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Sample records for disease neuroimaging initiative

  1. The informatics core of the Alzheimer's Disease Neuroimaging Initiative

    PubMed Central

    Toga, Arthur W.; Crawford, Karen L.

    2010-01-01

    The Alzheimer's Diseases Neuroimaging Initiative project has brought together geographically distributed investigators, each collecting data on the progression of Alzheimer's disease. The quantity and diversity of the imaging, clinical, cognitive, biochemical, and genetic data acquired and generated throughout the study necessitated sophisticated informatics systems to organize, manage, and disseminate data and results. We describe, here, a successful and comprehensive system that provides powerful mechanisms for processing, integrating, and disseminating these data not only to support the research needs of the investigators who make up the Alzheimer's Diseases Neuroimaging Initiative cores, but also to provide widespread data access to the greater scientific community for the study of Alzheimer's Disease. PMID:20451873

  2. The Worldwide Alzheimer's Disease Neuroimaging Initiative: An update.

    PubMed

    Hendrix, James A; Finger, Brad; Weiner, Michael W; Frisoni, Giovanni B; Iwatsubo, Takeshi; Rowe, Christopher C; Kim, Seong Yoon; Guinjoan, Salvador M; Sevlever, Gustavo; Carrillo, Maria C

    2015-07-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI), launched in 2004, has worked to accelerate drug development by validating imaging and blood/cerebrospinal fluid biomarkers for Alzheimer's disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public-private partnership, the initiative has set a new standard for data sharing without embargo and for the use of biomarkers in dementia research. The ADNI effort in North America is not the only such effort in the world. The Alzheimer's Association recognized these global efforts and formed Worldwide ADNI (WW-ADNI). By creating a platform for international collaboration and cooperation, WW-ADNI's goals are to harmonize projects and results across geographical regions and to facilitate data management and availability to investigators around the world. WW-ADNI projects include those based in North America, Europe, Japan, Australia, Korea, and Argentina. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  3. Alzheimer's Disease Neuroimaging Initiative 2 Clinical Core: Progress and plans.

    PubMed

    Aisen, Paul S; Petersen, Ronald C; Donohue, Michael; Weiner, Michael W

    2015-07-01

    This article reviews the current status of the Clinical Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI), and summarizes planning for the next stage of the project. Clinical Core activities and plans were synthesized based on discussions among the Core leaders and external advisors. The longitudinal data in ADNI-2 provide natural history data on a clinical trials population and continue to inform refinement and standardization of assessments, models of trajectories, and clinical trial methods that have been extended into sporadic preclinical Alzheimer's disease (AD). Plans for the next phase of the ADNI project include maintaining longitudinal follow-up of the normal and mild cognitive impairment cohorts, augmenting specific clinical cohorts, and incorporating novel computerized cognitive assessments and patient-reported outcomes. A major hypothesis is that AD represents a gradually progressive disease that can be identified precisely in its long presymptomatic phase, during which intervention with potentially disease-modifying agents may be most useful. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  4. The Alzheimer's Disease Neuroimaging Initiative (ADNI): MRI Methods

    PubMed Central

    Jack, Clifford R.; Bernstein, Matt A.; Fox, Nick C.; Thompson, Paul; Alexander, Gene; Harvey, Danielle; Borowski, Bret; Britson, Paula J.; Whitwell, Jennifer L.; Ward, Chadwick; Dale, Anders M.; Felmlee, Joel P.; Gunter, Jeffrey L.; Hill, Derek L.G.; Killiany, Ron; Schuff, Norbert; Fox-Bosetti, Sabrina; Lin, Chen; Studholme, Colin; DeCarli, Charles S.; Krueger, Gunnar; Ward, Heidi A.; Metzger, Gregory J.; Scott, Katherine T.; Mallozzi, Richard; Blezek, Daniel; Levy, Joshua; Debbins, Josef P.; Fleisher, Adam S.; Albert, Marilyn; Green, Robert; Bartzokis, George; Glover, Gary; Mugler, John; Weiner, Michael W.

    2008-01-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal multisite observational study of healthy elders, mild cognitive impairment (MCI), and Alzheimer's disease. Magnetic resonance imaging (MRI), (18F)-fluorode-oxyglucose positron emission tomography (FDG PET), urine serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical/psychometric assessments are acquiredat multiple time points. All data will be cross-linked and made available to the general scientific community. The purpose of this report is to describe the MRI methods employed in ADNI. The ADNI MRI core established specifications thatguided protocol development. A major effort was devoted toevaluating 3D T1-weighted sequences for morphometric analyses. Several options for this sequence were optimized for the relevant manufacturer platforms and then compared in a reduced-scale clinical trial. The protocol selected for the ADNI study includes: back-to-back 3D magnetization prepared rapid gradient echo (MP-RAGE) scans; B1-calibration scans when applicable; and an axial proton density-T2 dual contrast (i.e., echo) fast spin echo/turbo spin echo (FSE/TSE) for pathology detection. ADNI MRI methods seek to maximize scientific utility while minimizing the burden placed on participants. The approach taken in ADNI to standardization across sites and platforms of the MRI protocol, postacquisition corrections, and phantom-based monitoring of all scanners could be used as a model for other multisite trials. PMID:18302232

  5. The Alzheimer's Disease Neuroimaging Initiative positron emission tomography core.

    PubMed

    Jagust, William J; Bandy, Dan; Chen, Kewei; Foster, Norman L; Landau, Susan M; Mathis, Chester A; Price, Julie C; Reiman, Eric M; Skovronsky, Daniel; Koeppe, Robert A

    2010-05-01

    This is a progress report of the Alzheimer's Disease Neuroimaging Initiative (ADNI) positron emission tomography (PET) Core. The Core has supervised the acquisition, quality control, and analysis of longitudinal [(18)F]fluorodeoxyglucose PET (FDG-PET) data in approximately half of the ADNI cohort. In an "add on" study, approximately 100 subjects also underwent scanning with [(11)C] Pittsburgh compound B PET for amyloid imaging. The Core developed quality control procedures and standardized image acquisition by developing an imaging protocol that has been widely adopted in academic and pharmaceutical industry studies. Data processing provides users with scans that have identical orientation and resolution characteristics despite acquisition on multiple scanner models. The Core labs have used many different approaches to characterize differences between subject groups (Alzheimer's disease, mild cognitive impairment, controls), to examine longitudinal change over time in glucose metabolism and amyloid deposition, and to assess the use of FDG-PET as a potential outcome measure in clinical trials. ADNI data indicate that FDG-PET increases statistical power over traditional cognitive measures, might aid subject selection, and could substantially reduce the sample size in a clinical trial. Pittsburgh compound B PET data showed expected group differences, and identified subjects with significant annual increases in amyloid load across the subject groups. The next activities of the PET core in ADNI will entail developing standardized protocols for amyloid imaging using the [(18)F]-labeled amyloid imaging agent AV45, which can be delivered to virtually all ADNI sites. ADNI has demonstrated the feasibility and utility of multicenter PET studies and is helping to clarify the role of biomarkers in the study of aging and dementia. Copyright 2010 The Alzheimer

  6. The Alzheimer’s Disease Neuroimaging Initiative Informatics Core: A Decade in Review

    PubMed Central

    Toga, Arthur W.; Crawford, Karen L.

    2015-01-01

    The Informatics Core of the Alzheimer’s Diseases Neuroimaging Initiative (ADNI) has coordinated data integration and dissemination for a continually growing and complex dataset in which both data contributors and recipients span institutions, scientific disciplines and geographic boundaries. This article provides an update on the accomplishments and future plans. PMID:26194316

  7. The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

    SciTech Connect

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Morris, John C.; Petersen, Ronald C.; Salazar, Jennifer; Saykin, Andrew J.; Shaw, Leslie M.; Toga, Arthur W.; Trojanowski, John Q.

    2016-12-05

    Overall, the goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition. Multimodal analyses will provide insight into AD pathophysiology and disease progression. Finally, ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments.

  8. The Alzheimer's disease neuroimaging initiative: perspectives of the Industry Scientific Advisory Board.

    PubMed

    Schmidt, Mark E; Siemers, Eric; Snyder, Peter J; Potter, William Z; Cole, Patricia; Soares, Holly

    2010-05-01

    The Industry Scientific Advisory Board (ISAB) consists of representatives from the private companies and nonprofit foundations participating as sponsors of Alzheimer's Disease Neuroimaging Initiative (ADNI). Currently 21 companies are represented including pharmaceutical, imaging, and biotech concerns, and two foundations including the Alzheimer's Association. ISAB members meet regularly by teleconference or face-to-face at ADNI meetings and participate in the ADNI Core groups, all administered and organized by the Foundation for the National Institutes of Health. ISAB 'deliverables' include dissemination of information to sponsors, assisting in scientific review of protocols and results, initiation and consideration of "add-on" studies and analyses, and generation of consensus positions on industry priorities and concerns. Although positioned as an advisory body, ISAB also actively contributes to the ADNI mission of identifying biomarkers of disease progression.

  9. PENN Biomarker Core of the Alzheimer’s Disease Neuroimaging Initiative

    PubMed Central

    Shaw, Leslie M.

    2009-01-01

    There is a pressing need to develop effective prevention and disease-modifying treatments for Alzheimer’s disease (AD), a dreaded affliction whose incidence increases almost logarithmically with age starting at about 65 years. A key need in the field of AD research is the validation of imaging and biochemical biomarkers. Biomarker tests that are shown to reliably predict the disease before it is clinically expressed would permit testing of new therapeutics at the earliest time point possible in order to give the best chance for delaying the onset of dementia in these patients. In this review the current state of AD biochemical biomarker research is discussed. A new set of guidelines for the diagnosis of AD in the research setting places emphasis on the inclusion of selected imaging and biochemical biomarkers, in addition to neuropsychological behavioral testing. Importantly, the revised guidelines were developed to identify patients at the earliest stages prior to full-blown dementia as well as patients with the full spectrum of the disease. The Alzheimer’s Disease Neuroimaging Initiative is a multicenter consortium study that includes as one of its primary goals the development of standardized neuroimaging and biochemical biomarker methods for AD clinical trials, as well as using these to measure changes over time in mildly cognitively impaired patients who convert to AD as compared to the natural variability of these in control subjects and their further change over time in AD patients. Validation of the biomarker results by correlation analyses with neuropsychological and neurobehavioral test data is one of the primary outcomes of this study. This validation data will hopefully provide biomarker test performance needed for effective measurement of the efficacy of new treatment and prevention therapeutic agents. PMID:18097156

  10. Impact of the Alzheimer’s Disease Neuroimaging Initiative, 2004 to 2014

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Cedarbaum, Jesse; Donohue, Michael C.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Shaw, Leslie; Thompson, Paul M.; Toga, Arthur W.; Trojanowski, John Q.

    2015-01-01

    Introduction The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was established in 2004 to facilitate the development of effective treatments for Alzheimer’s disease (AD) by validating biomarkers for AD clinical trials. Methods We searched for ADNI publications using established methods. Results ADNI has (1) developed standardized biomarkers for use in clinical trial subject selection and as surrogate outcome measures; (2) standardized protocols for use across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives investigating traumatic brain injury and post-traumatic stress disorder in military populations, and depression, respectively, as an AD risk factor; (5) acted as a data-sharing model; (6) generated data used in over 600 publications, leading to the identification of novel AD risk alleles, and an understanding of the relationship between biomarkers and AD progression; and (7) inspired other public-private partnerships developing biomarkers for Parkinson’s disease and multiple sclerosis. Discussion ADNI has made myriad impacts in its first decade. A competitive renewal of the project in 2015 would see the use of newly developed tau imaging ligands, and the continued development of recruitment strategies and outcome measures for clinical trials. PMID:26194320

  11. The Alzheimer’s Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans

    PubMed Central

    Kang, Ju-Hee; Korecka, Magdalena; Figurski, Michal J.; Toledo, Jon B.; Blennow, Kaj; Zetterberg, Henrik; Waligorska, Teresa; Brylska, Magdalena; Fields, Leona; Shah, Nirali; Soares, Holly; Dean, Robert A.; Vanderstichele, Hugo; Petersen, Ronald C.; Aisen, Paul S.; Saykin, Andrew J.; Weiner, Michael W.; Trojanowski, John Q.; Shaw, Leslie M.

    2016-01-01

    Introduction We describe Alzheimer’s Disease Neuroimaging Initiative (ADNI) Biomarker Core progress including: the Biobank; cerebrospinal fluid (CSF) amyloid beta (Aβ1–42), t-tau, and p-tau181 analytical performance, definition of Alzheimer’s disease (AD) profile for plaque, and tangle burden detection and increased risk for progression to AD; AD disease heterogeneity; progress in standardization; and new studies using ADNI biofluids. Methods Review publications authored or coauthored by ADNI Biomarker core faculty and selected non-ADNI studies to deepen the understanding and interpretation of CSF Aβ1–42, t-tau, and p-tau181 data. Results CSFAD biomarker measurements with the qualified AlzBio3 immunoassay detects neuropathologic AD hallmarks in preclinical and prodromal disease stages, based on CSF studies in non-ADNI living subjects followed by the autopsy confirmation of AD. Collaboration across ADNI cores generated the temporal ordering model of AD biomarkers varying across individuals because of genetic/environmental factors that increase/decrease resilience to AD pathologies. Discussion Further studies will refine this model and enable the use of biomarkers studied in ADNI clinically and in disease-modifying therapeutic trials. PMID:26194312

  12. The Alzheimer’s Disease Neuroimaging Initiative: Progress report and future plans

    PubMed Central

    Weiner, Michael W.; Aisen, Paul S.; Jack, Clifford R.; Jagust, William J.; Trojanowski, John Q.; Shaw, Leslie; Saykin, Andrew J.; Morris, John C.; Cairns, Nigel; Beckett, Laurel A.; Toga, Arthur; Green, Robert; Walter, Sarah; Soares, Holly; Snyder, Peter; Siemers, Eric; Potter, William; Cole, Patricia E.; Schmidt, Mark

    2010-01-01

    The Alzheimer’s Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year re-search project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer’s disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C-11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid β (Aβ) and species of tau, with clinical/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C-11 Pittsburgh compound B PET, and CSF measurements of Aβ and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA/LONI/ADNI, without embargo. ADNI-like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD. PMID:20451868

  13. Brain collection, standardized neuropathologic assessment, and comorbidity in Alzheimer's Disease Neuroimaging Initiative 2 participants.

    PubMed

    Franklin, Erin E; Perrin, Richard J; Vincent, Benjamin; Baxter, Michael; Morris, John C; Cairns, Nigel J

    2015-07-01

    The Alzheimer's Disease Neuroimaging Initiative Neuropathology Core (ADNI-NPC) facilitates brain donation, ensures standardized neuropathologic assessments, and maintains a tissue resource for research. The ADNI-NPC coordinates with performance sites to promote autopsy consent, facilitate tissue collection and autopsy administration, and arrange sample delivery to the NPC, for assessment using National Institute on Aging-Alzheimer's Association neuropathologic diagnostic criteria. The ADNI-NPC has obtained 45 participant specimens, and neuropathologic assessments have been completed in 36 to date. Challenges in obtaining consent at some sites have limited the voluntary autopsy rate to 58%. Among assessed cases, clinical diagnostic accuracy for Alzheimer disease (AD) is 97%; however, 58% of cases show neuropathologic comorbidities. Challenges facing autopsy consent and coordination are largely resource related. The neuropathologic assessments indicate that ADNI's clinical diagnostic accuracy for AD is high; however, many AD cases have comorbidities that may impact the clinical presentation, course, and imaging and biomarker results. These neuropathologic data permit multimodal and genetic studies of these comorbidities to improve diagnosis and provide etiologic insights. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  14. Dynamics of brain structure and cognitive function in the Alzheimer's disease neuroimaging initiative.

    PubMed

    Song, Xiaowei; Mitnitski, Arnold; Zhang, Ningnannan; Chen, Wei; Rockwood, Kenneth

    2013-01-01

    On average, cognition declines as people age, but improvement can also occur. To evaluate the dynamics of age-related changes in brain structure and cognitive function in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI) and in healthy control (HC) older adults. High-resolution 3-Tesla MRI and clinical data were obtained from the Alzheimer's Disease Neuroimaging Initiative in 187 subjects (a cohort aged 55-91 years; AD=43, MCI=84, HC=60). At 24 months, 151 people had clinical and 128 had MRI follow-up. Brain structure was assessed using the Medial Temporal Atrophy Scale (MTAS) and the Brain Atrophy and Lesion Index (BALI). Cognition was assessed using the Mini-Mental State Examination (MMSE) and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Responsiveness was tested. Changes were analysed using a multistate dynamic model, adjusted for age, gender, ApoE4 genotype and vascular risk factors. Over 2 years, decline in brain structure and cognition predominated, each showing detectable effect sizes (Cohen's d=0.33 for MTAS, 0.32 for BALI, 0.41 for MMSE, 0.38 for ADAS-cog; standard response mean=0.71, 0.69, 0.50 and 0.47, respectively). Structural improvement was observed (10.2% in BALI and 0.8% in MTAS), as was cognitive improvement (23.2% MMSE, 27.2% ADAS-cog). Most people (66.7%) whose BALI score improved also improved in either the MMSE or ADAS-cog. No patient with MCI whose MTAS or BALI improved converted to AD. Despite average decline in brain structure, improvement was observed and related to cognition and MCI-AD conversion. Ageing-related brain changes reflect a dynamic process.

  15. Treatment With Cholinesterase Inhibitors and Memantine of Patients in the Alzheimer’s Disease Neuroimaging Initiative

    PubMed Central

    Schneider, Lon S.; Insel, Philip S.; Weiner, Michael W.

    2011-01-01

    Objectives To assess the clinical characteristics and course of patients with mild cognitive impairment (MCI) and mild Alzheimer disease (AD) treated with cholinesterase inhibitors (ChEIs) and memantine hydrochloride. Design Cohort study. Setting The 59 recruiting sites for the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants Outpatients with MCI and AD in ADNI. Main Outcome Measures The AD Assessment Scale–cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) scale, and Functional Activities Questionnaire (FAQ). Results A total of 177 (44.0%) of 402 MCI patients and 159 (84.6%) of 188 mild-AD patients were treated with ChEIs and 11.4% of MCI patients and 45.7% of AD patients with memantine at entry. Mild-cognitive-impairment patients who received ChEIs with or without memantine were more impaired, showed greater decline in scores, and progressed to dementia sooner than patients who did not receive ChEIs. Alzheimer-disease patients who received ChEIs and memantine took them longer, were more functionally impaired, and showed greater decline on the MMSE and CDR (but not on the ADAS-cog or FAQ) than those who received ChEIs only. Conclusions Academic physicians frequently prescribe ChEIs and memantine earlier than indicated in the US Food and Drug Administration–approved labeling to patients who are relatively more severely impaired or who are rapidly progressing toward cognitive impairment. The use of these medications in ADNI is associated with clinical decline and may affect the interpretation of clinical trial outcomes. Study Registration clinicalTrials.gov Identifier: NCT00106899 PMID:21220675

  16. Predicting episodic memory performance using different biomarkers: results from Argentina-Alzheimer’s Disease Neuroimaging Initiative

    PubMed Central

    Russo, María Julieta; Cohen, Gabriela; Chrem Mendez, Patricio; Campos, Jorge; Nahas, Federico E; Surace, Ezequiel I; Vazquez, Silvia; Gustafson, Deborah; Guinjoan, Salvador; Allegri, Ricardo F; Sevlever, Gustavo

    2016-01-01

    Purpose Argentina-Alzheimer’s Disease Neuroimaging Initiative (Arg-ADNI) is the first ADNI study to be performed in Latin America at a medical center with the appropriate infrastructure. Our objective was to describe baseline characteristics and to examine whether biomarkers related to Alzheimer’s disease (AD) physiopathology were associated with worse memory performance. Patients and methods Fifteen controls and 28 mild cognitive impairment and 13 AD dementia subjects were included. For Arg-ADNI, all biomarker parameters and neuropsychological tests of ADNI-II were adopted. Results of positron emission tomography (PET) with fluorodeoxyglucose and 11C-Pittsburgh compound-B (PIB-PET) were available from all participants. Cerebrospinal fluid biomarker results were available from 39 subjects. Results A total of 56 participants were included and underwent baseline evaluation. The three groups were similar with respect to years of education and sex, and they differed in age (F=5.10, P=0.01). Mean scores for the baseline measurements of the neuropsychological evaluation differed significantly among the three groups at P<0.001, showing a continuum in their neuropsychological performance. No significant correlations were found between the principal measures (long-delay recall, C-Pittsburgh compound-B scan, left hippocampal volume, and APOEε4) and either age, sex, or education (P>0.1). Baseline amyloid deposition and left hippocampal volume separated the three diagnostic groups and correlated with the memory performance (P<0.001). Conclusion Cross-sectional analysis of baseline data revealed links between cognition, structural changes, and biomarkers. Follow-up of a larger and more representative cohort, particularly analyzing cerebrospinal fluid and brain biomarkers, will allow better characterization of AD in our country. PMID:27695331

  17. Cerebrospinal Fluid Biomarker Signature in Alzheimer’s Disease Neuroimaging Initiative Subjects

    PubMed Central

    Shaw, Leslie M.; Vanderstichele, Hugo; Knapik-Czajka, Malgorzata; Clark, Christopher M.; Aisen, Paul S.; Petersen, Ronald C.; Blennow, Kaj; Soares, Holly; Simon, Adam; Lewczuk, Piotr; Dean, Robert; Siemers, Eric; Potter, William; Lee, Virginia M.-Y.; Trojanowski, John Q.

    2009-01-01

    Objective Develop a cerebrospinal fluid biomarker signature for mild Alzheimer’s disease (AD) in Alzheimer’s Disease Neuroimaging Initiative (ADNI) subjects. Methods Amyloid-β 1 to 42 peptide (Aβ1-42), total tau (t-tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy-confirmed AD cases and 52 age-matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t-tau and Aβ1-42 in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy-confirmed CSF data. Results CSF Aβ1-42 was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for Aβ1-42, t-tau, and APOε4 allele count provided the best assessment delineation of mild AD. An AD-like baseline CSF profile for t-tau/Aβ1-42 was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. Interpretation The CSF biomarker signature of AD defined by Aβ1-42 and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. PMID:19296504

  18. Ways toward an early diagnosis in Alzheimer’s disease: The Alzheimer’s Disease Neuroimaging Initiative (ADNI)

    PubMed Central

    Mueller, Susanne G.; Weiner, Michael W.; Thal, Leon J.; Petersen, Ronald C.; Jack, Clifford R.; Jagust, William; Trojanowski, John Q.; Toga, Arthur W.; Beckett, Laurel

    2007-01-01

    With the increasing life expectancy in developed countries, the incidence of Alzheimer’s disease (AD) and thus its socioeconomic impact are growing. Increasing knowledge over the last years about the pathomechanisms involved in AD allow for the development of specific treatment strategies aimed at slowing down or even preventing neuronal death in AD. However, this requires also that (1) AD can be diagnosed with high accuracy, because non-AD dementias would not benefit from an AD-specific treatment; (2) AD can be diagnosed in very early stages when any intervention would be most effective; and (3) treatment efficacy can be reliably and meaningfully monitored. Although there currently is no ideal biomarker that would fulfill all these requirements, there is increasing evidence that a combination of currently existing neuroimaging and cerebrospinal fluid (CSF) and blood biomarkers can provide important complementary information and thus contribute to a more accurate and earlier diagnosis of AD. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is exploring which combinations of these biomarkers are the most powerful for diagnosis of AD and monitoring of treatment effects. PMID:17476317

  19. Development and assessment of a composite score for memory in the Alzheimer's Disease Neuroimaging Initiative (ADNI).

    PubMed

    Crane, Paul K; Carle, Adam; Gibbons, Laura E; Insel, Philip; Mackin, R Scott; Gross, Alden; Jones, Richard N; Mukherjee, Shubhabrata; Curtis, S McKay; Harvey, Danielle; Weiner, Michael; Mungas, Dan

    2012-12-01

    We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer's Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.

  20. A Computational Neurodegenerative Disease Progression Score: Method and Results with the Alzheimer’s Disease Neuroimaging Initiative Cohort

    PubMed Central

    Jedynak, Bruno M.; Lang, Andrew; Liu, Bo; Katz, Elyse; Zhang, Yanwei; Wyman, Bradley T.; Raunig, David; Jedynak, C. Pierre; Caffo, Brian; Prince, Jerry L.

    2012-01-01

    While neurodegenerative diseases are characterized by steady degeneration over relatively long timelines, it is widely believed that the early stages are the most promising for therapeutic intervention, before irreversible neuronal loss occurs. Developing a therapeutic response requires a precise measure of disease progression. However, since the early stages are for the most part asymptomatic, obtaining accurate measures of disease progression is difficult. Longitudinal databases of hundreds of subjects observed during several years with tens of validated biomarkers are becoming available, allowing the use of computational methods. We propose a widely applicable statistical methodology for creating a disease progression score (DPS), using multiple biomarkers, for subjects with a neurodegenerative disease. The proposed methodology was evaluated for Alzheimer’s disease (AD) using the publicly available AD Neuroimaging Initiative (ADNI) database, yielding an Alzheimer’s DPS or ADPS score for each subject and each time-point in the database. In addition, a common description of biomarker changes was produced allowing for an ordering of the biomarkers. The Rey Auditory Verbal Learning Test delayed recall was found to be the earliest biomarker to become abnormal. The group of biomarkers comprising the volume of the hippocampus and the protein concentration amyloid beta and Tau were next in the timeline, and these were followed by three cognitive biomarkers. The proposed methodology thus has potential to stage individuals according to their state of disease progression relative to a population and to deduce common behaviors of biomarkers in the disease itself. PMID:22885136

  1. 2014 Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception.

