Cardiovascular Risk Scales Association with Cerebrospinal Fluid Alzheimer's Disease Biomarkers in Cardiovascular Low Cardiovascular Risk Regions.

BACKGROUND: Cardiovascular risk factors are associated with Alzheimer's Disease (AD) development. However, few studies compare the overall cardiovascular risk with AD biomarkers, and when done, they are mainly performed in moderate cardiovascular risk regions. OBJECTIVES: To determine whether cardiovascular risk in older adults is associated with pathological cerebrospinal fluid (CSF) biomarkers of AD in a low cardiovascular risk population. DESIGN: This is a cross-sectional study performed between 2017 and 2020. PARTICIPANTS: The present work included patients between 50 and 75 years old who were negative for CSF AD biomarkers and had minimum cognitive alterations (controls) and patients with positive CSF AD biomarkers and in early stages of AD (cases). MEASUREMENTS: CSF biomarkers included total tau, phosphorylated tau 181 and amyloid ß42 (Aß42). Analytical variables were obtained. ERICE, SCORE2 and Framingham scales were used to calculate the overall patient's cardiovascular risk. The Aß42/Aß40 ratio and neurofilaments were explored when available. RESULTS: Two hundred and thirty-three patients were included. Nearly 76% of the sample had AD. AD patients had higher cardiovascular risk than controls (p-value < 0.05). ERICE and SCORE2 were associated with AD presence. Framingham was not. A correlation between elevated cardiovascular risk and higher total tau and NfL levels was observed when adjusted by age. CONCLUSION: Cardiovascular risk assessment may be helpful in neurodegenerative disorders detection, as it is associated with CSF total tau and NfL. ERICE and SCORE2 may be useful scales in low cardiovascular risk regions to improve cardiovascular control and prevent neurodegenerative pathologies.

Emotion recognition and baseline cortisol levels relationship in early Alzheimer disease.

BACKGROUND: Emotion recognition is often impaired in early Alzheimer's disease (AD) and can be evaluated using the Reading the Mind in the Eyes Test (RMET). Similarly, cortisol levels can affect cognition and could be considered a biomarker of AD. OBJECTIVES: The aim of this study was to analyse the relationship between the emotion recognition task and cortisol levels in participants with early Alzheimer Disease (AD). METHODS: Complex emotion recognition was assessed with RMET, and plasma cortisol levels were determined by mass spectrometry in participants classified into mild cognitive impairment (MCI) due to AD (n = 25), mild dementia (MD) due to AD (n = 20), MCI non-AD (n = 34), MD non-AD (n = 13) and healthy controls (HC) (n = 16) groups. RESULTS: Significantly lower positive emotion recognition was found in the MCI non-AD group (p = 0.02) and lower emotion recognition in MD (AD and non-AD) groups (p < 0.01) compared to the healthy group. In addition, significant differences were observed between cortisol and all RMET scores among the MCI and MD groups (p < 0.01). A significant correlation was also obtained between total and neutral RMET scores and cortisol levels in MD groups (p = 0.01). CONCLUSIONS: These outcomes suggest that detection of positive emotion dysfunction could help to identify MCI non-AD patients. Furthermore, general impaired emotion recognition and high cortisol levels may be associated with cognitive impairment at mild dementia level.

Strength of association of classical vascular risk factors in young patients with ischaemic stroke: a case-control study.

