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Find video protocols related to scientific articles indexed in Pubmed.
Widespread alterations in functional brain network architecture in amnestic mild cognitive impairment.
J. Alzheimers Dis.
PUBLISHED: 10-31-2014
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We investigated changes in functional network architecture in amnestic mild cognitive impairment using graph-based analysis of task-free functional magnetic resonance imaging and fine cortical parcellation. Widespread disconnection was observed primarily in cortical hubs known to manifest early Alzheimer's disease pathology, namely precuneus, parietal lobules, supramarginal and angular gyri, and cuneus, with additional involvement of subcortical regions, sensorimotor cortex and insula. The connectivity changes determined using graph-based analysis significantly exceed those detected using independent component analysis both in amplitude and topographical extent, and are largely decoupled from the presence of overt atrophy. This superior ability of graph-based analysis to detect disease-related disconnection highlights its potential use in the determination of biomarkers of early dementia. Graph-based analysis source code is provided as supplementary material.
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The Impact of Cognitive Reserve on Brain Functional Connectivity in Alzheimer's Disease.
J. Alzheimers Dis.
PUBLISHED: 09-10-2014
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One factor believed to impact brain resilience to the pathological damage of Alzheimer's disease (AD) is the so-called "cognitive reserve" (CR). A critical issue that still needs to be fully understood is the mechanism by which environmental enrichment interacts with brain plasticity to determine resilience to AD pathology. Previous work using PET suggests that increased brain connectivity might be at the origin of the compensatory mechanisms implicated in this process. This study aims to further clarify this issue using resting-state functional MRI. Resting-state functional MRI was collected for 11 patients with AD, 18 with mild cognitive impairment (MCI), and 16 healthy controls, and analyzed to isolate the default mode network (DMN). A quantitative score of CR was obtained by combining information about number of years of education and type of schools attended. Consistent with previous reports, education was found to modulate functional connectivity in the posterior cingulate cortex, whose disconnection with the temporal lobes is known to be critical for the conversion from MCI to AD. This effect was highly significant in AD patients, less so in patients with MCI, and absent in healthy subjects. These findings show the potential neural mechanisms underlying the individual's ability to cope with brain damage, although they should be treated with some caution based on small numbers.
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Neuropsychological predictors of conversion from mild cognitive impairment to Alzheimer's disease.
J. Alzheimers Dis.
PUBLISHED: 07-18-2014
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The construct of mild cognitive impairment (MCI) has been proposed to identify patients at risk of developing Alzheimer's disease (AD) in the pre-clinical stage. Although subjects with MCI have an increased risk of progressing to dementia, most remain stable or return to normality. The new criteria for diagnosing prodromal AD assume that, to increase the predictive value of the MCI, in addition to a defect of delayed recall there must also be the presence of abnormal biomarkers, investigating structural and molecular neuroimaging and cerebrospinal fluid (CSF) analysis of amyloid-? or tau proteins. Although acknowledging that the use of CSF degeneration biomarkers is advisable not only for research, but also for clinical purposes, the present review is centered upon the neuropsychological markers of conversion to AD, which are equally clinically important. In particular, results of this review suggest the following: (a) measures of delayed recall are the best neuropsychological predictors of conversion from MCI to AD; (b) memory tests providing controlled encoding and cued recall are not necessarily better predictors than free recall tests; (c) stringent cut-off points are necessary to increase the specificity of these predictors; (d) multi-domain amnestic MCI patients are the best candidates for clinical trials, but not for treatment with disease-modifying drugs; and (e) not only episodic but also semantic memory is significantly impaired in patients who will convert to AD. These data and the underlying neural mechanisms will be discussed, trying to distinguish results obtained in MCI patients from those obtained in a pre-MCI stage of the AD progression.
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Typicality of words produced on a semantic fluency task in amnesic mild cognitive impairment: linguistic analysis and risk of conversion to dementia.
J. Alzheimers Dis.
PUBLISHED: 07-16-2014
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Semantic and, to a lesser extent, phonological verbal fluency tasks are impaired in Alzheimer's disease (AD) and in amnesic mild cognitive impairment (aMCI). Furthermore, both fluency tasks have been considered as possible markers of conversion from aMCI to AD. Up to recent years, the use of fluency tasks has been limited to word count, but, more recently, linguistic variables, such as word frequency, age of acquisition, familiarity, and typicality, have also been considered. In particular, attention has been focused on typicality of words produced on semantic verbal fluency tasks, because the tendency to produce only the more typical members of various categories points to an impoverishment of semantic memory. The aim of our study was to compare in aMCI, AD, and control subjects a lexical (word frequency) and a lexical-semantic variable (item typicality) in a semantic verbal fluency task, and to evaluate the possible value of these variables in predicting conversion from aMCI to AD during a 2 years follow-up period. We found no difference in mean typicality of words produced by aMCI and AD subjects whereas both groups produced words of higher mean typicality than control subjects. Furthermore, to assess the relationship between typicality values and risk of conversion to AD, the aMCI group was split in two subgroups, including subjects who obtained a mean typicality value lower or higher than the median value of the whole aMCI group. Consistent with our hypothesis, conversion to AD was significantly more frequent in high typicality than in low typicality subjects.
