330 research outputs found
Quaternary Stratigraphy and soil development at the southern border of the Central Alps, the Bagaggera sequence
No full textPalaeomagnetic stratigraphy and archaeologic finds indicate that the sediments of the Bagaggera basin accumulated at least from Early Pleistocene up to Late Pleistocene. Five glacial stages are recorded in the sedimentary sequence, the oldest one dating back to Early Pleistocene, and only the last 2 are directly connected with the front of the Alpine glaciers. Five different paleosols are interlayered in the basin fill; 4 indicate that, during Interglacial period of Middle and part of Early Pleistocene, soil forming processes were not very different from those which operated in Postglacial times. On the contrary the oldest paleosol, dating back to Early Pleistocene or Late Pliocene, is due to stronger weathering and probably developed in a different pedoclimatic environment. -from Author
Structure of the geomagnetic field during polarity transitions and excursions
No full textSIGLELD:D50455/84 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration.
No full textOBJECTIVE: To quantify the regional and global cerebral atrophy rates and assess acceleration rates in healthy controls, subjects with mild cognitive impairment (MCI), and subjects with mild Alzheimer disease (AD). METHODS: Using 0-, 6-, 12-, 18-, 24-, and 36-month MRI scans of controls and subjects with MCI and AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we calculated volume change of whole brain, hippocampus, and ventricles between all pairs of scans using the boundary shift integral. RESULTS: We found no evidence of acceleration in whole-brain atrophy rates in any group. There was evidence that hippocampal atrophy rates in MCI subjects accelerate by 0.22%/year2 on average (p = 0.037). There was evidence of acceleration in rates of ventricular enlargement in subjects with MCI (p = 0.001) and AD (p < 0.001), with rates estimated to increase by 0.27 mL/year2 (95% confidence interval 0.12, 0.43) and 0.88 mL/year2 (95% confidence interval 0.47, 1.29), respectively. A post hoc analysis suggested that the acceleration of hippocampal loss in MCI subjects was mainly driven by the MCI subjects that were observed to progress to clinical AD within 3 years of baseline, with this group showing hippocampal atrophy rate acceleration of 0.50%/year2 (p = 0.003). CONCLUSIONS: The small acceleration rates suggest a long period of transition to the pathologic losses seen in clinical AD. The acceleration in hippocampal atrophy rates in MCI subjects in the ADNI seems to be driven by those MCI subjects who concurrently progressed to a clinical diagnosis of AD
Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease
No full textIntroduction
Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment.
Methods
We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally.
Results
Our risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%–98.2%]) and improved prediction beyond established methods based on familial age of onset.
Discussion
Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials.Fil: Keret, Ophir. University of California; Estados Unidos.Fil: Staffaroni, Adam M. University of California; Estados Unidos.Fil: Ringman, John M. University of Southern California; Estados Unidos.Fil: Cobigo, Yann. University of California; Estados Unidos.Fil: Goh, Sheng-Yang M. University of California; Estados Unidos.Fil: Wolf, Amy. University of California; Estados Unidos.Fil: Allen, Isabel Elaine. University of California; Estados Unidos.Fil: Salloway, Stephen. Brown University; Estados Unidos.Fil: Chhatwal, Jasmeer P. Harvard Medical School; Estados Unidos.Fil: Brickman, Adam M. Columbia University; Estados Unidos.Fil: Reyes-Dumeyer, Dolly. Columbia University; Estados Unidos.Fil: Bateman, Randall J. Washington University School of Medicine; Estados Unidos.Fil: Benzinger, Tammie L.S. Washington University School of Medicine; Estados Unidos.Fil: Morris, John C. Washington University School of Medicine; Estados Unidos.Fil: Ances, Beau M. Washington University School of Medicine; Estados Unidos.Fil: Joseph-Mathurin, Nelly. Washington University School of Medicine; Estados Unidos.Fil: Perrin, Richard J. Washington University School of Medicine; Estados Unidos.Fil: Gordon, Brian A. Washington University School of Medicine; Estados Unidos.Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Chrem Méndez, Patricio. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina
Neurofilament ELISA validation
No full textBackground: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance.Methods: The UmanDiagnostics NF-light (R) enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68 kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories' accuracy and preparation of standards were documented and used for the statistical analyses.Results: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R = 0.60, p < 0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R = 0.98, p < 0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss' multi-rater kappa and Gwet's AC1 statistics.Conclusion: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online. (C) 2009 Elsevier B.V. All rights reserved
The Behavioural Dyscontrol Scale-Validation of a computerised version in a non-clinical New Zealand population
No full textThe objective of this study was to evaluate the validity of a new computerised version of the Behavioural Dyscontrol Scale (BDS) in comparison to the original manual version which research has shown to be a sensitive, reliable and valid measure of executive function (EF), and in particular of control over voluntary behaviour. A.J Luria deconstructed the complex construct of EF into Three Functional Units of working memory (Fluid Intelligence Factor), motor programming (Motor Programming Factor), and inappropriate response inhibition (Environmental Independence Factor) which he regarded to be predictive of a person’s capacity to function independently and autonomously in their environment. This theoretical framework and demonstrated ecological utility is what differentiates the BDS from other traditional clinical measures of EF. The subjective scoring system has restricted the use of the BDS; the development of a valid and reliable computerised version would address this limitation generating a much greater depth and range of finite objective data. Participants were 38 tertiary students who completed a demographic questionnaire, the Hamilton Anxiety and Depression self-report Scale (HADS), the Integrated Visual and Auditory Continuous Performance Test (IVACPT), Trail Making Test A and B, the manual and computerised versions of the Behavioural Dyscontrol Scale. Findings showed good levels of internal reliability and construct validity for the CBDS which yielded high sensitivity and specificity across all Three Functional Units, together with a high level of correspondence to scores generated by the manual version and by the Trails and IVACPT measures. Potential clinical applications, limitations and future directions are discussed
