The memory associative test of the district of Seine-Saint-Denis (tma-93) validation as Alzheimer's disease diagnosis test

INTRODUCTION Alzheimer's disease (AD) is the most frequent cause of dementia (60-80%). Loss of binding and difficulties in encoding new information are early signs of hippocampal dysfunction and may facilitate an early AD diagnosis, a challenge for clinicians who evaluate patients with memory complaints. To detect hippocampal dysfunction, we employ screening and memory tests. As we live in a low-educated population area, verbal memory tests have several limitations. In this context, we aimed to validate the "Associative memory test of the Seine-Saint-Denis district" TMA-93, which examines "visual relational binding." Through this doctoral work, we travel to TMA-93 validation and normative studies. METHODS AND RESULTS In the preliminary TMA-93 validation (phase I), we compared its diagnostic accuracy with FCSRT to differentiate patients with amnestic mild cognitive impairment (aMCI) from Healthy Controls (HCs), including 41.7% low-educated participants. ROC curve analysis determined an AUC of 0.97 (95% CI: 0.89 - 1.00, p <.001) to distinguish between aMCI patients and HCs. The TMA-93 accuracy did not show significant differences with the FCSRT. Within the test reliability, the TMA-93 internal consistency between the related pictures was "optimal" (Cronbach's alpha = 0.936). TMA-93 showed a “good” test-retest reliability at 2-4 months for HCs [ICC = 0.802 (95% CI = 0.653 - 0.887)], suggesting stability in the over-time performance. The inter-rater TMA-93 reliability was “optimal” for the total score [ICC = 0.999, 95% CI 0.999 - 1], number of errors [ICC = 0.996, 95% CI 0.993 - 0.998], and number of intrusions [ ICC = 0.985, 95% CI 0.974- 0.992]. All participants completed the test, without significant differences in administration time regarding educational level, with an average time of 6 minutes in aMCI patients. TMA-93 Spanish normative study provides normative percentiles data through a systematized recruitment study on an 1131 participants' sample. We describe the healthy population's reference scores with a broad representation of our region's community. TMA-93 total score was influenced by age and educational level, but not by gender. We finally validated the test’s diagnostic accuracy by comparing TMA-93 and FCSRT variables’ predictive value with biomarkers’ result (CSF or Amyloid-PET), considered the Gold-Standard. TMA-93 demonstrated "reasonable" diagnostic utility in discriminating between "positive" and "negative" biomarker groups (AUC = 0.72; 95% CI: 0.62 - 0.82, p <.001), higher than FCSRT variables. The sequential use of the TMA-93 after the pictorial FCSRT increased the diagnostic sensitivity up to 95.3%. DISCUSSION TMA-93 uses ten semantically related pairs of drawings, assessing binding. Binding ability decreases in prodromal AD so that it could facilitate an early diagnosis. TMA-93 is a specific memory test suitable for elder and low-educated patients. It is probably more accurate for diagnosing aMCI than others testing episodic memory, and its short administration time turns the test suitable for Primary Care or General Neurology outpatient clinics, in which there is limited time per patient. We first validated TMA-93, comparing its diagnostic accuracy with FCSRT to differentiate aMCI patients from HCs, finding a similar diagnostic accuracy. Afterwards, we studied test’s reliability, finding an “optimal” internal consistency (Cronbach's alpha = 0.936), “good” test-retest, and “optimal” inter-rater reliability. TMA-93 showed itself feasible as all participants completed the test in an average time of 6 minutes in aMCI patients. Through the normative study, we provide normative percentiles data through a representative population. TMA-93 was influenced by age and educational level but not by gender. This study showed wide variations of the 5th and 10th TMA-93 percentiles, lower for the older and less educated groups, suggesting that the ability to learn by visual association is lower and more sensitive to aging in the low-educated group. We finally validated TMA-93 by comparing it and the FCSRT variables with biomarkers (Gold Standard). The TMA-93 demonstrated "reasonable" diagnostic utility in discriminating between biomarker groups (positive or negative). Memory impaired patients with an MMSE ≥ 22 and TMA-93 total score ≤ 5th and 10th percentiles showed 75% and 86% sensitivity and 41% and 29% specificity, respectively, for AD biological diagnosis. These high sensitivity values position the TMA-93 as a good memory screening test, particularly for limited face-to-face time settings. Therefore, we propose the patients' memory examination to start with the TMA-93 (as screening), followed by the AD-pathology confirmation with the highest specific test at present: biomarkers. The sequential use of the TMA-93 after the pictorial FCSRT increased the diagnostic sensitivity up to 95.3%. CONCLUSIONS TMA-93 is highly discriminative to distinguish MCI patients without excluding loweducated individuals. It has a high internal consistency and precision, with high interobserver and good test-retest reliability. TMA-93 administration spends between 3-7 minutes, suitable for Primary Care. It seems as accurate as FCSRT to discriminate between positive and negative AD biomarkers' results, improved by adding TMA-93 to FCSRT variables. All together, position the test as a good screening tool in limit face-toface consultations

Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus

Brain aquaporin 1 (AQP1) and AQP4 are involved in cerebrospinal fluid (CSF) homeostasis and might participate in the origin of hydrocephalus. Studies have shown alterations of perivascular AQP4 expression in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer’s disease (AD). Due to the overlapping of clinical signs between iNPH and certain neurological conditions, mainly AD, specific biomarkers might improve the diagnostic accuracy for iNPH. The goal of the present study was to analyze and quantify the presence of AQP1 and AQP4 in the CSF of patients with iNPH and AD to determine whether these proteins can be used as biomarkers of iNPH. We examined AQP1 and AQP4 protein levels in the CSF of 179 participants (88 women) classified into 5 groups: possible iNPH (81 participants), hydrocephalus associated with other neurological disorders (13 participants), AD (41 participants), non-AD dementia (32 participants) and healthy controls (12 participants). We recorded each participant’s demographic and clinical variables and indicated, when available in the clinical history, the record of cardiovascular and respiratory complications. An ELISA showed virtually no AQP content in the CSF. Information on the vascular risk factors (available for 61 patients) confirmed some type of vascular risk factor in 86% of the patients with possible iNPH and 58% of the patients with AD. In conclusion, the ELISA analysis showed insufficient sensitivity to detect the presence of AQP1 and AQP4 in CSF, ruling out the possible use of these proteins as biomarkers for diagnosing iNPH.This research was funded by grants PI16/00493 and PI19/01096 to M.E. from the Spanish Ministry of Economy and Competitiveness, co-financed by the Carlos III Health Institute (ISCIII) and European Regional Development Fund (FEDER). J.L.T-C. was partially supported by the Regional Government of Andalusia and FEDER funds through a program for recruitment of young researchers

Chronic Glaucoma Using Biodegradable Microspheres to Induce Intraocular Pressure Elevation. Six-Month Follow-Up

Altres ajuts: Rio Hortega Research Grant M17/00213, Research Group UCM 920415, UCM-Santander fellowship (CT17/17-CT17-18).Background: To compare two prolonged animal models of glaucoma over 24 weeks of follow-up. A novel pre-trabecular model of chronic glaucoma was achieved by injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (10-20 µm) (Ms20/10) into the ocular anterior chamber to progressively increase ocular hypertension (OHT). Methods: Rat right eyes were injected to induce OHT: 50% received a suspension of Ms20/10 in the anterior chamber at 0, 2, 4, 8, 12, 16 and 20 weeks, and the other 50% received a sclerosing episcleral vein injection biweekly (EPIm). Ophthalmological clinical signs, intraocular pressure (IOP), neuroretinal functionality measured by electroretinography (ERG), and structural analysis of the retina, retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) protocols using optical coherence tomography (OCT) and histological exams were performed. Results: Both models showed progressive neuroretinal degeneration (p < 0.05), and contralateral eye affectation. The Ms20/10 model showed a more progressive increase in IOP and better preservation of ocular surface. Although no statistical differences were found between models, the EPIm showed a tendency to produce thicker retinal and thinner GCL thicknesses, slower latency and smaller amplitude as measured using ERG, and more aggressive disturbances in retinal histology. In both models, while the GCL showed the greatest percentage loss of thickness, the RNFL showed the greatest and earliest rate of thickness loss. Conclusions: The intracameral model with biodegradable microspheres resulted more like the conditions observed in humans. It was obtained by a less-aggressive mechanism, which allows for adequate study of the pathology over longer periods