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Constructional apraxia as a distinctive cognitive and structural brain feature of pre-senile Alzheimer's disease.
J. Alzheimers Dis.
PUBLISHED: 06-28-2014
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Constructional apraxia (CA) is often, but not always, observed in patients with Alzheimer's disease (AD). CA is usually explained by impairment of either basic perceptual and motor abilities, or executive functions. This study aims to evaluate the structural correlates of CA in AD. Forty-eight patients with AD and 20 healthy age-matched controls underwent a thorough neuropsychological investigation and an MRI scan to collect high-resolution T1-weighted data. Patients were classified as having (ADca) or not having (ADnonca) CA based on performance on the Freehand copying of drawings task. T1-weighted volumes were process according to the voxel based morphometry protocol, to assess the presence of significant differences in local to grey matter volumes in patients compared to controls and in ADca compared to ADnonca. Post-hoc, the mean grey matter volume of clusters that resulted significantly different between groups was regressed against the neuropsychological scores in which the two patient groups performed differently. A pre-senile disease onset was significantly more frequent in patients with CA compared to ADnonca. ADca patients also showed worse performances than patients with ADnonca at some tests requiring the processing of visuo-spatial data and testing working memory. They also showed widespread reductions in grey matter volume, mainly located in areas known to be implicated in object recognition and localization, and in maintenance and re-orienting of spatial attention. These findings suggest that the occurrence of CA in AD is often associated with a peculiar clinical onset (i.e., pre-senile), neuropsychological profile, and distribution of grey matter atrophy.
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A systems medicine clinical platform for understanding and managing non- communicable diseases.
Curr. Pharm. Des.
PUBLISHED: 03-12-2014
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Non-Communicable Diseases (NCDs) are among the most pressing global health problems of the twenty-first century. Their rising incidence and prevalence is linked to severe morbidity and mortality, and they are putting economic and managerial pressure on healthcare systems around the world. Moreover, NCDs are impeding healthy aging by negatively affecting the quality of life of a growing number of the global population. NCDs result from the interaction of various genetic, environmental and habitual factors, and cluster in complex ways, making the complex identification of resulting phenotypes not only difficult, but also a top research priority. The degree of complexity required to interpret large patient datasets generated by advanced high-throughput functional genomics assays has now increased to the point that novel computational biology approaches are essential to extract information that is relevant to the clinical decision-making process. Consequently, system-level models that interpret the interactions between extensive tissues, cellular and molecular measurements and clinical features are also being created to identify new disease phenotypes, so that disease definition and treatment are optimized, and novel therapeutic targets discovered. Likewise, Systems Medicine (SM) platforms applied to extensively-characterized patients provide a basis for more targeted clinical trials, and represent a promising tool to achieve better prevention and patient care, thereby promoting healthy aging globally. The present paper: (1) reviews the novel systems approaches to NCDs; (2) discusses how to move efficiently from Systems Biology to Systems Medicine; and (3) presents the scientific and clinical background of the San Raffaele Systems Medicine Platform.
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Rivastigmine for refractory REM behavior disorder in mild cognitive impairment.
Curr Alzheimer Res
PUBLISHED: 03-07-2014
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Mild Cognitive Impairment (MCI) and REM Behavior Disorder (RBD) are both associated with a degeneration of ponto-medullary cholinergic pathways.
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Human brain networks in cognitive decline: a graph theoretical analysis of cortical connectivity from EEG data.
J. Alzheimers Dis.
PUBLISHED: 03-01-2014
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The aim of this study was to investigate the neuronal network characteristics in physiological and pathological brain aging. A database of 378 participants divided in three groups was analyzed: Alzheimer's disease (AD), mild cognitive impairment (MCI), and normal elderly (Nold) subjects. Through EEG recordings, cortical sources were evaluated by sLORETA software, while graph theory parameters (Characteristic Path Length ?, Clustering coefficient ?, and small-world network ?) were computed to the undirected and weighted networks, obtained by the lagged linear coherence evaluated by eLORETA software. EEG cortical sources from spectral analysis showed significant differences in delta, theta, and alpha 1 bands. Furthermore, the analysis of eLORETA cortical connectivity suggested that for the normalized Characteristic Path Length (?) the pattern differences between normal cognition and dementia were observed in the theta band (MCI subjects are find similar to healthy subjects), while for the normalized Clustering coefficient (?) a significant increment was found for AD group in delta, theta, and alpha 1 bands; finally, the small world (?) parameter presented a significant interaction between AD and MCI groups showing a theta increase in MCI. The fact that AD patients respect the MCI subjects were significantly impaired in theta but not in alpha bands connectivity are in line with the hypothesis of an intermediate status of MCI between normal condition and overt dementia.
