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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.
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Cognición , Disfunción Cognitiva , Trasplante de Hígado , Humanos , Estudios Transversales , Trasplante de Hígado/efectos adversos , Persona de Mediana Edad , Masculino , Femenino , Brasil/epidemiología , Factores de Riesgo , Anciano , Prevalencia , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/psicología , Resultado del Tratamiento , Factores de Edad , Medición de Riesgo , Hepatopatías Alcohólicas/cirugía , Hepatopatías Alcohólicas/psicología , Hepatopatías Alcohólicas/epidemiología , Hepatopatías Alcohólicas/diagnósticoRESUMEN
Purpose: Cognitive dysfunction caused by chronic cerebral hypoperfusion (CCH) is the leading cause of vascular dementia. Therefore, it is necessary to explore the mechanism that causes cerebral injury and find an effective therapy. Methods: Bone marrow mononuclear cells (BMMNCs) were extracted to detect the activity by CCK-8 kit and verify the transfection efficiency using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). A CCH rat model was established. Superparamagnetic iron oxide nanoparticles (BMPs)-PEI-Slit2/BMMNCs were injected into the tail vein and intervened with an external magnetic field. Hematoxylin and eosin staining was used to observe the pathological changes in brain tissue. The Slit/Robo pathway-related proteins Slit2 and Robo4 were detected by RT-qPCR and Western blotting. Results: The neurological score of the CCH group significantly increased compared with that of the sham group (P<0.05). The levels of brain injury markers S-100ß and NSE were significantly higher in the CCH group than in the sham group (P<0.05). Neuronal apoptosis in the frontal cortex and hippocampus of CCH rats significantly increased compared with that of the sham group (P<0.05). The expression levels of Slit2 and Robo4 mRNAs and proteins in brain tissue of CCH rats significantly increased (P<0.05). The neurological function scores of CCH rats treated with BMP-PEI-Slit2/BMMNC significantly increased after Robo4 siRNA administration (P<0.05). Conclusion: BMP combination with the CCH-related gene Slit2 can effectively improve the efficiency of BMMNC transplantation in treatment.
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Isquemia Encefálica , Disfunción Cognitiva , Modelos Animales de Enfermedad , Péptidos y Proteínas de Señalización Intercelular , Proteínas del Tejido Nervioso , Animales , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Ratas , Disfunción Cognitiva/terapia , Disfunción Cognitiva/etiología , Isquemia Encefálica/terapia , Isquemia Encefálica/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Humanos , Masculino , Nanopartículas de Magnetita/administración & dosificación , Nanopartículas de Magnetita/química , Nanopartículas Magnéticas de Óxido de Hierro/administración & dosificación , Células de la Médula Ósea , Apoptosis/genética , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Ratas Sprague-Dawley , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Terapia Genética/métodos , Proteínas RoundaboutRESUMEN
Background: DATATOP was a study of early Parkinson's disease (PD) conducted in the 1980âs, before mandatory folic acid fortification in the United States. Our analysis of its baseline serum samples revealed a geometric mean vitamin B12 of 369âpg/mL and homocysteine (tHcy) of 9.5µmol/l. We also found that low B12 predicted greater worsening of ambulatory capacity (AC) and elevated tHcy (>15µmol/L) predicted greater declines in cognitive function. Objective: We sought to measure B12 and tHcy in contemporary trial participants with early PD who had not started dopaminergic treatment and to determine whether these analytes were associated with clinical progression. Methods: We measured B12 and tHcy from baseline and end-of-study blood samples from three recent clinical trials. Results: Baseline geometric mean B12 levels for these studies ranged from 484- 618âpg/ml and for tHcy ranged from 7.4- 10µmol/L. Use of B12-containing supplements ranged from 41- 61%, and those taking supplements had higher B12 and lower tHcy. Those who began levodopa, but were not taking B12-supplements, had greater end-of-study tHcy. There was no association of baseline tHcyâ>â15µmol/L with annualized change in Montreal Cognitive Assessment and no association of baseline B12 tertiles with change in AC. Conclusions: In these longitudinal trials, B12 levels were higher than for DATATOP, due in large part to increased B12-supplement intake, while tHcy levels were similar. Initiation of levodopa was associated with increases of tHcy in those not taking a B12-containing supplement. These smaller studies did not replicate prior findings of low B12 and elevated tHcy with features of progression, possibly due to higher baseline B12.