    PubMed

    Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Cedarbaum, Jesse; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Luthman, Johan; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie; Shen, Li; Schwarz, Adam; Toga, Arthur W; Trojanowski, John Q

    2015-06-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer's Dis 2006;9(Suppl 3):151-3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [(18)F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers,

  2. Recent publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing progress toward improved AD clinical trials.

    PubMed

    Weiner, Michael W; Veitch, Dallas P; Aisen, Paul S; Beckett, Laurel A; Cairns, Nigel J; Green, Robert C; Harvey, Danielle; Jack, Clifford R; Jagust, William; Morris, John C; Petersen, Ronald C; Saykin, Andrew J; Shaw, Leslie M; Toga, Arthur W; Trojanowski, John Q

    2017-04-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the over 400 publications using ADNI data during 2014 and 2015. We used standard searches to find publications using ADNI data. (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses. Models of prion-like spreading of Aβ pathology along WM tracts predict known patterns of cortical Aβ deposition and declines in glucose metabolism; (7) New AD risk and protective gene loci have been identified using biologically informed approaches; (8) Cognitively normal and mild cognitive impairment (MCI) subjects are heterogeneous and include groups typified not only by "classic" AD pathology but also by normal biomarkers, accelerated decline, and suspected non-Alzheimer's pathology; (9) Selection of subjects at risk of imminent decline on the basis of one or more pathologies improves the power of clinical trials; (10) Sensitivity of cognitive outcome measures to early changes in cognition has been improved and

  3. The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

    2012-01-01

    The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD and 200 normal controls and $67 million funding was provided by both the public and private sectors including the National Institutes on Aging, thirteen pharmaceutical companies and two Foundations that provided support through the Foundation for NIH (FNIH). This article reviews all papers published since the inception of the initiative and summarizes the results as of February, 2011. The major accomplishments of ADNI have been 1) the development of standardized methods for clinical, magnetic resonance imaging (MRI) and positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers in a multi-center setting; 2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control, MCI and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β amyloid (Aβ) cascade [1] and tau mediated neurodegeneration hypotheses for AD while brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; 3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities including MRI, FDG-PET, CSF biomarkers and clinical tests; 4) the development of methods for the early detection of AD. CSF biomarkers, Aβ42 and tau as well as amyloid PET may reflect the earliest steps in AD pathology in mildly or even non-symptomatic subjects and are leading candidates for the detection of AD in its preclinical stages; 5) the improvement of clinical trial efficiency through the identification of subjects most

  4. The Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Liu, Enchi; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Schmidt, Mark E.; Shaw, Leslie; Shen, Li; Siuciak, Judith A.; Soares, Holly; Toga, Arthur W.; Trojanowski, John Q.

    2014-01-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, β-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates

  5. The pilot European Alzheimer’s Disease Neuroimaging Initiative (E-ADNI) of the European Alzheimer’s Disease Consortium

    PubMed Central

    Frisoni, Giovanni B; Henneman, Wouter JP; Weiner, Michael W; Scheltens, Philip; Vellas, Bruno; Reynish, Emma; Hudecova, Jaroslava; Hampel, Harald; Burger, Katharina; Blennow, Kaj; Waldemar, Gunhild; Johannsen, Peter; Wahlund, Lars-Olof; Zito, Giancarlo; Rossini, Paolo M; Winblad, Bengt; Barkhof, Frederik

    2008-01-01

    Background In North-America, the Alzheimer’s Disease Neuroimaging Initiative (ADNI) has established a platform to track the brain changes of Alzheimer’s disease. A pilot study has been carried out in Europe to test the feasibility of the adoption of the ADNI platform (pilot E-ADNI). Methods Seven academic sites of the European Alzheimer’s Disease Consortium (EADC) enrolled 19 patients with MCI, 22 with AD, and 18 older healthy persons using the ADNI clinical and neuropsychological battery. ADNI compliant MR scans, CSF and blood samples were shipped to central repositories. Medial temporal atrophy (MTA) and white matter hyperintensities (WMH) were assessed by a single rater using visual rating scales. Results Recruitment rate was 3.5 subjects per month per site. The cognitive, behavioural and neuropsychological features of the European subjects were very similar to their US counterparts. 3D T1-weighted MRI sequences were successfully performed on all subjects and CSF samples obtained from 77%, 68%, and 83% of AD, MCI, and controls. Mean MTA score showed a significant increase from controls (left, right: 0.4, 0.3) to MCI (0.9, 0.8) to AD (2.3, 2.0), while mean WMH score did not differ among the three diagnostic groups (between 0.7 and 0.9). The distribution of both MRI markers was comparable to matched US ADNI subjects. Conclusions Academic EADC centres can adopt the ADNI platform to enrol MCI and AD patients and older controls with global cognitive and structural imaging features remarkably similar to those of the US ADNI. PMID:18631976

  6. Longitudinal Changes in White Matter Disease and Cognition in the First Year of the Alzheimer Disease Neuroimaging Initiative

    PubMed Central

    Carmichael, Owen; Schwarz, Christopher; Drucker, David; Fletcher, Evan; Harvey, Danielle; Beckett, Laurel; Jack, Clifford R.; Weiner, Michael; DeCarli, Charles

    2011-01-01

    Objective To evaluate relationships between magnetic resonance imaging (MRI)–based measures of white matter hyperintensities (WMHs), measured at baseline and longitudinally, and 1-year cognitive decline using a large convenience sample in a clinical trial design with a relatively mild profile of cardiovascular risk factors. Design Convenience sample in a clinical trial design. Subjects A total of 804 participants in the Alzheimer Disease Neuroimaging Initiative who received MRI scans, cognitive testing, and clinical evaluations at baseline, 6-month follow-up, and 12-month follow-up visits. For each scan, WMHs were detected automatically on coregistered sets of T1, proton density, and T2 MRI images using a validated method. Mixed-effects regression models evaluated relationships between risk factors for WMHs, WMH volume, and change in outcome measures including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Scale sum of boxes scores. Covariates in these models included race, sex, years of education, age, apolipoprotein E genotype, baseline clinical diagnosis (cognitively normal, mild cognitive impairment, or Alzheimer disease), cardiovascular risk score, and MRI-based hippocampal and brain volumes. Results Higher baseline WMH volume was associated with greater subsequent 1-year increase in ADAS-Cog and decrease in MMSE scores. Greater WMH volume at follow-up was associated with greater ADAS-Cog and lower MMSE scores at follow-up. Higher baseline age and cardiovascular risk score and more impaired baseline clinical diagnosis were associated with higher baseline WMH volume. Conclusions White matter hyperintensity volume predicts 1-year cognitive decline in a relatively healthy convenience sample that was similar to clinical trial samples, and therefore should be considered as a covariate of interest at baseline and longitudinally in future AD treatment trials. PMID:21060014

  7. Longitudinal changes in white matter disease and cognition in the first year of the Alzheimer disease neuroimaging initiative.

    PubMed

    Carmichael, Owen; Schwarz, Christopher; Drucker, David; Fletcher, Evan; Harvey, Danielle; Beckett, Laurel; Jack, Clifford R; Weiner, Michael; DeCarli, Charles

    2010-11-01

    To evaluate relationships between magnetic resonance imaging (MRI)-based measures of white matter hyperintensities (WMHs), measured at baseline and longitudinally, and 1-year cognitive decline using a large convenience sample in a clinical trial design with a relatively mild profile of cardiovascular risk factors. Convenience sample in a clinical trial design. A total of 804 participants in the Alzheimer Disease Neuroimaging Initiative who received MRI scans, cognitive testing, and clinical evaluations at baseline, 6-month follow-up, and 12-month follow-up visits. For each scan, WMHs were detected automatically on coregistered sets of T1, proton density, and T2 MRI images using a validated method. Mixed-effects regression models evaluated relationships between risk factors for WMHs, WMH volume, and change in outcome measures including Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Clinical Dementia Rating Scale sum of boxes scores. Covariates in these models included race, sex, years of education, age, apolipoprotein E genotype, baseline clinical diagnosis (cognitively normal, mild cognitive impairment, or Alzheimer disease), cardiovascular risk score, and MRI-based hippocampal and brain volumes. Higher baseline WMH volume was associated with greater subsequent 1-year increase in ADAS-Cog and decrease in MMSE scores. Greater WMH volume at follow-up was associated with greater ADAS-Cog and lower MMSE scores at follow-up. Higher baseline age and cardiovascular risk score and more impaired baseline clinical diagnosis were associated with higher baseline WMH volume. White matter hyperintensity volume predicts 1-year cognitive decline in a relatively healthy convenience sample that was similar to clinical trial samples, and therefore should be considered as a covariate of interest at baseline and longitudinally in future AD treatment trials.

  8. Multivariate Protein Signatures of Pre-Clinical Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) Plasma Proteome Dataset

    PubMed Central

    Johnstone, Daniel; Milward, Elizabeth A.; Berretta, Regina; Moscato, Pablo

    2012-01-01

    Background Recent Alzheimer's disease (AD) research has focused on finding biomarkers to identify disease at the pre-clinical stage of mild cognitive impairment (MCI), allowing treatment to be initiated before irreversible damage occurs. Many studies have examined brain imaging or cerebrospinal fluid but there is also growing interest in blood biomarkers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) has generated data on 190 plasma analytes in 566 individuals with MCI, AD or normal cognition. We conducted independent analyses of this dataset to identify plasma protein signatures predicting pre-clinical AD. Methods and Findings We focused on identifying signatures that discriminate cognitively normal controls (n = 54) from individuals with MCI who subsequently progress to AD (n = 163). Based on p value, apolipoprotein E (APOE) showed the strongest difference between these groups (p = 2.3×10−13). We applied a multivariate approach based on combinatorial optimization ((α,β)-k Feature Set Selection), which retains information about individual participants and maintains the context of interrelationships between different analytes, to identify the optimal set of analytes (signature) to discriminate these two groups. We identified 11-analyte signatures achieving values of sensitivity and specificity between 65% and 86% for both MCI and AD groups, depending on whether APOE was included and other factors. Classification accuracy was improved by considering “meta-features,” representing the difference in relative abundance of two analytes, with an 8-meta-feature signature consistently achieving sensitivity and specificity both over 85%. Generating signatures based on longitudinal rather than cross-sectional data further improved classification accuracy, returning sensitivities and specificities of approximately 90%. Conclusions Applying these novel analysis approaches to the powerful and well-characterized ADNI dataset has identified sets of

  9. Perspective: The Alzheimer's Disease Neuroimaging Initiative and the role and contributions of the Private Partner Scientific Board (PPSB).

    PubMed

    Liu, Enchi; Luthman, Johan; Cedarbaum, Jesse M; Schmidt, Mark E; Cole, Patricia E; Hendrix, James; Carrillo, Maria C; Jones-Davis, Dorothy; Tarver, Erika; Novak, Gerald; De Santi, Susan; Soares, Holly D; Potter, William Z; Siemers, Eric; Schwarz, Adam J

    2015-07-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partner Scientific Board (PPSB) is comprised of representatives of private, for-profit entities (including pharmaceutical, biotechnology, diagnostics, imaging companies, and imaging contract research organizations), and nonprofit organizations that provide financial and scientific support to ADNI through the Foundation for the National Institutes of Health. The PPSB serves as an independent, open, and precompetitive forum in which all private sector and not-for-profit partners in ADNI can collaborate, share information, and offer scientific and private-sector perspectives and expertise on issues relating to the ADNI project. In this article, we review and highlight the role, activities, and contributions of the PPSB within the ADNI project, and provide a perspective on remaining unmet needs and future directions.

  10. Identification of Successful Cognitive Aging in the Alzheimer's Disease Neuroimaging Initiative Study.

    PubMed

    Lin, Feng V; Wang, Xixi; Wu, Rachel; Rebok, George W; Chapman, Benjamin P

    2017-01-01

    The present prospective observational study aimed to identify the existence of successful cognitive agers among a group of well-defined cognitively healthy older adults (n = 354, mean age = 75 years), and to examine baseline individual-level predictors and associated health outcomes over time. Episodic memory (EM) and executive function (EF) composite scores and multiple health outcomes were obtained annually over 5 years. Potential individual-level predictors that were related to Alzheimer's disease pathology or genetic risk, neurodegeneration, and vascular risks were collected at baseline. Three latent classes with matched age and education were identified using growth mixture modeling: a group of participants who exhibited high, stable EM and EF (40.7% of the sample, "successful agers"); a group who had initial high cognitive performance that declined over time (21.2%, "declining agers"); and a group who had normal (EM) or poor (EF) but stable cognitive performance over time (38.1%, "low stable agers"). The group classification predicted significant differences in the incidence of global cognitive impairment, the development of at least one depressive symptom, and everyday functional impairment. Sex, apolipoprotein E allele 4, amyloid-β1-42, and t-tau significantly contributed to the difference in cognitive trajectories between the successful agers and the other two groups. Characterizing successful cognitive agers who are relatively resistant to both tau and amyloid pathology provides potential pathways for promoting successful cognitive aging and preventing cognitive decline.

  11. Higher homocysteine associated with thinner cortical gray matter in 803 participants from the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Madsen, Sarah K; Rajagopalan, Priya; Joshi, Shantanu H; Toga, Arthur W; Thompson, Paul M

    2015-01-01

    A significant portion of our risk for dementia in old age is associated with lifestyle factors (diet, exercise, and cardiovascular health) that are modifiable, at least in principle. One such risk factor, high-homocysteine levels in the blood, is known to increase risk for Alzheimer's disease and vascular disorders. Here, we set out to understand how homocysteine levels relate to 3D surface-based maps of cortical gray matter distribution (thickness, volume, and surface area) computed from brain magnetic resonance imaging in 803 elderly subjects from the Alzheimer's Disease Neuroimaging Initiative data set. Individuals with higher plasma levels of homocysteine had lower gray matter thickness in bilateral frontal, parietal, occipital, and right temporal regions and lower gray matter volumes in left frontal, parietal, temporal, and occipital regions, after controlling for diagnosis, age, and sex and after correcting for multiple comparisons. No significant within-group associations were found in cognitively healthy people, patients with mild cognitive impairment, or patients with Alzheimer's disease. These regional differences in gray matter structure may be useful biomarkers to assess the effectiveness of interventions, such as vitamin B supplements, that aim to prevent homocysteine-related brain atrophy by normalizing homocysteine levels.

  12. Cognitive reserve and Aβ1-42 in mild cognitive impairment (Argentina-Alzheimer’s Disease Neuroimaging Initiative)

    PubMed Central

    Harris, Paula; Fernandez Suarez, Marcos; Surace, Ezequiel I; Chrem Méndez, Patricio; Martín, María Eugenia; Clarens, María Florencia; Tapajóz, Fernanda; Russo, Maria Julieta; Campos, Jorge; Guinjoan, Salvador M; Sevlever, Gustavo; Allegri, Ricardo F

    2015-01-01

    Background The purpose of this study was to investigate the relationship between cognitive reserve and concentration of Aβ1-42 in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment, those with Alzheimer’s disease, and in control subjects. Methods Thirty-three participants from the Argentina-Alzheimer’s Disease Neuroimaging Initiative database completed a cognitive battery, the Cognitive Reserve Questionnaire (CRQ), and an Argentinian accentuation reading test (TAP-BA) as a measure of premorbid intelligence, and underwent lumbar puncture for CSF biomarker quantification. Results The CRQ significantly correlated with TAP-BA, education, and Aβ1-42. When considering Aβ1-42 levels, significant differences were found in CRQ scores; higher levels of CSF Aβ1-42 were associated with higher CRQ scores. Conclusion Reduced Aβ1-42 in CSF is considered as evidence of amyloid deposition in the brain. Previous results suggest that individuals with higher education, higher occupational attainment, and participation in leisure activities (cognitive reserve) have a reduced risk of developing Alzheimer’s disease. Our results support the notion that enhanced neural activity has a protective role in mild cognitive impairment, as evidenced by higher CSF Aβ1-42 levels in individuals with more cognitive reserve. PMID:26504392

  13. Morphological and Microstructural Changes of the Hippocampus in Early MCI: A Study Utilizing the Alzheimer's Disease Neuroimaging Initiative Database

    PubMed Central

    Lee, Peter; Ryoo, Hojin

    2017-01-01

    Background and Purpose With the aim of facilitating the early detection of Alzheimer's disease, the Alzheimer's Disease Neuroimaging Initiative proposed two stages based on the memory performance: early mild cognitive impairment (EMCI) and late mild cognitive impairment (LMCI). The current study was designed to investigate structural differences in terms of surface atrophy and microstructural changes of the hippocampus in EMCI and LMCI. Methods Hippocampal shape modeling based on progressive template surface deformation was performed on T1-weighted MRI images obtained from 20 cognitive normal (CN) subjects, 17 EMCI patients, and 20 LMCI patients. A template surface in CN was used as a region of interest for diffusion-tensor imaging (DTI) voxel-based morphometry (VBM) analysis. Cluster-wise group comparison was performed based on DTI indices within the hippocampus. Linear regression was performed to identify correlations between DTI metrics and clinical scores. Results The hippocampal surface analysis showed significant atrophies in bilateral CA1 regions and the right ventral subiculum in EMCI, in contrast to widespread atrophy in LMCI. DTI VBM analysis showed increased diffusivity in the CA2–CA4 regions in EMCI and additionally in the subiculum region in LMCI. Hippocampal diffusivity was significantly correlated with scores both for the Mini Mental State Examination and on the Modified Alzheimer Disease Assessment Scale cognitive subscale. However, the hippocampal diffusivity did not vary significantly with the fractional anisotropy. Conclusions EMCI showed hippocampal surface changes mainly in the CA1 region and ventral subiculum. Diffusivity increased mainly in the CA2–CA4 regions in EMCI, while it decreased throughout the hippocampus in LMCI. Although axial diffusivity showed prominent changes in the right hippocampus in EMCI, future studies need to confirm the presence of this laterality difference. In addition, diffusivity is strongly correlated with the

  14. Comparison of imaging biomarkers in the Alzheimer Disease Neuroimaging Initiative and the Mayo Clinic Study of Aging.

    PubMed

    Whitwell, Jennifer L; Wiste, Heather J; Weigand, Stephen D; Rocca, Walter A; Knopman, David S; Roberts, Rosebud O; Boeve, Bradley F; Petersen, Ronald C; Jack, Clifford R

    2012-05-01

    To determine whether magnetic resonance imaging measurements observed in the Alzheimer Disease Neuroimaging Initiative (ADNI) convenience sample differ from those observed in the Mayo Clinic Study of Aging (MCSA) population-based sample. Comparison of 2 samples. Fifty-nine recruiting sites for the ADNI in the United States and Canada and the MCSA, a population-based cohort in Olmsted County, Minnesota. Cognitively normal subjects and amnestic subjects with mild cognitive impairment were selected from the ADNI convenience cohort and MCSA population-based cohort. A simple random sample of subjects from both cohorts in the same age range was selected, and a second sample applied matching for age, sex, educational level, apolipoprotein E genotype, and Mini-Mental State Examination score. Baseline hippocampal volumes and annual percentage of decline in hippocampal volume. In the population-based sample, MCSA subjects were older, had less education, performed worse on the Mini-Mental State Examination, and had a family history of Alzheimer disease less often than did ADNI subjects. Baseline hippocampal volumes were larger in ADNI compared with MCSA cognitively normal subjects in the random sample, although no differences were observed after matching. Rates of decline in hippocampal volume were greater in the ADNI compared with the MCSA for cognitively normal subjects and those with amnestic mild cognitive impairment, even after matching. Rates of decline in hippocampal volume suggest that ADNI subjects have a more aggressive brain pathologic process than MCSA subjects and hence may not be representative of the general population. These findings have implications for treatment trials that use ADNI-like recruitment mechanisms and for studies validating new diagnostic criteria for Alzheimer disease in its various stages.

  15. Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative.

    PubMed

    Gomar, Jesus J; Bobes-Bascaran, Maria T; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E

    2011-09-01

    Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological Aβ1-42 and total tau, cognitive measures, and individual risk factors. To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Longitudinal study. We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. The Alzheimer's Disease Neuroimaging Initiative public database. Primary outcome measures were odds ratios, pseudo- R(2)s, and effect sizes. In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic

  16. A composite score for executive functioning, validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with baseline mild cognitive impairment.

    PubMed

    Gibbons, Laura E; Carle, Adam C; Mackin, R Scott; Harvey, Danielle; Mukherjee, Shubhabrata; Insel, Philip; Curtis, S McKay; Mungas, Dan; Crane, Paul K

    2012-12-01

    The Alzheimer's Disease Neuroimaging Initiative (ADNI) measures abilities broadly related to executive function (EF), including WAIS-R Digit Symbol Substitution, Digit Span Backwards, Trails A and B, Category Fluency, and Clock Drawing. This study investigates whether a composite executive function measure based on these multiple indicators has better psychometric characteristics than the widely used individual components. We applied item response theory methods to 800 ADNI participants to derive an EF composite score (ADNI-EF) from the above measures. We then compared ADNI-EF with component measures in 390 longitudinally-followed participants with mild cognitive impairment (MCI) with respect to: (1) Ability to detect change over time; (2) Ability to predict conversion to dementia; (3) Strength of cross-sectional association with MRI-derived measures of structures involved in frontal systems, and (4) Strength of baseline association with cerebrospinal fluid (CSF) levels of amyloid β₁₋₄₂, total tau, and phosphorylated tau(181P). ADNI-EF showed the greatest change over time, followed closely by Category Fluency. ADNI-EF needed a 40 % smaller sample size to detect change. ADNI-EF was the strongest predictor of AD conversion. ADNI-EF was the only measure significantly associated with all the MRI regions, though other measures were more strongly associated in a few of the regions. ADNI-EF was associated with all the CSF measures. ADNI-EF appears to be a useful composite measure of EF in MCI, as good as or better than any of its composite parts. This study demonstrates an approach to developing a psychometrically sophisticated composite score from commonly-used tests.

  17. Diagnostic neuroimaging across diseases

    PubMed Central

    Klöppel, Stefan; Abdulkadir, Ahmed; Jack, Clifford R.; Koutsouleris, Nikolaos; Mourao-Miranda, Janaina; Vemuri, Prashanthi

    2012-01-01

    Fully automated classification algorithms have been successfully applied to diagnose a wide range of neurological and psychiatric diseases. They are sufficiently robust to handle data from different scanners for many applications and in specific cases outperform radiologists. This article provides an overview of current applications taking structural imaging in Alzheimer's Disease and schizophrenia as well as functional imaging to diagnose depression as examples. In this context, we also report studies aiming to predict the future course of the disease and the response to treatment for the individual. This has obvious clinical relevance but is also important for the design of treatment studies that may aim to include a cohort with a predicted fast disease progression to be more sensitive to detect treatment effects. In the second part, we present our own opinions on i) the role these classification methods can play in the clinical setting; ii) where their limitations are at the moment and iii) how those can be overcome. Specifically, we discuss strategies to deal with disease heterogeneity, diagnostic uncertainties, a probabilistic framework for classification and multi-class classification approaches. PMID:22094642

  18. 2014 Update of the Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Aisen, Paul S.; Beckett, Laurel A.; Cairns, Nigel J.; Cedarbaum, Jesse; Green, Robert C.; Harvey, Danielle; Jack, Clifford R.; Jagust, William; Luthman, Johan; Morris, John C.; Petersen, Ronald C.; Saykin, Andrew J.; Shaw, Leslie; Shen, Li; Schwarz, Adam; Toga, Arthur W.; Trojanowski, John Q.

    2016-01-01

    The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). The initial study, ADNI-1, enrolled 400 subjects with early mild cognitive impairment (MCI), 200 with early AD, and 200 cognitively normal elderly controls. ADNI-1 was extended by a 2-year Grand Opportunities grant in 2009 and by a competitive renewal, ADNI-2, which enrolled an additional 550 participants and will run until 2015. This article reviews all papers published since the inception of the initiative and summarizes the results to the end of 2013. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are largely consistent with disease trajectories predicted by β-amyloid cascade (Hardy, J Alzheimer’s Dis 2006;9(Suppl 3):151–3) and tau-mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers select and combine optimum features from multiple modalities, including MRI, [18F]-fluorodeoxyglucose-PET, amyloid PET, CSF biomarkers, and clinical tests; (4) the development of blood biomarkers for AD as potentially noninvasive and low-cost alternatives to CSF biomarkers for AD diagnosis and the assessment of α-syn as an additional biomarker; (5) the development of methods for the early detection of AD. CSF biomarkers,

  19. White matter hyperintensity burden in elderly cohort studies: The Sunnybrook Dementia Study, Alzheimer's Disease Neuroimaging Initiative, and Three-City Study.

    PubMed

    Ramirez, Joel; McNeely, Alicia A; Scott, Christopher J M; Masellis, Mario; Black, Sandra E

    2016-02-01

    Given the recent acknowledgement of the complex mixed pathologies that contribute to the clinical expression of dementia, various cohort studies have aimed to examine Alzheimer's disease and cerebrovascular disease as comorbid pathologies, with neuroimaging playing a central role in these studies. Using white matter hyperintensities (WMH) as a biomarker of cerebrovascular disease, we compared WMH burden between the Sunnybrook Dementia Study, the Alzheimer's Disease Neuroimaging Initiative (ADNI-1), the Three-City Study, and various other studies around the world. Based on our findings, it was evident that ADNI-1 had minimal WMH burden relative to other large studies that examine aging and dementia. This low WMH burden in ADNI-1 may be considered as both an advantage, representing a relatively "pure" sample with little confounding vasculopathy, and a disadvantage, as it limits generalizability to "real-world" patient populations with mixed pathologies and to nondemented groups with baseline vascular disease. We explore possible reasons for this distinction, including management of vascular risk factors, gaps in diagnostic criteria, and future directions for clinical research. Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  20. Reference standard space hippocampus labels according to the European Alzheimer's Disease Consortium-Alzheimer's Disease Neuroimaging Initiative harmonized protocol: Utility in automated volumetry.

