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Teipel S.J.,University of Rostock | Teipel S.J.,German Center for Neurodegenerative Diseases | Wegrzyn M.,German Center for Neurodegenerative Diseases | Meindl T.,Ludwig Maximilians University of Munich | And 8 more authors.
Journal of Alzheimer's Disease | Year: 2012

Diffusion tensor imaging (DTI) detects microstructural changes of the cerebral white matter in Alzheimer's disease (AD). The use of DTI for the diagnosis of AD in a multicenter setting has not yet been investigated. We used voxel-based analysis of fractional anisotropy, mean diffusivity, and grey matter volumes from multimodal magnetic resonance imaging data of 137 AD patients and 143 healthy elderly controls collected across 9 different scanners. We compared different univariate analysis approaches to model the effect of scanner, including a linear model across all scans with a scanner covariate, a random effects model with scanner as a random variable as well as a voxel-based meta-analysis. We found significant reduction of fractional anisotropy and significant increase of mean diffusivity in core areas of AD pathology including corpus callosum, medial and lateral temporal lobes, as well as fornix, cingulate gyrus, precuneus, and prefrontal lobe white matter. Grey matter atrophy was most pronounced in medial and lateral temporal lobe as well as parietal and prefrontal association cortex. The effects of group were spatially more restricted with random effects modeling of scanner effects compared to simple pooled analysis. All three analysis approaches yielded similar accuracy of group separation in block-wise cross-validated logistic regression. Our results suggest similar effects of center on group separation based on different analysis approaches and confirm a typical pattern of cortical and subcortical microstructural changes in AD using a large multimodal multicenter data set. © 2012 - IOS Press and the authors. All rights reserved.

Caroli A.,Mario Negri Institute for Pharmacological Research | Caroli A.,Irccs Centro San Giovanni Of Dio | Antiga L.,Mario Negri Institute for Pharmacological Research | Cafaro M.,Azienda Ospedaliera Ospedali Riuniti di Bergamo | And 5 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2010

Background and objectives: No medical treatment is available for polycystic liver disease, a frequent manifestation of autosomal-dominant polycystic kidney disease (ADPKD). In a prospective, randomized, double-blind, crossover study, 6 months of octreotide (40 mg every 28 days) therapy limited kidney volume growth more effectively than placebo in 12 patients with ADPKD. Design, setting, participants, & measurements: In this secondary, post hoc analysis of the above study, octreotide-induced changes in liver volumes compared with placebo and the relationship between concomitant changes in liver and kidney volumes were evaluated. Those analyzing liver and kidney volumes were blinded to treatment. Results: Liver volumes significantly decreased from 1595 ± 478 ml to 1524 ± 453 ml with octreotide whereas they did not appreciably change with placebo. Changes in liver volumes were significantly different between the two treatment periods (-71 ± 57 ml versus +14 ± 85 ml). Octreotide-induced liver volume reduction was fully explained by a reduction in parenchyma volume from 1506 ± 431 ml to 1432 ± 403 ml. Changes in liver volumes were significantly correlated with concomitant changes in kidney volumes (r = 0.67) during octreotide but not during placebo treatment. Liver and kidney volume changes significantly differed with both treatments (octreotide: -71 ± 57 ml versus +71 ± 107; placebo: +14 ± 85 ml versus +162 ± 114), but net reductions in liver (-85 ± 103 ml) and kidney (-91 ± 125 ml) volume growth on octreotide versus placebo were similar. Conclusions: Octreotide therapy reduces liver volumes in patients with ADPKD and is safe. Copyright © 2010 by the American Society of Nephrology.

Kilimann I.,German Center for Neurodegenerative Diseases | Kilimann I.,University of Rostock | Grothe M.,German Center for Neurodegenerative Diseases | Heinsen H.,University of Wurzburg | And 14 more authors.
Journal of Alzheimer's Disease | Year: 2014

Histopathological studies in Alzheimer's disease (AD) suggest severe and region-specific neurodegeneration of the basal forebrain cholinergic system (BFCS). Here, we studied the between-center reliability and diagnostic accuracy of MRI-based BFCS volumetry in a large multicenter data set, including participants with prodromal (n = 41) or clinically manifest AD (n = 134) and 148 cognitively healthy controls. Atrophy was determined using voxel-based and region-of-interest based analyses of high-dimensionally normalized MRI scans using a newly created map of the BFCS based on postmortem in cranio MRI and histology. The AD group showed significant volume reductions of all subregions of the BFCS, which were most pronounced in the posterior nucleus basalis Meynert (NbM). The mild cognitive impairment-AD group showed pronounced volume reductions in the posterior NbM, but preserved volumes of anterior-medial regions. Diagnostic accuracy of posterior NbM volume was superior to hippocampus volume in both groups, despite higher multicenter variability of the BFCS measurements. The data of our study suggest that BFCS morphometry may provide an emerging biomarker in AD. © 2014 IOS Press and the authors. All rights reserved.

Pievani M.,Irccs Centro San Giovanni Of Dio | de Haan W.,VU University Amsterdam | Wu T.,Capital Medical University | Seeley W.W.,University of California at San Francisco | Frisoni G.B.,Irccs Centro San Giovanni Of Dio
The Lancet Neurology | Year: 2011

Despite advances towards understanding the molecular pathophysiology of the neurodegenerative dementias, the mechanisms linking molecular changes to neuropathology and neuropathological changes to clinical symptoms remain largely obscure. Connectivity is a distinctive feature of the brain and the integrity of functional network dynamics is crucial for normal functioning. A better understanding of network disruption in the neurodegenerative dementias might help bridge the gap between molecular changes, pathological changes, and symptoms. Recent findings on functional network disruption as assessed with resting-state or intrinsic connectivity functional MRI and electroencephalography and magnetoencephalography have shown distinct patterns of network disruption across the major neurodegenerative diseases. These network abnormalities are somewhat specific to the clinical syndromes and, in Alzheimer's disease and frontotemporal dementia, network disruption tracks the pattern of pathological changes. These findings might have practical implications for diagnostic accuracy, allowing earlier detection of neurodegenerative diseases even at the presymptomatic stage, and tracking of disease progression. © 2011 Elsevier Ltd.

Zaninotto L.,University of Bologna | Zaninotto L.,Catholic University of the Sacred Heart | Souery D.,Free University of Colombia | Souery D.,Psy Pluriel Center Europeen Of Psychologie Medicale | And 8 more authors.
Annals of Clinical Psychiatry | Year: 2013

BACKGROUND: Depressive subtypes generally have been neglected in research on treatment efficacy. We studied a sample of 699 severe unipolar depressed patients to detect any association between depressive features and treatment resistance. METHODS: Participants were divided into psychotic (PSY, n = 90), melancholic (MEL, n = 430) and non-melancholic (n = 179) subjects according to clinical features. Formal diagnostic criteria (Mini International Neuropsychiatric Interview items), and items from 17-item Hamilton Rating Scale for Depression (HRSD17) were compared across groups. Non-responders were defined by a HRSD17 cut-off score of !17 after the last adequate antidepressant treatment. Treatment-resistant depression (TRD) was defined as the failure to respond to !2 adequate antidepressant trials. Non-linear regression models were designed to detect associations between depressive subtypes and TRD. RESULTS: PSY and MEL patients appeared to be more severely affected and to share some "core" melancholic symptoms. Both PSY and MEL patients reported a higher rate of seasonality. However, we found no clinical or illness course variable associated with TRD. CONCLUSIONS: Our results indicate that psychotic and melancholic depression share some "core" melancholia symptoms, while no distinguishing psychopathological feature appears to be associated with TRD in severely depressed patients.

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