INTRODUCTION: Recent studies have reported an increasing incidence of ischaemic stroke among young adults. However, the strength of the association between traditional vascular risk factors has not been fully established. METHODS: We compared 120 patients with a first ischaemic stroke before the age of 55 years admitted to the stroke unit of our centre with 600 healthy non-stroke controls from a population-based cohort study (HERMEX), matched for sex. Risk factors assessed included: hypertension, obesity, auricular fibrillation, current smoking, estimated glomerular filtration rate (eGFR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C) and diabetes mellitus. We used logistic regression analysis and calculated population attributable risk. We performed an overall analysis, by sex and aetiological subgroup. RESULTS: Using logistic regression analysis, we found that overall, the significant risk factors were: hypertension (OR: 1.58; 95%CI: 1.01-2.50), atrial fibrillation (OR: 4.77; 95%CI: 1.20-19.00), low eGFR (OR: 4.74; 95%CI: 1.3-21.94) and low HDL-C (OR: 5.20; 95%CI: 3.29-8.21), as well as smoking for males (OR: 1.86; 95%CI: 1.14-3.03). LDL-C showed an inverse association with stroke. The population attributable risk for HDL-C was 37.8% and for hypertension 21.1%. In terms of aetiological subgroups, only low HDL-C was associated with stroke of undetermined aetiology. CONCLUSIONS: Hypertension, auricular fibrillation, low eGFR, and low HDL-C, plus tobacco use in men, are the main risk factors among patients under 55 years of age with a first ischaemic stroke. We believe that it would be of particular interest to further explore the management of low HDL-C levels as part of preventive strategies in young stroke patients.

Prevenir la demencia y promover el envejecimiento saludable. una acción bidireccional médico-farmacéutico / Preventing dementia and promoting healthy ageing. a bidirectional medical-pharmaceutical action

JUSTIFICACIÓN: la farmacia comunitaria atiende regularmente a pacientes de edad avanzada, lo que le permite detectar cambios anómalos en la conducta. Ofrecer resultados de escalas cognitivas a atención primaria, con tiempo limitado por paciente, podría facilitar la detección de casos de deterioro cognitivo (DC) y disminuir el tiempo de diagnóstico.OBJETIVOS: elaborar un protocolo que facilite la colaboración médico-farmacéutico efectiva, capaz de detectar de manera precoz el DC y de disminuir el tiempo de diagnóstico.MATERIAL Y MÉTODOS: se establecen dos grupos: un grupo de colaboración interprofesional (IPC), n=26 farmacias y otro sin colaboración interprofesional (No-IPC), n=9 farmacias. Se facilita a las farmacias IPC material y formación para detectar pacientes con posible DC mediante la plataforma de un Colegio Oficial de Farmacéuticos. Simultáneamente, se contacta con los centros de salud y hospitales pertenecientes a dichas áreas y se les explica el protocolo, valorando la derivación de pacientes de fuera de su área de salud en caso necesario. Se designa a un coordinador que facilita la comunicación entre los centros y seguimiento de los pacientes, elaborándose una campaña de comunicación del proyecto. En el grupo No-IPC, no se facilitan los recursos ni la coordinación mencionada previamente. Las diferencias entre los grupos respecto a la detección eficaz de pacientes con alta probabilidad de presentar DC han sido analizadas estadísticamente mediante el test chi-cuadrado mediante el programa R Commander. Este trabajo ha sido aprobado por dos Comités Éticos, bajo los registros, CEI18/027 y MOR-ROY-2018- 013. Todos los pacientes firmaron el consentimiento informado.RESULTADOS/DISCUSIÓN: se han cribado 349 pacientes en las farmacias IPC y 138 pacientes en las farmacias No-IPC. (AU)

Effects of bilingualism on white matter atrophy in mild cognitive impairment: a diffusion tensor imaging study.

BACKGROUND AND PURPOSE: Previous investigations show that bilinguals exhibit the first symptoms of dementia 4-5 years later than monolinguals. Therefore, bilingualism has been proposed as a cognitive reserve mechanism. Recent studies have advanced towards an understanding of the brain mechanisms underlying bilingualism's protection against dementia, but none of them deals with white matter (WM) diffusion. METHODS: In this study, the topic was investigated by measuring WM integrity in a sample of 35 bilinguals and 53 passive bilinguals with mild cognitive impairment. RESULTS: No significant differences were found between the groups in cognitive level, education, age or sex. However, bilinguals showed higher mean diffusivity in the fornix, but higher fractional anisotropy, lower mean diffusivity, axial diffusivity and radial diffusivity in the parahippocampal cingulum, and lower radial diffusivity in the right uncinate fasciculus. Significant correlations were also found between WM integrity in the left parahippocampal cingulum and the Boston Naming Test in passive bilinguals. CONCLUSIONS: These results suggest that bilingualism contributes to a differential pattern of WM disintegration due to mild cognitive impairment in fibers related to bilingualism and memory.