Analysis of parainflammation in chronic glaucoma using vitreous-oct imaging

Glaucoma causes blindness due to the progressive death of retinal ganglion cells. The immune response chronically and subclinically mediates a homeostatic role. In current clinical practice, it is impossible to analyse neuroinflammation non-invasively. However, analysis of vitreous images using optical coherence tomography detects the immune response as hyperreflective opacities. This study monitors vitreous parainflammation in two animal models of glaucoma, comparing both healthy controls and sexes over six months. Computational analysis characterizes in vivo the hyperreflective opacities, identified histologically as hyalocyte-like Iba-1+ (microglial marker) cells. Glaucomatous eyes showed greater intensity and number of vitreous opacities as well as dynamic fluctuations in the percentage of activated cells (50–250 microns2 ) vs. non-activated cells (10–50 microns2 ), isolated cells (10 microns2) and complexes (&gt;250 microns2 ). Smaller opacities (isolated cells) showed the highest mean intensity (intracellular machinery), were the most rounded at earlier stages (recruitment) and showed the greatest change in orientation (motility). Study of vitreous parainflammation could be a biomarker of glaucoma onset and progression. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)

Epidemiologia, vigilancia y control de Rabia transmitida por Murciélagos Insectívoros

An exhaustive bibliographic search was carried out on epidemiology,surveillance and control strategies for Rabies variant 4 transmitted byinsectivorous bats. Likewise, as a case study, a retrospective study ofinsectivorous bats captured by passive surveillance and analyzed todetermine the presence of rabies virus was carried out in the Provinceof Río Negro, Argentina. The objective was to update the informationon the epidemiology of rabies variant 4 and to analyze the effectivenessof the control measures usually recommended by health services.The review carried out shows only 5 notifications in South Americacorresponding to canines and felines between 2009 and 2019 andwith regard to people, three cases were reported: in Chile in 1963 and2013 and in Colombia in 2012. The identification of insectivorous batscarrying rabies ranges from 4% to 15%. For its part, the veterinarypublic health service of the Health Ministry of Rio Negro collectedinsectivorous bats from passive surveillance activities. The bats weresent to the Laboratory of the Luis Pasteur Institute in the city of BuenosAires for identification of rabies virus. A total of 294 insectivorous batswere analyzed in 26 locations. The proportion of the infected ones was14.6% (95% CI 9.5-17.8) although there were no cases in dogs, cats orpeople. Insectivorous bats can be a risk factor for canines, felines, andhumans, although notifications of variant 4 cases in these species areextremely low in South America, so an evaluation of the recommendedand applied control strategy seems to be required, so far, as it is not cost-effective, and involves increasing operating costs in financial andhuman resources, proposing more efficient risk control alternatives.Se efectuó una búsqueda bibliográfica exhaustiva sobre epidemiologia, vigilancia epidemiológica y estrategias de control de Rabia variante 4 transmitida por murciélagos insectívoros. Asimismo, como estudio de caso se efectuó un estudio retrospectivo de murciélagos insectívoros capturados por vigilancia pasiva y analizados para determinar presencia de virus rábico en la Provincia de Río Negro, Argentina. El objetivo fue actualizar la información sobre la epidemiologia de la rabia variante 4 y analizar la eficacia de las medidas de control habitualmente recomendadas por los servicios de salud. La revisión efectuada muestra en Sudamérica solo 5 notificaciones correspondientes a caninos y felinos entre 2009 y 2019 y en relación a las personas, se reportaron tres casos: en Chile en 1963 y 2013 y uno en Colombia en 2012. La identificación de murciélagos insectívoros portadores de rabia varia del del 4% al 15%. Por su parte, el servicio de salud pública veterinaria del Ministerio de Salud de Rio Negro  recogió murciélagos insectívoros a partir de actividades de vigilancia pasiva. Los murciélagos fueron remitidos al Laboratorio del Instituto Luis Pasteur de la ciudad de Buenos Aires para identificación de virus rábico. Se analizaron un total de 294 quirópteros insectívoros en 26 localidades. La proporción de infectados fue del 14,6% (IC95% 9,5-17,8) aunque sin casos en perros, gatos o personas. Los murciélagos insectívoros pueden ser un factor de riesgo para caninos, felinos y seres humanos, aunque las notificaciones de casos a variante 4 en estas especies es extremadamente bajo en América del Sur por lo que parece requerirse una evaluación de la estrategia de control recomendada y aplicada hasta el momento por no ser costo - efectiva, e implicar crecientes costos operativos en recursos financieros y humanos, proponiéndose alternativas más eficientes de control de riesgos

