that FT can be reliably used to monitor changes during rehabilitation.

Population-level trends in self-reported healthcare utilization among older adults in Mexico with and without cognitive impairment.

BACKGROUND: Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico. METHODS: Data came from five waves (2001-2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and being screened for cholesterol, diabetes, and hypertension in the past two years. Cognitive impairment was defined using a modified version of the Cross Cultural Cognitive Examination that assessed verbal memory, visuospatial and visual scanning. Total sample included 5,673 participants with cognitive impairment and 34,497 without cognitive impairment interviewed between 2001 and 2018. Generalized Estimating Equation models that adjusted for time-varying demographic and health characteristics and included an interaction term between time and cognitive status were used. RESULTS: For all participants, the risk for one or more overnight hospital stays, doctor visits, and dental visits in the past year, and being screened for diabetes, hypertension, and high cholesterol increased from 2001 to 2012 and leveled off or decreased in 2015 and 2018. Conversely, seeing a homeopathic doctor decreased. Cognitive impairment was associated with higher risk of hospitalization (RR = 1.13, 1.03-1.23) but lower risk of outpatient services (RR = 0.95, 0.93-0.97), cholesterol screening (RR = 0.93, 0.91-0.96), and diabetes screening (RR = 0.95, 0.92-0.97). No significant difference was observed in the use of pharmacists, homeopathic doctors, or folk healers based on cognitive status. Interaction effects indicated participants with cognitive impairment had lower risk for dental visits and hypertension screening but that these trajectories differed over time compared to participants without cognitive impairment. CONCLUSIONS: We identified distinct population-level trends in self-reported healthcare utilization and differences according to cognitive status, particularly for elective and screening services. These findings highlight the necessity for policy interventions to ensure older adults with cognitive impairment have their healthcare needs met.

Risk factors of atrial fibrillation complicated with cognitive impairment and the relationship between cardiac function parameters and the degree of cognitive impairment.

OBJECTIVE: To explore the risk factors of Atrial Fibrillation (AF) with Cognitive Impairment (CI) and to analyze the relationship between cardiac function parameters and the degree of CI in patients. METHODS: 120 AF patients were selected, and Montreal Cognitive Assessment (MoCA) was used to distinguish between AF patients with and without CI. Univariate analysis and multivariate Logistic regression analysis were used to evaluate the impact of sociodemographic data, disease-related data, and clinical data on risk factors for AF with CI. Pearson's method was used to analyze the correlation between cardiac function parameters and cognitive function scores in AF patients. RESULTS: There were 89 patients with CI and 31 patients without CI, and the MoCA scores of patients with CI were lower than those in patients without CI. Age, occupational status, educational level, combined smoking history, drinking history, and heart failure, as well as systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, C-reactive protein, free thyroxine, free triiodothyronine, and D-dimer were risk factors for the patient with CI. Left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left atrial maximum volume in patients with CI were higher than those in patients without CI, and left ventricular ejection fraction and peak early diastolic velocity/peak late-diastolic mitral velocity ratio were lower. CONCLUSION: The cardiac function parameters of patients are closely related to attention, orientation, memory, visuospatial, and executive ability. Cardiac function parameters were closely related to cognitive functions.

Omics-derived biological modules reflect metabolic brain changes in Alzheimer's disease.

INTRODUCTION: Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive. METHODS: Here, we integrated [18F]FDG-PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel-wise linear regression analysis. RESULTS: Our results showed that multiple transcriptomic modules are associated with brain [18F]FDG-PET metabolism, with the top hits being a protein serine/threonine kinase activity gene cluster (peak-t(223) = 4.86, P value < 0.001) and zinc-finger-related regulatory units (peak-t(223) = 3.90, P value < 0.001). DISCUSSION: By integrating transcriptomics with PET imaging data, we identified that serine/threonine kinase activity-associated genes and zinc-finger-related regulatory units are highly associated with brain metabolic changes in AD. HIGHLIGHTS: We conducted an integrated analysis of system-based transcriptomics and fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) at the voxel level in Alzheimer's disease (AD). The biological process of serine/threonine kinase activity was the most associated with [18F]FDG-PET in the AD brain. Serine/threonine kinase activity alterations are associated with brain vulnerable regions in AD [18F]FDG-PET. Zinc-finger transcription factor targets were associated with AD brain [18F]FDG-PET metabolism.