    PubMed

    Wolf, Dominik; Bocchetta, Martina; Preboske, Gregory M; Boccardi, Marina; Grothe, Michel J

    2017-08-01

    A harmonized protocol (HarP) for manual hippocampal segmentation on magnetic resonance imaging (MRI) has recently been developed by an international European Alzheimer's Disease Consortium-Alzheimer's Disease Neuroimaging Initiative project. We aimed at providing consensual certified HarP hippocampal labels in Montreal Neurological Institute (MNI) standard space to serve as reference in automated image analyses. Manual HarP tracings on the high-resolution MNI152 standard space template of four expert certified HarP tracers were combined to obtain consensual bilateral hippocampus labels. Utility and validity of these reference labels is demonstrated in a simple atlas-based morphometry approach for automated calculation of HarP-compliant hippocampal volumes within SPM software. Individual tracings showed very high agreement among the four expert tracers (pairwise Jaccard indices 0.82-0.87). Automatically calculated hippocampal volumes were highly correlated (rL/R = 0.89/0.91) with gold standard volumes in the HarP benchmark data set (N = 135 MRIs), with a mean volume difference of 9% (standard deviation 7%). The consensual HarP hippocampus labels in the MNI152 template can serve as a reference standard for automated image analyses involving MNI standard space normalization. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  1. Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer's disease in veterans, using the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Weiner, Michael W; Veitch, Dallas P; Hayes, Jacqueline; Neylan, Thomas; Grafman, Jordan; Aisen, Paul S; Petersen, Ronald C; Jack, Clifford; Jagust, William; Trojanowski, John Q; Shaw, Leslie M; Saykin, Andrew J; Green, Robert C; Harvey, Danielle; Toga, Arthur W; Friedl, Karl E; Pacifico, Anthony; Sheline, Yvette; Yaffe, Kristine; Mohlenoff, Brian

    2014-06-01

    Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the

  2. Medication for Alzheimer’s Disease and Associated Fall Hazard: a Retrospective Cohort Study from the Alzheimer’s Disease Neuro-Imaging Initiative

    PubMed Central

    Epstein, Noam U.; Guo, Rong; Farlow, Martin R.; Singh, Jaswinder P.; Fisher, Morris

    2014-01-01

    Background Falls are common in the elderly, especially in those with cognitive impairment. The elderly are often treated with several medications which may have both beneficial and deleterious effects. The use and type of medication in Alzheimer’s patients and association with falls is limited. Objective We examined the association between falls and medication use in the Alzheimer’s Disease Neuro-Imaging Initiative (ADNI). Methods Diagnosis, demographics, medication use, apolipoprotein E4 allele status and functional activity level at baseline were gathered for 810 participants enrolled in ADNI including healthy controls and subjects with mild cognitive impairment or Alzheimer’s. Adverse event fall reports were tabulated. Baseline characteristics were compared between subjects with and without one or more falls. Cox proportional hazards models were conducted to evaluate the association between subject characteristics and hazard of first fall. Results Age (p<0.0001), functional activities questionnaire (p=0.035), Beers list (p=0.0477) and medications for treating cognitive symptoms of Alzheimer’s (p=0.0019) were associated with hazard of fall in the univariate model. In the final multivariate model, after adjusting for covariates, Alzheimer’s medication use (p=0.0005) was associated with hazard of fall. Medication was changed after an adverse fall event by the clinician in 9% of the falls. About 7% of the falls were reported as serious adverse events and 6% were reported to be severe. Conclusion We found a significant association between use of symptomatic medication treating cognitive symptoms in Alzheimer’s disease and hazard of fall after adjusting for age and Beers list medication use. Additional pharmaco-vigilance of the association between falls and Alzheimer’s medication use is warranted. PMID:24357133

  3. Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Russo, María J; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F

    2017-01-01

    Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ(2) = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI.

  4. Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative

    PubMed Central

    Russo, María J.; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F.; Weiner, Michael W.

    2017-01-01

    Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ2 = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI. PMID:28344552

  5. Neuroimaging Biomarkers of Neurodegenerative Diseases and Dementia

    PubMed Central

    Risacher, Shannon L.; Saykin, Andrew J.

    2014-01-01

    Neurodegenerative disorders leading to dementia are common diseases that affect many older and some young adults. Neuroimaging methods are important tools for assessing and monitoring pathological brain changes associated with progressive neurodegenerative conditions. In this review, the authors describe key findings from neuroimaging studies (magnetic resonance imaging and radionucleotide imaging) in neurodegenerative disorders, including Alzheimer’s disease (AD) and prodromal stages, familial and atypical AD syndromes, frontotemporal dementia, amyotrophic lateral sclerosis with and without dementia, Parkinson’s disease with and without dementia, dementia with Lewy bodies, Huntington’s disease, multiple sclerosis, HIV-associated neurocognitive disorder, and prion protein associated diseases (i.e., Creutzfeldt-Jakob disease). The authors focus on neuroimaging findings of in vivo pathology in these disorders, as well as the potential for neuroimaging to provide useful information for differential diagnosis of neurodegenerative disorders. PMID:24234359

  6. Psychosis in Alzheimer's disease is associated with frontal metabolic impairment and accelerated decline in working memory: findings from the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Koppel, Jeremy; Sunday, Suzanne; Goldberg, Terry E; Davies, Peter; Christen, Erica; Greenwald, Blaine S

    2014-07-01

    An ascendant body of evidence suggests that Alzheimer disease with psychosis (AD+P) is a distinct variant of illness with its own genetic diathesis and a unique clinical course. Impaired frontal lobe function has been previously implicated in AD+P. The current exploratory study, presented in two parts, evaluates both the regional brain metabolic and psychometric correlates of psychosis in a longitudinal sample of subjects with AD, made available by the Alzheimer's Disease Neuroimaging Initiative (ADNI). In Part 1 of the study, 21 ADNI participants with AD who developed psychotic symptoms during the study but were not psychotic at baseline were matched with 21 participants with AD who never became psychotic during the study period, and mean brain [F(18)]fluorodeoxyglucose positron emission tomography (FDG-PET) Cerebral metabolic rate for glucose (CMRgl) by regions of interest (ROIs) were compared Additionally, 39 participants with active psychosis at the time of image acquisition were matched with 39 participants who were never psychotic during the study period, and mean brain FDG-PET CMRgl by sROI were compared. In Part 2 of the study, 354 ADNI participants with AD who were followed for 24 months with serial psychometric testing were identified, and cognitive performance and decline were evaluated for correlation with psychotic symptoms. Part 1: There were no regional brain metabolic differences between those with AD destined to become psychotic and those who did not become psychotic. There was a significant reduction in mean orbitofrontal brain metabolism in those with active psychosis. Part 2: Over the course of study follow-up, psychosis was associated with accelerated decline in functional performance as measured by the Functional Assessment Questionnaire, the Mini-Mental State Examination, and Forward Digit Span. In a sample drawn from the ADNI dataset, our exploratory FDG-PET findings and longitudinal cognitive outcomes support the hypofrontality model of AD

  7. The impact of the Alzheimer's Disease Neuroimaging Initiative 2: What role do public-private partnerships have in pushing the boundaries of clinical and basic science research on Alzheimer's disease?

    PubMed

    Jones-Davis, Dorothy M; Buckholtz, Neil

    2015-07-01

    In the growing landscape of biomedical public-private-partnerships, particularly for Alzheimer's disease, the question is posed as to their value. What impacts do public-private-partnerships have on clinical and basic science research in Alzheimer's disease? The authors answer the question using the Alzheimer's Disease Neuroimaging Initiative (ADNI) as a test case and example. ADNI is an exemplar of how public-private-partnerships can make an impact not only on clinical and basic science research and practice (including clinical trials), but also of how similar partnerships using ADNI as an example, can be designed to create a maximal impact within their fields.

  8. Low plasma ApoE levels are associated with smaller hippocampal size in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort

    PubMed Central

    Teng, Edmond; Chow, Nicole; Hwang, Kristy S.; Thompson, Paul M.; Gylys, Karen H.; Cole, Gregory M.; Jack, Clifford R.; Shaw, Leslie M.; Trojanowski, John Q.; Soares, Holly D.; Weiner, Michael W.; Apostolova, Liana G.

    2014-01-01

    Apoliproprotein E (APOE) genotype is the strongest known genetic risk factor for sporadic Alzheimer’s disease (AD), but the utility of plasma ApoE levels for assessing the severity of underlying neurodegenerative changes remains uncertain. Here we examined cross-sectional associations between plasma ApoE levels and volumetric magnetic resonance imaging (MRI) indices of the hippocampus from 541 participants [57 with normal cognition (NC), 375 with mild cognitive impairment (MCI), and 109 with mild AD] who were enrolled in the Alzheimer’s Disease Neuroimaging Initiative. Across the NC and MCI groups, lower plasma ApoE levels were significantly correlated with smaller hippocampal size, as measured by either hippocampal volume or hippocampal radial distance. These associations were driven primarily by findings from carriers of an APOE ε4 allele, and are consistent with prior reports that lower plasma ApoE levels correlate with greater global cortical Pittsburgh Compound B retention. In this high-risk group, plasma ApoE levels may represent a peripheral marker of underlying AD neuropathology in nondemented elderly individuals. PMID:25547651

  9. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN).

    PubMed

    Cairns, Nigel J; Perrin, Richard J; Franklin, Erin E; Carter, Deborah; Vincent, Benjamin; Xie, Mingqiang; Bateman, Randall J; Benzinger, Tammie; Friedrichsen, Karl; Brooks, William S; Halliday, Glenda M; McLean, Catriona; Ghetti, Bernardino; Morris, John C

    2015-08-01

    It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (eight), Australia (three), UK (one) and Germany (two). By 2014, 41 ADNI and 24 DIAN autopsies (involving nine participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final "gold standard" neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared.

  10. Neuropathologic assessment of participants in two multi-center longitudinal observational studies: the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN)

    PubMed Central

    Cairns, Nigel J.; Perrin, Richard J.; Franklin, Erin E.; Carter, Deborah; Vincent, Benjamin; Xie, Mingqiang; Bateman, Randall J.; Benzinger, Tammie; Friedrichsen, Karl; Brooks, William S; Halliday, Glenda M.; McLean, Catriona; Ghetti, Bernardino; Morris, John C.

    2015-01-01

    It has been hypothesized that the relatively rare autosomal dominant Alzheimer disease (ADAD) may be a useful model of the more frequent, sporadic, late-onset AD (LOAD). Individuals with ADAD have a predictable age at onset and the biomarker profile of ADAD participants in the preclinical stage may be used to predict disease progression and clinical onset. However, the extent to which the pathogenesis and neuropathology of ADAD overlaps with that of LOAD is equivocal. To address this uncertainty, two multicenter longitudinal observational studies, the Alzheimer Disease Neuroimaging Initiative (ADNI) and the Dominantly Inherited Alzheimer Network (DIAN), leveraged the expertise and resources of the existing Knight Alzheimer Disease Research Center (ADRC) at Washington University School of Medicine, St. Louis, Missouri, USA, to establish a Neuropathology Core (NPC). The ADNI/DIAN-NPC is systematically examining the brains of all participants who come to autopsy at the 59 ADNI sites in the USA and Canada and the 14 DIAN sites in the USA (8), Australia (3), UK (1), and Germany (2). By 2014, 41 ADNI and 24 DIAN autopsies (involving 9 participants and 15 family members) had been performed. The autopsy rate in the ADNI cohort in the most recent year was 93% (total since NPC inception: 70%). In summary, the ADNI/DIAN NPC has implemented a standard protocol for all sites to solicit permission for brain autopsy and to send brain tissue to the NPC for a standardized, uniform, and state-of-the-art neuropathologic assessment. The benefit to ADNI and DIAN of the implementation of the NPC is very clear. The NPC provides final ‘gold standard’ neuropathological diagnoses and data against which the antecedent observations and measurements of ADNI and DIAN can be compared. PMID:25964057

  11. Development and Evaluation of a Multiplexed Mass Spectrometry-Based Assay for Measuring Candidate Peptide Biomarkers in Alzheimer’s Disease Neuroimaging Initiative (ADNI) CSF

    PubMed Central

    Spellman, Daniel S.; Wildsmith, Kristin R.; Honigberg, Lee A.; Tuefferd, Marianne; Baker, David; Raghavan, Nandini; Nairn, Angus C.; Croteau, Pascal; Schirm, Michael; Allard, Rene; Lamontagne, Julie; Chelsky, Daniel; Hoffmann, Steven; Potter, William Z.

    2015-01-01

    Purpose We describe the outcome of the Biomarkers Consortium CSF Proteomics Project, a public-private partnership of government, academia, non-profit, and industry. The goal of this study was to evaluate a multiplexed mass spectrometry-based approach for the qualification of candidate Alzheimer’s Disease (AD) biomarkers using CSF samples from the AD Neuroimaging Initiative (ADNI). Experimental Design Reproducibility of sample processing, analytic variability, and ability to detect a variety of analytes of interest were thoroughly investigated. Multiple approaches to statistical analyses assessed whether panel analytes were associated with baseline pathology (MCI, AD) vs. Healthy Controls (CN) or associated with progression for MCI patients, and included: (i) univariate association analyses, (ii) univariate prediction models, (iii) exploratory multivariate analyses, and (iv) supervised multivariate analysis. Results A robust targeted mass spectrometry-based approach for the qualification of candidate AD biomarkers was developed. The results identified several peptides with potential diagnostic or predictive utility, with the most significant differences observed for the following peptides for differentiating (including peptides from Hemoglobin A (HBA), Hemoglobin B (HBB), and Superoxide dismutase (SODE)) or predicting (including peptides from Neuronal pentraxin-2 (NPTX2), Neurosecretory protein VGF (VGF), and Secretogranin-2 (SCG2)) progression vs. non-progression from mild cognitive impairment to AD. Conclusions and Clinical Relevance These data provide potential insights into the biology of CSF in AD and MCI progression and provide a novel tool for AD researchers and clinicians working to improve diagnostic accuracy, evaluation of treatment efficacy, and early diagnosis. PMID:25676562

  12. Neuroimaging of Parkinson's disease: Expanding views.

    PubMed

    Weingarten, Carol P; Sundman, Mark H; Hickey, Patrick; Chen, Nan-kuei

    2015-12-01

    Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson's disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Atypical neuroimaging in Wilson’s disease

    PubMed Central

    Patell, Rushad; Dosi, Rupal; Joshi, Harshal K; Storz, Dennis

    2014-01-01

    Wilson's disease is a rare metabolic disease involving copper metabolism. Neuroimaging plays an important part in evaluation of patients with a neuropsychiatric presentation. We present a case of a 14-year-old girl with atypical confluent white matter disease and cystic degeneration on MRI, with a rapidly progressive course, who succumbed to complications despite treatment with trientine. Wilson's disease should be considered as a differential for leucoencephalopathy in young patients with progressive neurological disease for its early recognition and optimum outcome. PMID:24907221

  14. Structural Neuroimaging Genetics Interactions in Alzheimer’s Disease

    PubMed Central

    Moon, Seok Woo; Dinov, Ivo D.; Kim, Jaebum; Zamanyan, Alen; Hobel, Sam; Thompson, Paul M.; Toga, Arthur W.

    2016-01-01

    This article investigates late-onset cognitive impairment using neuroimaging and genetics biomarkers for subjects participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Eight hundred and eight ADNI subjects were identified and divided into three groups: those with Alzheimer’s Disease (AD), those with mild cognitive impairment (MCI), and asymptomatic normal control (NC) group. Two hundred of the subjects qualified for AD diagnosis at the baseline; three hundred and eighty-three had MCI; and 225 were included in the NC group. The structural magnetic resonance imaging (MRI) data were parcellated using BrainParser, and the 80 most important neuroimaging biomarkers were extracted using the Global Shape Analysis (GSA) Pipeline workflow. We obtained 80 SNPs using Plink analysis via the Pipeline environment. In the AD cohort, rs2137962 was significantly associated with changes in left and right hippocampi and bilaterally in parahippocampal gyri, and rs1498853, rs288503, and rs288496 were significantly associated with hippocampi bilaterally, the right parahippocampal gyrus, and left inferior temporal gyrus. In the MCI cohort, rs17028008 and rs17027976 were significantly associated with right caudate and right fusiform gyrus, and rs2075650 (TOMM40) was significantly associated with right caudate, rs1334496 and rs4829605 were significantly associated with right inferior temporal gyrus. In the NC cohort, Chromosome 15 [rs734854 (STOML1), rs11072463 (PML), rs4886844 (PML) and rs1052242 (PML)] was significantly associated with the both hippocampi and both insular cortex and rs4899412 (RGS6) was significantly associated with caudate related biomarkers. We observed significant correlations between the SNPs and the neuroimaging phenotypes in the 808 subjects in terms of neuroimaging genetics. These results illustrate some of the neuroimaging-genetics associations between the AD, MCI and NC cohorts. PMID:26444770

  15. Early neuroimaging diagnosis of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Jiao, Jianling; Liu, Timon C.; Li, Yan; Liu, Songhao

    2002-04-01

    Neuroimaging has played an important role in evaluating the Alzheimer's disease (AD) patients, and its uses are growing. Magnetic resonance imaging (MRI) may show the presence of cerebral infarcts and white matter disease. Single photon emission computed tomography (SPECT) and positron emission tomography (PET), which visualize such cerebral functions as glucose metabolism and blood flow, may provide positive evidence to support the diagnosis of AD. Electrical impedance tomography (EIT) is a recently developed technique which enables the internal impedance of an object to be imaged noninvasively.

  16. Effects of traumatic brain injury and posttraumatic stress disorder on development of Alzheimer's disease in Vietnam Veterans using the Alzheimer's Disease Neuroimaging Initiative: Preliminary Report.

    PubMed

    Weiner, Michael W; Harvey, Danielle; Hayes, Jacqueline; Landau, Susan M; Aisen, Paul S; Petersen, Ronald C; Tosun, Duygu; Veitch, Dallas P; Jack, Clifford R; Decarli, Charles; Saykin, Andrew J; Grafman, Jordan; Neylanthe, Thomas C

    2017-06-01

    Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) have previously been reported to be associated with increased risk of Alzheimer's disease (AD). We are using biomarkers to study Vietnam Veterans with/without mild cognitive impairment with a history of at least one TBI and/or ongoing PTSD to determine whether these contribute to the development of AD. Potential subjects identified by Veterans Administration records underwent an initial telephone screen. Consented subjects underwent clinical evaluation, lumbar puncture, structural MRI and amyloid PET scans. We observed worse cognitive functioning in PTSD and TBI + PTSD groups, worse global cognitive functioning in the PTSD group, lower superior parietal volume in the TBI + PTSD group, and lower amyloid positivity in the PTSD group, but not the TBI group compared to controls without TBI/PTSD. Medial temporal lobe atrophy was not increased in the PTSD and/or TBI groups. Preliminary results do not indicate that TBI or PTSD increase the risk for AD measured by amyloid PET. Additional recruitment, longitudinal follow-up, and tau PET scans will provide more information in the future.

  17. Soluble BACE-1 Activity and sAβPPβ Concentrations in Alzheimer's Disease and Age-Matched Healthy Control Cerebrospinal Fluid from the Alzheimer's Disease Neuroimaging Initiative-1 Baseline Cohort.

    PubMed

    Savage, Mary J; Holder, Daniel J; Wu, Guoxin; Kaplow, June; Siuciak, Judith A; Potter, William Z

    2015-01-01

    β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) plays an important role in the development of Alzheimer's disease (AD), freeing the amyloid-β (Aβ) N-terminus from the amyloid-β protein precursor (AβPP), the first step in Aβ formation. Increased BACE1 activity in AD brain or cerebrospinal fluid (CSF) has been reported. Other studies, however, found either no change or a decrease with AD diagnosis in either BACE1 activity or sAβPPβ, the N-terminal secreted product of BACE1 (sBACE1) activity on AβPP. Here, sBACE1 enzymatic activity and secreted AβPPβ (sAβPPβ) were measured in Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1) baseline CSF samples and no statistically significant changes were found in either measure comparing healthy control, mild cognitively impaired, or AD individual samples. While CSF sBACE1 activity and sAβPPβ demonstrated a moderate yet significant degree of correlation with each other, there was no correlation of either analyte to CSF Aβ peptide ending at residue 42. Surprisingly, a stronger correlation was demonstrated between CSF sBACE1 activity and tau, which was comparable to that between CSF Aβ₄₂ and tau. Unlike for these latter two analytes, receiver-operator characteristic curves demonstrate that neither CSF sBACE1 activity nor sAβPPβ concentrations can be used to differentiate between healthy elderly and AD individuals.

  18. Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer’s disease in veterans, using the Alzheimer’s Disease Neuroimaging Initiative

    PubMed Central

    Weiner, Michael W.; Veitch, Dallas P.; Hayes, Jacqueline; Neylan, Thomas; Grafman, Jordan; Aisen, Paul S.; Petersen, Ronald C.; Jack, Clifford; Jagust, William; Trojanowski, John Q.; Shaw, Leslie M.; Saykin, Andrew J.; Green, Robert C.; Harvey, Danielle; Toga, Arthur W.; Friedl, Karl E.; Pacifico, Anthony; Sheline, Yvette; Yaffe, Kristine; Mohlenoff, Brian

    2015-01-01

    Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer’s disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid bio-markers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the

  19. Twelve-Month Metabolic Declines in Probable Alzheimer's Disease and Amnestic Mild Cognitive Impairment Assessed Using an Empirically Pre-Defined Statistical Region-of-Interest: Findings from the Alzheimer's Disease Neuroimaging Initiative

    PubMed Central

    Chen, Kewei; Langbaum, Jessica B.S.; Fleisher, Adam S.; Ayutyanont, Napatkamon; Reschke, Cole; Lee, Wendy; Liu, Xiaofen; Bandy, Dan; Alexander, Gene E.; Thompson, Paul M.; Foster, Norman L.; Harvey, Danielle J.; de Leon, Mony J.; Koeppe, Robert A.; Jagust, William J.; Weiner, Michael W.; Reiman, Eric M.

    2010-01-01

    Alzheimer's disease (AD) is characterized by specific and progressive reductions in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose (CMRgl), some of which may precede the onset of symptoms. In this report, we describe twelve-month CMRgl declines in 69 probable AD patients, 154 amnestic mild cognitive impairment (MCI) patients, and 79 cognitively normal controls (NCs) from the AD Neuroimaging Initiative (ADNI) using statistical parametric mapping (SPM). We introduce the use of an empirically predefined statistical region-of-interest (sROI) to characterize CMRgl declines with optimal power and freedom from multiple comparisons, and we estimate the number of patients needed to characterize AD-slowing treatment effects in multi-center randomized clinical trials (RCTs). The AD and MCI groups each had significant twelve-month CMRgl declines bilaterally in posterior cingulate, medial and lateral parietal, medial and lateral temporal, frontal and occipital cortex, which were significantly greater than those in the NC group and correlated with measures of clinical decline. Using sROIs defined based on training sets of baseline and follow-up images to assess CMRgl declines in independent test sets from each patient group, we estimate the need for 66 AD patients or 217 MCI patients per treatment group to detect a 25% AD-slowing treatment effect in a twelve-month, multi-center RCT with 80% power and two-tailed alpha=0.05, roughly one-tenth the number of the patients needed to study MCI patients using clinical endpoints. Our findings support the use of FDG PET, brain-mapping algorithms and empirically pre-defined sROIs in RCTs of AD-slowing treatments. PMID:20202480

  20. Twelve-month metabolic declines in probable Alzheimer's disease and amnestic mild cognitive impairment assessed using an empirically pre-defined statistical region-of-interest: findings from the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Chen, Kewei; Langbaum, Jessica B S; Fleisher, Adam S; Ayutyanont, Napatkamon; Reschke, Cole; Lee, Wendy; Liu, Xiaofen; Bandy, Dan; Alexander, Gene E; Thompson, Paul M; Foster, Norman L; Harvey, Danielle J; de Leon, Mony J; Koeppe, Robert A; Jagust, William J; Weiner, Michael W; Reiman, Eric M

    2010-06-01

    Alzheimer's disease (AD) is characterized by specific and progressive reductions in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose (CMRgl), some of which may precede the onset of symptoms. In this report, we describe twelve-month CMRgl declines in 69 probable AD patients, 154 amnestic mild cognitive impairment (MCI) patients, and 79 cognitively normal controls (NCs) from the AD Neuroimaging Initiative (ADNI) using statistical parametric mapping (SPM). We introduce the use of an empirically pre-defined statistical region-of-interest (sROI) to characterize CMRgl declines with optimal power and freedom from multiple comparisons, and we estimate the number of patients needed to characterize AD-slowing treatment effects in multi-center randomized clinical trials (RCTs). The AD and MCI groups each had significant twelve-month CMRgl declines bilaterally in posterior cingulate, medial and lateral parietal, medial and lateral temporal, frontal and occipital cortex, which were significantly greater than those in the NC group and correlated with measures of clinical decline. Using sROIs defined based on training sets of baseline and follow-up images to assess CMRgl declines in independent test sets from each patient group, we estimate the need for 66 AD patients or 217 MCI patients per treatment group to detect a 25% AD-slowing treatment effect in a twelve-month, multi-center RCT with 80% power and two-tailed alpha=0.05, roughly one-tenth the number of the patients needed to study MCI patients using clinical endpoints. Our findings support the use of FDG PET, brain-mapping algorithms and empirically pre-defined sROIs in RCTs of AD-slowing treatments. Copyright 2010 Elsevier Inc. All rights reserved.

  1. Neuroimaging in Alzheimer disease: an evidence-based review.

    PubMed

    Kantarci, Kejal; Jack, Clifford R

    2003-05-01

    Current clinical criteria (DSM-IIIR and NINCDS-ADRDA) for the diagnosis of dementia and AD are reliable; however, these criteria remain to be validated by clinicians of different levels of expertise at different clinical settings. Structural neuroimaging has an important role in initial evaluation of dementia for ruling out potentially treatable causes. Although CT is the appropriate choice when brain tumors, subdural hematoma, or normal pressure hydrocephalus is suspected, MR imaging is more sensitive to the white-matter changes in vascular dementia. The diagnostic accuracy of PET, SPECT, 1H MRS, and MR volumetry of the hippocampus for distinguishing patients with AD from healthy elderly individuals is comparable to the accuracy of a pathologically confirmed clinical diagnosis. Sensitivity of PET for distinguishing patients with dementia with Lewy bodies from AD, however, is higher than that of clinical evaluation; similarly, SPECT and 1H MRS may be adjuncts to clinical evaluation for distinguishing patients with frontotemporal dementia from those with AD. Neuroimaging is valuable in predicting future development of AD in patients with MCI and in carriers of the ApoE epsilon 4 allele who are at a higher risk of developing AD than are cognitively normal elderly individuals. Quantitative MR techniques (e.g., MR volumetry, DWI, magnetization transfer MR imaging, and 1H MRS) and PET are sensitive to the structural and functional changes in the brains of patients with MCI, and hippocampal volumes on MR imaging are associated with future development of AD in these individuals. PET is also sensitive to the regional metabolic decline in the brains of carriers of the ApoE epsilon 4 allele. The longitudinal decrease of whole brain and hippocampal volumes on MR imaging, NAA levels on 1H MRS, cerebral glucose metabolism on PET, and cerebral blood flow on SPECT are associated with rate of cognitive decline in patients with AD. These neuroimaging markers may be useful for

  2. Neuroimaging in Alzheimer's disease: preclinical challenges toward clinical efficacy.

    PubMed

    Dustin, Derek; Hall, Benjamin M; Annapragada, Ananth; Pautler, Robia G

    2016-09-01

    The scope of this review focuses on recent applications in preclinical and clinical magnetic resonance imaging (MRI) toward accomplishing the goals of early detection and responses to therapy in animal models of Alzheimer's disease (AD). Driven by the outstanding efforts of the Alzheimer's Disease Neuroimaging Initiative (ADNI), a truly invaluable resource, the initial use of MRI in AD imaging has been to assess changes in brain anatomy, specifically assessing brain shrinkage and regional changes in white matter tractography using diffusion tensor imaging. However, advances in MRI have led to multiple efforts toward imaging amyloid beta plaques first without and then with the use of MRI contrast agents. These technological advancements have met with limited success and are not yet appropriate for the clinic. Recent developments in molecular imaging inclusive of high-power liposomal-based MRI contrast agents as well as fluorine 19 ((19)F) MRI and manganese enhanced MRI have begun to propel promising advances toward not only plaque imaging but also using MRI to detect perturbations in subcellular processes occurring within the neuron. This review concludes with a discussion about the necessity for the development of novel preclinical models of AD that better recapitulate human AD for the imaging to truly be meaningful and for substantive progress to be made toward understanding and effectively treating AD. Furthermore, the continued support of outstanding programs such as ADNI as well as the development of novel molecular imaging agents and MRI fast scanning sequences will also be requisite to effectively translate preclinical findings to the clinic.