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Multisite longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging of healthy elderly subjects.
Neuroimage
PUBLISHED: 02-19-2014
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Large-scale longitudinal neuroimaging studies with diffusion imaging techniques are necessary to test and validate models of white matter neurophysiological processes that change in time, both in healthy and diseased brains. The predictive power of such longitudinal models will always be limited by the reproducibility of repeated measures acquired during different sessions. At present, there is limited quantitative knowledge about the across-session reproducibility of standard diffusion metrics in 3T multi-centric studies on subjects in stable conditions, in particular when using tract based spatial statistics and with elderly people. In this study we implemented a multi-site brain diffusion protocol in 10 clinical 3T MRI sites distributed across 4 countries in Europe (Italy, Germany, France and Greece) using vendor provided sequences from Siemens (Allegra, Trio Tim, Verio, Skyra, Biograph mMR), Philips (Achieva) and GE (HDxt) scanners. We acquired DTI data (2 × 2 × 2 mm(3), b = 700 s/mm(2), 5 b0 and 30 diffusion weighted volumes) of a group of healthy stable elderly subjects (5 subjects per site) in two separate sessions at least a week apart. For each subject and session four scalar diffusion metrics were considered: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial (AD) diffusivity. The diffusion metrics from multiple subjects and sessions at each site were aligned to their common white matter skeleton using tract-based spatial statistics. The reproducibility at each MRI site was examined by looking at group averages of absolute changes relative to the mean (%) on various parameters: i) reproducibility of the signal-to-noise ratio (SNR) of the b0 images in centrum semiovale, ii) full brain test-retest differences of the diffusion metric maps on the white matter skeleton, iii) reproducibility of the diffusion metrics on atlas-based white matter ROIs on the white matter skeleton. Despite the differences of MRI scanner configurations across sites (vendors, models, RF coils and acquisition sequences) we found good and consistent test-retest reproducibility. White matter b0 SNR reproducibility was on average 7 ± 1% with no significant MRI site effects. Whole brain analysis resulted in no significant test-retest differences at any of the sites with any of the DTI metrics. The atlas-based ROI analysis showed that the mean reproducibility errors largely remained in the 2-4% range for FA and AD and 2-6% for MD and RD, averaged across ROIs. Our results show reproducibility values comparable to those reported in studies using a smaller number of MRI scanners, slightly different DTI protocols and mostly younger populations. We therefore show that the acquisition and analysis protocols used are appropriate for multi-site experimental scenarios.
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Does Semantic Memory Impairment in Amnestic MCI with Hippocampal Atrophy Conform to a Distinctive Pattern of Progression?
Curr Alzheimer Res
PUBLISHED: 02-05-2014
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Subjects with Mild Cognitive Impairment (MCI) are normally classified according to the presence of episodic memory deficits associated or not to disturbances of other cognitive domains. The present study had two aims: to identify discrete subtypes of amnestic MCI (a-MCI) with hippocampal atrophy; and to assess if the identified subtypes show different rates of progression to dementia. Sixty-seven a-MCI subjects were enrolled, all showing significant hippocampal atrophy on MRI. The subjects underwent at baseline and at follow-up a comprehensive neuropsychological examination, and were followed-up for five years to detect the conversion to dementia. An exploratory factor analysis on neuropsychological performances at baseline identified three main factors that were subsequently used to perform a k-means cluster analysis. Three cluster of a-MCI subjects were identified: "pure amnestic" (N=29), "multiple domain"(N=16), and "amnestic/semantic"(N=22). The successive discriminant functions were able to correctly classify 88% of the subjects. During the follow-up, 33 subjects converted to dementia (49.2%), 14 "pure amnestic" (48.3%), 11 "multiple domain" (68.5%) and 8 "amnestic/semantic" (36.4%; log-rank: p=0.016); median survival was respectively 36, 22, and 39 months. On Cox proportional hazard model, baseline MMSE (HR=0,709; p=0.006), education (HR=1,115; p=0.011) and belonging to the "multiple domain" subgroup (HR=2,706; p=0.013) were significantly associated to higher rate of conversion to dementia. Our findings confirm the tendency to worst outcome of subjects with multiple domain MCI, and show that the association of episodic and semantic memory deficits, without other cognitive disturbances, could identify a specific cognitive pattern associated to slower cognitive decline, as previously reported in Alzheimer's Disease.
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Asymmetries in gender-related familiarity with different semantic categories. Data from normal adults.
Behav Neurol
PUBLISHED: 10-22-2013
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The mechanisms subsuming the brain organization of categories and the corresponding gender related asymmetries are controversial. Some authors believe that the brain organization of categories is innate, whereas other authors maintain that it is shaped by experience. According to these interpretations, gender-related asymmetries should respectively be inborn or result from the influence of social roles. In a previous study, assessing the familiarity of young students with different biological and artefact categories, we had observed no gender-related difference on any of these categories. Since these data could be due to the fact that our students belonged to a generation in which the traditional social roles have almost completely disappeared, we predicted that gender-related asymmetries should be found in older men and women. The familiarity of young and elderly men and women with various semantic categories was, therefore, studied presenting in the verbal and pictorial modality different kinds of living and artefact categories. Results confirmed the hypothesis, because elderly women showed a greater familiarity for flowers and elderly men for animals. These findings are consistent with the hypothesis assuming that gender-related asymmetries for different semantic categories is due to the influence of gender-related social roles.
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The evaluation of sources of knowledge underlying different conceptual categories.
Front Hum Neurosci
PUBLISHED: 02-03-2013
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According to the "embodied cognition" theory and the "sensory-motor model of semantic knowledge": (a) concepts are represented in the brain in the same format in which they are constructed by the sensory-motor system and (b) various conceptual categories differ according to the weight of different kinds of information in their representation. In this study, we tried to check the second assumption by asking normal elderly subjects to subjectively evaluate the role of various perceptual, motor and language-mediated sources of knowledge in the construction of different semantic categories. Our first aim was to rate the influence of different sources of knowledge in the representation of animals, plant life and artifact categories, rather than in living and non-living beings, as many previous studies on this subject have done. We also tried to check the influence of age and stimulus modality on these evaluations of the "sources of knowledge" underlying different conceptual categories. The influence of age was checked by comparing results obtained in our group of elderly subjects with those obtained in a previous study, conducted with a similar methodology on a sample of young students. And the influence of stimulus modality was assessed by presenting the stimuli in the verbal modality to 50 subjects and in the pictorial modality to 50 other subjects. The distinction between "animals" and "plant life" in the "living" categories was confirmed by analyzing their prevalent sources of knowledge and by a cluster analysis, which allowed us to distinguish "plant life" items from animals. Furthermore, results of the study showed: (a) that our subjects considered the visual modality as the main source of knowledge for all categories taken into account; and (b) that in biological categories the next most important source of information was represented by other perceptual modalities, whereas in artifacts it was represented by the actions performed with them. Finally, age and stimulus modality did not significantly influence judgment of relevance of the sources of knowledge involved in the construction of different conceptual categories.
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Probable Alzheimers disease patients presenting as "focal temporal lobe dysfunction" show a slow rate of cognitive decline.
J Int Neuropsychol Soc
PUBLISHED: 11-24-2011
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Several authors have recently shown that anterograde amnesia is often associated with semantic memory impairment in amnesic MCI patients. Similarly, after the MCI condition, some patients who convert to Alzheimers disease (AD) show the classic onset (cAD) characterized by the impairment of memory and executive functions, whereas other AD patients show isolated defects of episodic and semantic memory without deficits in other cognitive domains. The latter have been considered an AD variant characterized by focal Temporal Lobe Dysfunction (TLD). The aim of the present study was to assess the differences in disease progression between cAD and TLD. For this purpose a continuous series of newly diagnosed probable AD patients presenting as cAD (n = 30) and TLD (n = 25), matched for severity, and 65 healthy controls underwent a comprehensive neuropsychological evaluation at baseline; TLD and cAD were re-evaluated at a 24-month follow-up. At follow-up, TLD patients showed no significant worsening of cognitive functions, whereas cAD subjects displayed a significant worsening in all explored cognitive domains. In conclusion, our results confirm that probable AD presenting as TLD represents a specific onset of AD characterized by a slower rate of progression.
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Early evaluation of cerebral metabolic rate of glucose (CMRglu) with 18F-FDG PET/CT and clinical assessment in idiopathic normal pressure hydrocephalus (INPH) patients before and after ventricular shunt placement: preliminary experience.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 07-29-2011
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We evaluated the relationships between the cerebral metabolic rate of glucose (CMRglu) measured by dynamic (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and the clinical and neuropsychological assessment before and after the surgical procedure in idiopathic normal pressure hydrocephalus (INPH) patients.