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Homocisteína , Enfermedad de Parkinson , Vitamina B 12 , Humanos , Vitamina B 12/sangre , Homocisteína/sangre , Masculino , Femenino , Anciano , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/tratamiento farmacológico , Persona de Mediana Edad , Progresión de la Enfermedad , Antiparkinsonianos/uso terapéutico , Levodopa/administración & dosificación , Levodopa/farmacología , Suplementos Dietéticos , Disfunción Cognitiva/sangre , Disfunción Cognitiva/etiología , Disfunción Cognitiva/tratamiento farmacológicoRESUMEN
BACKGROUND: Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. METHODS: A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. RESULTS: WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261-1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032-4.371, P for trend < 0.001). CONCLUSIONS: Our study illustrated that higher WHRadjBMI is likely to be associated with an increased risk of CI among patients with T2DM. These findings support the detrimental effects of excess visceral fat accumulation on cognitive function in middle-aged and elderly T2DM patients.
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Índice de Masa Corporal , Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Relación Cintura-Cadera , Humanos , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , Disfunción Cognitiva/etiología , Disfunción Cognitiva/epidemiología , Obesidad Abdominal/epidemiología , Obesidad Abdominal/complicaciones , Factores de Riesgo , Adulto , China/epidemiologíaRESUMEN
BACKGROUND: The use of self-report pain scales in persons with aphasia can be challenging due to communication and cognitive problems, while for assessing pain self-report pain is considered the gold standard (Harrison RA, Field TS. Post stroke pain: identification, assessment, and therapy. Cerebrovasc Dis. 2015;39(3-4):190-201.). An observational scale may be used as an alternative. This study examines the validity and reliability of the observational Pain Assessment in Impaired Cognition (PAIC15) scale in persons with aphasia. METHODS: Persons with aphasia were observed during rest and transfer by two observers using the PAIC15. The PAIC15 comprises 15 items covering the three domains of facial expressions, body movements, and vocalizations. When able, the participant completed four self-report pain scales after each observation. The observations were repeated within one week. For criterion validity, correlations between the PAIC15 and self-report pain scales were calculated and for construct validity, three hypotheses were tested. Reliability was determined by assessing internal consistency, and intra- and interobserver agreement. RESULTS: PAIC15 observations were obtained for 71 persons (mean age 75.5 years) with aphasia. Fair positive correlations (rest: 0.35-0.50; transfer: 0.38-0.43) were reported between PAIC15 and almost all self-report pain scales. Results show that significantly more pain was observed in persons with aphasia during transfer than during rest. No differences were found for observed pain between persons with aphasia who use pain medication and those without, or persons who have joint diseases compared to those without. Results showed acceptable internal consistency. Intra- and interobserver agreement was high for most PAIC15 items, particularly for the domains body movements and vocalizations during rest and transfer. CONCLUSIONS: Recognition of pain in persons aphasia using the PAIC15 showed mixed yet promising results.
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Afasia , Dimensión del Dolor , Humanos , Afasia/diagnóstico , Afasia/etiología , Afasia/psicología , Femenino , Masculino , Anciano , Reproducibilidad de los Resultados , Dimensión del Dolor/métodos , Dimensión del Dolor/normas , Anciano de 80 o más Años , Persona de Mediana Edad , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Disfunción Cognitiva/etiología , Autoinforme/normas , Dolor/diagnóstico , Dolor/psicología , Dolor/etiología , Expresión FacialRESUMEN
BACKGROUND: The serotonin type 7 (5-HT7) receptor is one of 14 5-HT receptors. It has received attention for its possible role in mood disorders and cognition. The 5-HT7 receptor antagonist, JNJ-18038683, has been reported to be effective in rodent models of depression and REM sleep. Also, 5-HT7 receptor blockade has been postulated to be a key component of cognitive enhancement in a number of drugs. Bipolar disorder (BD) usually endures cognitive impairment (CI); however, no treatment for CI in BD has been approved. This study aimed to evaluate the efficacy of JNJ-18038683 to improve the CI of BD compared to a placebo. METHODS: We conducted a placebo-controlled, 8-week trial of JNJ-18038683 in BD patients. Each patient's data were analyzed and reassessed blindly with a comprehensive neuropsychological battery, depression and hypomania ratings, and overall social and work function measures. RESULTS: Of 60 patients, 38 (63%) were female, 43 (72%) had BD type 1, and most patients were Caucasian and married. The overall time effect for the combined group shows statistically significant improvement from baseline to week 8 for most of the neurocognitive battery measures. This indicates a significant improvement in psychopathology and cognition during the study time in both JNJ-18038683 and placebo groups, but no difference between groups. CONCLUSIONS: This study showed no efficacy for the improvement of CIBD or mood symptoms with JNJ-18038683 compared to the placebo.