The relationship between cognitive function and functional capacity, and cognitive reserve and reaction time in patients with multiple sclerosis.

BACKGROUND: Cognitive dysfunction is frequently seen in multiple sclerosis (MS). However, there are conflicting findings regarding the factors it is associated with. OBJECTIVE: To investigate the relationship between aerobic capacity, strength, disability, depression, fatigue, and cognitive reserve and function. METHODS: The mobile applications Trail Making Test (TMT A-B), Digit Span Test (DST), Visuospatial Memory Test (VSMT), and Tap Fast were used in the cognitive function evaluation. Functional performance was assessed with the 6-minute walk test (6MWT), 5-Time Sit-to-Sand (5STS) test, and grip strength. Cognitive Reserve Index (CRI), Beck Depression Inventory, Fatigue Severity Scale (FSS), and Nottingham Health Profile were also used. RESULTS: A significant difference was found between the MS and control groups only in the 6MWT, STS-5, grip strength, TMT, VSMT, and Tap Fast. Good correlation was found between the TMT-A and 6MWT and physical mobility. A fair correlation was shown between grip strength, energy, and pain status. A good correlation was found between TMT-B and 6MWT, and a fair relationship with disability, cognitive reserve, and pain. Good correlation was observed between the DST and 6MWT, left grip strength, pain, and energy status; fair correlations were found between right grip strength, cognitive reserve, and physical mobility. Good correlation was found between the VSMT and energy. A fair relationship between disability, cognitive reserve, and pain was demonstrated. Good correlation was observed between the Tap Fast score and disability, 5STS, FSS, energy, and physical mobility. A fair relationship was found between pain and social isolation. CONCLUSION: It has been shown that cognitive performance in MS is related to disability, functional performance, cognitive reserve, fatigue, and general health. TRIAL REGISTRATION: NCT06084182.

ANTECEDENTES: A disfunção cognitiva é frequentemente observada na esclerose múltipla (EM). No entanto, existem resultados conflitantes sobre os fatores aos quais está associada. OBJETIVO: Investigar a relação entre capacidade aeróbica, força, incapacidade, depressão, fadiga e reserva e função cognitiva. MéTODOS: Os aplicativos móveis Trail Making Test (TMT A-B), Digit Span Test (DST), Visuoespacial Memory Test (VSMT) e Tap Fast foram utilizados na avaliação da função cognitiva. O desempenho funcional foi avaliado por meio do teste de caminhada de 6 minutos (TC6), Teste de Sentar-Levantar Cinco Vezes (TSL5) e força de preensão manual. Também foram utilizados Índice de Reserva Cognitiva (IRC), Inventário de Depressão de Beck, Escala de Gravidade de Fadiga (EGF) e Perfil de Saúde de Nottingham. RESULTADOS: Foi encontrada diferença significativa entre os grupos EM e controle apenas no TC6, TSL5, força de preensão, TMT, VSMT e Tap Fast. Foi encontrada boa correlação entre o TMT-A e o TC6 e a mobilidade física. Foi demonstrada uma correlação razoável entre força de preensão, energia e estado de dor. Foi encontrada uma boa correlação entre o TMT-B e o TC6, e uma relação razoável com incapacidade, reserva cognitiva e dor. Foi observada boa correlação entre o DST e o TC6, força de preensão esquerda, dor e estado energético; correlações justas foram encontradas entre força de preensão direita, reserva cognitiva e mobilidade física. Foi encontrada boa correlação entre o VSMT e a energia. Foi demonstrada uma relação justa entre incapacidade, reserva cognitiva e dor. Foi observada boa correlação entre o escore Tap Fast e incapacidade, TLS5, EGF, energia e mobilidade física. Foi encontrada uma relação justa entre dor e isolamento social. CONCLUSãO: Foi demonstrado que o desempenho cognitivo na EM está relacionado com incapacidade, desempenho funcional, reserva cognitiva, fadiga e saúde geral. REGISTRO DE TESTE: NCT06084182.