  3. Neuroimaging of Parkinson’s Disease: Expanding views

    PubMed Central

    Weingarten, Carol P.; Sundman, Mark H.; Hickey, Patrick; Chen, Nankuei

    2015-01-01

    Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson’s disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD. PMID:26409344

  4. Neuroimaging in Parkinson disease: from research setting to clinical practice.

    PubMed

    Politis, Marios

    2014-12-01

    Over the past three decades, neuroimaging studies-including structural, functional and molecular modalities-have provided invaluable insights into the mechanisms underlying Parkinson disease (PD). Observations from multimodal neuroimaging techniques have indicated changes in brain structure and metabolic activity, and an array of neurochemical changes that affect receptor sites and neurotransmitter systems. Characterization of the neurobiological alterations that lead to phenotypic heterogeneity in patients with PD has considerably aided the in vivo investigation of aetiology and pathophysiology, and the identification of novel targets for pharmacological or surgical treatments, including cell therapy. Although PD is now considered to be very complex, no neuroimaging modalities are specifically recommended for routine use in clinical practice. However, conventional MRI and dopamine transporter imaging are commonly used as adjuvant tools in the differential diagnosis between PD and nondegenerative causes of parkinsonism. First-line neuroimaging tools that could have an impact on patient prognosis and treatment strategies remain elusive. This Review discusses the lessons learnt from decades of neuroimaging research in PD, and the promising new approaches with potential applicability to clinical practice.

  5. Alzheimer's disease neuroimaging initiative: a one-year follow up study using tensor-based morphometry correlating degenerative rates, biomarkers and cognition.

    PubMed

    Leow, Alex D; Yanovsky, Igor; Parikshak, Neelroop; Hua, Xue; Lee, Suh; Toga, Arthur W; Jack, Clifford R; Bernstein, Matt A; Britson, Paula J; Gunter, Jeffrey L; Ward, Chadwick P; Borowski, Bret; Shaw, Leslie M; Trojanowski, John Q; Fleisher, Adam S; Harvey, Danielle; Kornak, John; Schuff, Norbert; Alexander, Gene E; Weiner, Michael W; Thompson, Paul M

    2009-04-15

    Tensor-based morphometry can recover three-dimensional longitudinal brain changes over time by nonlinearly registering baseline to follow-up MRI scans of the same subject. Here, we compared the anatomical distribution of longitudinal brain structural changes, over 12 months, using a subset of the ADNI dataset consisting of 20 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with mild cognitive impairment (MCI). Each individual longitudinal change map (Jacobian map) was created using an unbiased registration technique, and spatially normalized to a geometrically-centered average image based on healthy controls. Voxelwise statistical analyses revealed regional differences in atrophy rates, and these differences were correlated with clinical measures and biomarkers. Consistent with prior studies, we detected widespread cerebral atrophy in AD, and a more restricted atrophic pattern in MCI. In MCI, temporal lobe atrophy rates were correlated with changes in mini-mental state exam (MMSE) scores, clinical dementia rating (CDR), and logical/verbal learning memory scores. In AD, temporal atrophy rates were correlated with several biomarker indices, including a higher CSF level of p-tau protein, and a greater CSF tau/beta amyloid 1-42 (ABeta42) ratio. Temporal lobe atrophy was significantly faster in MCI subjects who converted to AD than in non-converters. Serial MRI scans can therefore be analyzed with nonlinear image registration to relate ongoing neurodegeneration to a variety of pathological biomarkers, cognitive changes, and conversion from MCI to AD, tracking disease progression in 3-dimensional detail.

  6. A review of β-amyloid neuroimaging in Alzheimer's disease

    PubMed Central

    Adlard, Paul A.; Tran, Bob A.; Finkelstein, David I.; Desmond, Patricia M.; Johnston, Leigh A.; Bush, Ashley I.; Egan, Gary F.

    2014-01-01

    Alzheimer's disease (AD) is the most common cause of dementia worldwide. As advancing age is the greatest risk factor for developing AD, the number of those afflicted is expected to increase markedly with the aging of the world's population. The inability to definitively diagnose AD until autopsy remains an impediment to establishing effective targeted treatments. Neuroimaging has enabled in vivo visualization of pathological changes in the brain associated with the disease, providing a greater understanding of its pathophysiological development and progression. However, neuroimaging biomarkers do not yet offer clear advantages over current clinical diagnostic criteria for them to be accepted into routine clinical use. Nonetheless, current insights from neuroimaging combined with the elucidation of biochemical and molecular processes in AD are informing the ongoing development of new imaging techniques and their application. Much of this research has been greatly assisted by the availability of transgenic mouse models of AD. In this review we summarize the main efforts of neuroimaging in AD in humans and in mouse models, with a specific focus on β-amyloid, and discuss the potential of new applications and novel approaches. PMID:25400539

  7. Neuroimaging of Cerebrovascular Disease in the Aging Brain

    PubMed Central

    Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.

    2012-01-01

    Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721

  8. Neuroimaging of spinal diseases: a pictorial review.

    PubMed

    Kasdan, Richard B; Howard, Jaime L

    2008-09-01

    Magnetic resonance imaging (MRI) has become a valuable noninvasive, cost-effective tool for accurately evaluating spine disorders. This article affords a comprehensive review of normal anatomy as it relates to MRI interpretation with specific attention to accurately defining nerve root abnormalities. It gives in-depth detail on disc herniation nomenclature with specific examples of disc bulge, disc protrusion, disc extrusion, and disc sequestration. In addition, there are illustrations of various forms of degenerative spine disease, including intradiscal degenerative disease, reactive end plate changes, spinal stenosis, synovial cyst formation, and spinal instability. Differentiating features for separating osteoporotic spine fracture from underlying neoplastic pathologic fracture are illustrated. Finally, examples of both benign and malignant disease are illustrated in the spine with corresponding clinical and MRI examples.

  9. Cross-View Neuroimage Pattern Analysis in Alzheimer's Disease Staging

    PubMed Central

    Liu, Sidong; Cai, Weidong; Pujol, Sonia; Kikinis, Ron; Feng, Dagan D.

    2016-01-01

    The research on staging of pre-symptomatic and prodromal phase of neurological disorders, e.g., Alzheimer's disease (AD), is essential for prevention of dementia. New strategies for AD staging with a focus on early detection, are demanded to optimize potential efficacy of disease-modifying therapies that can halt or slow the disease progression. Recently, neuroimaging are increasingly used as additional research-based markers to detect AD onset and predict conversion of MCI and normal control (NC) to AD. Researchers have proposed a variety of neuroimaging biomarkers to characterize the patterns of the pathology of AD and MCI, and suggested that multi-view neuroimaging biomarkers could lead to better performance than single-view biomarkers in AD staging. However, it is still unclear what leads to such synergy and how to preserve or maximize. In an attempt to answer these questions, we proposed a cross-view pattern analysis framework for investigating the synergy between different neuroimaging biomarkers. We quantitatively analyzed nine types of biomarkers derived from FDG-PET and T1-MRI, and evaluated their performance in a task of classifying AD, MCI, and NC subjects obtained from the ADNI baseline cohort. The experiment results showed that these biomarkers could depict the pathology of AD from different perspectives, and output distinct patterns that are significantly associated with the disease progression. Most importantly, we found that these features could be separated into clusters, each depicting a particular aspect; and the inter-cluster features could always achieve better performance than the intra-cluster features in AD staging. PMID:26941639

  10. [Neuroimaging for patients with Alzheimer disease in routine practice].

    PubMed

    Matsuda, Hiroshi

    2010-07-01

    In routine practice neuroimaging has been applied as an adjunct technique for early and differential diagnosis of Alzheimer disease in routine practice. Of the several neuroimaging modalities, magnetic resonance imaging (MRI) and brain perfusion single-photon emission computed tomography (SPECT) have been commonly used in Japan; further software programs are used to aid statistical analysis of the imaging results. For example voxel-based specific regional analysis system for Alzheimer disease (VSRAD) for MRI and easy Z-score imaging system (eZIS) are used for the analysis of MRI and SPECT. In the early stage of Alzheimer disease, specific findings of regional atrophy and perfusion reduction are observed in some areas. In the posterior cingulate gyrus precuneus and parietal cortex, perfusion reduction was more frequently observed than atrophy. On the other hand, in the medial temporal structures, perfusion reduction was less frequently observed than atrophy. Perfusion reduction in the the posterior cingulate gyrus precuneus and in the parietal cortex was more prominent in the case of patients with early-onset Alzheimer disease than in the case of patients with late-onset Alzheimer disease. Further, atrophy in the medial temporal structures was more prominent in the case of patients with late-onset Alzheimer disease than in the case of those with early-onset Alzheimer disease. These findings are helpful for differentiating of Alzheimer disease from other diseases characterized by dementia.

  11. The neurobiology of Alzheimer disease defined by neuroimaging.

    PubMed

    Masdeu, Joseph C; Kreisl, William C; Berman, Karen F

    2012-08-01

    In 2011, a new set of new guidelines for the research diagnosis of three stages of Alzheimer disease was promulgated by the US National Institute of Aging and the Alzheimer Association. For the first time, they include the diagnosis of presymptomatic Alzheimer disease, recognizing that the disease process begins years before cognitive impairment develops. Awareness of this fact has largely been driven by neuroimaging, and particularly by imaging amyloid β (abeta) deposition in the brain, a procedure approved by the US Food and Drug Administration for clinical use in April 2012. In Alzheimer disease, abeta deposition antecedes, probably by decades, the onset of cognitive impairment. In brain regions with greatest abeta deposition, synaptic dysfunction can be imaged beginning at preclinical stages. In regions that are not identical with the ones with greatest abeta deposition but heavily connected with them, regional atrophy and loss of white-matter anisotropy can be detected later in the course of the disease, near the time when mild cognitive impairment supervenes. Together with neuropsychological testing, imaging can improve the prediction of worsening to Alzheimer disease among patients with mild cognitive impairment. These findings have huge implications for research on therapeutic approaches to Alzheimer disease. For instance, while so far only patients with the clinical diagnosis have been treated with immunotherapy targeting abeta removal, a consensus is building that to be effective, this therapy should be given in the preclinical stages of the disease, which are assessed most advantageously by means of neuroimaging.

  12. Graphical Neuroimaging Informatics: Application to Alzheimer’s Disease

    PubMed Central

    Bowman, Ian; Joshi, Shantanu H.; Greer, Vaughan

    2013-01-01

    The Informatics Visualization for Neuroimaging (INVIZIAN) framework allows one to graphically display image and meta-data information from sizeable collections of neuroimaging data as a whole using a dynamic and compelling user interface. Users can fluidly interact with an entire collection of cortical surfaces using only their mouse. In addition, users can cluster and group brains according in multiple ways for subsequent comparison using graphical data mining tools. In this article, we illustrate the utility of INVIZIAN for simultaneous exploration and mining a large collection of extracted cortical surface data arising in clinical neuroimaging studies of patients with Alzheimer’s Disease, mild cognitive impairment, as well as healthy control subjects. Alzheimer’s Disease is particularly interesting due to the wide-spread effects on cortical architecture and alterations of volume in specific brain areas associated with memory. We demonstrate INVIZIAN’s ability to render multiple brain surfaces from multiple diagnostic groups of subjects, showcase the interactivity of the system, and showcase how INVIZIAN can be employed to generate hypotheses about the collection of data which would be suitable for direct access to the underlying raw data and subsequent formal statistical analysis. Specifically, we use INVIZIAN show how cortical thickness and hippocampal volume differences between group are evident even in the absence of more formal hypothesis testing. In the context of neurological diseases linked to brain aging such as AD, INVIZIAN provides a unique means for considering the entirety of whole brain datasets, look for interesting relationships among them, and thereby derive new ideas for further research and study. PMID:24203652

  13. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease

    PubMed Central

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice. PMID:27190672

  14. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease.

    PubMed

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice.

  15. Neuroimaging studies of striatum in cognition part II: Parkinson's disease

    PubMed Central

    Hanganu, Alexandru; Provost, Jean-Sebastien; Monchi, Oury

    2015-01-01

    In recent years a gradual shift in the definition of Parkinson's disease (PD) has been established, from a classical akinetic-rigid movement disorder to a multi-system neurodegenerative disease. While the pathophysiology of PD is complex and goes much beyond the nigro-striatal degeneration, the striatum has been shown to be responsible for many cognitive functions. Patients with PD develop impairments in multiple cognitive domains and the PD model is probably the most extensively studied regarding striatum dysfunction and its influence on cognition. Up to 40% of PD patients present cognitive impairment even in the early stages of disease development. Thus, understanding the key patterns of striatum and connecting regions' influence on cognition will help develop more specific approaches to alleviate cognitive impairment and slow down its decline. This review focuses on the contribution of neuroimaging studies in understanding how striatum impairment affects cognition in PD. PMID:26500512

  16. Ethics Analysis of Neuroimaging in Alzheimer’s Disease

    PubMed Central

    Illes, J.; Rosen, A.; Greicius, M.; Racine, E.

    2009-01-01

    This article focuses on the prospects and ethics of using neuroimaging to predict Alzheimer’s disease (AD). It is motivated by consideration of the historical roles of science in medicine and society, and considerations specifically contemporary of capabilities in imaging and aging, and the benefits and hope they bring. A general consensus is that combinations of imaging methods will ultimately be most fruitful in predicting disease. Their roll-out into translational practice will not be free of complexity, however, as culture and values differ in terms of what defines benefit and risk, who will benefit and who is at risk, what methods must be in place to assure the maximum safety, comfort, and protection of subjects and patients, and educational and policy needs. Proactive planning for the ethical and societal implications of predicting diseases of the aging brain is critical and will benefit all stakeholders— researchers, patients and families, health care providers, and policy makers. PMID:17413029

  17. Neuroimaging biomarkers for Parkinson disease: facts and fantasy.

    PubMed

    Perlmutter, Joel S; Norris, Scott A

    2014-12-01

    In this grand rounds, we focus on development, validation, and application of neuroimaging biomarkers for Parkinson disease (PD). We cover whether such biomarkers can be used to identify presymptomatic individuals (probably yes), provide a measure of PD severity (in a limited fashion, but frequently done poorly), investigate pathophysiology of parkinsonian disorders (yes, if done carefully), play a role in differential diagnosis of parkinsonism (not well), and investigate pathology underlying cognitive impairment (yes, in conjunction with postmortem data). Along the way, we clarify several issues about definitions of biomarkers and surrogate endpoints. The goal of this lecture is to provide a basis for interpreting current literature and newly proposed clinical tools in PD. In the end, one should be able to critically distinguish fact from fantasy. © 2014 American Neurological Association.

  18. Neuroimaging enrichment strategy for secondary prevention trials in Alzheimer disease.

    PubMed

    McEvoy, Linda K; Edland, Steven D; Holland, Dominic; Hagler, Donald J; Roddey, J Cooper; Fennema-Notestine, Christine; Salmon, David P; Koyama, Alain K; Aisen, Paul S; Brewer, James B; Dale, Anders M

    2010-01-01

    We examined the improvement in statistical power that could be obtained in therapeutic trials for early (predementia) Alzheimer disease by constraining enrollment to individuals with amnestic mild cognitive impairment (MCI) and an atrophy pattern on a screening magnetic resonance imaging (MRI) scan previously found to be predictive of clinical decline, or to individuals with MCI and the apolipoprotein E epsilon 4 genetic risk factor for Alzheimer disease. Treatable effects were defined as absolute change versus change relative to healthy controls (HCs). Data from 168 HC and 299 MCI participants were analyzed to determine sample sizes required to detect 25% slowing in mean rate of decline using global function, cognitive function, and structural measures as outcome variables. Reductions in estimated sample sizes of 10% to 43% were observed using the genetic enrichment strategy; reductions of 43% to 60% were observed with the neuroimaging enrichment strategy. Sample sizes needed to detect slowing in rate of atrophy in MCI relative to HC were dramatically larger than those needed to detect absolute change in atrophy rates. Constraining enrollment to MCI subjects with predictive atrophy on a screening MRI scan could improve the efficiency of clinical trials. Failure to take into account normal age-related changes risks under-powering trials designed to test disease-modifying properties of potential treatments.

  19. Neuroimaging and the search for a cure for Alzheimer disease.

    PubMed

    Petrella, Jeffrey R

    2013-12-01

    As radiologists, our role in the workup of the dementia patient has long been limited by the sensitivity of our imaging tools and lack of effective treatment options. Over the past 30 years, we have made tremendous strides in understanding the genetic, molecular, and cellular basis of Alzheimer disease (AD). We now know that the pathologic features of AD are present 1 to 2 decades prior to development of symptoms, though currently approved symptomatic therapies are administered much later in the disease course. The search for true disease-modifying therapy continues and many clinical trials are underway. Current outcome measures, based on cognitive tests, are relatively insensitive to pathologic disease progression, requiring long, expensive trials with large numbers of participants. Biomarkers, including neuroimaging, have great potential to increase the power of trials by matching imaging methodology with therapeutic mechanism. One of the most important advances over the past decade has been the development of in vivo imaging probes targeted to amyloid beta protein, and one agent is already available for clinical use. Additional advances include automated volumetric imaging methods to quantitate cerebral volume loss. Use of such techniques in small, early phase trials are expected to significantly increase the number and quality of candidate drugs for testing in larger trials. In addition to a critical role in trials, structural, molecular, and functional imaging techniques can give us a window on the etiology of AD and other neurodegenerative diseases. This combination of developments has potential to bring diagnostic radiology to the forefront in AD research, therapeutic trials, and patient care.

  20. Emerging Global Initiatives in Neurogenetics: The Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) Consortium.

    PubMed

    Bearden, Carrie E; Thompson, Paul M

    2017-04-19

    The Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) Consortium is a global team science effort, now including over 800 scientists spread across 340 institutions in 35 countries, with the shared goal of understanding disease and genetic influences on the brain. This "crowdsourcing" approach to team neuroscience has unprecedented power for advancing our understanding of both typical and atypical human brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Neuroimaging correlates of cognitive impairment and dementia in Parkinson's disease.

    PubMed

    Mak, Elijah; Su, Li; Williams, Guy B; O'Brien, John T

    2015-08-01

    There has been a gradual shift in the definition of Parkinson's disease, from a movement disorder to a neurodegenerative condition affecting multiple cognitive domains. Mild cognitive impairment (PD-MCI) is a frequent comorbidity in PD that is associated with progression to dementia (PDD) and debilitating consequences for patients and caregivers. At present, the pathophysiology underpinning cognitive impairment in PD is not established, although emerging evidence has suggested that multi-modal imaging biomarkers could be useful in the early diagnosis of PD-MCI and PDD, thereby identifying at-risk patients to enable treatment at the earliest stage possible. Structural MRI studies have revealed prominent grey matter atrophy and disruptions of white matter tracts in PDD, although findings in non-demented PD have been more variable. There is a need for further longitudinal studies to clarify the spatial and temporal progression of morphological changes in PD, as well as to assess their underlying involvement in the evolution of cognitive deficits. In this review, we discuss the aetiology and neuropsychological profiles of PD-MCI and PDD, summarize the putative imaging substrates in light of evidence from multi-modal neuroimaging studies, highlight limitations in the present literature, and suggest recommendations for future research.

  2. Unilateral subthalamotomy in Parkinson's disease: Cognitive, psychiatric and neuroimaging changes.

    PubMed

    Obeso, Ignacio; Casabona, Enrique; Rodríguez-Rojas, Rafael; Bringas, Maria Luisa; Macías, Raúl; Pavón, Nancy; Obeso, Jose A; Jahanshahi, Marjan

    2017-09-01

    Unilateral subthalamotomy is an effective treatment for the cardinal motor features of Parkinson's disease (PD). However, non-motor changes possibly associated with right or left subthalamotomy remain unknown. Our aim was to assess cognitive, psychiatric and neuroimaging changes after treatment with unilateral subthalamotomy. Fourteen medicated patients with PD were evaluated before and after (mean 6 months after operation) unilateral subthalamotomy (5 right, 9 left). In addition to motor assessments, cognitive (global cognition and executive functions), psychiatric (apathy, depression, anxiety, mania, hypo- and hyperdopaminergic behaviours, impulsivity), quality of life evaluations and volume of lesions were obtained. After surgery, significant improvement of motor signs was observed. Unilateral subthalamotomy improved general cognitive status, but left subthalamotomy reduced semantic verbal fluency compared to the pre-operative state. Depression and quality of life were improved with both right and left subthalamotomy. However, hyper-emotionality was present after surgery and right subthalamotomy increased impulsivity and disinhibition (on NeuroPsychiatric Inventory and Ardouin Scale for Behaviour in PD), a result linked to larger lesion volumes. We conclude that unilateral subthalamotomy is effective for treating the cardinal motor features of PD and improves mood. Right subthalamotomy is associated with greater risk of impulsivity and disinhibition, while left subthalamotomy induces further impairment of semantic verbal fluency. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The Ontario Neurodegenerative Disease Research Initiative (ONDRI).

    PubMed

    Farhan, Sali M K; Bartha, Robert; Black, Sandra E; Corbett, Dale; Finger, Elizabeth; Freedman, Morris; Greenberg, Barry; Grimes, David A; Hegele, Robert A; Hudson, Chris; Kleinstiver, Peter W; Lang, Anthony E; Masellis, Mario; McIlroy, William E; McLaughlin, Paula M; Montero-Odasso, Manuel; Munoz, David G; Munoz, Douglas P; Strother, Stephen; Swartz, Richard H; Symons, Sean; Tartaglia, Maria Carmela; Zinman, Lorne; Strong, Michael J

    2017-03-01

    Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.

  4. Neuroimaging markers for the prediction and early diagnosis of Alzheimer’s disease dementia

    PubMed Central

    Ewers, Michael; Sperling, Reisa A.; Klunk, William E.; Weiner, Michael W.; Hampel, Harald

    2011-01-01

    Alzheimer’s disease (AD) is a progressive age-related neurodegenerative disease. At the time of clinical manifestation of dementia, significant irreversible brain damage is already present, rendering the diagnosis of AD at early stages of the disease an urgent prerequisite for therapeutic treatment to halt, or at least slow, disease progression. In this Review, we discuss various neuroimaging measures that are proving to have potential value as biomarkers of AD pathology for the detection and prediction of AD before the onset of dementia. Recent studies that have identified AD-like structural and functional brain changes in elderly people who are cognitively within the normal range or who have mild cognitive impairment (MCI) are discussed. A dynamic sequence model of changes that occur in neuroimaging markers during the different disease stages is presented and the predictive value of multimodal neuroimaging for AD dementia is considered. PMID:21696834

  5. Structural Neuroimaging of the Medial Temporal Lobe in Alzheimer's Disease Clinical Trials.

    PubMed

    Menéndez-González, Manuel; de Celis Alonso, Benito; Salas-Pacheco, José; Arias-Carrión, Oscar

    2015-01-01

    Atrophy in the medial temporal lobe (MTA) is being used as a criterion to support a diagnosis of Alzheimer's disease (AD). There are several structural neuroimaging approaches for quantifying MTA, including semiquantitative visual rating scales, volumetry (3D), planimetry (2D), and linear measures (1D). Current applications of structural neuroimaging in Alzheimer's disease clinical trials (ADCTs) incorporate it as a tool for improving the selection of subjects for enrollment or for stratification, for tracking disease progression, or providing evidence of target engagement for new therapeutic agents. It may also be used as a surrogate marker, providing evidence of disease-modifying effects. However, despite the widespread use of volumetric magnetic resonance imaging (MRI) in ADCTs, there are some important challenges and limitations, such as difficulties in the interpretation of results, limitations in translating results into clinical practice, and reproducibility issues, among others. Solutions to these issues may arise from other methodologies that are able to link the results of volumetric MRI from trials with conventional MRIs performed in routine clinical practice (linear or planimetric methods). Also of potential benefit are automated volumetry, using indices for comparing the relative rate of atrophy of different regions instead of absolute rates of atrophy, and combining structural neuroimaging with other biomarkers. In this review, authors present the existing structural neuroimaging approaches for MTA quantification. They then discuss solutions to the limitations of the different techniques as well as the current challenges of the field. Finally, they discuss how the current advances in AD neuroimaging can help AD diagnosis.

  6. Evolution of autobiographical memory impairments in Alzheimer's disease and frontotemporal dementia - A longitudinal neuroimaging study.

    PubMed

    Irish, Muireann; Landin-Romero, Ramon; Mothakunnel, Annu; Ramanan, Siddharth; Hsieh, Sharpley; Hodges, John R; Piguet, Olivier

    2017-03-10

    Compromised autobiographical memory (ABM) retrieval is well established in dementia, attributable to degeneration of a core memory brain network. It remains unclear, however, how the progressive spread of atrophy with advancing disease severity impacts ABM retrieval across life epochs. To this end, we conducted a longitudinal study of recent and remote ABM in Alzheimer's disease (AD, n =11), and a frontotemporal lobar degeneration group (FTD, n =13) comprising 7 behavioral variant FTD and 6 semantic dementia patients, in comparison with 23 healthy older Controls. Patients were re-assessed approximately one year following their initial visit and underwent repeat testing and brain imaging. Linear mixed modeling neuroimaging analyses explored disease-specific cortical changes driving ABM alterations over time. AD patients showed comparable ABM profiles across assessment periods however, follow-up performance correlated strongly with lateral temporal lobe integrity. In contrast, recent ABMs were disproportionately disrupted at follow-up relative to baseline in the FTD group, attributable to cortical thinning in posterior brain regions, including the right posterior cingulate cortex. Our findings offer new insights regarding the potential time-specific role of discrete cortical regions in ABM retrieval and the differential fate of formerly evocative memories with advancing disease severity in dementia syndromes.