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Trastorno Bipolar , Humanos , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/complicaciones , Femenino , Masculino , Adulto , Persona de Mediana Edad , Método Doble Ciego , Receptores de Serotonina/efectos de los fármacos , Antagonistas de la Serotonina/farmacología , Antagonistas de la Serotonina/administración & dosificación , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Resultado del Tratamiento , Pruebas NeuropsicológicasRESUMEN
Worldwide, around 50 million people live with dementia, and this number is projected to triple by 2050. It has been estimated that 20% of all dementia cases have a predominant cerebrovascular pathology, while perhaps another 20% of vascular diseases contribute to a mixed dementia picture. Therefore, the vascular contribution to dementia affects 20 million people currently and will increase markedly in the next few decades, particularly in lower- and middle-income countries.In this review, we discuss the mechanisms of vascular cognitive impairment (VCI) and review management. VCI refers to the spectrum of cerebrovascular pathologies that contribute to any degree of cognitive impairment, ranging from subjective cognitive decline, to mild cognitive impairment, to dementia. While acute cognitive decline occurring soon after a stroke is the most recognized form of VCI, chronic cerebrovascular disease, in particular cerebral small-vessel disease, can cause insidious cognitive decline in the absence of stroke. Moreover, cerebrovascular disease not only commonly co-occurs with Alzheimer's disease (AD) and increases the probability that AD pathology will result in clinical dementia, but may also contribute etiologically to the development of AD pathologies.Despite its enormous health and economic impact, VCI has been a neglected research area, with few adequately powered trials of therapies, resulting in few proven treatments. Current management of VCI emphasizes prevention and treatment of stroke and vascular risk factors, with most evidence for intensive hypertension control. Reperfusion therapies in acute stroke may attenuate the risk of VCI. Associated behavioral symptoms such as apathy and poststroke emotionalism are common. We also highlight novel treatment strategies that will hopefully lead to new disease course-modifying therapies. Finally, we highlight the importance of including cognitive endpoints in large cardiovascular prevention trials and the need for an increased research focus and funding for this important area.
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Demencia Vascular , Humanos , Demencia Vascular/terapia , Disfunción Cognitiva/etiología , Disfunción Cognitiva/terapia , Trastornos Cerebrovasculares/complicaciones , Trastornos Cerebrovasculares/terapia , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/terapiaRESUMEN
The COVID-19 pandemic faced the public health sector with unprecedented challenges. While the immediate impact on society seems to diminish, reports of long-term health consequences persist. Among the most frequently reported symptoms are neurological complaints such as persistent fatigue and cognitive impairments. Scientific understanding is evolving rapidly, and first therapeutic approaches are emerging. However, many questions still remain unanswered.
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COVID-19 , Disfunción Cognitiva , Enfermedades del Sistema Nervioso , COVID-19/complicaciones , COVID-19/psicología , COVID-19/epidemiología , Humanos , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/virología , Enfermedades del Sistema Nervioso/terapia , Disfunción Cognitiva/etiología , Disfunción Cognitiva/psicología , Pandemias , Fatiga/etiología , SARS-CoV-2RESUMEN
Alzheimer's disease (AD) is characterized by progressive episodic memory dysfunction. A prominent hallmark of AD is gradual brain atrophy. Despite extensive research on brain pathology, the understanding of spinal cord pathology in AD and its association with cognitive decline remains understudied. We analyzed serial magnetic resonance imaging (MRI) scans from the ADNI data repository to assess whether progressive cord atrophy is associated with clinical worsening. Cervical cord morphometry was measured in 45 patients and 49 cognitively normal controls (CN) at two time points over 1.5 years. Regression analysis examined associations between cord atrophy rate and cognitive worsening. Cognitive and functional activity performance declined in patients during follow-up. Compared with controls, patients showed a greater rate of decline of the anterior-posterior width of the cross-sectional cord area per month (- 0.12%, p = 0.036). Worsening in the mini-mental state examination (MMSE), clinical dementia rating (CDR), and functional assessment questionnaire (FAQ) was associated with faster rates of cord atrophy (MMSE: r = 0.320, p = 0.037; CDR: r = - 0.361, p = 0.017; FAQ: r = - 0.398, p = 0.029). Progressive cord atrophy occurs in AD patients; its rate over time being associated with cognitive and functional activity decline.