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Central cholinergic dysfunction measured "in vivo" correlates with different behavioral disorders in Alzheimers disease and dementia with Lewy body.
Brain Stimul
PUBLISHED: 04-12-2011
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Cholinergic deficits have been largely correlated to behavioral disorders in dementia. However, cholinergic deficits are not homogeneous and they are distributed differently in the basal forebrain and brainstem among Alzheimers disease (AD) and dementia with Lewy bodies (DLB). The different cholinergic networks involved suggest different patterns of behavior symptomatology in the two groups.
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Differential contribution of right and left temporo-occipital and anterior temporal lesions to face recognition disorders.
Front Hum Neurosci
PUBLISHED: 04-06-2011
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In the study of prosopagnosia, several issues (such as the specific or non-specific manifestations of prosopagnosia, the unitary or non-unitary nature of this syndrome and the mechanisms underlying face recognition disorders) are still controversial. Two main sources of variance partially accounting for these controversies could be the qualitative differences between the face recognition disorders observed in patients with prevalent lesions of the right or left hemisphere and in those with lesions encroaching upon the temporo-occipital (TO) or the (right) anterior temporal cortex. Results of our review seem to confirm these suggestions. Indeed, they show that (a) the most specific forms of prosopagnosia are due to lesions of a right posterior network including the occipital face area and the fusiform face area, whereas (b) the face identification defects observed in patients with left TO lesions seem due to a semantic defect impeding access to person-specific semantic information from the visual modality. Furthermore, face recognition defects resulting from right anterior temporal lesions can usually be considered as part of a multimodal people recognition disorder. The implications of our review are, therefore, the following: (1) to consider the components of visual agnosia often observed in prosopagnosic patients with bilateral TO lesions as part of a semantic defect, resulting from left-sided lesions (and not from prosopagnosia proper); (2) to systematically investigate voice recognition disorders in patients with right anterior temporal lesions to determine whether the face recognition defect should be considered a form of "associative prosopagnosia" or a form of the "multimodal people recognition disorder."
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Quantitative magnetization transfer provides information complementary to grey matter atrophy in Alzheimers disease brains.
Neuroimage
PUBLISHED: 03-28-2011
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Preliminary studies, based on a region-of-interest approach, suggest that quantitative magnetization transfer (qMT), an extension of magnetization transfer imaging, provides complementary information to conventional magnetic resonance imaging (MRI) in the characterisation of Alzheimers disease (AD). The aim of this study was to extend these findings to the whole brain, using a voxel-wise approach. We recruited 19AD patients and 11 healthy subjects (HS). All subjects had an MRI acquisition at 3.0T including a T(1)-weighted volume, 12 MT-weighted volumes for qMT, and data for computing T(1) and B(1) maps. The T(1)-weighted volumes were processed to yield grey matter (GM) volumetric maps, while the other sequences were used to compute qMT parametric maps of the whole brain. qMT maps were warped to standard space and smoothed, and subsequently compared between groups. Of all the qMT parameters considered, only the forward exchange rate, RM(0)(B), showed significant group differences. These images were therefore retained for the multimodal statistical analysis, designed to locate brain regions of RM(0)(B) differences between AD and HS groups, adjusting for local GM atrophy. Widespread areas of reduced RM(0)(B) were found in AD patients, mainly located in the hippocampus, in the temporal lobe, in the posterior cingulate and in the parietal cortex. These results indicate that, among qMT parameters, RM(0)(B) is the most sensitive to AD pathology. This quantity is altered in the hippocampus of patients with AD (as found by previous works) but also in other brain areas, that PET studies have highlighted as involved with both, reduced glucose metabolism and amyloid ? deposition. RM(0)(B) might reflect, through the measurement of the efficiency of MT exchange, some information with a specific pathological counterpart. Given previous evidence of a strict relationship between RM(0)(B) and intracellular pH, an intriguing speculation is that our findings might reflect metabolic changes related to mitochondrial dysfunction, which has been proposed as a contributor to neurodegeneration in AD.
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Position paper of the Italian Society for the study of Dementias (SINDEM) on the proposal of a new lexicon on Alzheimer disease.
Neurol. Sci.