Technical note: Assessment of neutrophil endocytosis and proteolytic degradation and its relationship with phagocytosis and oxidative burst in dairy cows.

Conventional assays of polymorphonuclear cell (PMN, neutrophil) function such as oxidative burst (OB) and phagocytosis (PC) are widely used to evaluate innate immunity in the transition period of dairy cows. Oxidative burst is commonly evaluated by measuring PMN median fluorescence intensity (MFI) involving the release of reactive oxygen species after in vitro stimulation. Phagocytosis can be measured by engulfment of fluorescent beads by PMN. DQ-ovalbumin (DQ-OVA) is a molecule suitable for the assessment of intracellular proteolytic degradation, so it might be informative about an additional pathway of pathogen handling by PMN. In this study, we evaluated the use of the DQ-OVA assay for the assessment of PMN function and the relationships among OB, PC, and DQ-OVA results in PMN isolated from blood of dairy cows between 5 and 21 d post partum. Results of the DQ-OVA validation assay were assessed with mixed linear regression models. Pearson correlation tests and kappa values for agreement were used to associate the MFI between each PMN function assay (OB, PC, and DQ-OVA). For the validation assay (9 cows in 3 replicates), PMN incubated with DQ-OVA were stimulated with IFN-γ or inhibited with cytochalasin D, and fluorescence was compared with untreated PMN. Stimulated and inhibited PMN had greater (970 ± 160 units) and lesser (593 ± 55 units) MFI relative to untreated PMN (791 ± 154 units), respectively, indicating that DQ-OVA fluorescence reflected enhanced or reduced endocytic and proteolytic function. To associate the MFI outcomes among OB, PC, and DQ-OVA, 153 samples from 40 cows were analyzed. Results showed significant, although weak association between DQ-OVA and PC MFI (Pearson r = 0.16). When values of MFI were categorized according to the first ("high" PMN functionality), second and third ("moderate" PMN functionality), or fourth ("low" PMN functionality) quartiles, agreement beyond chance (κ) was moderate: κ = 0.38 for DQ-OVA and OB, κ = 0.43 for DQ-OVA and PC, and κ = 0.43 for OB and PC. The DQ-OVA assay may complement traditional PMN functional assays because it provides additional information regarding the combination of endocytosis and proteolytic degradation, but it is not a substitute for assessment of OB or PC.

A preliminary study investigating effects of oral monensin sodium in an enteric Mycobacterium avium ssp. paratuberculosis infection model of calves.

Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of Johne's disease, an enteric infection of ruminants that causes significant economic burden for dairy and beef producers. Efforts to control MAP in endemic herds typically focus on herd management practices such as limiting exposure or early culling of infected animals and, occasionally, vaccination. The ionophore monensin sodium may have protective effects against MAP both in vivo and in vitro; however, this has not been thoroughly evaluated experimentally. Using a direct intestinal MAP challenge model, we have observed similarities regarding persistence of MAP in tissues and apparent resilience to infection compared with experimental oral infection or natural disease. Here we sought to investigate the effects of oral monensin supplementation in experimentally MAP-infected calves. We examined the persistence of MAP in the intestinal tissues, MAP-induced intestinal inflammation, fecal MAP shedding, and seroconversion using a commercial serologic assay. Monensin-supplemented MAP-infected calves demonstrated evidence for resilience to MAP infection earlier in this study compared with monensin-free MAP-infected calves. However, statistical modeling did not identify a significant effect of monensin on outcomes of infection, and more work is required to understand how monensin affects early tissue colonization of MAP in calves.

Neuropsychological assessment and cortisol levels in biofluids from early Alzheimer's disease patients.