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Enfermedad de Alzheimer , Atrofia , Médula Cervical , Disfunción Cognitiva , Progresión de la Enfermedad , Imagen por Resonancia Magnética , Humanos , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Masculino , Femenino , Anciano , Disfunción Cognitiva/patología , Disfunción Cognitiva/etiología , Médula Cervical/diagnóstico por imagen , Médula Cervical/patología , Anciano de 80 o más AñosRESUMEN
Neurodevelopmental disorders are currently one of the major complications faced by patients with congenital heart disease (CHD). Chronic hypoxia in the prenatal and postnatal preoperative brain may be associated with neurological damage and impaired long-term cognitive function, but the exact mechanisms are unknown. In this study, we find that delayed neuronal migration and impaired synaptic development are attributed to altered Atoh1 under chronic hypoxia. This is due to the fact that excessive Atoh1 facilitates expression of Kif21b, which causes excess in free-state α-tubulin, leading to disrupted microtubule dynamic stability. Furthermore, the delay in neonatal brain maturation induces cognitive disabilities in adult mice. Then, by down-regulating Atoh1 we alleviate the impairment of cell migration and synaptic development, improving the cognitive behavior of mice to some extent. Taken together, our work unveil that Atoh1 may be one of the targets to ameliorate hypoxia-induced neurodevelopmental disabilities and cognitive impairment in CHD.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Disfunción Cognitiva , Neuronas , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Ratones , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Neuronas/metabolismo , Hipoxia/metabolismo , Femenino , Neurogénesis , Animales Recién Nacidos , Ratones Endogámicos C57BL , Masculino , Movimiento CelularRESUMEN
BACKGROUND: Midlife obesity is a significant risk factor for Alzheimer's disease, but the effects of obesity on cognitive function, either detrimental or beneficial, are controversial among older individuals. This study aims to assess this associations of body mass index (BMI) or waist circumference (WC) with cognitive function among United States older individuals. METHODS: A cross-sectional research study was conducted utilizing data from the 2011 to 2014 National Health and Nutrition Examination Survey (NHANES). Initially, the study compared differences in cognitive function among the normal weight, overweight, and obese groups. Subsequently, we examined the relationships between BMI or WC and cognitive function using multivariate linear regression. Finally, structural equation models were constructed to assess the relationships among body shape, lifestyle, and cognitive function pathways. RESULTS: The study included 2254 individuals. Obese subjects had lower scores in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word list learning tasks (CERAD-WL) (χ2 = 7.804, p = .020) and digit symbol substitution test (χ2 = 8.869, p = .012). The regression analysis showed that WC was negatively connected with the CERAD-WL score after adjusting for confounding factors (ß = -.029, p = .045). Moreover, WC had a mediating effect on the path from lifestyle to cognition (CERAD-WL). However, there was no difference in the CERAD delayed recall score and the animal fluency test between the obese and the other groups. CONCLUSIONS: Obese older adults exhibited impaired cognitive abilities in terms of learning and working memory performance. The impact of lifestyle on cognition was mediated by obesity-related anthropometric indices. Sleep, physical activity, and diet influenced the degree of obesity, which subsequently determined cognitive function. Prioritizing weight management in elderly people is crucial for safeguarding cognitive function.