Awareness of Diagnosis in Persons with Early-Stage Alzheimer's Disease : An Observational Study in Spain

Limited information is available on people's experiences of living with Alzheimer's disease (AD) at earlier stages. This study assessed awareness of diagnosis among people with early-stage AD and its impact on different person-centered outcome measures. We conducted an observational, cross-sectional study in 21 memory clinics in Spain. Persons aged 50-90 years, diagnosed with prodromal or mild AD (NIA/AA criteria), a Mini Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5 or 1.0 were recruited. The Representations and Adjustment to Dementia Index (RADIX) was used to assess participants' beliefs about their condition and its consequences. A total of 149 persons with early-stage AD were studied. Mean (SD) age was 72.3 (7.0) years and 50.3% were female. Mean duration of AD was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1) and 87.2% had a CDR-GS score of 0.5. Most participants (n = 84, 57.5%) used a descriptive term related to specific AD symptoms (e.g., memory difficulties) when asked what they called their condition. Participants aware of their diagnosis using the term AD (n = 66, 45.2%) were younger, had more depressive symptoms, and poorer life satisfaction and quality of life compared to those without awareness of their specific diagnosis. Practical and emotional consequences RADIX scores showed a significant negative correlation with Quality of Life in Alzheimer's Disease score (rho = − 0.389 and − 0.413, respectively; p < 0.0001). Years of education was the only predictor of awareness of AD diagnosis [OR = 1.04 (95% CI 1.00-1.08); p = 0.029]. Awareness of diagnosis was a common phenomenon in persons with early-stage AD negatively impacting their quality of life. Understanding illness representations in earlier stages may facilitate implementing optimized care that supports improved quality of life and well-being

Determinación de procesos de fractura sobre huesos frescos: un sistema de análisis de los ángulos de los planos de fracturación como discriminador de agentes bióticos

The breakage planes of bones have diversely been used to classify breakage patterns. However, no diagnosis seems to be currently valid to differentiate between humans and carnivores as the main breaking agents. This work presents the results of experimentation focused on the analysis of the angles of each plane between the cortical and medullary surfaces resulting from breakage. It is shown that this approach can be fairly resolutive since both types of agents break bones through different physical processes (percussion and pression) which produce different angles in each fracture episode, as a result of the use of dynamic and static loading processes.Los paños de fractura de los huesos siempre se han prestado a diversos análisis de clasificación, pero con menor éxito se ha podido averiguar el (los) agente(s) responsable( s) de su ruptura. De los diversos atributos utilizados, uno de ellos (los ángulos de los planos de fractura) se ha sometido a exhaustivo análisis, con los resultados que se ofrecen en el presente trabajo. Se concluye que dichos ángulos, en su consideración global en una muestra pueden ser resolutivos ya que los diversos agentes bióticos que rompen huesos (humanos y carnívoros) lo hacen por procesos físicos distintos (percusión y presión) que provocan diagnosis diferenciadas en el modo en que los huesos aparecen fracturados

Medical help-seeking intentions among patients with early Alzheimer’s disease

BackgroundLimited information is available on the active process of seeking medical help in patients with Alzheimer’s disease (AD) at early stages. The aim of this study was to assess the phenomenon of medical help-seeking in early AD and to identify associated factors.MethodsA multicenter, non-interventional study was conducted including patients of 50–90 years of age with prodromal or mild AD (National Institute on Aging/Alzheimer’s Association criteria), a Mini-Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5–1.0. A multivariate logistic regression analysis was conducted.ResultsA total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years, 50.3% were female, and 87.2% had a CDR-GS score of 0.5. Mean disease duration was 1.4 (1.8) years. Ninety-four (63.1%) patients sought medical help, mostly from neurologists. Patients with help-seeking intentions were mostly female (60.6%) with a CDR-GS score of 0.5 (91.5%) and had a greater awareness of diagnosis, poorer quality of life, more depressive symptoms, and a more severe perception of their condition than their counterparts. Lack of help-seeking intentions was associated with male sex (p = 0.003), fewer years of education (p = 0.005), a low awareness of diagnosis (p = 0.005), and a low emotional consequence of the condition (p = 0.016).ConclusionUnderstanding the phenomenon of active medical help-seeking may facilitate the design of specific strategies to improve the detection of cognitive impairment, especially in patients with a lower level of educational attainment and poor awareness of their condition

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica