503 research outputs found
Cerebrospinal fluid Aβ42/40 corresponds better than Aβ42 to amyloid PET in Alzheimer’s disease
Background: Decreased concentrations of amyloid-β 1-42 (Aβ(42)) in cerebrospinal fluid (CSF) and increased retention of Aβ tracers in the brain on positron emission tomography (PET) are considered the earliest biomarkers of Alzheimer’s disease (AD). However, a proportion of cases show discrepancies between the results of the two biomarker modalities which may reflect inter-individual differences in Aβ metabolism. The CSF Aβ(42/40) ratio seems to be a more accurate biomarker of clinical AD than CSF Aβ(42) alone. Objective: We tested whether CSF Aβ(42) alone or the Aβ(42/40) ratio corresponds better with amyloid PET status and analyzed the distribution of cases with discordant CSF-PET results. Methods: CSF obtained from a mixed cohort (n = 200) of cognitively normal and abnormal research participants who had undergone amyloid PET within 12 months (n = 150 PET-negative, n = 50 PET-positive according to a previously published cut-off) was assayed for Aβ(42) and Aβ(40) using two recently developed immunoassays. Optimal CSF cut-offs for amyloid positivity were calculated, and concordance was tested by comparison of the areas under receiver operating characteristic (ROC) curves (AUC) and McNemar’s test for paired proportions. Results: CSF Aβ(42/40) corresponded better than Aβ(42) with PET results, with a larger proportion of concordant cases (89.4% versus 74.9%, respectively, p < 0.0001) and a larger AUC (0.936 versus 0.814, respectively, p < 0.0001) associated with the ratio. For both CSF biomarkers, the percentage of CSF-abnormal/PET-normal cases was larger than that of CSF-normal/PET-abnormal cases. Conclusion: The CSF Aβ(42/40) ratio is superior to Aβ(42) alone as a marker of amyloid-positivity by PET. We hypothesize that this increase in performance reflects the ratio compensating for general between-individual variations in CSF total Aβ
Osteogenic activity of vanadyl(IV)–ascorbate complex: evaluation of its mechanism of action
We have previously shown that different vanadium(IV) complexes regulate osteoblastic growth. Since vanadium compounds are accumulated in vivo in bone, they may affect bone turnover. The development of vanadium complexes with different ligands could be an alternative strategy of use in skeletal tissue engineering. In this study, we have investigated the osteogenic properties of a vanadyl(IV)–ascorbate (VOAsc) complex, as well as its possible mechanisms of action, on two osteoblastic cell lines in culture.
VOAsc (2.5–25 M) significantly stimulated osteoblastic proliferation (113–125% basal, p &lt; 0.01) in UMR106 cells, but not in the MC3T3E1 cell line. VOAsc (5–100 M) dose-dependently stimulated type-I collagen production (107–156% basal) in osteoblasts.
After 3 weeks of culture, 5–25 M VOAsc increased the formation of nodules of mineralization in MC3T3E1 cells (7.7–20-fold control, p &lt; 0.001). VOAsc (50–100 M) significantly stimulated apoptosis in both cell lines (170–230% basal, p &lt; 0.02–0.002), but did not affect reactive oxygen species production. The complex inhibited alkaline and neutral phosphatases from osteoblastic extracts with semi-maximal effect at 10 M doses. VOAsc induced the activation and redistribution of P-ERK in a time- and dose-dependent manner. Inhibitors of the mitogen activated protein kinases (MAPK) pathway (PD98059 and UO126) partially blocked the VOAsc-enhanced osteoblastic proliferation and collagen production. In addition, wortmanin, a PI-3-K inhibitor and type-L channel blocker nifedipine also partially abrogated these effects of VOAsc on osteoblasts. Our in vitro results suggest that this vanadyl(IV)–ascorbate complex could be a useful pharmacological tool for bone tissue regeneration
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The European Prevention of Alzheimer's Dementia (EPAD) Longitudinal Cohort Study: Baseline Data Release V500.0.
