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Iorio M.,Neuropsychiatry Laboratory | Spalletta G.,Neuropsychiatry Laboratory | Chiapponi C.,Neuropsychiatry Laboratory | Luccichenti G.,Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation | And 5 more authors.
Frontiers in Aging Neuroscience | Year: 2013

White matter hyperintensities (WMH) are brain areas of increased signal on T2-weighted or fluid-attenuated inverse recovery magnetic resonance imaging (MRI) scans. In this study we present a new semi-automated method to measure WMH load that is based on the segmentation of the intensity histogram of fluid-attenuated inversion recovery images. Thirty patients with mild cognitive impairment with variable WMH load were enrolled. The semi-automated WMH segmentation included removal of non-brain tissue, spatial normalization, removal of cerebellum and brain stem, spatial filtering, thresholding to segment probable WMH, manual editing for correction of false positives and negatives, generation of WMH map, and volumetric estimation of the WMH load. Accuracy was quantitatively evaluated by comparing semi-automated and manual WMH segmentations performed by two independent raters. Differences between the two procedures were assessed using Student's t-tests and similarity was evaluated using linear regression model and Dice similarity coefficient (DSC). The volumes of the manual and semi-automated segmentations did not statistically differ (t-value = -1.79, DF = 29, p = 0.839 for rater 1; t-value = 1.113, DF = 29, p = 0.2749 for rater 2), were highly correlated [R2 = 0.921, F(1,29) = 155.54, p < 0.0001 for rater 1; R2 = 0.935, F(1,29) = 402.709, p < 0.0001 for rater 2] and showed a very strong spatial similarity (mean DSC = 0.78, for rater 1 and 0.77 for rater 2). In conclusion, our semi-automated method to measure the load of WMH is highly reliable and could represent a good tool that could be easily implemented in routinely neuroimaging analyses to map clinical consequences of WMH. © 2013 Iorio, Spalletta, Chiapponi, Luccichenti, Cacciari, Orfei, Caltagirone and Piras.


Storace D.,University of Genoa | Cammarata S.,Galliera Hospital | Borghi R.,University of Genoa | Sanguineti R.,University of Genoa | And 12 more authors.
Archives of Neurology | Year: 2010

Objective: To develop a blood-based test for screening populations at risk for Alzheimer disease. Design: Case-control study. Subjects: A total of 180 patients with mild cognitive impairment (MCI) and 105 age-matched, cognitively normal controls. Interventions: The titer of β-amyloid 1-42 autoantibodies in the plasma was obtained at the time of diagnosis and evaluated by enzyme-linked immunosorbent assay before and after dissociation of the antigenantibody complexes.Atotal of 107 patients with MCI were followed up for 36 months; 70 of the 107 cases progressed to Alzheimer disease. Results: The average level of β-amyloid 1-42 plasma autoantibodies in patients with MCI that progressed to Alzheimer disease, but not that of the stable cases, was significantly higher than in cognitively normal controls (P<.001). Conclusions: The results suggest that the plasma β-amyloid 1-42 autoantibodies parallel β-amyloid 42 deposition in the brain, which is known to precede by several years the clinical onset of Alzheimer disease. The evaluation of β-amyloid 1-42 autoantibodies after dissociation of the complexes is a simple and inexpensive method that can be used to predict the occurrence of Alzheimer disease. ©2010 American Medical Association. All rights reserved.


Simonetti A.,University of Rome La Sapienza | Simonetti A.,Centro Lucio BiniIA | Sani G.,University of Rome La Sapienza | Sani G.,Centro Lucio BiniIA | And 10 more authors.
Bipolar Disorders | Year: 2016

Objectives: Patients diagnosed with bipolar disorder (BP) may experience hippocampal atrophy. Lithium exposure has been associated with increased hippocampal volumes. However, its effects on hippocampal subfields remain to be clarified. Methods: We investigated the effects of short- and long-term lithium exposure on the hippocampus and its subfields in patients affected by bipolar I disorder (BP-I). Hippocampal subfields and total hippocampal volumes were measured in 60 subjects divided into four groups: 15 patients with BP-I who were never exposed to lithium [no-exposure group (NE)], 15 patients with BP-I exposed to lithium for < 24 months [short-exposure group (SE)], 15 patients with BP-I exposed to lithium for > 24 months [long-exposure group (LE)], and 15 healthy control subjects (HC). Results: The SE and NE groups showed smaller total hippocampal volumes and smaller bilateral cornu ammonis CA2-3, CA4-dentate gyrus (DG), presubiculum, and subiculum volumes compared with HC. The LE group showed larger total hippocampal volumes and bilateral CA2-3, left CA4-DG, left presubiculum, and right subiculum volumes compared with the NE group, and larger volumes of the right CA2-3, left CA4-DG, left presubiculum, and right subiculum compared with the SE group. No differences were found between the LE group and HC or between the SE and NE groups. Conclusions: Long-term, but not short-term, exposure to lithium treatment may exert neuroprotective effects on specific hippocampal subfields linked to disease progression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


Phillips O.,Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation | Sanchez-Castaneda C.,Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation | Elifani F.,Center for Neurogenetics and Rare Diseases | Maglione V.,Center for Neurogenetics and Rare Diseases | And 7 more authors.
PLoS ONE | Year: 2013

White matter abnormalities have been shown in presymptomatic and symptomatic Huntington's disease (HD) subjects using Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) methods. The largest white matter tract, the corpus callosum (CC), has been shown to be particularly vulnerable; however, little work has been done to investigate the regional specificity of tract abnormalities in the CC. Thus, this study examined the major callosal tracts by applying DTI-based tractography. Using TrackVis, a previously defined region of interest tractography method parcellating CC into seven major tracts based on target region was applied to 30 direction DTI data collected from 100 subjects: presymptomatic HD (Pre-HD) subjects (n = 25), HD patients (n = 25) and healthy control subjects (n = 50). Tractography results showed decreased fractional anisotropy (FA) and increased radial diffusivity (RD) across broad regions of the CC in Pre-HD subjects. Similar though more severe deficits were seen in HD patients. In Pre-HD and HD, callosal FA and RD were correlated with Disease Burden/CAG repeat length as well as motor (UHDRSI) and cognitive (URDRS2) assessments. These results add evidence that CC pathways are compromised prior to disease onset with possible demyelination occurring early in the disease and suggest that CAG repeat length is a contributing factor to connectivity deficits. Furthermore, disruption of these callosal pathways potentially contributes to the disturbances of motor and cognitive processing that characterize HD. © 2013 Phillips et al.

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