PUBLISHED: 01-15-2011
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A panel of Italian neurologists of the Italian Society for the study of Dementias (SINDEM) discussed the recently proposed new lexicon for Alzheimer disease (AD) and the related diagnostic criteria for the different phases of the disease (Preclinical AD, prodromal AD and Alzheimers dementia) (Dubois et al. in Lancet Neurol 6:734-746, 2007; in Lancet Neurol 9:1118-1127, 2010). The aim of this discussion was to reach a consensus, among the Italian neurologists involved in the study and care of persons with dementia, in particular in reference to the potential use of the proposed diagnostic criteria in clinical practice. After having critically revised the scientific evidence related to the new lexicon and to the new proposed diagnostic criteria, the panel concluded that the proposed new diagnostic criteria and the new proposed lexicon for AD are conceptually attractive. However, the evidence about the instrumental and laboratory markers for the diagnosis of the preclinical and asymptomatic states of the disease are, until to now, insufficient to support the routine clinical use of these investigations.
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Damage to the cingulum contributes to Alzheimers disease pathophysiology by deafferentation mechanism.
Hum Brain Mapp
PUBLISHED: 01-05-2011
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This study investigates the differential contribution of gray matter (GM) atrophy and deafferentation through white matter (WM) damage in the clinical progression of Alzheimers disease (AD). Thirty-one patients with probable AD, 23 with amnestic mild cognitive impairment (a-MCI), and 14 healthy subjects underwent MRI scanning at 3T. Voxel-based morphometry was used to assess regional GM atrophy in AD and a-MCI patients. Diffusion tensor-MRI tractography was used to reconstruct the cingulum bilaterally, and to quantify, voxel-by-voxel, its fractional anisotropy (FA) and mean diffusivity (MD) (measures of microscopic WM integrity). Atrophy of the cinguli was also assessed by means of jacobian determinants (JD) of local transformations. In AD patients, four clusters of reduced GM were found nearby the cinguli, in the posterior (PCC) and anterior cingulate cortex, and in the hippocampal/parahippocampal areas. Widespread areas of reduced FA and increased MD were found in the cinguli of both, AD and a-MCI patients. A region of macroscopic atrophy was detectable in AD patients only. Strong associations were found between local GM densities in the four identified clusters, and measures of micro- and (to a lesser extent) macroscopic damage of patients cinguli. Linear regression analyses revealed that MD in the cinguli predicts patients measures of episodic memory in combination with GM density of hippocampal/parahippocampal areas, and measures of global cognition in combination with GM density of the PCC. This study indicates that brain deafferentation though the cingulum is likely to play a remarkable role in progressive development of cognitive impairment in AD.
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Neuroanatomical correlates of cognitive reserve in Alzheimer disease.
Rejuvenation Res
PUBLISHED: 01-04-2011
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Cognitive reserve (CR), for which formal education represents a proxy index, has been claimed as a factor mitigating the clinical manifestations of Alzheimer disease (AD). The aim of this study was to assess the impact of formal education in modifying the relationship between cerebral grey matter (GM) damage and clinical manifestations in a large cohort of patients with AD or amnesic mild cognitive impairment (a-MCI). We recruited 22 patients with AD and 23 with a-MCI, and we classified them in subjects with high (HEL) or low educational level (LEL). All patients underwent a neuropsychological assessment and magnetic resonance imaging (MRI) scanning at 3T. T1-weighted volumes were analyzed, using voxel-based morphometry, for GM investigation. A 1-year clinical follow-up was available for part of the a-MCI patients. There were no between-groups differences in clinical features, memory, and language functions. Conversely, HEL subjects performed better in all tests assessing visuo-spatial abilities. GM volumes of LEL compared with HEL patients were reduced in the supramarginal gyrus bilaterally and in the right posterior cingulate/precuneus and frontal opercular cortex. Conversely, HEL compared with LEL patients showed reduced GM volumes in the entorhinal cortices and temporal poles, regions typically affected by AD pathology. These results remained unchanged when including in the analysis of only patients with clinically proven AD (AD and a-MCI converters). This study suggests that CR produces selective GM changes that mitigate the clinical impact of AD. Moreover, it supports the idea that CR is based on several "brain reserves" rather than on a generalized increase of brain plasticity.
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Mental representation of normal subjects about the sources of knowledge in different semantic categories and unique entities.
Neuropsychology
PUBLISHED: 11-11-2009
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According to the "sensory-motor model of semantic knowledge," different categories of knowledge differ for the weight that different "sources of knowledge" have in their representation. Our study aimed to evaluate this model, checking if subjective evaluations given by normal subjects confirm the different weight that various sources of knowledge have in the representation of different biological and artifact categories and of unique entities, such as famous people or monuments. Results showed that the visual properties are considered as the main source of knowledge for all the living and nonliving categories (as well as for unique entities), but that the clustering of these "sources of knowledge" is different for biological and artifacts categories. Visual data are, indeed, mainly associated with other perceptual (auditory, olfactory, gustatory, and tactual) attributes in the mental representation of living beings and unique entities, whereas they are associated with action-related properties and tactile information in the case of artifacts.