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Índice de Masa Corporal , Cognición , Encuestas Nutricionales , Obesidad , Circunferencia de la Cintura , Humanos , Obesidad/epidemiología , Obesidad/fisiopatología , Masculino , Femenino , Anciano , Estudios Transversales , Persona de Mediana Edad , Estados Unidos/epidemiología , Cognición/fisiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/epidemiología , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Cognitive impairment is highly prevalent among patients with chronic kidney disease, who face an increased risk of cognitive decline. The aim of this study was to investigate the relationship between the Geriatric Nutritional Risk Index (GNRI) and cognitive function in older individuals, both with and without chronic kidney disease (CKD). METHODS: In this study, we analyzed data from 2728 participants in the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Cognitive function was measured using the Consortium to Establish a Registry for the Alzheimer's Disease Word Learning subtest (CERAD W-L), the animal fluency test (AFT), the digit symbol substitution test (DSST), and the global cognitive z-score. The GNRI, representing whole-body nutritional status, was calculated based on serum albumin, body weight, and ideal body weight. We employed weighted multiple linear regression analyses and subgroup analyses to assess the independent association of GNRI with cognitive function in CKD and non-CKD populations. Smoothing techniques were used to fit curves, and interaction tests were used to assess the robustness and specificity of the findings. RESULTS: Our analyses revealed a significant positive association between higher GNRI levels and cognitive function in the older US population (for global z-score: ß = 0.01; 95% confidence interval [CI] = 0.00, 0.01). This association remained consistent across various subgroup analyses, including those for different gender groups, age groups, smoking statuses, diabetes statuses, hypertension statuses, individuals with a BMI below 25, individuals who consumed alcohol, and non-Hispanic white individuals. Smoothed curve-fitting analyses indicated that the GNRI was linearly related to cognitive function. No statistically significant interactions were detected among these variables. CONCLUSION: Our findings emphasize the positive association between GNRI and cognitive health in individuals with or without CKD, especially when combined with other risk factors. Consequently, enhancing the nutritional status of the elderly may serve as a viable strategy to thwart the onset of cognitive decline.
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Cognición , Disfunción Cognitiva , Encuestas Nutricionales , Estado Nutricional , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Anciano , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/epidemiología , Estado Nutricional/fisiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/epidemiología , Cognición/fisiología , Anciano de 80 o más Años , Evaluación Geriátrica/métodos , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
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.
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Disfunción Cognitiva , Depresión , Lupus Eritematoso Sistémico , Pruebas Neuropsicológicas , Calidad de Vida , Humanos , Femenino , Estudios Transversales , Colombia/epidemiología , Masculino , Adulto , Persona de Mediana Edad , Disfunción Cognitiva/etiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/psicología , Depresión/epidemiología , Depresión/etiología , Vasculitis por Lupus del Sistema Nervioso Central/psicología , Vasculitis por Lupus del Sistema Nervioso Central/epidemiología , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Vasculitis por Lupus del Sistema Nervioso Central/complicacionesRESUMEN
BACKGROUND: While several studies in cerebral amyloid angiopathy (CAA) focus on cognitive function, data on neuropsychiatric symptoms (NPS) and lifelong mental activities in these patients are scarce. Since NPS are associated with functional impairment, faster cognitive decline and faster progression to death, replication studies in more diverse settings and samples are warranted. METHODS: We prospectively recruited n = 69 CAA patients and n = 18 cognitively normal controls (NC). The number and severity of NPS were assessed using the Alzheimer's Disease (AD) Assessment Scale's (ADAS) noncognitive subscale. We applied different regression models exploring associations between NPS number or severity and group status (CAA vs. NC), CAA severity assessed with magnetic resonance imaging (MRI) or cognitive function (Mini-Mental State Examination (MMSE), ADAS cognitive subscale), adjusting for age, sex, years of education, arterial hypertension, AD pathology, and apolipoprotein E status. Mediation analyses were performed to test indirect effects of lifelong mental activities on CAA severity and NPS. RESULTS: Patients with CAA had 4.86 times (95% CI 2.20-10.73) more NPS and 3.56 units (95% CI 1.94-5.19) higher expected NPS severity than NC. Higher total CAA severity on MRI predicted 1.14 times (95% CI 1.01.-1.27) more NPS and 0.57 units (95% CI 0.19-0.95) higher expected NPS severity. More severe white matter hyperintensities were associated with 1.21 times more NPS (95% CI 1.05-1.39) and 0.63 units (95% CI 0.19-1.08) more severe NPS. NPS number (MMSE mean difference - 1.15, 95% CI -1.67 to -0.63; ADAS cognitive mean difference 1.91, 95% CI 1.26-2.56) and severity (MMSE - 0.55, 95% CI -0.80 to -0.30; ADAS cognitive mean difference 0.89, 95% CI 0.57-1.21) predicted lower cognitive function. Greater lifelong mental activities partially mediated the relationship between CAA severity and NPS (indirect effect 0.05, 95% CI 0.0007-0.13), and greater lifelong mental activities led to less pronounced CAA severity and thus to less NPS (indirect effect - 0.08, 95% CI -0.22 to -0.002). DISCUSSION: This study suggests that NPS are common in CAA, and that this relationship may be driven by CAA severity. Furthermore, NPS seem to be tied to lower cognitive function. However, lifelong mental activities might mitigate the impact of NPS in CAA.