  7. Disease progression and regression in sporadic small vessel disease-insights from neuroimaging.

    PubMed

    van Leijsen, Esther M C; de Leeuw, Frank-Erik; Tuladhar, Anil M

    2017-06-01

    Cerebral small vessel disease (SVD) is considered the most important vascular contributor to the development of dementia. Comprehensive characterization of the time course of disease progression will result in better understanding of aetiology and clinical consequences of SVD. SVD progression has been studied extensively over the years, usually describing change in SVD markers over time using neuroimaging at two time points. As a consequence, SVD is usually seen as a rather linear, continuously progressive process. This assumption of continuous progression of SVD markers was recently challenged by several studies that showed regression of SVD markers. Here, we provide a review on disease progression in sporadic SVD, thereby taking into account both progression and regression of SVD markers with emphasis on white matter hyperintensities (WMH), lacunes and microbleeds. We will elaborate on temporal dynamics of SVD progression and discuss the view of SVD progression as a dynamic process, rather than the traditional view of SVD as a continuous progressive process, that might better fit evidence from longitudinal neuroimaging studies. We will discuss possible mechanisms and clinical implications of a dynamic time course of SVD, with both progression and regression of SVD markers. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  8. Neuroimaging and genetic risk for Alzheimer's disease and addiction-related degenerative brain disorders.

    PubMed

    Roussotte, Florence F; Daianu, Madelaine; Jahanshad, Neda; Leonardo, Cassandra D; Thompson, Paul M

    2014-06-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer's disease (AD). Here we describe how multi-modal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimaging studies of genetic polymorphisms associated with increased risk for late-onset Alzheimer's disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear.

  9. Relationships between Cognitive Performance, Neuroimaging and Vascular Disease: The DHS-MIND Study.

    PubMed

    Hsu, Fang-Chi; Raffield, Laura M; Hugenschmidt, Christina E; Cox, Amanda; Xu, Jianzhao; Carr, J Jeffery; Freedman, Barry I; Maldjian, Joseph A; Williamson, Jeff D; Bowden, Donald W

    2015-01-01

    Type 2 diabetes mellitus increases the risk of cognitive decline and dementia, and elevated burdens of vascular disease are hypothesized to contribute to this risk. These relationships were examined in the Diabetes Heart Study-MIND using a battery of cognitive tests, neuroimaging measures and subclinical cardiovascular disease (CVD) burden assessed by coronary artery calcified (CAC) plaque. We hypothesized that CAC would attenuate the association between neuroimaging measures and cognition performance. Associations were examined using marginal models in this family-based cohort of 572 European Americans from 263 families. All models were adjusted for age, gender, education, type 2 diabetes and hypertension, with some neuroimaging measures additionally adjusted for intracranial volume. Higher total brain volume was associated with better performance on the Digit Symbol Substitution Task and Semantic Fluency (both p ≤ 7.0 × 10(-4)). Higher gray matter volume was associated with better performance on the Modified Mini-Mental State Examination and Semantic Fluency (both p ≤ 9.0 × 10(-4)). Adjusting for CAC caused minimal changes to the results. Relationships exist between neuroimaging measures and cognitive performance in a type 2 diabetes-enriched European American cohort. Associations were minimally attenuated after adjusting for subclinical CVD. Additional work is needed to understand how subclinical CVD burden interacts with other factors and impacts relationships between neuroimaging and cognitive testing measures. © 2015 S. Karger AG, Basel.

  10. Physiological fluctuations in white matter are increased in Alzheimer's disease and correlate with neuroimaging and cognitive biomarkers.

    PubMed

    Makedonov, Ilia; Chen, J Jean; Masellis, Mario; MacIntosh, Bradley J

    2016-01-01

    The objective of this study was to determine whether physiological fluctuations in white matter (PFWM) on resting-state functional magnetic resonance images could be used as an index of neurodegeneration and Alzheimer's disease (AD). Using resting-state functional magnetic resonance image data from participants in the Alzheimer's Disease Neuroimaging Initiative, PFWM was compared across cohorts: cognitively healthy, mild cognitive impairment, or probable AD. Secondary regression analyses were conducted between PFWM and neuroimaging, cognitive, and cerebrospinal fluid biomarkers. There was an effect of cohort on PFWM (t = 5.08, degree of freedom [df] = 424, p < 5.7 × 10(-7)), after accounting for nuisance effects from head displacement and global signal (t > 6.16). From the neuroimaging data, PFWM was associated with glucose metabolism (t = -2.93, df = 96, p = 0.004) but not ventricular volume (p < 0.49) or hippocampal volume (p > 0.44). From the cognitive data, PFWM was associated with composite memory (t = -3.24, df = 149, p = 0.0015) but not executive function (p > 0.21). PFWM was not associated with cerebrospinal fluid biomarkers. In one final omnibus model to explain PFWM (n = 124), glucose metabolism (p = 0.04) and cohort (p = 0.008) remained significant, as were global and head motion root-mean-square terms, whereas memory was not (p = 0.64). PFWM likely reflects end-arteriole intracranial pulsatility effects that may provide additional diagnostic potential in the context of AD neurodegeneration.

  11. Multimodal neuroimaging of male and female brain structure in health and disease across the life span

    PubMed Central

    Thompson, Paul M.

    2016-01-01

    Sex differences in brain development and aging are important to identify, as they may help to understand risk factors and outcomes in brain disorders that are more prevalent in one sex compared with the other. Brain imaging techniques have advanced rapidly in recent years, yielding detailed structural and functional maps of the living brain. Even so, studies are often limited in sample size, and inconsistent findings emerge, one example being varying findings regarding sex differences in the size of the corpus callosum. More recently, large‐scale neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium have formed, pooling together expertise, data, and resources from hundreds of institutions around the world to ensure adequate power and reproducibility. These initiatives are helping us to better understand how brain structure is affected by development, disease, and potential modulators of these effects, including sex. This review highlights some established and disputed sex differences in brain structure across the life span, as well as pitfalls related to interpreting sex differences in health and disease. We also describe sex‐related findings from the ENIGMA consortium, and ongoing efforts to better understand sex differences in brain circuitry. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc. PMID:27870421

  12. Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis.

    PubMed

    Conrado, Daniela J; Nicholas, Timothy; Tsai, Kuenhi; Macha, Sreeraj; Sinha, Vikram; Stone, Julie; Corrigan, Brian; Bani, Massimo; Muglia, Pierandrea; Watson, Ian A; Kern, Volker D; Sheveleva, Elena; Marek, Kenneth; Stephenson, Diane T; Romero, Klaus

    2017-07-27

    Given the recognition that disease-modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed-effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was -3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  13. Alzheimer's Disease Cerebrospinal Fluid and Neuroimaging Biomarkers: Diagnostic Accuracy and Relationship to Drug Efficacy.

    PubMed

    Khan, Tapan K; Alkon, Daniel L

    2015-01-01

    Widely researched Alzheimer's disease (AD) biomarkers include in vivo brain imaging with PET and MRI, imaging of amyloid plaques, and biochemical assays of Aβ 1 - 42, total tau, and phosphorylated tau (p-tau-181) in cerebrospinal fluid (CSF). In this review, we critically evaluate these biomarkers and discuss their clinical utility for the differential diagnosis of AD. Current AD biomarker tests are either highly invasive (requiring CSF collection) or expensive and labor-intensive (neuroimaging), making them unsuitable for use in the primary care, clinical office-based setting, or to assess drug efficacy in clinical trials. In addition, CSF and neuroimaging biomarkers continue to face challenges in achieving required sensitivity and specificity and minimizing center-to-center variability (for CSF-Aβ 1 - 42 biomarkers CV = 26.5% ; http://www.alzforum.org/news/conference-coverage/paris-standardization-hurdle-spinal-fluid-imaging-markers). Although potentially useful for selecting patient populations for inclusion in AD clinical trials, the utility of CSF biomarkers and neuroimaging techniques as surrogate endpoints of drug efficacy needs to be validated. Recent trials of β- and γ-secretase inhibitors and Aβ immunization-based therapies in AD showed no significant cognitive improvements, despite changes in CSF and neuroimaging biomarkers. As we learn more about the dysfunctional cellular and molecular signaling processes that occur in AD, and how these processes are manifested in tissues outside of the brain, new peripheral biomarkers may also be validated as non-invasive tests to diagnose preclinical and clinical AD.

  14. The Use of Neuroimaging in the Diagnosis of Mitochondrial Disease

    ERIC Educational Resources Information Center

    Friedman, Seth D.; Shaw, Dennis W. W.; Ishak, Gisele; Gropman, Andrea L.; Saneto, Russell P.

    2010-01-01

    Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation…

  15. The Use of Neuroimaging in the Diagnosis of Mitochondrial Disease

    ERIC Educational Resources Information Center

    Friedman, Seth D.; Shaw, Dennis W. W.; Ishak, Gisele; Gropman, Andrea L.; Saneto, Russell P.

    2010-01-01

    Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation…

  16. Aging, neurodegenerative disease, and traumatic brain injury: the role of neuroimaging.

    PubMed

    Esopenko, Carrie; Levine, Brian

    2015-02-15

    Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease.

  17. Correlations of clinical, neuroimaging, and electrophysiological features in Hirayama disease

    PubMed Central

    Liao, Ming-Feng; Chang, Hong-Shiu; Chang, Kuo-Hsuan; Ro, Long-Sun; Chu, Chun-Che; Kuo, Hung-Chou; Lyu, Rong-Kuo

    2016-01-01

    Abstract Hirayama disease (HD) is characterized by development of asymmetric forearm muscle atrophy during adolescence with or without focal cervical spinal cord atrophy. The purpose of this study is to assess the correlation of clinical symptoms, disease progression, and electrophysiological findings with cervical spine magnetic resonance imaging (MRI) findings. The medical records, cervical spine MRIs, and electrophysiological findings of 44 HD patients were retrospectively reviewed and analyzed. Denervation changes in any single C5 to C7 root-innervated muscle (deltoid, biceps, triceps, or extensor digitorum communis) occurred more frequently in the 25 patients with cord atrophy than the 19 patients without cord atrophy (88% vs 53%, P = 0.02). Onset age, duration of disease progression, neurological examinations, nerve conduction study, and electromyographic findings from individual muscles were similar between patient groups. Compared with HD patients without cord atrophy, HD patients with cord atrophy experience a more severe denervation change in C5 to C7 root-innervated muscles. PMID:27428223

  18. The role of neuroimaging in the early diagnosis and evaluation of Parkinson's disease.

    PubMed

    Seibyl, J; Jennings, D; Tabamo, R; Marek, K

    2005-10-01

    The development of imaging biomarkers which target specific sites in the brain represents a significant advance in neurodegenerative diseases and Parkinson's disease with the promise of new and improved approaches for the early and accurate diagnosis of disease as well as novel ways to monitor patients and assess treatment. The 3 major applications of imaging may play a role in Parkinson's disease include: 1) the use of neuroimaging as a biomarker of disease in order to improve the accuracy, timeliness, and reliability of diagnosis; 2) objective monitoring of the progression of disease to provide a molecular phenotype of Parkinson's disease which may illuminate some of the sources of clinical variability; 3) the evaluation of so-called ''disease-modifying'' treatments designed to retard the progression of disease by interfering with pathways thought implicated in the ongoing neuronal loss or replace dopamine-producing cells. Each of these areas has shown a numbers of critical clinical investigations which have better defined the utility of the imaging tools to these tasks. Nonetheless, current unresolved issues around the clinical role of neuroimaging in monitoring patients over time and validation of quantitative imaging measures of dopaminergic function are immediate issues for the field and the subject of current research efforts and the extension of the lessons learned in Parkinson's to other neurodegenerative diseases including Alzheimer's dementia.

  19. Defining multivariate normative rules for healthy aging using neuroimaging and machine learning: an application to Alzheimer's disease.

    PubMed

    Andrade de Oliveira, Ailton; Carthery-Goulart, Maria Teresa; Oliveira Júnior, Pedro Paulo de Magalhães; Carrettiero, Daniel Carneiro; Sato, João Ricardo

    2015-01-01

    Neuroimaging techniques combined with computational neuroanatomy have been playing a role in the investigation of healthy aging and Alzheimer's disease (AD). The definition of normative rules for brain features is a crucial step to establish typical and atypical aging trajectories. To introduce an unsupervised pattern recognition method; to define multivariate normative rules of neuroanatomical measures; and to propose a brain abnormality index. This study was based on a machine learning approach (one class classification or novelty detection) to neuroanatomical measures (brain regions, volume, and cortical thickness) extracted from the Alzheimer's Disease Neuroimaging Initiative (ADNI)'s database. We applied a ν-One-Class Support Vector Machine (ν-OC-SVM) trained with data from healthy subjects to build an abnormality index, which was compared with subjects diagnosed with mild cognitive impairment and AD. The method was able to classify AD subjects as outliers with an accuracy of 84.3% at a false alarm rate of 32.5%. The proposed brain abnormality index was found to be significantly associated with group diagnosis, clinical data, biomarkers, and future conversion to AD. These results suggest that one-class classification may be a promising approach to help in the detection of disease conditions. Our findings support a framework considering the continuum of brain abnormalities from healthy aging to AD, which is correlated with cognitive impairment and biomarkers measurements.

  20. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration

    PubMed Central

    Wardlaw, Joanna M; Smith, Eric E; Biessels, Geert J; Cordonnier, Charlotte; Fazekas, Franz; Frayne, Richard; Lindley, Richard I; O'Brien, John T; Barkhof, Frederik; Benavente, Oscar R; Black, Sandra E; Brayne, Carol; Breteler, Monique; Chabriat, Hugues; DeCarli, Charles; de Leeuw, Frank-Erik; Doubal, Fergus; Duering, Marco; Fox, Nick C; Greenberg, Steven; Hachinski, Vladimir; Kilimann, Ingo; Mok, Vincent; Oostenbrugge, Robert van; Pantoni, Leonardo; Speck, Oliver; Stephan, Blossom C M; Teipel, Stefan; Viswanathan, Anand; Werring, David; Chen, Christopher; Smith, Colin; van Buchem, Mark; Norrving, Bo; Gorelick, Philip B; Dichgans, Martin

    2013-01-01

    Summary Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE). PMID:23867200

  1. Cognitive and Brain Profiles Associated with Current Neuroimaging Biomarkers of Preclinical Alzheimer's Disease.

    PubMed

    Besson, Florent L; La Joie, Renaud; Doeuvre, Loïc; Gaubert, Malo; Mézenge, Florence; Egret, Stéphanie; Landeau, Brigitte; Barré, Louisa; Abbas, Ahmed; Ibazizene, Meziane; de La Sayette, Vincent; Desgranges, Béatrice; Eustache, Francis; Chételat, Gaël

    2015-07-22

    Neuroimaging biomarkers, namely hippocampal volume loss, temporoparietal hypometabolism, and neocortical β-amyloid (Aβ) deposition, are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our aim was to characterize the cognitive and brain profiles of elders classified as positive or negative for each biomarker to further our understanding of their use in the preclinical diagnosis of AD. Fifty-four cognitively normal individuals (age = 65.8 ± 8.3 years) underwent neuropsychological tests (structural MRI, FDG-PET, and Florbetapir-PET) and were dichotomized into positive or negative independently for each neuroimaging biomarker. Demographic, neuropsychological, and neuroimaging data were compared between positive and negative subgroups. The MRI-positive subgroup had lower executive performances and mixed patterns of lower volume and metabolism in AD-characteristic regions and in the prefrontal cortex. The FDG-positive subgroup showed only hypometabolism, predominantly in AD-sensitive areas extending to the whole neocortex, compared with the FDG-negative subgroup. The amyloid-positive subgroup was older and included more APOE ε4 carriers compared with the amyloid-negative subgroup. When considering MRI and/or FDG biomarkers together (i.e., the neurodegeneration-positive), there was a trend for an inverse relationship with Aβ deposition such that those with neurodegeneration tended to show less Aβ deposition and the reverse was true as well. Our findings suggest that: (1) MRI and FDG biomarkers provide complementary rather than redundant information and (2) relatively young cognitively normal elders tend to have either neurodegeneration or Aβ deposition, but not both, suggesting additive rather than sequential/causative links between AD neuroimaging biomarkers at this age. Significance statement: Neuroimaging biomarkers are included in

  2. Visuospatial processing in early Alzheimer's disease: a multimodal neuroimaging study.

    PubMed

    Jacobs, Heidi I L; Gronenschild, Ed H B M; Evers, Elisabeth A T; Ramakers, Inez H G B; Hofman, Paul A M; Backes, Walter H; Jolles, Jelle; Verhey, Frans R J; Van Boxtel, Martin P J

    2015-03-01

    Dorsal pathway dysfunctions are thought to underlie visuospatial processing problems in Alzheimer disease (AD). Prior studies reported compensatory mechanisms in the dorsal or ventral pathway in response to these functional changes. Since functional and structural connectivity are interrelated, these functional changes could be interpreted as a disconnection between both pathways. To better understand functional alterations in the dorsal pathway, we combined functional imaging with diffusion tensor imaging (DTI) in patients with mild cognitive impairment (MCI), a likely prodromal stage of AD. Eighteen older male individuals with amnestic MCI (aMCI) and 18 male cognitively healthy individuals, matched for age (range 59-75 years) and education, performed an object recognition task in the Magnetic Resonance Imaging (MRI) scanner. Neural activation was measured during recognition of non-canonically versus canonically oriented objects. Regions showing activation differences between groups were also investigated by DTI. Recognition of non-canonical objects elicited increased frontal, temporal and parietal activation. Combining the functional MRI (fMRI) with the DTI results showed less deactivation in areas with decreased diffusion (mediolateral parietal and orbitofrontal) and increased activation in areas with increased diffusion (parietal and temporal) in aMCI patients. Finally, in aMCI patients decreased diffusion was found in the hippocampal cingulum, connecting both pathways. Our results showed increased activation in early AD patients in ventral and dorsal pathways. A decrease in deactivation and diffusion suggests functional reorganization, while increased activation and diffusion suggests compensatory processes. This is the first study showing structural evidence for functional reorganization, which may be related to connectivity loss in the cingulum. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Brain structure and function related to depression in Alzheimer's disease: contributions from neuroimaging research.

    PubMed

    Brommelhoff, Jessica A; Sultzer, David L

    2015-01-01

    The development of minimally invasive in vivo methods for imaging the brain has allowed for unprecedented advancement in our understanding of brain-behavior relationships. Structural, functional, and multimodal neuroimaging techniques have become more sophisticated in detecting structural and physiological abnormalities that may underlie various affective disorders and neurological illnesses such as depression in Alzheimer's disease (AD). In general, neuroimaging studies of depression in AD investigate whether depression is associated with damage to structures in specific neural networks involving frontal and subcortical structures or with functional disruption of cortical neural systems. This review provides an overview of how various imaging modalities have contributed to our understanding of the neurobiology of depression in AD. At present, the literature does not conclusively support any specific pathogenesis for depression, and it is not clear whether patients with AD and depression have histopathological and neurochemical characteristics that contribute to mood symptoms that are different from cognitively intact individuals with depression. Neuroimaging studies suggest that atrophy of temporal or frontal structures, white matter lesions in frontal lobe or subcortical systems, reduced activity in dorsolateral frontal cortex, or small vessel cerebrovascular disease may be associated with depression in AD. Conceptual, clinical, and methodological challenges in studying this relationship are discussed. Further work is needed to understand the specific brain structures, relevant white matter tracts, and interactions among them that are most important. This review concludes with potential directions for future research.

  4. The search for neuroimaging biomarkers of Alzheimer's disease with advanced MRI techniques.

    PubMed

    Li, Tie-Qiang; Wahlund, Lars-Olof

    2011-03-01

    The aim of this review is to examine the recent literature on using advanced magnetic resonance imaging (MRI) techniques for finding neuroimaging biomarkers that are sensitive to the detection of risks for Alzheimer's disease (AD). Since structural MRI techniques, such as brain structural volumetry and voxel-based morphometry (VBM), have been widely used for AD studies and extensively reviewed, we will only briefly touch on the topics of volumetry and morphometry. The focus of the current review is about the more recent developments in the search for AD neuroimaging biomarkers with functional MRI (fMRI), resting-state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), arterial spin-labeling (ASL), and magnetic resonance spectroscopy (MRS).

  5. The Use of Neuroimaging to Assess Associations Among Diet, Nutrients, Metabolic Syndrome, and Alzheimer's Disease.

    PubMed

    Pistollato, Francesca; Cano, Sandra Sumalla; Elio, Iñaki; Vergara, Manuel Masias; Giampieri, Francesca; Battino, Maurizio

    2015-01-01

    In the last decade, specific dietary patterns, mainly characterized by high consumption of vegetables and fruits, have been proven beneficial for the prevention of both metabolic syndrome (MetS)-related dysfunctions and neurodegenerative disorders, such as Alzheimer's disease (AD). Nowadays, neuroimaging readouts can be used to diagnose AD, investigate MetS effects on brain functionality and anatomy, and assess the effects of dietary supplementations and nutritional patterns in relation to neurodegeneration and AD-related features. Here we review scientific literature describing the use of the most recent neuroimaging techniques to detect AD- and MetS-related brain features, and also to investigate associations between consolidated dietary patterns or nutritional interventions and AD, specifically focusing on observational and intervention studies in humans.

  6. Multimodal Neuroimaging Feature Learning with Multimodal Stacked Deep Polynomial Networks for Diagnosis of Alzheimer's Disease.

    PubMed

    Shi, Jun; Zheng, Xiao; Li, Yan; Zhang, Qi; Ying, Shihui

    2017-01-19

    The accurate diagnosis of Alzheimer's disease (AD) and its early stage, i.e. mild cognitive impairment (MCI), is essential for timely treatment and possible delay of AD. Fusion of multimodal neuroimaging data, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), has shown its effectiveness for AD diagnosis. The deep polynomial networks (DPN) is a recently proposed deep learning algorithm, which performs well on both large-scale and small-size datasets. In this study, a multimodal stacked DPN (MM-SDPN) algorithm, which MM-SDPN consists of two-stage SDPNs, is proposed to fuse and learn feature representation from multimodal neuroimaging data for AD diagnosis. Specifically speaking, two SDPNs are first used to learn high-level features of MRI and PET, respectively, which are then fed to another SDPN to fuse multimodal neuroimaging information. The proposed MM-SDPN algorithm is applied to the ADNI dataset to conduct both binary classification and multiclass classification tasks. Experimental results indicate that MM-SDPN is superior over the state-of-the-art multimodal feature learning based algorithms for AD diagnosis.

  7. ANIMA: A data-sharing initiative for neuroimaging meta-analyses.

    PubMed

    Reid, Andrew T; Bzdok, Danilo; Genon, Sarah; Langner, Robert; Müller, Veronika I; Eickhoff, Claudia R; Hoffstaedter, Felix; Cieslik, Edna-Clarisse; Fox, Peter T; Laird, Angela R; Amunts, Katrin; Caspers, Svenja; Eickhoff, Simon B

    2016-01-01

    Meta-analytic techniques allow cognitive neuroscientists to pool large amounts of data across many individual task-based functional neuroimaging experiments. These methods have been aided by the introduction of online databases such as Brainmap.org or Neurosynth.org, which collate peak activation coordinates obtained from thousands of published studies. Findings from meta-analytic studies typically include brain regions which are consistently activated across studies for specific contrasts, investigating cognitive or clinical hypotheses. These regions can be subsequently used as the basis for seed-based connectivity analysis, or formally compared to neuroimaging data in order to help interpret new findings. To facilitate such approaches, we have developed a new online repository of meta-analytic neuroimaging results, named the Archive of Neuroimaging Meta-analyses (ANIMA). The ANIMA platform consists of an intuitive online interface for querying, downloading, and contributing data from published meta-analytic studies. Additionally, to aid the process of organizing, visualizing, and working with these data, we present an open-source desktop application called Volume Viewer. Volume Viewer allows users to easily arrange imaging data into composite stacks, and save these sessions as individual files, which can also be uploaded to the ANIMA database. The application also allows users to perform basic functions, such as computing conjunctions between images, or extracting regions-of-interest or peak coordinates for further analysis. The introduction of this new resource will enhance the ability of researchers to both share their findings and incorporate existing meta-analytic results into their own research. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration.

    PubMed

    Wardlaw, Joanna M; Smith, Eric E; Biessels, Geert J; Cordonnier, Charlotte; Fazekas, Franz; Frayne, Richard; Lindley, Richard I; O'Brien, John T; Barkhof, Frederik; Benavente, Oscar R; Black, Sandra E; Brayne, Carol; Breteler, Monique; Chabriat, Hugues; Decarli, Charles; de Leeuw, Frank-Erik; Doubal, Fergus; Duering, Marco; Fox, Nick C; Greenberg, Steven; Hachinski, Vladimir; Kilimann, Ingo; Mok, Vincent; Oostenbrugge, Robert van; Pantoni, Leonardo; Speck, Oliver; Stephan, Blossom C M; Teipel, Stefan; Viswanathan, Anand; Werring, David; Chen, Christopher; Smith, Colin; van Buchem, Mark; Norrving, Bo; Gorelick, Philip B; Dichgans, Martin

    2013-08-01

    Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE). Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Cognitive Impairment and Structural Neuroimaging Abnormalities Among Patients with Chronic Kidney Disease.

    PubMed

    Pi, Hai-Chen; Xu, Yu-Feng; Xu, Rong; Yang, Zhi-Kai; Qu, Zhen; Chen, Yu-Qing; Liu, Gui-Ling; Dong, Jie

    2016-01-01

    Cognitive impairment and abnormal structural neuroimaging is common in chronic kidney disease patients. We aimed to explore its association with dialysis modality and the relationship between cognitive impairment and abnormal structural neuroimaging. Sixty peritoneal dialysis patients and 30 hemodialysis and 30 non-dialyzed stage 3-5 chronic kidney disease patients without history of stroke were enrolled for the study. Participants were matched for age, gender, education, diabetes status, and dialysis duration (if appropriate). Cognitive functions were measured using a battery of recognized instruments. Brain features were examined with 3-dimensional magnetic resonance imaging. Cognitive impairment was significantly more severe in dialysis patients than in non-dialyzed patients. The global and specific cognitive function were not significantly different between patients on peritoneal dialysis and hemodialysis. Hemodialysis patients had more severe white matter hyperintensity, sulcal and ventricular atrophy, and SVIs than other patients. In all groups, higher white matter grade, ventricular grade, and hippocampal atrophy were significantly associated with global cognitive impairment, with hazard ratios of 1.80 (1.22-2.64), 1.67 (1.09-2.57), and 2.49 (1.07-5.77), respectively. White matter grade was also significantly associated with delayed memory (hazard ratio 1.63; 1.12-2.39). Dialysis modality showed no association with cognitive impairment, although hemodialysis patients had more severe neuroimaging abnormalities. For the whole group, white matter hyperintensity, and ventricular and hippocampal atrophy, were independently associated with global cognitive impairment in chronic kidney disease patients. © 2016 The Author(s) Published by S. Karger AG, Basel.

  10. Applied Neuroimaging to the Diagnosis of Alzheimer's Disease: A Multicriteria Model

    NASA Astrophysics Data System (ADS)

    Tamanini, Isabelle; de Castro, Ana Karoline; Pinheiro, Plácido Rogério; Pinheiro, Mirian Calíope Dantas

    In the last few years, Alzheimer's disease has been the most frequent cause of dementia and it is responsible, alone or in association with other diseases, for 50% of the cases in western countries. Dementias are syndromes characterized by a decline in memory and other neuropsychological changes, especially occurring in elderly people and increasing exponentially along the aging process. The main focus of this work is to develop a multicriteria model for aiding in decision making on the diagnosis of Alzheimer's disease by using the Aranau Tool, structured on the Verbal Decision Analysis. In this work, the modeling and evaluation processes were conducted with the aid of a medical expert, bibliographic sources and questionnaires. The questionnaires taken into account were based mainly on patients' neuroimaging tests, and we analyzed wheter or not there were problems in the patients' brain that could be relevant to the diagnosis of Alzheimer's disease.

  11. Multi-Modal Neuroimaging Feature Learning for Multi-Class Diagnosis of Alzheimer’s Disease

    PubMed Central

    Liu, Siqi; Liu, Sidong; Cai, Weidong; Che, Hangyu; Pujol, Sonia; Kikinis, Ron; Feng, Dagan; Fulham, Michael J.

    2015-01-01

    The accurate diagnosis of Alzheimers disease (AD) is essential for patient care and will be increasingly important as disease modifying agents become available, early in the course of the disease. Although studies have applied machine learning methods for the computer aided diagnosis (CAD) of AD, a bottleneck in the diagnostic performance was shown in previous methods, due to the lacking of efficient strategies for representing neuroimaging biomarkers. In this study, we designed a novel diagnostic framework with deep learning architecture to aid the diagnosis of AD. This framework uses a zero-masking strategy for data fusion to extract complementary information from multiple data modalities. Compared to the previous state-of-the-art workflows, our method is capable of fusing multi-modal neuroimaging features in one setting and has the potential to require less labelled data. A performance gain was achieved in both binary classification and multi-class classification of AD. The advantages and limitations of the proposed framework are discussed. PMID:25423647

  12. Structural and Functional Neuroimaging of Visual Hallucinations in Lewy Body Disease: A Systematic Literature Review

    PubMed Central

    Cagnin, Annachiara; Bandmann, Oliver; Venneri, Annalena

    2017-01-01

    Patients with Lewy body disease (LBD) frequently experience visual hallucinations (VH), well-formed images perceived without the presence of real stimuli. The structural and functional brain mechanisms underlying VH in LBD are still unclear. The present review summarises the current literature on the neural correlates of VH in LBD, namely Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). Following a systematic literature search, 56 neuroimaging studies of VH in PD and DLB were critically reviewed and evaluated for quality assessment. The main structural neuroimaging results on VH in LBD revealed grey matter loss in frontal areas in patients with dementia, and parietal and occipito-temporal regions in PD without dementia. Parietal and temporal hypometabolism was also reported in hallucinating PD patients. Disrupted functional connectivity was detected especially in the default mode network and fronto-parietal regions. However, evidence on structural and functional connectivity is still limited and requires further investigation. The current literature is in line with integrative models of VH suggesting a role of attention and perception deficits in the development of VH. However, despite the close relationship between VH and cognitive impairment, its associations with brain structure and function have been explored only by a limited number of studies. PMID:28714891

  13. Potential neuroimaging biomarkers of pathologic brain changes in Mild Cognitive Impairment and Alzheimer's disease: a systematic review.

    PubMed

    Ruan, Qingwei; D'Onofrio, Grazia; Sancarlo, Daniele; Bao, Zhijun; Greco, Antonio; Yu, Zhuowei

    2016-05-16

    Neuroimaging-biomarkers of Mild Cognitive Impairment (MCI) allow an early diagnosis in preclinical stages of Alzheimer's disease (AD). The goal in this paper was to review of biomarkers for Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), with emphasis on neuroimaging biomarkers. A systematic review was conducted from existing literature that draws on markers and evidence for new measurement techniques of neuroimaging in AD, MCI and non-demented subjects. Selection criteria included: 1) age ≥ 60 years; 2) diagnosis of AD according to NIAAA criteria, 3) diagnosis of MCI according to NIAAA criteria with a confirmed progression to AD assessed by clinical follow-up, and 4) acceptable clinical measures of cognitive impairment, disability, quality of life, and global clinical assessments. Seventy-two articles were included in the review. With the development of new radioligands of neuroimaging, today it is possible to measure different aspects of AD neuropathology, early diagnosis of MCI and AD become probable from preclinical stage of AD to AD dementia and non-AD dementia. The panel of noninvasive neuroimaging-biomarkers reviewed provides a set methods to measure brain structural and functional pathophysiological changes in vivo, which are closely associated with preclinical AD, MCI and non-AD dementia. The dynamic measures of these imaging biomarkers are used to predict the disease progression in the early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials.

  14. Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson’s disease

    PubMed Central

    Locascio, Joseph J.; Eberly, Shirley; Liao, Zhixiang; Liu, Ganqiang; Hoesing, Ashley N.; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Hung, Albert Y.; Flaherty, Alice W.; Schwarzschild, Michael A.; Hayes, Michael T.; Wills, Anne-Marie; Shivraj Sohur, U.; Mejia, Nicte I.; Selkoe, Dennis J.; Oakes, David; Shoulson, Ira; Dong, Xianjun; Marek, Ken; Zheng, Bin; Ivinson, Adrian; Hyman, Bradley T.; Growdon, John H.; Sudarsky, Lewis R.; Schlossmacher, Michael G.; Ravina, Bernard

    2015-01-01

    There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson’s disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson’s disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson’s disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson’s disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson’s disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease. PMID:26220939

  15. Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.

    PubMed

    Locascio, Joseph J; Eberly, Shirley; Liao, Zhixiang; Liu, Ganqiang; Hoesing, Ashley N; Duong, Karen; Trisini-Lipsanopoulos, Ana; Dhima, Kaltra; Hung, Albert Y; Flaherty, Alice W; Schwarzschild, Michael A; Hayes, Michael T; Wills, Anne-Marie; Shivraj Sohur, U; Mejia, Nicte I; Selkoe, Dennis J; Oakes, David; Shoulson, Ira; Dong, Xianjun; Marek, Ken; Zheng, Bin; Ivinson, Adrian; Hyman, Bradley T; Growdon, John H; Sudarsky, Lewis R; Schlossmacher, Michael G; Ravina, Bernard; Scherzer, Clemens R

    2015-09-01

    There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease.

  16. Bilateral occipital calcification, epilepsy and coeliac disease: clinical and neuroimaging features of a new syndrome.

    PubMed Central

    Magaudda, A; Dalla Bernardina, B; De Marco, P; Sfaello, Z; Longo, M; Colamaria, V; Daniele, O; Tortorella, G; Tata, M A; Di Perri, R

    1993-01-01

    Twenty patients affected by bilateral occipital cortical-subcortical calcification (BOC) are described, 19 (95%) had epilepsy. In 8 of 16 cases studied, intestinal biopsy revealed coeliac disease. Fourteen patients had occipital partial epilepsy with a relatively benign outcome, while 4 patients were affected by a severe form of epilepsy, with very frequent, drug-resistant, generalised and partial seizures with mental deterioration. One patient had a single episode of convulsive status epilepticus at four months of age. The neurological examination was normal in all patients. CT showed flocculo-nodular, cortico-subcortical BOC, without enhancement and without lobar or hemispheric atrophy. MRI was normal. The clinical and neuroimaging features of these patients are different therefore from those with the Sturge-Weber Syndrome. The study confirms a high prevalence of coliac disease in patients with BOC, but the relationship between these two pathologies still needs to be clarified. Images PMID:8350105

  17. Contribution of neuroimaging to the diagnosis of Alzheimer's disease and vascular dementia.

    PubMed

    Román, Gustavo; Pascual, Belén

    2012-11-01

    The aim of this study was to review, summarize and analyze recent findings relevant to the contribution of neuroimaging to the diagnosis of Alzheimer's disease (AD) and vascular dementia (VaD). Computerized tomography (CT) or magnetic resonance imaging (MRI) provide accurate demonstration of the location and rate of progression of atrophic changes affecting the brain in AD and the different types of vascular lesions observed in mixed dementias and in pure VaD. Quantification of cortical thickness allows early diagnosis and rate of progression from mild cognitive impairment (MCI) to dementia. White matter involvement can also be quantified with diffusion tensor imaging (DTI) and functional methods including fMRI, functional connectivity, and MR spectroscopy (MRS). Isotope-based techniques such as positron emission tomography (PET) allow measurement of regional cerebral glucose metabolism using (18)F-2-fluoro-deoxy-D-glucose (FDG). Cerebral blood flow can be measured using PET with H(2)(15)O or with single photon emission computerized tomography (SPECT) with technetium ((99m)Tc-HMPAO) or, more recently, arterial spin label (ASL) imaging. There are isotope markers for amyloid-beta ((11)O-PIB, (18)F-florbetapir), tau ((18)FDDNP) and activated microglia ((11)C-PK11195). Neuroimaging markers are particularly useful at the early symptomatic and preclinical asymptomatic phases of AD, as well as serving as endpoints in clinical trials.

  18. Neuroimaging of brain changes associated with cognitive impairment in Parkinson’s disease

    PubMed Central

    Christopher, Leigh; Strafella, Antonio P.

    2014-01-01

    Cognitive impairment occurs frequently in Parkinson’s disease (PD) and the concept of Mild Cognitive Impairment in PD (PD-MCI) has recently emerged. Patients with mild impairment are at risk of developing dementia, and thus it is a topic of growing interest. Many previous studies have investigated the neural correlates of cognitive impairment, in particular executive dysfunction, in PD patients without dementia using neuroimaging techniques including structural MRI, functional MRI and PET imaging. These studies, which have provided a foundation for understanding which brain regions and neurotransmitter systems may be involved in executive dysfunction in PD, will be reviewed. Recent neuroimaging studies that have used specific criteria to classify patients as PD-MCI, in the hopes of gaining further insight into the underlying neural mechanisms will also be discussed. In particular, this review will cover key findings involving structural MRI investigating grey and white matter changes, functional MRI to examine changes in neural activation and PET imaging to investigate metabolic and neurochemical changes that have led to an improved understanding of pathology associated with executive dysfunction in PD without dementia and PD-MCI. PMID:23551844

  19. Noncognitive Behavioral Changes Associated With Alzheimer's Disease: Implications of Neuroimaging Findings.

    PubMed

    Victoroff, Jeff; Lin, Feng V; Coburn, Kerry L; Shillcutt, Samuel D; Voon, Valerie; Ducharme, Simon

    2017-09-06

    Alzheimer's disease (AD) is commonly associated with noncognitive behavioral changes (NCBCs). The authors systematically reviewed whether neuroimaging has helped with understanding the pathophysiology, diagnosis, or management of NCBCs associated with AD, including depression, aggression or agitation, anxiety, apathy, psychosis, and sleep disorder. The authors identified dissociable neural substrates with multimodal imaging: depression implicates the lateral and superior prefrontal cortex; apathy and agitation implicate the dorsal anterior cingulate; psychosis implicates right lateralized frontal and medial temporal areas; and anxiety implicates mesial temporal regions. Frontal white matter changes appear to underlie many NCBCs, emphasizing the preventative management of vascular risk factors. Further delineation of underlying neurocircuitry and pathophysiology in larger data sets might lead to biomarker identification for diagnosis and optimizing treatment targets.

  20. Neuroimaging and Other Biomarkers for Alzheimer's Disease: The Changing Landscape of Early Detection

    PubMed Central

    Risacher, Shannon L.; Saykin, Andrew J.

    2014-01-01

    The goal of this review is to provide an overview of biomarkers for Alzheimer's disease (AD), with emphasis on neuroimaging and cerebrospinal fluid (CSF) biomarkers. We first review biomarker changes in patients with late-onset AD, including findings from studies using structural and functional magnetic resonance imaging (MRI), advanced MRI techniques (diffusion tensor imaging, magnetic resonance spectroscopy, perfusion), positron emission tomography with fluorodeoxyglucose, amyloid tracers, and other neurochemical tracers, and CSF protein levels. Next, we evaluate findings from these biomarkers in preclinical and prodromal stages of AD including mild cognitive impairment (MCI) and pre-MCI conditions conferring elevated risk. We then discuss related findings in patients with dominantly inherited AD. We conclude with a discussion of the current theoretical framework for the role of biomarkers in AD and emergent directions for AD biomarker research. PMID:23297785

  1. The behavioural/dysexecutive variant of Alzheimer's disease: clinical, neuroimaging and pathological features.

    PubMed

    Ossenkoppele, Rik; Pijnenburg, Yolande A L; Perry, David C; Cohn-Sheehy, Brendan I; Scheltens, Nienke M E; Vogel, Jacob W; Kramer, Joel H; van der Vlies, Annelies E; La Joie, Renaud; Rosen, Howard J; van der Flier, Wiesje M; Grinberg, Lea T; Rozemuller, Annemieke J; Huang, Eric J; van Berckel, Bart N M; Miller, Bruce L; Barkhof, Frederik; Jagust, William J; Scheltens, Philip; Seeley, William W; Rabinovici, Gil D

    2015-09-01

    A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer's disease pathology. The description of this rare Alzheimer's disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer's disease with a behavioural-predominant presentation (behavioural Alzheimer's disease) and a neuropathological diagnosis of high-likelihood Alzheimer's disease (n = 17) and/or biomarker evidence of Alzheimer's disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer's disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer's disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer's disease: 53%; dysexecutive Alzheimer's disease: 83%) than behavioural (behavioural Alzheimer's disease: 25%; dysexecutive Alzheimer's disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer's disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer's disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer's disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer's disease (typical Alzheimer's disease, n = 58), autopsy-confirmed/Alzheimer's disease biomarker-negative behavioural variant frontotemporal dementia (n = 59

  2. The behavioural/dysexecutive variant of Alzheimer’s disease: clinical, neuroimaging and pathological features

    PubMed Central

    Pijnenburg, Yolande A. L.; Perry, David C.; Cohn-Sheehy, Brendan I.; Scheltens, Nienke M. E.; Vogel, Jacob W.; Kramer, Joel H.; van der Vlies, Annelies E.; Joie, Renaud La; Rosen, Howard J.; van der Flier, Wiesje M.; Grinberg, Lea T.; Rozemuller, Annemieke J.; Huang, Eric J.; van Berckel, Bart N. M.; Miller, Bruce L.; Barkhof, Frederik; Jagust, William J.; Scheltens, Philip; Seeley, William W.; Rabinovici, Gil D.

    2015-01-01

    A ‘frontal variant of Alzheimer’s disease’ has been described in patients with predominant behavioural or dysexecutive deficits caused by Alzheimer’s disease pathology. The description of this rare Alzheimer’s disease phenotype has been limited to case reports and small series, and many clinical, neuroimaging and neuropathological characteristics are not well understood. In this retrospective study, we included 55 patients with Alzheimer’s disease with a behavioural-predominant presentation (behavioural Alzheimer’s disease) and a neuropathological diagnosis of high-likelihood Alzheimer’s disease (n = 17) and/or biomarker evidence of Alzheimer’s disease pathology (n = 44). In addition, we included 29 patients with autopsy/biomarker-defined Alzheimer’s disease with a dysexecutive-predominant syndrome (dysexecutive Alzheimer’s disease). We performed structured chart reviews to ascertain clinical features. First symptoms were more often cognitive (behavioural Alzheimer’s disease: 53%; dysexecutive Alzheimer’s disease: 83%) than behavioural (behavioural Alzheimer’s disease: 25%; dysexecutive Alzheimer’s disease: 3%). Apathy was the most common behavioural feature, while hyperorality and perseverative/compulsive behaviours were less prevalent. Fifty-two per cent of patients with behavioural Alzheimer’s disease met diagnostic criteria for possible behavioural-variant frontotemporal dementia. Overlap between behavioural and dysexecutive Alzheimer’s disease was modest (9/75 patients). Sixty per cent of patients with behavioural Alzheimer’s disease and 40% of those with the dysexecutive syndrome carried at least one APOE ε4 allele. We also compared neuropsychological test performance and brain atrophy (applying voxel-based morphometry) with matched autopsy/biomarker-defined typical (amnestic-predominant) Alzheimer’s disease (typical Alzheimer’s disease, n = 58), autopsy-confirmed/Alzheimer’s disease biomarker-negative behavioural

  3. Identification of Early-Stage Alzheimer's Disease Using Sulcal Morphology and Other Common Neuroimaging Indices

    PubMed Central

    Cai, Kunpeng; Xu, Hong; Guan, Hao; Zhu, Wanlin; Jiang, Jiyang; Cui, Yue; Zhang, Jicong; Liu, Tao; Wen, Wei

    2017-01-01

    Identifying Alzheimer’s disease (AD) at its early stage is of major interest in AD research. Previous studies have suggested that abnormalities in regional sulcal width and global sulcal index (g-SI) are characteristics of patients with early-stage AD. In this study, we investigated sulcal width and three other common neuroimaging morphological measures (cortical thickness, cortical volume, and subcortical volume) to identify early-stage AD. These measures were evaluated in 150 participants, including 75 normal controls (NC) and 75 patients with early-stage AD. The global sulcal index (g-SI) and the width of five individual sulci (the superior frontal, intra-parietal, superior temporal, central, and Sylvian fissure) were extracted from 3D T1-weighted images. The discriminative performances of the other three traditional neuroimaging morphological measures were also examined. Information Gain (IG) was used to select a subset of features to provide significant information for separating NC and early-stage AD subjects. Based on the four modalities of the individual measures, i.e., sulcal measures, cortical thickness, cortical volume, subcortical volume, and combinations of these individual measures, three types of classifiers (Naïve Bayes, Logistic Regression and Support Vector Machine) were applied to compare the classification performances. We observed that sulcal measures were either superior than or equal to the other measures used for classification. Specifically, the g-SI and the width of the Sylvian fissure were two of the most sensitive sulcal measures and could be useful neuroanatomical markers for detecting early-stage AD. There were no significant differences between the three classifiers that we tested when using the same neuroanatomical features. PMID:28129351

  4. APOE genotype and neuroimaging markers of Alzheimer’s disease: systematic review and meta-analysis

    PubMed Central

    Liu, Ying; Yu, Jin-Tai; Wang, Hui-Fu; Han, Pei-Ran; Tan, Chen-Chen; Wang, Chong; Meng, Xiang-Fei; Risacher, Shannon L; Saykin, Andrew J

    2015-01-01

    Objective We aimed to examine the association of apolipoprotein E (APOE) ε4 genotype with neuroimaging markers of Alzheimer’s disease: hippocampal volume, brain amyloid deposition and cerebral metabolism. Methods We performed a systematic review and meta-analysis of 14 cross-sectional studies identified in Pubmed from 1996 to 2014 (n=1628). The pooled standard mean difference (SMD) was used to estimate the association between APOE and hippocampal volume and amyloid deposition. Meta-analysis was performed using effect size signed differential mapping using coordinates extracted from clusters with statistically significant difference in cerebral metabolic rate for glucose between APOE ε4+ and ε4− groups. Results APOE ε4 carrier status was associated with atrophic hippocampal volume (pooled SMD: −0.47; 95% CI −0.82 to −0.13; p=0.007) and increased cerebral amyloid positron emission tomography tracer (pooled SMD: 0.62, 95% CI 0.27 to 0.98, p=0.0006). APOE ε4 was also associated with decreased cerebral metabolism, especially in right middle frontal gyrus. Conclusions APOE ε4 was associated with atrophic hippocampal volume in MRI markers, increased cerebral amyloid deposition and cerebral hypometabolism. Theses associations may indicate the potential role of the APOE gene in the pathophysiology of Alzheimer’s disease. PMID:24838911

  5. An unusual neuroimaging finding and response to immunotherapy in a child with genetically confirmed vanishing white matter disease.

    PubMed

    Singh, Rahul Raman; Livingston, John; Lim, Ming; Berry, Ian R; Siddiqui, Ata

    2017-03-01

    We present an unusual neuroimaging finding in a young girl with genetically confirmed vanishing white matter disease and a possible response to immunotherapy. 2.5 yr old girl, presented with acute onset unsteadiness and encephalopathy following a viral illness. MRI showed global symmetric white matter abnormality, with symmetric enhancement of cranial nerves (III and V) and of cervical and lumbar roots. She received immunotherapy for her encephalopathic illness with white matter changes. Follow up neuroimaging showed resolution of white matter edema and resolution of the change in the brainstem. Genetic testing confirmed a diagnosis of vanishing white matter disease (VWMD). Craniospinal nerve enhancement and possible response to immunotherapy has not been described in vanishing white matter disease. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  6. Initiation of Parkinson's disease treatment.

    PubMed

    Reichmann, Heinz

    2008-09-01

    Parkinson therapy should be commenced as soon as patients feel impaired by motor or other symptoms. Recently it has been stated, however, to start treatment immediately after the diagnosis of PD has been made, in order to offer some neuroprotection to active dopaminergic neurons and to prevent deleterious compensatory mechanisms in dopaminergic cells. The selection of the medication depends on the state of the disease, the clinical symptoms, concomitant diseases and age. In de novo patients, most guidelines, including those of the German Neurological Society, advocate to start with a dopamine agonist. In my opinion, initial treatment with a MAO-B-inhibitor and subsequent combination with a long-acting dopamine agonist may be even more promising with regard to neuroprotection, modification of the disease, avoidance of dyskinesia and good motor improvement.

  7. Examining the relationship between head trauma and neurodegenerative disease: A review of epidemiology, pathology and neuroimaging techniques

    PubMed Central

    Sundman, Mark H; Hall, Eric E; Chen, Nan-kuei

    2014-01-01

    Traumatic brain injuries (TBI) are induced by sudden acceleration-deceleration and/or rotational forces acting on the brain. Diffuse axonal injury (DAI) has been identified as one of the chief underlying causes of morbidity and mortality in head trauma incidents. DAIs refer to microscopic white matter (WM) injuries as a result of shearing forces that induce pathological and anatomical changes within the brain, which potentially contribute to significant impairments later in life. These microscopic injuries are often unidentifiable by the conventional computed tomography (CT) and magnetic resonance (MR) scans employed by emergency departments to initially assess head trauma patients and, as a result, TBIs are incredibly difficult to diagnose. The impairments associated with TBI may be caused by secondary mechanisms that are initiated at the moment of injury, but often have delayed clinical presentations that are difficult to assess due to the initial misdiagnosis. As a result, the true consequences of these head injuries may go unnoticed at the time of injury and for many years thereafter. The purpose of this review is to investigate these consequences of TBI and their potential link to neurodegenerative disease (ND). This review will summarize the current epidemiological findings, the pathological similarities, and new neuroimaging techniques that may help delineate the relationship between TBI and ND. Lastly, this review will discuss future directions and propose new methods to overcome the limitations that are currently impeding research progress. It is imperative that improved techniques are developed to adequately and retrospectively assess TBI history in patients that may have been previously undiagnosed in order to increase the validity and reliability across future epidemiological studies. The authors introduce a new surveillance tool (Retrospective Screening of Traumatic Brain Injury Questionnaire, RESTBI) to address this concern. PMID:25324979

  8. I finally see what you see: Parkinson's disease visual hallucinations captured with functional neuroimaging.

    PubMed

    Goetz, Christopher G; Vaughan, Christina L; Goldman, Jennifer G; Stebbins, Glenn T

    2014-01-01

    Functional neuroimaging studies have described alterations in neural activation in PD patients with chronic hallucinations. These studies have not, however, captured neural activation patterns during an actual hallucinatory event. The objective of this work was to investigate neuroanatomical substrates active during visual hallucinations in a patient with Parkinson's disease (PD). We conducted an event-related functional magnetic resonance imaging (fMRI) case-study examination of a 66-year-old male PD patient with stereotypic, chronic, and frequent visual hallucinations. The patient reported 16 hallucinations during the fMRI scan. Increased activation during hallucinations was found in the cingulate, insula, frontal lobe, thalamus, and brain stem. Decreased activation was found in the lingual and fusiform gyri, inferior occipital gyrus, and middle frontal and superior temporal lobes. To our knowledge, this report is the first published case documenting the cortical activation patterns using fMRI techniques in a PD patient during active hallucinations. Our results suggest that during a visual hallucination, a marked desynchronization occurs between posterior and anterior cortical areas involved in visual processing. Copyright © 2013 Movement Disorder Society.

  9. Neuroimaging of major depression in Parkinson's disease: Cortical thickness, cortical and subcortical volume, and spectroscopy findings.

    PubMed

    Chagas, Marcos Hortes N; Tumas, Vitor; Pena-Pereira, Márcio A; Machado-de-Sousa, João Paulo; Carlos Dos Santos, Antonio; Sanches, Rafael Faria; Hallak, Jaime E C; Crippa, José Alexandre S

    2017-02-13

    Depression is the most common psychiatric disorder in Parkinson's disease (PD). The aim of this study was to compare PD patients with current Major Depressive Disorder (MDD), lifetime MDD, and no MDD using three neuroimaging techniques. A total of 43 PD patients were selected and divided into three groups: (i) current MDD (n = 15), (ii) previous MDD without current MDD (n = 10); and (iii) control group (no current or lifetime MDD; n = 18). All participants underwent magnetic resonance imaging to evaluate cortical thickness, cortical and subcortical volume, and spectroscopy in the bilateral putamen and cingulate cortex. Volumetric analysis showed volume decreases in frontal and temporal areas, bilateral amygdala, and left cerebellar white matter in the lifetime MDD group compared to the control group. Furthermore, the volumes of the anterior cingulate cortex, right amygdala, and left cerebellar white matter were smaller in the group with current MDD compared to the control group. Regarding cortical thickness, the left rostral anterior cingulate gyrus of the group with previous MDD was thinner compared to the control group. There was a weak negative correlation between the NAA/Cre ratio in the right putamen and depressive symptoms. The results suggested current and lifetime MDD have a negative impact on the neurodegenerative process of PD, with decreased volume and/or reduction of cortical thickness in temporal and frontal areas, anterior cingulate cortex, amygdala, and cerebellar white matter.