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Determinants of cognitive impairment in elderly myasthenia gravis patients.
Muscle Nerve
PUBLISHED: 09-22-2009
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The relationship between myasthenia gravis (MG) and cognitive dysfunction has been a matter of debate because of the possible association between peripheral and central nervous system (CNS) cholinergic dysfunction. The aim of this study was to evaluate cognitive function in a series of elderly MG patients in comparison to matched controls. In all, 100 consecutive MG patients aged over 60 years and 31 matched control subjects underwent an extensive neuropsychological test battery to explore multiple cognitive domains. There were no differences in cognitive performances between patients and controls. Severe MG was associated with impaired attention, constructional praxis, and frontal control. Logistic regression analysis showed that advanced age, diabetes, and thyroid dysfunction were independently associated with cognitive impairment. This study does not support the hypothesis of CNS cholinergic involvement in MG. The impairments of attention, memory, and control tasks in MG are related to general visual motor slowness and to the concomitant presence of other diseases.
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The relation between person identity nodes, familiarity judgment and biographical information. Evidence from two patients with right and left anterior temporal atrophy.
Brain Res.
PUBLISHED: 05-20-2009
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The aim of this study consisted of using neuropsychological data obtained in two patients (VL and StG) showing a selective atrophy of the anterior parts of the right (VL) and left (StG) temporal lobes to check current cognitive models of familiar people identification. According to these models, information coming from modality-specific "face", "voice" and "name" recognition units converge into "Person Identity Nodes" (PINs) where familiarity feelings are generated and which provide a modality-free gateway to a unitary semantic system, where information about people is stored in an amodal format. Data obtained in patient VL (and to a lesser degree in StG) were at variance with this model because VL showed: (1) a very impaired familiarity for faces, contrasting with a spared familiarity for names, indicating that familiarity judgments are generated at the level of modality-specific recognition units and not at a supramodal PIN; (2) a prevalent impairment of person-specific information available from faces rather than from names also for people that (being recognized as familiar from both their face and their name) should be normally represented at the PINs level. This last finding is at variance with the hypothesis assuming that the PINs may provide a modality-free gateway to a unitary semantic system, where information about people is stored in an amodal format.
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A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimers disease.
Aging Clin Exp Res
PUBLISHED: 05-19-2009
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Epidemiological studies have examined the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Alzheimers disease (AD). Recently, a variety of experimental studies indicates that a subset of NSAIDs, such as ibuprofen or flurbiprofen, also have Abeta-lowering properties in both AD transgenic mice and cell cultures of peripheral, glial and neuronal origin. In this trial, we evaluated whether the non-selective NSAID ibuprofen slows disease progression in patients with mild to moderate AD.
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Successful treatment of acute autoimmune limbic encephalitis with negative VGKC and NMDAR antibodies.
Cogn Behav Neurol
PUBLISHED: 04-18-2009
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To describe a case of acute nonherpetic limbic encephalitis (LE) with negative testing for antibodies directed against onconeuronal and cell membrane antigens, including voltage-gated potassium channels and N-methyl-D-aspartate receptor, that showed a dramatic response to immune therapy.
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Performing prototype distortion tasks requires no contribution from the explicit memory systems: evidence from amnesic MCI patients in a new experimental paradigm.
Neuropsychologia
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Evidence shows that amnesic patients are able to categorize new exemplars drawn from the same prototype as in previously encountered items. It is still unclear, however, whether this ability is due to a spared implicit learning system or residual explicit memory and/or working memory resources. In this study, we used a new paradigm devised expressly to rule out any possible contribution of episodic and working memory in performing a prototype distortion task. We enrolled patients with amnesic MCI and Normal Controls. Our paradigm consisted of a study phase and a test phase; two-thirds of the participants performed the study phase and all participants performed the test phase. In the study phase, participants had to judge how pleasant morphed faces, drawn from a single prototype, seemed to them. Half of the participants were shown faces drawn from the A-prototype and half from the B-prototype. A- and B-faces were opposite in a morphing space with a neutral human face at the center. In the test phase, participants had to judge the regularity of faces they had never seen before. Three different types of faces were shown in the test phase, that is, A-, B-, or neutral-faces. We expected that implicit learning of the category boundaries would lead to a category-specific increase in perceived regularity. The results confirmed our predictions. In fact, trained subjects (compared with subjects who did not undergo the study phase) assigned higher regularity scores to new faces drawn from the same prototype as the faces seen during training, and they gave lower regularity scores to new faces drawn from the opposite prototype. This effect was super imposable across subjects groups.