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Angiopatía Amiloide Cerebral , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Humanos , Femenino , Masculino , Anciano , Estudios Transversales , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Angiopatía Amiloide Cerebral/psicología , Persona de Mediana Edad , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most important independent risk factors for stroke that is closely related to the occurrence of cognitive impairment. The relationship between ICAS and vascular cognitive impairment (VCI) remains unclear. Cerebral hemodynamic changes are one of the main causes of cognitive impairment. Computed tomographic perfusion (CTP) imaging can quantitatively analyze cerebral blood perfusion and quantify cerebral hemodynamic changes. Previous research on the relationship between hypoperfusion induced by ICAS and cognitive impairment, as well as its underlying mechanisms, remains relatively insufficient. This study is dedicated to elucidating the characteristics and potential mechanisms of cognitive impairment in ICAS patients with abnormal perfusion, utilizing CTP imaging as our primary investigative tool. METHODS: This study recruited 82 patients who suffer from non-disabling ischemic stroke (IS group) and 28 healthy controls. All participants underwent comprehensive neuropsychological assessments both collectively and individually, in addition to CTP imaging. Within the patient group, we further categorized individuals into two subgroups: the ischemic penumbra group (IP, N = 28) and the benign oligemia group (BO, N = 54), based on CTP parameters-Tmax. The correlations between cognitive function and abnormal perfusion were explored. RESULTS: The cognitive function, including the overall cognitive, memory, attention, executive functions, and language, was significantly impaired in the IS group compared with that in the control group. Further, there are statistical differences in the stroop color-word test-dot (Stroop-D) and Montreal Cognitive Assessment (MoCA) sub-items (memory + language) between the BO and IP groups. In the BO group, the score of Stroop-D is lower, and the MoCA sub-items are higher than the IP group. There is no correlation between CTP parameters and cognitive function. CONCLUSION: Cognitive function is significantly impaired in patients with ICAS, which is related to cerebral perfusion. Executive, memory, and language function were better preserved in ICAS patients without IP. Hence, this study posits that managing hypoperfusion induced by ICAS may play a pivotal role in the development of VCI.
Asunto(s)
Circulación Cerebrovascular , Disfunción Cognitiva , Arteriosclerosis Intracraneal , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Arteriosclerosis Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/fisiopatología , Circulación Cerebrovascular/fisiología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Imagen de Perfusión/métodos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/fisiopatología , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/fisiopatología , Cognición/fisiología , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Major depressive disorder (MDD) is characterized by hippocampal volume reduction, impacting cognitive function. Inflammation, particularly elevated tumor necrosis factor-alpha (TNF-α) levels, is consistently implicated in MDD pathophysiology. This study investigates the relationships between TNF-α levels, hippocampal volume, beta-amyloid (Aß) burden, and cognitive abilities in MDD patients, aiming to illuminate the complex interplay among inflammatory markers, pathology indicators, structural brain alterations, and cognitive performance in non-demented MDD individuals. METHOD: Fifty-two non-demented MDD patients, comprising 25 with mild cognitive impairment (MCI), were recruited along with 10 control subjects. Each participant underwent a thorough assessment encompassing TNF-α blood testing, 18F-florbetapir positron emission tomography, magnetic resonance imaging scans, and neuropsychological testing. Statistical analyses, adjusted for age and education, were performed to investigate the associations between TNF-α levels, adjusted hippocampal volume (HVa), global Aß burden, and cognitive performance. RESULTS: MCI MDD patients displayed elevated TNF-α levels and reduced HVa relative to controls. Correlation analyses demonstrated inverse relationships between TNF-α level and HVa in MCI MDD, all MDD, and all subjects groups. Both TNF-α level and HVa exhibited significant correlations with processing speed across all MDD and all subjects. Notably, global 18F-florbetapir standardized uptake value ratio did not exhibit significant correlations with TNF-α level, HVa, and cognitive measures. CONCLUSION: This study highlights elevated TNF-α levels and reduced hippocampal volume in MCI MDD patients, indicating a potential association between peripheral inflammation and structural brain alterations in depression. Furthermore, our results suggest that certain cases of MDD may be affected by non-amyloid-mediated process, which impacts their TNF-α and hippocampal volume. These findings emphasize the importance of further investigating the complex interplay among inflammation, neurodegeneration, and cognitive function in MDD.