  10. Behavioural and neuroimaging correlates of impaired self-awareness of hypo- and hyperkinesia in Parkinson's disease.

    PubMed

    Maier, Franziska; Williamson, Kim L; Tahmasian, Masoud; Rochhausen, Luisa; Ellereit, Anna L; Prigatano, George P; Kracht, Lutz; Tang, Chris C; Herz, Damian M; Fink, Gereon R; Timmermann, Lars; Eggers, Carsten

    2016-09-01

    Anosognosia or impaired self-awareness of motor symptoms (ISAm) has been rarely investigated in Parkinson's disease (PD). We here studied the relationship between ISAm during periods with and without dopaminergic medication (ON- and OFF-state), and clinical, neuropsychological, and neuroimaging data to further elucidate behavioural aspects and the neurobiological underpinnings of ISAm. Thirty-one right-handed, non-demented, non-depressed PD patients were included. ISAm was evaluated using a recently developed scale that assesses awareness of dyskinesia, resting tremor, and bradykinesia. The test was applied during both ON- and OFF-states. Multiple correlation analyses between ISAm and behavioural data were conducted. In addition, imaging of glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was performed to investigate the neural basis of ISAm. A multiple regression approach was applied to investigate metabolism alterations related to ISAm. In the OFF-state, higher ISAm was associated with left-sided disease onset, older age, and shorter disease duration. Concerning FDG-PET data, there was a significant negative correlation between higher OFF-state ISAm and decreased glucose metabolism in the right inferior frontal gyrus (IFG). In the ON-state, ISAm was not significantly correlated with clinical or behavioural data. However, there was a significant correlation between higher ISAm and an increased metabolism in the bilateral medial frontal gyrus, left IFG, right superior frontal gyrus and right precentral gyrus. The results support the role of the right hemisphere in awareness of motor symptoms in the OFF-state. In the ON-state, dopaminergic medication and dyskinesia influence ISAm and relate to metabolism changes in bilateral frontal regions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Multivariate Data Analysis for Neuroimaging Data: Overview and Application to Alzheimer’s Disease

    PubMed Central

    Stern, Yaakov

    2010-01-01

    As clinical and cognitive neuroscience mature, the need for sophisticated neuroimaging analysis becomes more apparent. Multivariate analysis techniques have recently received increasing attention as they have many attractive features that cannot be easily realized by the more commonly used univariate, voxel-wise, techniques. Multivariate approaches evaluate correlation/covariance of activation across brain regions, rather than proceeding on a voxel-by-voxel basis. Thus, their results can be more easily interpreted as a signature of neural networks. Univariate approaches, on the other hand, cannot directly address functional connectivity in the brain. The covariance approach can also result in greater statistical power when compared with univariate techniques, which are forced to employ very stringent, and often overly conservative, corrections for voxel-wise multiple comparisons. Multivariate techniques also lend themselves much better to prospective application of results from the analysis of one dataset to entirely new datasets. Multivariate techniques are thus well placed to provide information about mean differences and correlations with behavior, similarly to univariate approaches, with potentially greater statistical power and better reproducibility checks. In contrast to these advantages is the high barrier of entry to the use of multivariate approaches, preventing more widespread application in the community. To the neuroscientist becoming familiar with multivariate analysis techniques, an initial survey of the field might present a bewildering variety of approaches that, although algorithmically similar, are presented with different emphases, typically by people with mathematics backgrounds. We believe that multivariate analysis techniques have sufficient potential to warrant better dissemination. Researchers should be able to employ them in an informed and accessible manner. The following article attempts to provide a basic introduction with sample

  12. Pseudotumoral hemicerebellitis as a mimicker of Lhermitte-Duclos disease in children: does neuroimaging help to differentiate them?

    PubMed

    Bosemani, Thangamadhan; Steinlin, Maja; Toelle, Sandra P; Beck, Jürgen; Boltshauser, Eugen; Huisman, Thierry A G M; Poretti, Andrea

    2016-05-01

    The clinical presentation and neuroimaging findings of children with pseudotumoral hemicerebellitis (PTHC) and Lhermitte-Duclos disease (LDD) may be very similar. The differentiation between these entities, however, is important because their management and prognosis are different. We report on three children with PTHC. For all three children, in the acute situation, the differentiation between PTHC and LDD was challenging. A review of the literature shows that a detailed evaluation of conventional and neuroimaging data may help to differentiate between these two entities. A striated folial pattern, brainstem involvement, and prominent veins surrounding the thickened cerebellar foliae on susceptibility weighted imaging favor LDD, while post-contrast enhancement and an increased choline peak on (1)H-Magnetic resonance spectroscopy suggest PTHC.

  13. GM2-Gangliosidosis (Sandhoff and Tay Sachs disease): Diagnosis and Neuroimaging Findings (An Iranian Pediatric Case Series).

    PubMed

    Karimzadeh, Parvaneh; Jafari, Narjes; Nejad Biglari, Habibeh; Jabbeh Dari, Sayena; Ahmad Abadi, Farzad; Alaee, Mohammad-Reza; Nemati, Hamid; Saket, Sasan; Tonekaboni, Seyed Hasan; Taghdiri, Mohammad-Mahdi; Ghofrani, Mohammad

    2014-01-01

    GM2-Gangliosidosis disease is a rare autosomal recessive genetic disorder that includes two disorders (Tay-Sachs and Sandhoff disease).These disorders cause a progressive deterioration of nerve cells and inherited deficiency in creating hexosaminidases A, B, and AB. Patients who were diagnosed withGM2-Gangliosidosis in the Neurology Department of Mofid Children's Hospital in Tehran, Iran from October 2009 to February 2014were included in our study. The disorder was confirmed by neurometabolic and enzyme level detection of hexosaminidases A, B, and AB in reference to Wagnester Laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 9 patients with Sandhoff disease and 9 with Tay Sachs disease. 83% of our patients were the offspring of consanguineous marriages. All of them had a developmental disorder as a chief complaint. 38%of patients had a history of developmental delay or regression and 22% had seizures. The patients with Sandhoff and Tay Sachs disease were followed for approximately 5 years and the follow-up showed all patients were bedridden or had expired due to refractory seizures, pneumonia aspiration, or swallowing disorders. Neuro-imaging findings included bilateral thalamic involvement, brain atrophy, and hypo myelination in near half of our patients (48%). According to the results of this study, we suggest that cherry-red spots, hyperacusis, refractory seizures, and relative parents in children with developmental delay and/or regression should be considered for assessment of GM2-Gangliosidosis disease.

  14. Cognitive and neuroimaging profiles in mild cognitive impairment and Alzheimer's disease: data from the Spanish Multicenter Normative Studies (NEURONORMA Project).

    PubMed

    Sánchez-Benavides, Gonzalo; Peña-Casanova, Jordi; Casals-Coll, Marta; Gramunt, Nina; Molinuevo, José L; Gómez-Ansón, Beatriz; Aguilar, Miguel; Robles, Alfredo; Antúnez, Carmen; Martínez-Parra, Carlos; Frank-García, Anna; Fernández-Martínez, Manuel; Blesa, Rafael

    2014-01-01

    The aim of this study was to characterize the neuropsychological and neuroimaging profiles of mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients, and to study the magnitude of the differences by comparing both outcomes with healthy subjects in a cross-sectional manner. Five hundred and thirty-five subjects (356 cognitively normal adults (CONT), 79 MCI, and 100 AD) were assessed with the NEURONORMA neuropsychological battery. Thirty CONT, 23 MCI, and 23 AD subjects from this sample were included in the neuroimaging substudy. Patients' raw cognitive scores were converted to age and education-adjusted scaled ones (range 2-18) using co-normed reference values. Medians were plotted to examine the cognitive profile. MRIs were processed by means of FreeSurfer. Effect size indices (Cohen's d) were calculated in order to compare the standardized differences between patients and healthy subjects. Graphically, the observed cognitive profiles for MCI and AD groups produced near to parallel lines. Verbal and visual memories were the most impaired domains in both groups, followed by executive functions and linguistic/semantic ones. The largest effect size between AD and cognitively normal subjects was found for the FCSRT (d = 4.05, AD versus CONT), which doubled the value obtained by the best MRI measure, the right hippocampus (d = 1.65, AD versus CONT). Our results support the notion of a continuum in cognitive profile between MCI and AD. Neuropsychological outcomes, in particular the FCSRT, are better than neuroimaging ones at detecting differences among subjects.

  15. Neuroimaging Findings and Repeat Neuroimaging Value in Pediatric Chronic Ataxia.

    PubMed

    Salman, Michael S; Chodirker, Bernard N; Bunge, Martin

    2016-11-01

    Chronic ataxia, greater than two months in duration, is encountered relatively commonly in clinical pediatric neurology practise and presents with diagnostic challenges. It is caused by multiple and diverse disorders. Our aims were to describe the neuroimaging features and the value of repeat neuroimaging in pediatric chronic ataxia to ascertain their contribution to the diagnosis and management. A retrospective charts and neuroimaging reports review was undertaken in 177 children with chronic ataxia. Neuroimaging in 130 of 177 patients was also reviewed. Nineteen patients had head computed tomography only, 103 brain magnetic resonance imaging only, and 55 had both. Abnormalities in the cerebellum or other brain regions were associated with ataxia. Neuroimaging was helpful in 73 patients with 30 disorders: It was diagnostic in 9 disorders, narrowed down the diagnostic possibilities in 14 disorders, and revealed important but non-diagnostic abnormalities, e.g. cerebellar atrophy in 7 disorders. Having a normal magnetic resonance imaging scan was mostly seen in genetic diseases or in the early course of ataxia telangiectasia. Repeat neuroimaging, performed in 108 patients, was generally helpful in monitoring disease evolution and in making a diagnosis. Neuroimaging was not directly helpful in 36 patients with 10 disorders or by definition the 55 patients with unknown disease etiology. Normal or abnormal neuroimaging findings and repeat neuroimaging are very valuable in the diagnosis and management of disorders associated with pediatric chronic ataxia.

  16. GM2-Gangliosidosis (Sandhoff and Tay Sachs disease): Diagnosis and Neuroimaging Findings (An Iranian Pediatric Case Series)

    PubMed Central

    KARIMZADEH, Parvaneh; JAFARI, Narjes; NEJAD BIGLARI, Habibeh; JABBEH DARI, Sayena; AHMAD ABADI, Farzad; ALAEE, Mohammad-Reza; NEMATI, Hamid; SAKET, Sasan; TONEKABONI, Seyed Hasan; TAGHDIRI, Mohammad-Mahdi; GHOFRANI, Mohammad

    2014-01-01

    Objective GM2-Gangliosidosis disease is a rare autosomal recessive genetic disorder that includes two disorders (Tay–Sachs and Sandhoff disease).These disorders cause a progressive deterioration of nerve cells and inherited deficiency in creating hexosaminidases A, B, and AB. Materials & Methods Patients who were diagnosed withGM2-Gangliosidosis in the Neurology Department of Mofid Children’s Hospital in Tehran, Iran from October 2009 to February 2014were included in our study. The disorder was confirmed by neurometabolic and enzyme level detection of hexosaminidases A, B, and AB in reference to Wagnester Laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 9 patients with Sandhoff disease and 9 with Tay Sachs disease. Results 83% of our patients were the offspring of consanguineous marriages. All of them had a developmental disorder as a chief complaint. 38%of patients had a history of developmental delay or regression and 22% had seizures. The patients with Sandhoff and Tay Sachs disease were followed for approximately 5 years and the follow-up showed all patients were bedridden or had expired due to refractory seizures, pneumonia aspiration, or swallowing disorders. Neuro-imaging findings included bilateral thalamic involvement, brain atrophy, and hypo myelination in near half of our patients (48%). Conclusion According to the results of this study, we suggest that cherry-red spots, hyperacusis, refractory seizures, and relative parents in children with developmental delay and/or regression should be considered for assessment of GM2-Gangliosidosis disease. PMID:25143775

  17. The clinical value of large neuroimaging data sets in Alzheimer's disease.

    PubMed

    Toga, Arthur W

    2012-02-01

    Rapid advances in neuroimaging and cyberinfrastructure technologies have brought explosive growth in the Web-based warehousing, availability, and accessibility of imaging data on a variety of neurodegenerative and neuropsychiatric disorders and conditions. There has been a prolific development and emergence of complex computational infrastructures that serve as repositories of databases and provide critical functionalities such as sophisticated image analysis algorithm pipelines and powerful three-dimensional visualization and statistical tools. The statistical and operational advantages of collaborative, distributed team science in the form of multisite consortia push this approach in a diverse range of population-based investigations.

  18. Effect of EPHA1 genetic variation on cerebrospinal fluid and neuroimaging biomarkers in healthy, mild cognitive impairment and Alzheimer's disease cohorts.

    PubMed

    Wang, Hui-Fu; Tan, Lan; Hao, Xiao-Ke; Jiang, Teng; Tan, Meng-Shan; Liu, Ying; Zhang, Dao-Qiang; Yu, Jin-Tai

    2015-01-01

    Ephrin type-A receptor 1 (EPHA1) (11771145) was documented to be one of the most strongly associated locus with Alzheimer's disease (AD) in a recent meta-analysis of five genome wide association studies. However, its contribution to the pathogenesis of AD remains unclear to date. Here, we addressed the role of EPHA1 in AD by investigating the influence of EPHA1 on cerebrospinal fluid and neuroimaging biomarkers in three clinical stages from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We did not detect significant association of EPHA1 with amyloid-β deposition or tau protein. However, the A-allele in the mild cognitive impairment group remarkably prevented hippocampal atrophy (partial correlation coefficient 2.812, 95% CI 0.651 to 4.973) at two-year follow-up. Additionally, AD subjects with the A-allele displayed less atrophy and greater cerebral metabolic rate for glucose (CMRgl) in the right lateral occipitotemporal gyrus (volume: partial correlation coefficient 540.10, 95% CI 247.26 to 832.95; CMRgl: partial correlation coefficient 0.056, 95% CI 0.024 to 0.087) and inferior temporal gyrus (volume: partial correlation coefficient 327.98, 95% CI 11.65 to 644.31; CMRgl: partial correlation coefficient 0.055, 95% CI 0.019 to 0.091) at baseline. This study suggests EPHA1 (rs11771145) interferes with the pathological alteration of the hippocampus and the lateral occipitotemporal and inferior temporal gyri throughout the AD process, leading to a lower risk of AD. However, the limited sample size and follow-up as well as the diversity across ethnicities precluded explanation of these findings.

  19. Effect of CLU genetic variants on cerebrospinal fluid and neuroimaging markers in healthy, mild cognitive impairment and Alzheimer's disease cohorts.

    PubMed

    Tan, Lin; Wang, Hui-Fu; Tan, Meng-Shan; Tan, Chen-Chen; Zhu, Xi-Chen; Miao, Dan; Yu, Wan-Jiang; Jiang, Teng; Tan, Lan; Yu, Jin-Tai

    2016-05-27

    The Clusterin (CLU) gene, also known as apolipoprotein J (ApoJ), is currently the third most associated late-onset Alzheimer's disease (LOAD) risk gene. However, little was known about the possible effect of CLU genetic variants on AD pathology in brain. Here, we evaluated the interaction between 7 CLU SNPs (covering 95% of genetic variations) and the role of CLU in β-amyloid (Aβ) deposition, AD-related structure atrophy, abnormal glucose metabolism on neuroimaging and CSF markers to clarify the possible approach by that CLU impacts AD. Finally, four loci (rs11136000, rs1532278, rs2279590, rs7982) showed significant associations with the Aβ deposition at the baseline level while genotypes of rs9331888 (P = 0.042) increased Aβ deposition. Besides, rs9331888 was significantly associated with baseline volume of left hippocampus (P = 0.014). We then further validated the association with Aβ deposition in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. The results in sub-groups confirmed the association between CLU genotypes and Aβ deposition further. Our findings revealed that CLU genotypes could probably modulate the cerebral the Aβ loads on imaging and volume of hippocampus. These findings raise the possibility that the biological effects of CLU may be relatively confined to neuroimaging trait and hence may offer clues to AD.

  20. The importance of combining MRI and large-scale digital histology in neuroimaging studies of brain connectivity and disease

    PubMed Central

    Annese, Jacopo

    2012-01-01

    One of the major issues hindering a comprehensive connectivity model for the human brain is the difficulty in linking Magnetic Resonance Imaging (MRI) measurements to anatomical evidence produced by histological methods. In vivo and postmortem neuroimaging methodologies are still largely incompatible in terms of sample size, scale, and resolution. To help bridge the hiatus between different approaches we have established a program that characterizes the brain of individual subjects, combining MRI with postmortem neuroanatomy. The direct correlation of MRI and histological features is possible, because registered images from different modalities represent the same regions in the same brain. Comparisons are also facilitated by large-scale, digital microscopy techniques that afford images of the whole-brain sections at cellular resolution. The goal is to create a neuroimaging catalog representative of discrete age groups and specific neurological conditions. Individually, the datasets allow for investigating the relationship between different modalities; combined, they provide sufficient predictive power to inform analyses and interpretations made in the context of non-invasive studies of brain connectivity and disease. PMID:22536182

  1. Ethical and Legal Implications of the Methodological Crisis in Neuroimaging.

    PubMed

    Kellmeyer, Philipp

    2017-10-01

    Currently, many scientific fields such as psychology or biomedicine face a methodological crisis concerning the reproducibility, replicability, and validity of their research. In neuroimaging, similar methodological concerns have taken hold of the field, and researchers are working frantically toward finding solutions for the methodological problems specific to neuroimaging. This article examines some ethical and legal implications of this methodological crisis in neuroimaging. With respect to ethical challenges, the article discusses the impact of flawed methods in neuroimaging research in cognitive and clinical neuroscience, particularly with respect to faulty brain-based models of human cognition, behavior, and personality. Specifically examined is whether such faulty models, when they are applied to neurological or psychiatric diseases, could put patients at risk, and whether this places special obligations on researchers using neuroimaging. In the legal domain, the actual use of neuroimaging as evidence in United States courtrooms is surveyed, followed by an examination of ways that the methodological problems may create challenges for the criminal justice system. Finally, the article reviews and promotes some promising ideas and initiatives from within the neuroimaging community for addressing the methodological problems.

  2. Data sharing in neuroimaging research

    PubMed Central

    Poline, Jean-Baptiste; Breeze, Janis L.; Ghosh, Satrajit; Gorgolewski, Krzysztof; Halchenko, Yaroslav O.; Hanke, Michael; Haselgrove, Christian; Helmer, Karl G.; Keator, David B.; Marcus, Daniel S.; Poldrack, Russell A.; Schwartz, Yannick; Ashburner, John; Kennedy, David N.

    2012-01-01

    Significant resources around the world have been invested in neuroimaging studies of brain function and disease. Easier access to this large body of work should have profound impact on research in cognitive neuroscience and psychiatry, leading to advances in the diagnosis and treatment of psychiatric and neurological disease. A trend toward increased sharing of neuroimaging data has emerged in recent years. Nevertheless, a number of barriers continue to impede momentum. Many researchers and institutions remain uncertain about how to share data or lack the tools and expertise to participate in data sharing. The use of electronic data capture (EDC) methods for neuroimaging greatly simplifies the task of data collection and has the potential to help standardize many aspects of data sharing. We review here the motivations for sharing neuroimaging data, the current data sharing landscape, and the sociological or technical barriers that still need to be addressed. The INCF Task Force on Neuroimaging Datasharing, in conjunction with several collaborative groups around the world, has started work on several tools to ease and eventually automate the practice of data sharing. It is hoped that such tools will allow researchers to easily share raw, processed, and derived neuroimaging data, with appropriate metadata and provenance records, and will improve the reproducibility of neuroimaging studies. By providing seamless integration of data sharing and analysis tools within a commodity research environment, the Task Force seeks to identify and minimize barriers to data sharing in the field of neuroimaging. PMID:22493576

  3. Translational Perspectives for Computational Neuroimaging.

    PubMed

    Stephan, Klaas E; Iglesias, Sandra; Heinzle, Jakob; Diaconescu, Andreea O

    2015-08-19

    Functional neuroimaging has made fundamental contributions to our understanding of brain function. It remains challenging, however, to translate these advances into diagnostic tools for psychiatry. Promising new avenues for translation are provided by computational modeling of neuroimaging data. This article reviews contemporary frameworks for computational neuroimaging, with a focus on forward models linking unobservable brain states to measurements. These approaches-biophysical network models, generative models, and model-based fMRI analyses of neuromodulation-strive to move beyond statistical characterizations and toward mechanistic explanations of neuroimaging data. Focusing on schizophrenia as a paradigmatic spectrum disease, we review applications of these models to psychiatric questions, identify methodological challenges, and highlight trends of convergence among computational neuroimaging approaches. We conclude by outlining a translational neuromodeling strategy, highlighting the importance of openly available datasets from prospective patient studies for evaluating the clinical utility of computational models. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Neuroimaging in sleep medicine.

    PubMed

    Dang-Vu, Thien Thanh; Desseilles, Martin; Petit, Dominique; Mazza, Stéphanie; Montplaisir, Jacques; Maquet, Pierre

    2007-06-01

    The development of neuroimaging techniques has made possible the characterization of cerebral function throughout the sleep-wake cycle in normal human subjects. Indeed, human brain activity during sleep is segregated within specific cortical and subcortical areas in relation to the sleep stage, sleep physiological events and previous waking activity. This approach has allowed sleep physiological theories developed from animal data to be confirmed, but has also introduced original concepts about the neurobiological mechanisms of sleep, dreams and memory in humans. In contrast, at present, few neuroimaging studies have been dedicated to human sleep disorders. The available work has brought interesting data that describe some aspects of the pathophysiology and neural consequences of disorders such as insomnia, sleep apnea and narcolepsy. However, the interpretation of many of these results is restricted by limited sample size and spatial/temporal resolution of the employed technique. The use of neuroimaging in sleep medicine is actually restrained by concerns resulting from the technical experimental settings and the characteristics of the diseases. Nevertheless, we predict that future studies, conducted with state of the art techniques on larger numbers of patients, will be able to address these issues and contribute significantly to the understanding of the neural basis of sleep pathologies. This may finally offer the opportunity to use neuroimaging, in addition to the clinical and electrophysiological assessments, as a helpful tool in the diagnosis, classification, treatment and monitoring of sleep disorders in humans.

  5. Alterations of Myelin Content in Parkinson’s Disease: A Cross-Sectional Neuroimaging Study

    PubMed Central

    Sojkova, Jitka; Hurley, Samuel; Kecskemeti, Steven; Okonkwo, Ozioma; Bendlin, Barbara B.; Theisen, Frances; Johnson, Sterling C.; Alexander, Andrew L.; Gallagher, Catherine L.

    2016-01-01

    Alterations to myelin may be a core pathological feature of neurodegenerative diseases. Although white matter microstructural differences have been described in Parkinson's disease (PD), it is unknown whether such differences include alterations of the brain’s myelin content. Thus, the objective of the current study is to measure and compare brain myelin content between PD patients and age-matched controls. In this cross-sectional study, 63 participants from the Longitudinal MRI in Parkinson's Disease study underwent brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) scoring, and cognitive asessments. Subjects were imaged with the mcDEPSOT (multi-component driven equilibrium single pulse observation of T1 and T2), a multicomponent relaxometry technique that quantifies longitudinal and transverse relaxation rates (R1 and R2, respectively) and the myelin water fraction (VFM), a surrogate for myelin content. A voxel-wise approach was used to compare R1, R2, and VFM measures between PD and control groups, and to evaluate relationships with age as well as disease duration, UPDRS scores, and daily levodopa equivalent dose. PD subjects had higher VFM than controls in frontal and temporal white matter and bilateral thalamus. Greater age was strongly associated with lower VFM in both groups, while an age-by-group interaction suggested a slower rate of VFM decline in the left putamen with aging in PD. Within the PD group, measures of disease severity, including UPDRS, daily levodopa equivalent dose, and disease duration, were observed to be related with myelin content in diffuse brain regions. The age-by-group interaction suggests that either PD or dopaminergic therapies allay observed age-related myelin changes. The relationships between VFM and disease severity measures suggests that VFM may provide a surrogate marker for microstructural changes related to Parkinson’s disease. PMID:27706215

  6. Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures.

    PubMed

    Ye, Zheng; Rae, Charlotte L; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle-Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R; Maxwell, Helen; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

    2016-03-01

    Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double-blind randomized three-way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion-weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave-one-out cross-validation (LOOCV) to predict patients' responses in terms of improved stopping efficiency. We identified two optimal models: (1) a "clinical" model that predicted the response of an individual patient with 77-79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion-weighted imaging scan; and (2) a "mechanistic" model that explained the behavioral response with 85% accuracy for each drug, using drug-induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features.

  7. Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures

    PubMed Central

    Ye, Zheng; Rae, Charlotte L.; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle‐Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R.; Maxwell, Helen; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

    2016-01-01

    Abstract Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double‐blind randomized three‐way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion‐weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave‐one‐out cross‐validation (LOOCV) to predict patients’ responses in terms of improved stopping efficiency. We identified two optimal models: (1) a “clinical” model that predicted the response of an individual patient with 77–79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion‐weighted imaging scan; and (2) a “mechanistic” model that explained the behavioral response with 85% accuracy for each drug, using drug‐induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features. Hum Brain Mapp 37:1026–1037

  8. Constraints on the cerebral basis for semantic processing from neuroimaging studies of Alzheimer's disease

    PubMed Central

    Grossman, M.; Payer, F.; Onishi, K.; White-Devine, T.; Morrison, D.; D'Esposito, M.; Robinson, K.; Alavi, A.

    1997-01-01

    OBJECTIVE—Functional activation studies of semantic processing in healthy adults have yielded conflicting results. The purpose was to evaluate the relative role of the brain regions implicated in semantic processing with converging evidence from imaging studies of patients with impaired semantic processing.
METHODS—Semantic memory was assessed in patients with Alzheimer's disease using two measures, and these performance patterns were related to profiles of reduced cerebral functioning obtained with high resolution single photon emission computed tomography (SPECT). Patients with frontotemporal degeneration were similarly evaluated as a control group.
RESULTS—Reduced relative cerebral perfusion was seen in parietal and posterior temporal brain regions of patients with Alzheimer's disease but not patients with frontotemporal degeneration. Impairments on semantically guided category membership decision tasks were also seen in patients with Alzheimer's disease but not those with frontotemporal degeneration. Performance on the semantic measures correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere only in Alzheimer's disease. Relative perfusion was significantly lower in these regions in patients with Alzheimer's disease with semantic difficulty compared with patients with Alzheimer's disease with relatively preserved semantic processing.
CONCLUSION—These findings provide converging evidence to support the contribution of superior temporal and inferior parietal regions of the left hemisphere to semantic processing.