BACKGROUND: The European Prevention of Alzheimer's Dementia (EPAD) Programme is a pan-European project whose objective is to deliver a platform, adaptive, Phase 2 proof of concept (PoC) trial for the secondary prevention of Alzheimer's dementia. A component of this platform is the Longitudinal Cohort Study (LCS) which acts as a readiness cohort for the PoC Trial as well as generating data for disease modelling work in the preclinical and prodromal phases of Alzheimer's dementia. OBJECTIVES: The first data wave has been collected, quality checked, released and now available for analysis to answer numerous research questions. Here we describe the results from key variables in the EPAD LCS with the objective of using these results to compliment analyses of these data in the future. DESIGN: EPAD LCS is a cohort study whose primary objective is as a readiness cohort for the EPAD PoC Trial. As such recruitment is not capped at any particular number but will continue to facilitate delivery of the EPAD PoC Trial. Research Participants are seen annually (with an additional 6 month visit in the first year). SETTING: The EPAD Trial Delivery Network comprises currently 21 centres across Europe. PARTICIPANTS: Research participants are included if they are over 50 years old and do not have a diagnosis of dementia. MEASUREMENTS: All research participants undergo multiple assessments to fully characterise the biology of Alzheimer's disease and relate this to risk factors (both fixed and modifiable) and biomarker expression of disease through brain imaging, fluid samples (CSF, blood, urine and saliva), cognitive performance, functional abilities and neuropsychiatric symptomatology. RESULTS: V500.0 represents the first 500 research participants baselined into EPAD LCS. The mean age was 66.4 (SD=6.7) and 47.8% were male. The data was split for presentation into 4 groups: [1] CDR=0 and Amyloid + (preclinical AD), [2] CDR=0 and Amyloid -, [3] CDR=0.5 and Amyloid + (prodromal AD) and [4] CDR=0.5 and Amyloid -. CONCLUSIONS: The EPAD LCS is achieving its primary objective of trial readiness and the structured approach to data release as manifest by this first data release of V500.0 will assist researchers to describe and compare their findings as well as in systematic reviews and meta-analyses. It is anticipated given current recruitment rates that V1500.0 data release will take place in Autumn 2019. V500.1 (when the 1 year follow up is completed on the V500.0 (sub)cohort will be in Autumn 2019 also.IMI Fundin
Rotated balance in humans due to repetitive rotational movement
We show how asymmetries in the movement patterns during the process of regaining balance after perturbation from quiet stance can be modeled by a set of coupled vector fields for the derivative with respect to time of the angles between the resultant ground reaction forces and the vertical in the anteroposterior and mediolateral directions. In our model, which is an adaption of the model of Stirling and Zakynthinaki (2004), the critical curve, defining the set of maximum angles one can lean to and still correct to regain balance, can be rotated and skewed so as to model the effects of a repetitive training of a rotational movement pattern. For the purposes of our study a rotation and a skew matrix is applied to the critical curve of the model. We present here a linear stability analysis of the modified model, as well as a fit of the model to experimental data of two characteristic “asymmetric” elite athletes and to a “symmetric” elite athlete for comparison. The new adapted model has many uses not just in sport but also in rehabilitation, as many work place injuries are caused by excessive repetition of unaligned and rotational movement patterns
Design and validation of the 1-week memory battery for assessing episodic memory and accelerated long-term forgetting in cognitively unimpaired subjects
Subtle decline in memory is thought to arise in the preclinical phase of Alzheimer's disease (AD). However, detecting these initial cognitive difficulties cross-sectionally has been challenging, and the exact nature of the decline is still debated. Accelerated long-term forgetting (ALF) has been recently suggested as one of the earliest and most sensitive indicators of memory dysfunction in subjects at risk of developing AD. The objective of this study was to design and validate the 1-week memory battery (1WMB) for assessing episodic memory and ALF in cognitively unimpaired individuals.The 1WMB is unique in that it assesses multimodal memory and measures recall at both short delay (20 min) and at long term (1 week). Forty-five cognitively unimpaired subjects were assessed with 1WMB and standardized neuropsychological tests. Subjective cognitive decline (SCD), levels of anxiety and depression, and cognitive reserve were also measured.The tests of 1WMB showed a high internal consistency, and concurrent validity was observed with standard tests of episodic memory and executive functions. The analysis revealed a greater loss of information at 1 week compared to short-term forgetting (20 min). Performance in the 1WMB was affected by age and educational level, but was not associated with levels of anxiety and depression. Unlike standard tests, performance in the 1WMB correlated with measures of SCD.Our findings indicate that the 1WMB has good psychometric properties, and future studies are needed to explore its potential usefulness to assess cognitively unimpaired subjects at increased risk of developing AD. (PsycInfo Database Record (c) 2023 APA, all rights reserved)
Cerebral amyloid‐β load is associated with neurodegeneration and gliosis: Mediation by p‐tau and interactions with risk factors early in the Alzheimer's continuum
Introduction: The association between cerebral amyloid‐β accumulation and downstream CSF biomarkers is not fully understood, particularly in asymptomatic stages. /
Methods: In 318 cognitively unimpaired participants, we assessed the association between amyloid‐β PET (Centiloid), and cerebrospinal fluid (CSF) biomarkers of several pathophysiological pathways. Interactions by Alzheimer's disease risk factors (age, sex and APOE‐ε4), and the mediation effect of tau and neurodegeneration were also investigated. /