Predicting brain age from functional connectivity in symptomatic and preclinical Alzheimer disease
No full text"Brain-predicted age" quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18-89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and significantly younger in preclinical AD compared to controls. There was minimal correspondence between networks predictive of age and AD. Elevated FC-BAG may reflect network disruption during symptomatic AD. Reduced FC-BAG in preclinical AD was opposite to the expected direction, and may reflect a biphasic response to preclinical AD pathology or may be driven by inconsistency between age-related vs. AD-related networks. Overall, FC-predicted brain age may be a sensitive AD biomarker.Fil: Allegri, Ricardo Francisco. Fleni. Departamento de Neurología. Servicio de Neurología Cognitiva, Neuropsicología y Neuropsiquiatría; Argentina.Fil: Millar, Peter R. Washington University. Department of Neurology; Estados Unidos.Fil: Luckett, Patrick H. Washington University. Department of Neurology; Estados Unidos.Fil: Gordon, Brian A. Washington University. Department of Radiology; Estados Unidos.Fil: Benzinger, Tammie L.S. Washington University. Department of Radiology; Estados Unidos.Fil: Schindler, Suzanne E. Washington University. Department of Neurology; Estados Unidos.Fil: Fagan, Anne M. Washington University. Department of Neurology; Estados Unidos.Fil: Cruchaga, Carlos. Washington University. Department of Psychiatry; Estados Unidos.Fil: Bateman, Randall J. Washington University. Department of Neurology; Estados Unidos.Fil: Jucker, Mathias. German Center for Neurodegenerative Diseases (DZNE); Alemania. University of Tübingen. Hertie Institute for Clinical Brain Research; Alemania.Fil: Lee, Jae-Hong. University of Ulsan College of Medicine. Department of Neurology, Asan Medical Center; Corea.Fil: Mori, Hiroshi. Nagaoka Sutoku University; Japón. Osaka City University Medical School. Department of Clinical Neuroscience; Japón.Fil: Ances, Beau M. Washington University. Department of Neurology; Estados Unidos.Fil: Salloway, Stephen P. Brown University. Department of Neurology; Estados Unidos.Fil: Igor, Yakushev. Technical University of Munich. Department of Nuclear Medicine; Alemania.Fil: Morris, John C. Washington University. Department of Neurology; Estados Unidos
Guillain-Barré Syndrome-related campylobacter jejuni in Bangladesh: ganglioside mimicry and cross-reactive antibodies
No full textBACKGROUND:
<br/>
Campylobacter jejuni is the predominant antecedent infection in Guillain-Barré syndrome (GBS). Molecular mimicry and cross-reactive immune responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of GBS, although this mechanism has not been established in patients from developing countries. We determined the carbohydrate mimicry between C. jejuni LOS and gangliosides, and the cross-reactive antibody response in patients with GBS in Bangladesh.<br/>
METHODOLOGY:<br/>
Sera from 97 GBS patients, and 120 neurological and family controls were tested for antibody reactivity against LOS from C. jejuni isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94) by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity to LOS was determined by ELISA. The LOS outer core structures of C. jejuni strains associated with GBS/MFS were determined by mass spectrometry.<br/>
PRINCIPLE FINDINGS:<br/>
IgG antibodies to LOS from C. jejuni BD-07, BD-39, BD-10, and BD-67 IgG antibodies were found in serum from 56%, 58%, 14% and 15% of GBS patients respectively, as compared to very low frequency (<3%) in controls (p<0.001). Monoclonal antibodies specific for GM1 and GD1a reacted strongly with LOS from the C. jejuni strains (BD-07 and BD-39). Mass spectrometry analysis confirmed the presence of GM1 and GD1a carbohydrate mimics in the LOS from C. jejuni BD-07 and BD-39. Both BD-10 and BD-67 express the same LOS outer core, which appears to be a novel structure displaying GA2 and GD3 mimicry. Up to 90-100% of serum reactivity to gangliosides in two patients (DK-07 and DK-39) was inhibited by 50 µg/ml of LOS from the autologous C. jejuni isolates. However, patient DK-07 developed an anti-GD1a immune response while patient DK-39 developed an anti-GM1 immune response.<br/>
CONCLUSION:<br/>
Carbohydrate mimicry between C. jejuni LOS and gangliosides, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh
Development of screening guidelines and clinical criteria for predementia Alzheimer's disease
No full textItem does not contain fulltextBACKGROUND: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the multicentre DESCRIPA project, which is being conducted within the network of the European Alzheimer's Disease Consortium. METHODS: Clinical criteria will be based on a prospective cohort study of non-demented subjects older than 55 years and referred to a memory clinic. At baseline, a number of markers and risk factors for AD were collected, including demographic variables, measures of performance in activities of daily living, cognitive, neuroimaging and genetic markers, and serum and cerebrospinal fluid markers. Subjects will be reassessed annually for 2-3 years, and we will evaluate which combination of variables best predicts AD-type dementia at follow-up. RESULTS: Between 2003 and 2005, 881 subjects were included from 20 memory clinics. Subjects were on average 70.3 years old, and had 10.4 years of education. The average score on the Mini-Mental State Examination was 27.4
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