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Péptidos beta-Amiloides , Atrofia , Disfunción Cognitiva , Trastorno Depresivo Mayor , Hipocampo , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Factor de Necrosis Tumoral alfa , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/patología , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Hipocampo/metabolismo , Masculino , Femenino , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Anciano , Péptidos beta-Amiloides/metabolismo , Atrofia/patología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Persona de Mediana Edad , Pruebas Neuropsicológicas , Compuestos de Anilina , Glicoles de EtilenoRESUMEN
Objective: Major depressive disorder (MDD) is a common psychiatric disorder for which pharmacologic standard-of-care treatments have limited efficacy, particularly among individuals with cognitive dysfunction. Cognitive dysfunction is observed in approximately 25%-50% of those with MDD, wherein response to standard-of-care medications is reduced. Vortioxetine is an approved antidepressant that has shown evidence of procognitive effects in patients. It is not known if it has greater clinical efficacy in MDD patients with cognitive dysfunction, a more difficult to treat population, than other antidepressants.Methods: This study was a reanalysis of 1,812 subjects with MDD across 4 placebo controlled trials. Baseline cognition was measured by the Digit Symbol Substitution Test (DSST), the primary measure used to demonstrate vortioxetine's procognitive effects in clinical studies. Analyses examined whether baseline cognitive function was associated with differences in treatment outcomes.Results: Baseline DSST did not predict placebo-adjusted treatment effects of vortioxetine on depressive symptoms (pooled Cohen d = -0.02, 95% CI = -0.12 to 0.07). Analyses of additional cognitive measures similarly did not predict placebo-adjusted treatment effects on depression (all 95% CI contained zero). Finally, analyses of trials with selective serotonin reuptake inhibitors (SSRIs)/serotonin and norepinephrine reuptake inhibitors (SNRIs) as active comparators also revealed no prediction of SSRI/SNRI adjusted treatment effects of vortioxetine on depression.Conclusions: These findings, taken together, suggest that cognitive function does not moderate depression outcomes in vortioxetine, with results comparable to other antidepressants.
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Trastorno Depresivo Mayor , Vortioxetina , Humanos , Vortioxetina/uso terapéutico , Vortioxetina/farmacología , Trastorno Depresivo Mayor/tratamiento farmacológico , Adulto , Masculino , Femenino , Persona de Mediana Edad , Antidepresivos/uso terapéutico , Resultado del Tratamiento , Cognición/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
BACKGROUND: Poststroke cognitive impairment (PSCI) occurs in about 60% of patients with stroke in the first year after stroke. However, the question regarding risks of recurrent stroke and mortality in patients with PSCI remains controversial. The goal of this study was to conduct a meta-analysis of published literature to estimate the risks of stroke recurrence and mortality associated with PSCI. METHODS AND RESULTS: Electronic databases were screened for eligible studies published from 1990 to 2023. The primary end points of this study were recurrent stroke and mortality. Pooled estimates were calculated as hazard ratios (HR) with 95% CIs. Meta-regression analyses evaluated moderating effects of PSCI severity, study design, and study period on recurrent stroke and mortality. Pooled data from 27 studies comprised 39 412 patients with ischemic stroke. Nine studies evaluated the association between PSCI and risk of stroke recurrence that showed the hazard of recurrent stroke risk was significantly higher in patients with PSCI compared with those without it (HR, 1.59 [95% CI, 1.29-1.94]; I2=52.2%). Eighteen studies examined the impact of PSCI on mortality risk. The pooled hazard of mortality was significantly higher in the group with PSCI relative to the non-PSCI group (HR, 2.07 [95% CI, 1.65 -2.59]; I2=89.3%). Meta-regressions showed that the average effect of PSCI on mortality risk differed across study period and study design. CONCLUSIONS: Based on this meta-analysis PSCI was statistically significantly associated with increased risks of recurrent stroke and all-cause mortality. Poststroke neurocognitive assessment may identify patients at a higher risk who may require more aggressive interventions for secondary prevention.