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Different apathy profile in behavioral variant of frontotemporal dementia and Alzheimers disease: a preliminary investigation.
Curr Gerontol Geriatr Res
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Apathy is one of the most common behavioral symptoms of dementia; it is one of the salient features of behavioral variant of frontotemporal dementia (bvFTD) but is also very frequent in Alzheimers disease. This preliminary investigation was aimed at assessing the type of apathy-related symptoms in a population of bvFTD and AD subjects showing comparable apathy severity. Each patient underwent a comprehensive neuropsychological assessment; behavioral changes were investigated by the neuropsychiatric inventory (NPI), using the NPI-apathy subscale to detect apathetic symptoms. At univariate analysis, bvFTD subjects showed lack of initiation (?(2) = 4.602, p = 0.032), reduced emotional output (?(2) = 6.493, p = 0.008), and reduced interest toward friends and family members (?(2) = 4.898, p = 0.027), more frequently than AD subjects. BvFTD displayed higher scores than AD on NPI total score (p = 0.005) and on subscales assessing agitation (p = 0.004), disinhibition (p = 0.007) and sleep disturbances (p = 0.025); conversely, AD subjects were more impaired on memory, constructional abilities, and attention. On multivariate logistic regression, reduced emotional output was highly predictive of bvFTD (OR = 18.266; p = 0.008). Our preliminary findings support the hypothesis that apathy is a complex phenomenon, whose clinical expression is conditioned by the site of anatomical damage. Furthermore, apathy profile may help in differentiating bvFTD from AD.
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Post-stroke depression: Main phenomenological clusters and their relationships with clinical measures.
Behav Neurol
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To investigate the principal psychopathological dimensions of post-stroke depression (PSD) through the assessment of the factorial structure of the Post-Stroke Depression Rating Scale (PSDRS).
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Brain tissue modifications induced by cholinergic therapy in Alzheimers disease.
Hum Brain Mapp
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A previous preliminary investigation based on a novel MRI approach to map anatomical connectivity revealed areas of increased connectivity in Alzheimers disease (AD) but not in mild cognitive impairment patients. This prompted the hypothesis tested here, that these areas might reflect phenomena of brain plasticity driven by acetylcholinesterase inhibitors (AChEIs). Thirty-eight patients with probable AD (19 under medication with AChEIs and 19 drug-naïve) were recruited together with 11 healthy controls. All subjects had MRI scanning at 3T, including volumetric and diffusion-weighted scans. Probabilistic tractography was used to initiate streamlines from all parenchymal voxels, and anatomical connectivity maps (ACMs) were obtained by counting, among the total number of streamlines initiated, the fraction passing through each brain voxel. After normalization into standard space, ACMs were used to test for between-group comparisons, and for interactions between the exposure to AChEIs and global level of cognition. Patients with AD had reduced ACM values in the fornix, cingulum, and supramarginal gyri. The ACM value was strongly associated with the AChEI dosage-x-duration product in the anterior limb (non-motor pathway) of the internal capsule. Tractography from this region identified the anterior thalamic radiation as the main white matter (WM) tract passing through it. The reduced connectivity in WM bundles connecting the hippocampi with the rest of the brain (fornix/cingulum) suggests a possible mechanism for the spread of AD pathology. An intriguing explanation for the interaction between AChEIs and ACM is related to the mechanisms of brain plasticity, partially driven by neurotrophic properties of acetylcholine replacement.
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Presentation and validation of the multiple sclerosis depression rating scale: a test specifically devised to investigate affective disorders in multiple sclerosis patients.
Clin Neuropsychol
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Accurate diagnosis of depression in patients affected by MS is important, as it may be a cause of reduced quality of life and increased suicide risk. We present a new scale, the Multiple Sclerosis Depression Rating Scale (MSDRS), and assess its diagnostic accuracy in comparison to the Beck Depression Inventory (BDI). A total of 94 MS participants were classified as non-depressed (N = 44) or affected by mood disorder associated to MS with depressive manifestations (MSD-MDDM; N = 37) or with a major depression-like episode (MSD-MDL; N = 13). Each participant underwent a psychiatric interview, MSDRS, and BDI; diagnostic accuracy was evaluated using area under the ROC curve (AROC). The diagnostic accuracy of MSDRS and BDI was comparable when diagnosing both MSD-MDDM and MSD-MDL (AROC respectively 0.8998 and 0.8659); the MSDRS showed higher accuracy for the diagnosis of MSD-MDL (AROC respectively 0.9278 and 0.8314; p = .038). The MSDRS may be a reliable tool for the diagnosis of depression in MS.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.