Results: Centiloids were positively associated with CSF biomarkers of tau pathology (p‐tau), neurodegeneration (t‐tau, NfL), synaptic dysfunction (neurogranin) and neuroinflammation (YKL‐40, GFAP, sTREM2), presenting interactions with age (p‐tau, t‐tau, neurogranin) and sex (sTREM2, NfL). Most of these associations were mediated by p‐tau, except for NfL. The interaction between sex and amyloid‐β on sTREM2 and NfL was also tau‐independent. /
Discussion: Early amyloid‐β accumulation has a tau‐independent effect on neurodegeneration and a tau‐dependent effect on neuroinflammation. Besides, sex has a modifier effect on these associations independent of tau
Plasma levels of soluble TREM2 and neurofilament light chain in TREM2 rare variant carriers
Background: Results from recent clinical studies suggest that cerebrospinal fluid (CSF) biomarkers that are indicative of Alzheimer’s disease (AD) can be replicated in blood, e.g. amyloid-beta peptides (Aβ42 and Aβ40) and neurofilament light chain (NFL). Such data proposes that blood is a rich source of potential biomarkers reflecting central nervous system pathophysiology and should be fully explored for biomarkers that show promise in CSF. Recently, soluble fragments of the triggering receptor expressed on myeloid cells 2 (sTREM2) protein in CSF have been reported to be increased in prodromal AD and also in individuals with TREM2 rare genetic variants that increase the likelihood of developing dementia. /
Methods: In this study, we measured the levels of plasma sTREM2 and plasma NFL using the MesoScale Discovery and single molecule array platforms, respectively, in 48 confirmed TREM2 rare variant carriers and 49 non-carriers. /
Results: Our results indicate that there are no changes in plasma sTREM2 and NFL concentrations between TREM2 rare variant carriers and non-carriers. Furthermore, plasma sTREM2 is not different between healthy controls, mild cognitive impairment (MCI) or AD. /
Conclusion: Concentrations of plasma sTREM2 do not mimic the recent changes found in CSF sTREM2
PRACTICUM II de Psicologia Mèdica en els Centres d'Atenció Primària sobre la comunicació no verbal en la relació metge-pacient
La Unitat de Psicologia Mèdica de la Facultat de Medicina de la UAB va posar en marxa durant el curs 2005/2006 el Practicum II de Psicologia Mèdica en els Centres d'Atenció Primària amb l'objectiu que els estudiants comencin a copsar la importància de les conductes i dels estats psicològics de les persones en els processos de salut-malaltia que es veuen en els Centres d'Atenció Primària (CAP). El Practicum està dedicat específicament als aspectes no verbals de la comunicació entre el professional de la salut i el pacient. L'experiència forma part de l'assignatura "Bases Psicològiques dels Estats de Salut i de Malaltia", impartida a segon curs de Medicina; s'inscriu en el paradigma de l'aprenentatge des de la pràctica que protagonitzen els professionals del sistema sanitari; i s'emmarca en el context d'un procés impulsat pels equips deganals de la Facultat de Medicina de la UAB des del curs 2004/2005 per tal d'apropar l'estudiant a la pràctica clínica des del primer curs de carrera i avançar cap a la consecució dels objectius que marquen les directrius europees. Cada alumne realitza dues visites programades a un CAP i participa en quatre sessions de tutoria a la Facultat en grups reduïts. En les visites al CAP, ha d'assistir a sessions de consulta amb diversos professionals de l'àmbit de la salut. Ha d'observar, identificar i enregistrar els elements no verbals que es descriuen en els objectius del Practicum i el context en què ocorren. A les sessions de tutories s'entrena els alumnes per a fer les observacions mitjançant material audiovisual i es discuteixen les observacions realitzades en els CAP. A més, també s'utilitza com a material una monografia específica sobre el tema. L'experiència es valora favorablement. tant des del punt de vista dels resultats obtinguts pels alumnes com per la seva satisfacció.The Medical Psychology Unit of the UAB School of Medicine initiated during the academic year 2005/2006 the Medical Psychology Practicum II in primary care centers with the goal that students realize the importance of human behaviors and psychological states in health-illness processes in primary care centers. The Practicum is specifically oriented to non verbal communication between the health professional and the patient. The experience is part of the subject "Psychological Bases of Health and Illness", taught in second course of Medicine; it is registered "learning from the practice" paradigm that professionals from the health system lead; and it is framed in the context of a process promoted by the UAB School of Medicine Deanship since the academic year 2004/2005 with the goal of bringing the clinical practice to the student from the first academic year and advancing towards the achievement of the goals that the European guidelines mark. Each student does two programmed visits to primary health center and participates in four tutorials of reduced groups in the Faculty. During the visits to the primary health center, he has to attend sessions of consultation with professionals from several health areas. He has to observe, to identify and to record the non verbal elements that are described in the Practicum goals and the context in which they occur. At the tutorials, students are trained to observe through audiovisual didactic material and the observations carried out at the primary health center are argued. Moreover, a specific monograph is also used as a specific material about the subject. The experience of these last two years has been satisfactory so for the professionals of the primary care centres as for the tutors and the students. The experience is valued favorably considering students' academic results and their satisfaction
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