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Disfunción Cognitiva , Recurrencia , Accidente Cerebrovascular , Humanos , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/epidemiología , Factores de Riesgo , Medición de RiesgoRESUMEN
Cosmic radiation experienced during space travel may increase the risk of cognitive impairment. While simulated galactic cosmic radiation (GCRsim) has led to memory deficits in wildtype (WT) mice, it has not been investigated whether GCRsim in combination with genetic risk factors for Alzheimer's disease (AD) worsens memory further in aging mice. Here, we investigated the central nervous system (CNS) effects of 0 Gy (sham) or 0.75 Gy five-ion GCRsim or 2 Gy gamma radiation (IRR) in 14-month-old female and male APPNL-F/NL-F knock-in (KI) mice bearing humanized ApoE3 or ApoE4 (APP;E3F and APP;E4F). As travel to a specialized facility was required for irradiation, both traveled sham-irradiated C57BL/6J WT and KI mice and non-traveled (NT) KI mice acted as controls for potential effects of travel. Mice underwent four behavioral tests at 20 months of age and were euthanized for pathological and biochemical analyses 1 month later. Fecal samples were collected pre- and post-irradiation at four different time points. GCRsim seemed to impair memory in male APP;E3F mice compared to their sham counterparts. Travel tended to improve cognition in male APP;E3F mice and lowered total Aß in female and male APP;E3F mice compared to their non-traveled counterparts. Sham-irradiated male APP;E4F mice accumulated more fibrillar amyloid than their APP;E3F counterparts. Radiation exposure had only modest effects on behavior and brain changes, but travel-, sex-, and genotype-specific effects were seen. Irradiated mice had immediate and long-term differences in their gut bacterial composition that correlated to Alzheimer's disease phenotypes.
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Enfermedad de Alzheimer , Precursor de Proteína beta-Amiloide , Cognición , Radiación Cósmica , Ratones Transgénicos , Animales , Femenino , Masculino , Radiación Cósmica/efectos adversos , Ratones , Cognición/efectos de la radiación , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/metabolismo , Técnicas de Sustitución del Gen , Ratones Endogámicos C57BL , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Modelos Animales de Enfermedad , Factores Sexuales , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , HumanosRESUMEN
BACKGROUND: The hippocampus is susceptible to damage, leading to negative impacts on cognition. Conditioned medium (CM) obtained from adipose tissue-derived mesenchymal stem cells (MSCs) and acetylsalicylic acid (ASA) have shown neuroprotective effects independently. This study explored the synergistic potential of ASA and CM from adipose-derived MSCs against hippocampal injury. METHODS: Adult male Wistar rats received bilateral hippocampal ethidium bromide (EB) injections to induce hippocampal damage. Rats were treated with ASA and/or CM derived from adipose tissue MSCs every 48 h for 16 days. Behavioral tests (open field test, Morris water maze, novel object recognition, and passive avoidance), oxidative stress, Western blot analysis of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) expression, and hippocampal histological investigation were conducted. RESULTS: Administration of EB caused impairments in spatial, recognition, and passive avoidance memory, as well as heightened oxidative stress, reduced BDNF/CDNF expression, and pyramidal cell loss in the hippocampal CA1 region. Administration of ASA, CM, or a combination of both mitigated these hippocampal damages and cognitive deficits, elevated BDNF and CDNF levels, and alleviated the CA1 necrosis caused by EB. Moreover, co-administering ASA and CM resulted in greater improvements in spatial memory compared to administering ASA alone, suggesting possible synergistic interactions. CONCLUSIONS: The ability of ASA, CM obtained from adipose tissue-derived MSCs, and their combination therapy to alleviate hippocampal injuries highlights their promising therapeutic potential as a neuroprotection strategy against brain damage. Our findings provide preliminary evidence of the potential synergistic effects of ASA and CM, which warrants further investigations.