Effects of a dual intervention (motor and virtual reality-based cognitive) on cognition in patients with mild cognitive impairment: a single-blind, randomized controlled trial.

BACKGROUND: The increase in cases of mild cognitive impairment (MCI) underlines the urgency of finding effective methods to slow its progression. Given the limited effectiveness of current pharmacological options to prevent or treat the early stages of this deterioration, non-pharmacological alternatives are especially relevant. OBJECTIVE: To assess the effectiveness of a cognitive-motor intervention based on immersive virtual reality (VR) that simulates an activity of daily living (ADL) on cognitive functions and its impact on depression and the ability to perform such activities in patients with MCI. METHODS: Thirty-four older adults (men, women) with MCI were randomized to the experimental group (n = 17; 75.41 ± 5.76) or control (n = 17; 77.35 ± 6.75) group. Both groups received motor training, through aerobic, balance and resistance activities in group. Subsequently, the experimental group received cognitive training based on VR, while the control group received traditional cognitive training. Cognitive functions, depression, and the ability to perform activities of daily living (ADLs) were assessed using the Spanish versions of the Montreal Cognitive Assessment (MoCA-S), the Short Geriatric Depression Scale (SGDS-S), and the of Instrumental Activities of Daily Living (IADL-S) before and after 6-week intervention (a total of twelve 40-minutes sessions). RESULTS: Between groups comparison did not reveal significant differences in either cognitive function or geriatric depression. The intragroup effect of cognitive function and geriatric depression was significant in both groups (p < 0.001), with large effect sizes. There was no statistically significant improvement in any of the groups when evaluating their performance in ADLs (control, p = 0.28; experimental, p = 0.46) as expected. The completion rate in the experimental group was higher (82.35%) compared to the control group (70.59%). Likewise, participants in the experimental group reached a higher level of difficulty in the application and needed less time to complete the task at each level. CONCLUSIONS: The application of a dual intervention, through motor training prior to a cognitive task based on Immersive VR was shown to be a beneficial non-pharmacological strategy to improve cognitive functions and reduce depression in patients with MCI. Similarly, the control group benefited from such dual intervention with statistically significant improvements. TRIAL REGISTRATION: ClinicalTrials.gov NCT06313931; https://clinicaltrials.gov/study/NCT06313931 .

Gut Microbiome Is Related to Cognitive Impairment in Peritoneal Dialysis Patients.

Gut microbiota disturbances may influence cognitive function, increasing uremic toxins and inflammation in dialysis patients; therefore, we aimed to evaluate the association of the gut microbiota profile with cognitive impairment (CI) in patients on automated peritoneal dialysis (APD). In a cross-sectional study, cognitive function was evaluated using the Montreal Cognitive Assessment in 39 APD patients and classified as normal cognitive function and CI. The gut microbiota was analyzed using the 16S rRNA gene sequencing approach. All patients had clinical, biochemical and urea clearance evaluations. Eighty-two percent of patients were men, with a mean age of 47 ± 24 years and 11 (7-48) months on PD therapy; 64% had mild CI. Patients with CI were older (53 ± 16 vs. 38 ± 14, p = 0.006) and had a higher frequency of diabetes mellitus (56% vs. 21%, p = 0.04) and constipation (7% vs. 48%, p = 0.04) and lower creatinine concentrations (11.3 ± 3.7 vs. 14.9 ± 5.4, p = 0.02) compared to normal cognitive function patients. Patients with CI showed a preponderance of S24_7, Rikenellaceae, Odoribacteraceae, Odoribacter and Anaerotruncus, while patients without CI had a greater abundance of Dorea, Ruminococcus, Sutterella and Fusobacteria (LDA score (Log10) > 2.5; p < 0.05). After glucose and age adjustment, Odoribacter was still associated with CI. In conclusion, patients with CI had a different gut microbiota characterized by the higher abundance of indole-producing and mucin-fermenting bacteria compared to normal cognitive function patients.

An alpha 5-GABAA receptor positive allosteric modulator attenuates social and cognitive deficits without changing dopamine system hyperactivity in rats exposed to valproic acid in utero.

Autism spectrum disorders (ASDs) are characterized by core behavioral symptoms in the domains of sociability, language/communication, and repetitive or stereotyped behaviors. Deficits in the prefrontal and hippocampal excitatory/inhibitory balance due to a functional loss of GABAergic interneurons are proposed to underlie these symptoms. Increasing the postsynaptic effects of GABA with compounds that selectively modulate GABAergic receptors could be a potential target for treating ASD symptoms. In addition, deficits in GABAergic interneurons have been linked to dopamine (DA) system dysregulation, and, despite conflicting evidence, abnormalities in the DA system activity may underly some ASD symptoms. Here, we investigated whether the positive allosteric modulator of α5-containing GABAA receptors (α5-GABAARs) SH-053-2'F-R-CH3 (10 mg/kg) attenuates behavioral abnormalities in rats exposed to valproic acid (VPA) in utero, an established risk factor for autism. We also evaluated if animals exposed to VPA in utero present changes in the ventral tegmental area (VTA) DA system activity using in vivo electrophysiology and if SH-053-2'F-R-CH3 could attenuate these changes. SH-053-2'F-R-CH3 was administered intraperitoneally 30 min before each behavioral test and electrophysiology. In utero VPA exposure caused male and female rats to present increased repetitive behavior (self-grooming) in early adolescence and deficits in social interaction in adulthood. Male, but not female VPA rats, also presented deficits in recognition memory as adults. SH-053-2'F-R-CH3 attenuated the impairments in sociability and cognitive function in male VPA-exposed rats without attenuating the decreased social interaction in females. Adult male and female VPA-exposed rats also showed an increased VTA DA neuron population activity, which was not changed by SH-053-2'F-R-CH3. Despite sex differences, our findings indicate that α5-GABAARs positive allosteric modulators may effectively attenuate some core ASD symptoms.

Severe menopausal symptoms linked to cognitive impairment: an exploratory study.

OBJECTIVE: To evaluate the association between menopausal symptoms and cognitive decline in postmenopausal women. METHODS: This was a subanalysis of a cross-sectional, observational study conducted among women attending gynecological consultations across nine Latin American countries. The survey involved late postmenopausal women who were asked to complete a general questionnaire and the Menopause Rating Scale (MRS) to assess menopausal symptoms, with the Montreal Cognitive Assessment used to evaluate cognitive function as an outcome. A Montreal Cognitive Assessment score of less than 21 was used to define women with mild cognitive impairment (MCI). RESULTS: The study included 1,287 postmenopausal women with a mean age of 55.5 years and a mean body mass index of 26.3 kg/m 2 . On average, participants had 13.8 years of education and 2.3 ± 1.8 children, with 72.8% reporting having a partner. Additionally, 36.7% ever used menopausal hormone therapy. Regarding lifestyle factors, 50.3% engaged in a sedentary lifestyle, whereas 70.5% had never smoked. 15.3% of women had MCI exhibited significantly more intense menopausal symptoms compared with those without MCI (MRS total score 15.24 ± 12.58 vs 10.53 ± 8.84, respectively, P < 0.001). Logistic regression analysis revealed a significant association between severe menopausal symptoms (MRS total score ≥14 points) and MCI (odds ratio [OR], 1.74; 95% CI, 1.25-2.42). Conversely, a lower body mass index (OR, 0.96; 95% CI, 0.95-0.98), sexual activity (OR, 0.70; 95% CI, 0.51-0.96), physical exercise (OR, 0.55; 95% CI, 0.39-0.76), menopausal hormone therapy use (OR, 0.36; 95% CI, 0.24-0.55), and higher educational level (OR, 0.31; 95% CI, 0.21-0.46) were associated with lower odds for MCI. CONCLUSION: Severe menopausal symptoms in postmenopausal women were associated with cognitive impairment. This study highlights the intricate interplay between hormonal, lifestyle, and sociodemographic factors and cognitive health.