Cortisol dysregulation is proposed as a factor in the development of Alzheimer's disease (AD). AD patients can show high cortisol levels in prodromal phases of AD, early enough that neuropsychological alterations exist but activities of daily living remain unimpaired. Nevertheless, it is unknown if biofluid cortisol levels can have some AD predictive power together with neuropsychological assessment in prodromal stages in comparison with other cognitive disorders. In this work, an analytical method based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was applied to determine the cortisol levels in different biofluids (urine, plasma, saliva, cerebrospinal fluid). Early AD patients and non-AD patients recruited at out-patient neurological unit were classified from the standard cerebrospinal fluid biomarkers levels (ß-amyloid, tau, phosphorylated tau), and studied with an extensive neuropsychological assessment including global, neuropsychological, functional and affective scales. We used a logistic regression model to discriminate between the AD and non-AD groups. Higher plasma cortisol levels were found in the AD group than in the non-AD group (p < 0.001). Regarding neuropsychological evaluation, delayed memory was used as representative of the neuropsychological status, and lower scores were obtained in the AD group (p < 0.001). The prediction model, including plasma cortisol levels and delayed memory scores, achieved an AUC of 0.93, as well as a sensitivity of 97% and a specificity of 69.4%. In conclusion, plasma cortisol levels and delayed memory scores were specifically impaired in early AD, allowing the development of a new diagnostic model which could be employed as a very satisfactory screening system.

Diagnóstico de linfoma de Burkitt mediante PET cerebral con 11C-metionina en paciente VIH positivo con lesiones encefálicas indeterminadas / Burkitt lymphoma diagnosed on 11C-Methionine cerebral PET in an HIV-positive patient with undetermined brain injury

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Detección de metástasis extracraneal de glioblastoma multiforme mediante PET/TC cerebral con 11C-metionina / Extracranial metastasis of multiforme glioblastoma detected by 11C-methionine brain PET/CT

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Utilidad de la PET con 11C-metionina en la diferenciación precoz entre recurrencia tumoral y radionecrosis de pacientes tratados de glioma de alto grado con RM indeterminada / The value of 11C-methionine PET in the early differentiation between tumour recurrence and radionecrosis in patients treated for a high-grade glioma and indeterminate MRI

Objetivo. Valorar la contribución de la PET con 11C-metionina en la diferenciación precoz entre recurrencia tumoral y radionecrosis en pacientes tratados de gliomas de alto grado. Método. Treinta pacientes tratados de glioma (grado iii/iv) con cirugía/radioterapia/quimioterapia (5-18 meses) con RM indeterminada. A todos se les realizó estudio de PET con 11C-metionina (<15 días tras RM) con análisis visual (grado de intensidad y morfología de captación), cuantificación (relación SUV máximo lesión/SUV medio fondo) y corregistro PET/RM (3D-Flair). El manejo de los pacientes se decidió en el comité de neurooncología: seguimiento clínico-imagen, tratamiento de segunda línea o cirugía. Resultados. Veintitrés estudios de PET con 11C-metionina fueron visualmente positivos. La morfología fue: 15 focales, 4 difusos y 4 anulares. Tres de los focales fueron resecados (AP+). En 16 se realizó terapia de segunda línea (11 respuesta, 5 progresión). En los 4 de morfología anular se decidió seguimiento, con progresión en 2 (verdaderos positivos) y libres de enfermedad en 2 (6 y 7 meses después) (falsos positivos). Siete estudios de PET con 11C-metionina fueron visualmente negativos, todos ellos libres de enfermedad (3-12 meses). La relación SUV lesión/fondo en la recurrencia tumoral fue de 2,79±1,35 mientras que en la radionecrosis fue de 1,53±0,39 (p<0,05). Con umbral de corte SUV lesión/fondo de 2,35 se obtuvo una sensibilidad y especificidad del 90,5 y 100%. Conclusión. La valoración de la PET con 11C-metionina, con análisis visual, cuantitativo y corregistro PET/RM muestra un papel complementario en los pacientes con RM no concluyente, permitiendo una diferenciación precoz entre recurrencia tumoral y radionecrosis, que ayuda a la individualización de la terapia (AU)

Objective. To evaluate the contribution of 11C-Methionine PET in the early differentiation between tumour recurrence and radionecrosis in patients treated for a high grade glioma. Method. The study included 30 patients with glioma (III/IV grade) treated with surgery/radiotherapy/chemotherapy (5-8 months) and with an indeterminate MRI. All patients underwent a 11C-Methione PET (within 15 days of MRI) and studies were visually analysed (intensity and morphology of uptake), quantified (SUV max/SUV mean background), and coregistered to MRI (3D-Flair). Patient management was decided by the neuro-oncology committee to clinical and imaging follow-up, second-line treatment, or surgery. Results. There were 23 11C-Methionine PET studies visually positive. Morphology of uptake was focal in 15, diffuse in 4, and ring-shaped in 4. Three out of the focal uptake cases underwent resection (Histopathology +). Sixteen underwent second-line therapy (11 responded; 5 progressed). The 4 cases with ring-shaped uptake were followed-up, and progression was found in 2 (true-positive), and disease-free in 2 (follow-up of 6 and 7 months, respectively) (false-positive). Seven out of 11C-Methionine studies PET were visually negative, and all of them were disease-free (follow-up of 3-12 months). SUV lesion/background was 2.79±1.35 in tumour recurrence, and 1.53±0.39 in radionecrosis (P<.05). Taking into account a SUV lesion/background threshold of 2.35, the sensitivity and specificity values were 90.5% and 100%, respectively. Conclusion. Visual analysis, quantitative and PET/MRI coregistration of 11C-Methionine PET showed their complementary role in patients with indeterminate MRI results, thus allowing early differentiation between tumour recurrence and radionecrosis, and helping in the individual therapy approach (AU)

The value of 11C-methionine PET in the early differentiation between tumour recurrence and radionecrosis in patients treated for a high-grade glioma and indeterminate MRI. / Utilidad de la PET con 11C-metionina en la diferenciación precoz entre recurrencia tumoral y radionecrosis de pacientes tratados de glioma de alto grado con RM indeterminada.

OBJECTIVE: To evaluate the contribution of 11C-Methionine PET in the early differentiation between tumour recurrence and radionecrosis in patients treated for a high grade glioma. METHOD: The study included 30 patients with glioma (III/IV grade) treated with surgery/radiotherapy/chemotherapy (5-8 months) and with an indeterminate MRI. All patients underwent a 11C-Methione PET (within 15 days of MRI) and studies were visually analysed (intensity and morphology of uptake), quantified (SUV max/SUV mean background), and coregistered to MRI (3D-Flair). Patient management was decided by the neuro-oncology committee to clinical and imaging follow-up, second-line treatment, or surgery. RESULTS: There were 23 11C-Methionine PET studies visually positive. Morphology of uptake was focal in 15, diffuse in 4, and ring-shaped in 4. Three out of the focal uptake cases underwent resection (Histopathology +). Sixteen underwent second-line therapy (11 responded; 5 progressed). The 4 cases with ring-shaped uptake were followed-up, and progression was found in 2 (true-positive), and disease-free in 2 (follow-up of 6 and 7 months, respectively) (false-positive). Seven out of 11C-Methionine studies PET were visually negative, and all of them were disease-free (follow-up of 3-12 months). SUV lesion/background was 2.79±1.35 in tumour recurrence, and 1.53±0.39 in radionecrosis (P<.05). Taking into account a SUV lesion/background threshold of 2.35, the sensitivity and specificity values were 90.5% and 100%, respectively. CONCLUSION: Visual analysis, quantitative and PET/MRI coregistration of 11C-Methionine PET showed their complementary role in patients with indeterminate MRI results, thus allowing early differentiation between tumour recurrence and radionecrosis, and helping in the individual therapy approach.

Diagnóstico de recurrencia de un glioma y respuesta al tratamiento antiangiogénico mediante PET con 11C-metionina / Diagnosed recurrent glioma and antiangiogenic treatment response by 11C-Methionine PET

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Utilidad de la PET con 11C-metionina en el diagnóstico diferencial de los tumores epileptógenos / Usefulness of 11C-Methionine PET in diferential diagnosis of epileptogenic brain neoplasms

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