 PMID:9285450

  9. Neuroimaging of central breathlessness mechanisms.

    PubMed

    Pattinson, Kyle T S; Johnson, Miriam J

    2014-09-01

    Breathlessness debilitates millions of people with cardiorespiratory conditions and cancer. Symptoms correlate poorly with the objective measures of disease (e.g. spirometry). Altered brain processing of respiratory sensations may contribute to this disparity. This article summarizes how functional neuroimaging works, focussing on functional MRI (FMRI) and magnetoencephalography, how neuroimaging has shed light on the central mechanisms of breathlessness and thus how it may help target new therapies. Current understanding of central neural activity in breathlessness comes mainly from a small number of studies in healthy volunteers using models of induced acute breathlessness. Parallels with neuroimaging findings in pain and fear or anxiety have been used to interpret the neuroimaging studies of breathlessness to form hypotheses. Despite the lack of recent neuroimaging studies in breathlessness, there have been methodological advances in overcoming confounders with respiratory FMRI. In addition, developing interest in the distinction of emotional from the sensory aspects of breathlessness and the use of opioids for breathlessness has driven mechanistic understandings. Neuroimaging of breathlessness remains in its infancy. However, advances in the understanding of central perception, combined with novel neuroimaging techniques, means that we are poised to increase our understanding of the brain processes of breathlessness and their modulation.

  10. Neuroimaging of hippocampal atrophy in early recognition of Alzheimer's disease--a critical appraisal after two decades of research.

    PubMed

    Schröder, Johannes; Pantel, Johannes

    2016-01-30

    As a characteristic feature of Alzheimer's disease (AD) hippocampal atrophy (HA) can be demonstrated in the majority of patients by using neuroimaging techniques in particular magnetic resonance imaging (MRI). Hippocampal atrophy is associated with declarative memory deficits and can also be associated with changes of adjacent medial temporal substructures such as the parahippocampal gyrus or the the entorhinal cortex. Similar findings are present in patients with mild cognitive impairment (MCI) albeit to a lesser extent. While these finding facilitate the diagnostic process in patients with clinical suspicious AD, the metric properties of hippocampal atrophy for delineating healthy aging from MCI and mild AD still appear to be rather limited; as such it is not sufficient to establish the diagnosis of AD (and even more so of MCI). This limitation partly refers to methodological issues and partly to the fact that hippocampal tissue integrity is subject to various pathogenetic influences other than AD. Moreover,the effects of hippocampal atrophy on the behavioral level (e.g. cognitive deficits) are modulated by the individual's cognitive reserve. From a clinical standpoint these observations are in line with the hypothesis that the onset and course of AD is influenced by a number of peristatic factors which are partly conceptualized in the concepts of brain and/or cognitive reserve. These complex interactions have to be considered when using the presence of hippocampal atrophy in the routine diagnostic procedure of AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. The receiver operational characteristic for binary classification with multiple indices and its application to the neuroimaging study of Alzheimer's disease.

    PubMed

    Wu, Xia; Li, Juan; Ayutyanont, Napatkamon; Protas, Hillary; Jagust, William; Fleisher, Adam; Reiman, Eric; Yao, Li; Chen, Kewei

    2013-01-01

    Given a single index, the receiver operational characteristic (ROC) curve analysis is routinely utilized for characterizing performances in distinguishing two conditions/groups in terms of sensitivity and specificity. Given the availability of multiple data sources (referred to as multi-indices), such as multimodal neuroimaging data sets, cognitive tests, and clinical ratings and genomic data in Alzheimer’s disease (AD) studies, the single-index-based ROC underutilizes all available information. For a long time, a number of algorithmic/analytic approaches combining multiple indices have been widely used to simultaneously incorporate multiple sources. In this study, we propose an alternative for combining multiple indices using logical operations, such as “AND,” “OR,” and “at least n” (where n is an integer), to construct multivariate ROC (multiV-ROC) and characterize the sensitivity and specificity statistically associated with the use of multiple indices. With and without the “leave-one-out” cross-validation, we used two data sets from AD studies to showcase the potentially increased sensitivity/specificity of the multiV-ROC in comparison to the single-index ROC and linear discriminant analysis (an analytic way of combining multi-indices). We conclude that, for the data sets we investigated, the proposed multiV-ROC approach is capable of providing a natural and practical alternative with improved classification accuracy as compared to univariate ROC and linear discriminant analysis.

  12. Addison disease - diagnosis and initial management.

    PubMed

    O'Connell, Susan; Siafarikas, Aris

    2010-11-01

    Adrenal insufficiency is a rare disease caused by either primary adrenal failure (Addison disease) or by impairment of the hypothalamic-pituitary-adrenal axis. Steroid replacement therapy normalises quality of life, however, adherence can be problematic. This article provides information on adrenal insufficiency focusing on awareness of initial symptoms and on risk scenarios, emergency management and baseline investigations, complete investigations and long term management. Early recognition of adrenal insufficiency is essential to avoid associated morbidity and mortality. Initial diagnosis and decision to treat are based on history and physical examination. Appropriate management includes emergency resuscitation and steroid administration. Initial investigations can include sodium, potassium and blood glucose levels. However, complete investigations can be deferred. Specialist advice should be obtained and long term management includes a Team Care Arrangement. For patients, an emergency plan and emergency identification are essential.

  13. Identification of Disease-related Spatial Covariance Patterns using Neuroimaging Data

    PubMed Central

    Spetsieris, Phoebe; Ma, Yilong; Peng, Shichun; Ko, Ji Hyun; Dhawan, Vijay; Tang, Chris C.; Eidelberg, David

    2013-01-01

    The scaled subprofile model (SSM)1-4 is a multivariate PCA-based algorithm that identifies major sources of variation in patient and control group brain image data while rejecting lesser components (Figure 1). Applied directly to voxel-by-voxel covariance data of steady-state multimodality images, an entire group image set can be reduced to a few significant linearly independent covariance patterns and corresponding subject scores. Each pattern, termed a group invariant subprofile (GIS), is an orthogonal principal component that represents a spatially distributed network of functionally interrelated brain regions. Large global mean scalar effects that can obscure smaller network-specific contributions are removed by the inherent logarithmic conversion and mean centering of the data2,5,6. Subjects express each of these patterns to a variable degree represented by a simple scalar score that can correlate with independent clinical or psychometric descriptors7,8. Using logistic regression analysis of subject scores (i.e. pattern expression values), linear coefficients can be derived to combine multiple principal components into single disease-related spatial covariance patterns, i.e. composite networks with improved discrimination of patients from healthy control subjects5,6. Cross-validation within the derivation set can be performed using bootstrap resampling techniques9. Forward validation is easily confirmed by direct score evaluation of the derived patterns in prospective datasets10. Once validated, disease-related patterns can be used to score individual patients with respect to a fixed reference sample, often the set of healthy subjects that was used (with the disease group) in the original pattern derivation11. These standardized values can in turn be used to assist in differential diagnosis12,13 and to assess disease progression and treatment effects at the network level7,14-16. We present an example of the application of this methodology to FDG PET data of

  14. Recent advances in biomarkers for Parkinson's disease focusing on biochemicals, omics and neuroimaging.

    PubMed

    Ren, Rutong; Sun, Yi; Zhao, Xin; Pu, Xiaoping

    2015-09-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders, involving progressive loss of the nigro-striatal dopaminergic neurons. Cardinal symptoms including tremors, muscle rigidity, drooping posture, drooping, walking difficulty, and autonomic symptoms appear when a significant number of nigrostriatal dopaminergic neurons have already been destroyed. Hence, reliable biomarkers are needed for early and accurate diagnosis to measure disease progression and response to therapy. We review the current status of protein and small molecule biomarkers involved in oxidative stress, protein aggregation and inflammation etc. which are present in cerebrospinal fluid, human blood, urine or saliva. In recent years, advances in genomics, proteomics, metabolomics, and functional brain imaging techniques have led to new insights into the pathoetiology of PD. Further studies in the novel discovery of PD biomarkers will provide avenues to treat PD patients more effectively with few or no side effects.

  15. Longitudinal assessment of neuroimaging and clinical markers in autosomal dominant Alzheimer's disease: a prospective cohort study.

    PubMed

    Yau, Wai-Ying Wendy; Tudorascu, Dana L; McDade, Eric M; Ikonomovic, Snezana; James, Jeffrey A; Minhas, Davneet; Mowrey, Wenzhu; Sheu, Lei K; Snitz, Beth E; Weissfeld, Lisa; Gianaros, Peter J; Aizenstein, Howard J; Price, Julie C; Mathis, Chester A; Lopez, Oscar L; Klunk, William E

    2015-08-01

    The biomarker model of Alzheimer's disease postulates a dynamic sequence of amyloidosis, neurodegeneration, and cognitive decline as an individual progresses from preclinical Alzheimer's disease to dementia. Despite supportive evidence from cross-sectional studies, verification with long-term within-individual data is needed. For this prospective cohort study, carriers of autosomal dominant Alzheimer's disease mutations (aged ≥21 years) were recruited from across the USA through referrals by physicians or from affected families. People with mutations in PSEN1, PSEN2, or APP were assessed at the University of Pittsburgh Alzheimer's Disease Research Center every 1-2 years, between March 23, 2003, and Aug 1, 2014. We measured global cerebral amyloid β (Aβ) load using (11)C-Pittsburgh Compound-B PET, posterior cortical metabolism with (18)F-fluorodeoxyglucose PET, hippocampal volume (age and sex corrected) with T1-weighted MRI, verbal memory with the ten-item Consortium to Establish a Registry for Alzheimer's Disease Word List Learning Delayed Recall Test, and general cognition with the Mini Mental State Examination. We estimated overall biomarker trajectories across estimated years from symptom onset using linear mixed models, and compared these estimates with cross-sectional data from cognitively normal control individuals (age 65-89 years) who were negative for amyloidosis, hypometabolism, and hippocampal atrophy. In the mutation carriers who had the longest follow-up, we examined the within-individual progression of amyloidosis, metabolism, hippocampal volume, and cognition to identify progressive within-individual changes (a significant change was defined as an increase or decrease of more than two Z scores standardised to controls). 16 people with mutations in PSEN1, PSEN2, or APP, aged 28-56 years, completed between two and eight assessments (a total of 83 assessments) over 2-11 years. Significant differences in mutation carriers compared with controls (p<0

  16. Reward Prediction Errors in Drug Addiction and Parkinson's Disease: from Neurophysiology to Neuroimaging.

    PubMed

    García-García, Isabel; Zeighami, Yashar; Dagher, Alain

    2017-06-01

    Surprises are important sources of learning. Cognitive scientists often refer to surprises as "reward prediction errors," a parameter that captures discrepancies between expectations and actual outcomes. Here, we integrate neurophysiological and functional magnetic resonance imaging (fMRI) results addressing the processing of reward prediction errors and how they might be altered in drug addiction and Parkinson's disease. By increasing phasic dopamine responses, drugs might accentuate prediction error signals, causing increases in fMRI activity in mesolimbic areas in response to drugs. Chronic substance dependence, by contrast, has been linked with compromised dopaminergic function, which might be associated with blunted fMRI responses to pleasant non-drug stimuli in mesocorticolimbic areas. In Parkinson's disease, dopamine replacement therapies seem to induce impairments in learning from negative outcomes. The present review provides a holistic overview of reward prediction errors across different pathologies and might inform future clinical strategies targeting impulsive/compulsive disorders.

  17. Clinical, genetic, and neuroimaging features of Early Onset Alzheimer Disease: the challenges of diagnosis and treatment.

    PubMed

    Alberici, Antonella; Benussi, Alberto; Premi, Enrico; Borroni, Barbara; Padovani, Alessandro

    2014-01-01

    Early Onset Alzheimer Disease (EOAD) is a rare condition, frequently associated with genetic causes. The dissemination of genetic testing along with biomarker determinations have prompted a wider recognition of EOAD in experienced clinical settings. However, despite the great efforts in establishing the contribution of causative genes to EOAD, atypical disease presentation and clinical features still makes its diagnosis and treatment a challenge for the clinicians. This review aims to provide an extensive evaluation of literature data on EOAD, in order to improve understanding and knowledge of EOAD, underscore its significant impact on patients and their caregivers and influence public policies. This would be crucial to define the urgency of evidence-based treatment approaches.

  18. A Pilot Study on Clinical and Neuroimaging Characteristics of Chinese Posterior Cortical Atrophy: Comparison with Typical Alzheimer’s Disease

    PubMed Central

    Shi, Zhihong; Cai, Li; Liu, Shuai; Liu, Shuling; Han, Tong; Wang, Ying; Zhou, Yuying; Wang, Xinping; Gao, Shuo; Ji, Yong

    2015-01-01

    Posterior cortical atrophy (PCA) is a clinicoradiologic neurodegenerative syndrome characterized by predominant impairment of higher visual functions. Neuroimaging and neuropathological studies show that PCA is probably an atypical presentation of Alzheimer’s disease. However, in China PCA has rarely been studied and remains largely unknown. Our study therefore aimed to analyze the clinical manifestations and patterns of cerebral atrophy, amyloid beta deposition and regional glucose metabolism in Chinese PCA patients, comparing them directly with those of typical Alzheimer’s disease (TAD). Seven PCA patients, 6 TAD patients and 5 controls underwent neuropsychological assessment, MRI scan, 11C-PIB PET scan and 18F-FDG PET scan. Cerebral atrophy including ventricular enlargement, posterior atrophy and medial temporal lobe atrophy were evaluated with MRI. The uptake of 11C-PIB was quantified at the voxel level using the standardized uptake value ratio. Comparisons of regional cerebral glucose metabolism were calculated with statistical parametric mapping. PCA patients showed significant impairment on visuospatial function in neuropsychological assessment. And PCA patients showed more severe posterior atrophy and less severe left medial temporal lobe atrophy compared with TAD patients. The data from 11C-PIB PET scanning showed that amyloid beta deposition in PCA was comparable to TAD. Moreover, in PCA the results from 18F-FDG PET scanning revealed significant hypometabolism in the temporoparietooccipital region and identified specific hypometabolism in the right occipital lobe, compared with TAD. Our study thus provides a preliminary view of PCA in Chinese patients. A further study with a larger number of subjects would be recommended to confirm these findings. PMID:26267071

  19. Levodopa therapy in a Lesch-Nyhan disease patient: pathological, biochemical, neuroimaging, and therapeutic remarks.

    PubMed

    Serrano, Mercedes; Pérez-Dueñas, Belen; Ormazábal, Aida; Artuch, Rafael; Campistol, Jaume; Torres, Rosa J; García-Cazorla, Angels

    2008-07-15

    Lesch-Nyhan disease (LND) is a hereditary disorder of purine metabolism causing severe neurobehavioral disturbances in which an abnormal central nervous system dopaminergic function has been implied. However, levodopa treatment has rarely been used, and reports describe heterogeneous responses. We report an LND patient with low dopamine metabolite values in cerebrospinal fluid for whom early levodopa/carbidopa therapy was begun with a notable clinical improvement. We propose that very early treatment of LND patients with levodopa may improve their neurological symptoms and may contribute to a better outcome. (c) 2008 Movement Disorder Society.

  20. The Southern Cone Initiative against Chagas disease.

    PubMed

    Schofield, C J; Dias, J C

    1999-01-01

    Chagas disease (also known as American trypanosomiasis) is now ranked as the most serious parasitic disease of the Americas, with an economic impact far outranking the combined effects of other parasitic diseases such as malaria, schistosomiasis and leishmaniasis. Although the chronic infection remains virtually incurable, transmission can be halted by eliminating the domestic insect vectors and screening blood donors to avoid transfusional transmission. In line with this strategy, governments of the six Southern Cone countries (Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay) launched in 1991 an ambitious initiative to control Chagas disease through elimination of the main vector, Triatoma infestans, and large-scale screening of blood donors. Now at its mid-point, the programme has achieved remarkable success, with transmission halted over vast areas of the previously endemic regions. Well over 2 million rural houses have been sprayed to eliminate T. infestans, and the programme has already shown significant economic rates of return in addition to the medical and social benefits.

  1. Cholinesterase inhibitors are compatible with psychosocial intervention for Alzheimer disease patients suggested by neuroimaging findings.

    PubMed

    Meguro, Kenichi

    2017-01-30

    We previously reported that the frontal lobe was stimulated by psychosocial intervention for dementia patients, and that the parietal lobe was associated with logical judgment. We hypothesized that the combined therapeutic approach with symptomatic drug treatment can directly stimulate not only attention function but also judgment function indirectly to observing other participants' behaviors. Fifty-two patients with Alzheimer disease underwent the group reminiscence approach with reality orientation, as well as the donepezil treatment. The cerebral blood flow (CBF) was assessed with (99m)Tc-ECD SPECT. Two analyses were performed: Analysis 1 was to compare Responders vs. Non-responders as shown by MMSE scores, whereas Analysis 2 was to compare Good vs. Poor reminders of the intervention content. We found that the CBF in the frontal lobe was significantly higher in Responders (vs. Non-responders). The CBF in the parietal lobe, especially the left side, was significantly higher in the Good reminders (vs. Poor reminders). The donepezil stimulated the areas similar to where the psychosocial intervention was previously found to be stimulated directly, thus the drug was thought to be compatible for psychosocial intervention. The parietal lobe was stimulated indirectly, suggesting that the indirect effect of the intervention may be based on logical judgment function.

  2. Cognitive and neuroimaging evidence of impaired interaction between self and memory in Alzheimer's disease.

    PubMed

    Genon, Sarah; Bahri, Mohamed Ali; Collette, Fabienne; Angel, Lucie; d'Argembeau, Arnaud; Clarys, David; Kalenzaga, Sandrine; Salmon, Eric; Bastin, Christine

    2014-02-01

    In human cognition, self and memory processes strongly interact, as evidenced by the memory advantage for self-referential materials [Self-Reference Effect (SRE) and Self-Reference Recollection Effect (SRRE)]. The current study examined this interaction at the behavioural level and its neural correlates in patients with Alzheimer's disease (AD). Healthy older controls (HC) and AD patients performed trait-adjectives judgements either for self-relevance or for other-relevance (encoding phase). In a first experiment, the encoding and subsequent yes-no recognition phases were administrated in a Magnetic Resonance Imaging (MRI) scanner. Brain activation as measured by functional MRI (fMRI) was examined during self-relevance judgements and anatomical images were used to search for correlation between the memory advantage for self-related items and grey matter density (GMD). In a second experiment, participants described the retrieval experience that had driven their recognition decisions (familiarity vs recollective experience). The behavioural results revealed that the SRE and SRRE were impaired in AD patients compared to HC participants. Furthermore, verbal reports revealed that the retrieval of self-related information was preferentially associated with the retrieval of contextual details, such as source memory in the HC participants, but less so in the AD patients. Our imaging findings revealed that both groups activated the medial prefrontal cortex (MPFC) at encoding during self-relevance judgements. However, the variable and limited memory advantage for self-related information was associated with GMD in the lateral prefrontal cortex in the AD patients, a region supporting high-order processes linking self and memory. These findings suggest that even if AD patients engage MPFC during self-referential judgements, the retrieval of self-related memories is qualitatively and quantitatively impaired in relation with altered high-order processes in the lateral PFC

  3. Typical and atypical appearance of early-onset Alzheimer's disease: A clinical, neuroimaging and neuropathological study.

    PubMed

    Kawakatsu, Shinobu; Kobayashi, Ryota; Hayashi, Hiroshi

    2017-04-01

    The International Working Group (IWG) has classified Alzheimer's disease (AD) as two different types, the typical form and the atypical form, but clinicopathological studies of atypical AD are limited. Because atypical AD cases usually present with early-onset dementia, we investigated 12 patients with early-onset AD, including two patients with typical AD and 10 patients with atypical AD. Of these patients, six had the posterior variant, three had the frontal variant and one had the logopenic variant mixed with semantic dementia. We reported MRI, single-photon emission CT and neuropathological findings in six representative cases. We also described a "left temporal variant" of AD presenting with transcortical cortical sensory aphasia, which has not been reported previously and is another subtype of the posterior variant of AD. We found a significant correlation between regional cerebral blood flow and counts of NFTs in the cerebral cortices. An atypical presentation with focal neuropsychological symptoms roughly correlated with the density of NFTs in the cerebral cortex and more directly related to spongiform changes in the superficial layers of these areas. In contrast, the distribution of amyloid depositions was diffuse and did not necessarily correlate with focal neuropsychological symptoms. Braak staging or ABC score is not necessarily appropriate to evaluate atypical AD, and instead, spongiform changes in addition to tau pathology in the association cortices better explain the diversity of atypical AD. Interestingly, another patient with a posterior variant of AD had a novel type of atypical plaque, which we referred to as "lucent plaque". They were recognizable with HE staining in the circumference and dystrophic neurites were abundant with Gallyas-Braak staining. These plaques demonstrated intense immunoreactivity to both tau AT-8 and amyloid β (Aβ), suggesting a peculiar coexistence pattern of amyloid and tau in these plaques. Clinicopathological studies

  4. Different Clinical and Neuroimaging Characteristics in Early Stage Parkinson’s Disease with Dementia and Dementia with Lewy Bodies

    PubMed Central

    Takemoto, Mami; Sato, Kota; Hatanaka, Noriko; Yamashita, Toru; Ohta, Yasuyuki; Hishikawa, Nozomi; Abe, Koji

    2016-01-01

    Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) both commonly exhibit brain Lewy body pathology and similar end-stage symptoms, but early symptoms differ. To clarify these differences, we compared the demographic characteristics, symptoms, cognitive and affective functioning, activities of daily life, and neuroimaging results between PDD (n = 52) and DLB (n = 46) patients. In measures of cognitive functioning, PDD patients had worse Hasegawa dementia scale-revised (HDS-R) scores (11.2±4.8) and better frontal assessment battery (FAB) scores (11.3±4.1) compared with DLB (17.0±6.4, p = 0.013 and 8.6±4.7, p = 0.039, respectively). DLB patients performed worse than PDD patients in “orientation to place” tasks. In affective functions, DLB patients had worse GDS (7.6±3.4) and ABS (9.9±5.3) scores than PDD patients (5.1±4.1 and 4.8±3.0, respectively). 99mTc-ECD images showed greater CBF in the whole cingulate gyrus and a lower CBF in the precuneus area in DLB than in PDD. These results suggest that PDD patients’ lower average scores for “repetition” (MMSE), “recent memory” (HDS-R), and “lexical fluency” (FAB) were related to lower CBF in the cingulate gyrus than in DLB. Furthermore, DLB patients’ poorer average subscale scores of “orientation to place” (MMSE) and “similarities”, “conflicting instructions”, and “go-no go” (FAB) tasks may be related to the lower CBF in the precuneus area in DLB than PDD. PMID:27060948

  5. Neuroimaging tools to rate regional atrophy, subcortical cerebrovascular disease, and regional cerebral blood flow and metabolism: consensus paper of the EADC

    PubMed Central

    Frisoni, G; Scheltens, P; Galluzzi, S; Nobili, F; Fox, N; Robert, P; Soininen, H; Wahlund, L; Waldemar, G; Salmon, E

    2003-01-01

    Neuroimaging is a mainstay in the differential diagnosis of patients with cognitive impairment. The often equivocal clinical pictures, the prognostic uncertainty of the earliest stages of mild cognitive impairment, and the subtle brain changes mean that neuroimaging techniques are of potentially great incremental diagnostic value. A number of methods, ranging from very simple subjective visual ratings to highly sophisticated computerised tools, have been developed, which allow rating of structural and functional brain changes. The choice of the method is not obvious, and current guidelines provide no indications on which tools should be preferred. In this paper, we give indications for tools with demonstrated accuracy for detecting regional atrophy, cerebrovascular disease, and regional brain function, and discuss these according to increasing technological complexity, ranging from those with high feasibility that can be used at the patient's bedside to highly technological ones that require trained personnel and specific hardware and software. PMID:14570828

  6. Neuroimaging over the course of Parkinson's disease: from early detection of the at-risk patient to improving pharmacotherapy of later-stage disease.

    PubMed

    Seibyl, John; Russell, David; Jennings, Danna; Marek, Kenneth

    2012-11-01

    Brain imaging of striatal dopamine terminal degeneration serves an important role in the clinical management of Parkinson's disease (PD). Imaging biomarkers for interrogating dopaminergic systems are used for clarifying diagnosis when only subtle motor symptoms are present. However, motor dysfunction is not the earliest symptom of PD. There is increasing interest in identifying premotor PD patients, particularly because potential disease-modifying therapies are developed and the clinical imperative becomes early and accurate diagnosis. On the other end of the spectrum of the disease course, during later stages of PD, significant clinical challenges like levo-dopa-induced dyskinesias and medication on-off phenomenon become more prevalent. In this instance, better understanding of altered PD motor pathways suggests the potential utility of novel treatments targeting neuronal systems that are impacted by degenerating dopamine neurons and chronic dopamine replacement treatment. Molecular neuroimaging serves unique roles in both very early PD and later-stage disease, in the former, potentially pushing back the time of diagnosis, and in the latter, elucidating pathology relevant to new drug development. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Value of neuroimaging in the evaluation of neurologically normal children with recurrent headache.

    PubMed

    Alehan, Füsun Korkmaz

    2002-11-01

    Headache is one of the most frequent physical complaints in children. Although headaches in children are generally benign, neuroimaging studies are frequently performed in clinical practice for the fear of missing a serious underlying disease. Despite this, limited data exist about the utility of neuroimaging in recurrent headache of children with a normal neurologic examination. This prospective study was planned to determine the value of neuroimaging in neurologically normal children with migraine and tension-type headache. Among 95 consecutive patients presenting with headache, 72 patients receiving a diagnosis of migraine or tension-type headache were included in the study. Neuroimaging procedures were performed in 83%. Magnetic resonance imaging (MRI) was abnormal in 11 of 49 cases. Abnormalities consisted of foci of gliosis in four, sinusitis in two, pineal cyst in one, periventricular leukomalacia in one, arachnoid cyst in one, old traumatic changes in one, and cervical syrinx in one. Two of the 11 computed tomographic (CT) scans revealed sinus disease. The percentage of findings causally related to headache was about 10. None of the patients had undergone surgery because of neuroimaging results. In conclusion, the yield of neuroimaging in recurrent headaches of children with a normal neurologic examination is low, and neuroimaging should not be part of a routine initial examination of these patients.

  8. The Co-evolution of Neuroimaging and Psychiatric Neurosurgery

    PubMed Central

    Dyster, Timothy G.; Mikell, Charles B.; Sheth, Sameer A.

    2016-01-01

    The role of neuroimaging in psychiatric neurosurgery has evolved significantly throughout the field’s history. Psychiatric neurosurgery initially developed without the benefit of information provided by modern imaging modalities, and thus lesion targets were selected based on contemporary theories of frontal lobe dysfunction in psychiatric disease. However, by the end of the 20th century, the availability of structural and functional magnetic resonance imaging (fMRI) allowed for the development of mechanistic theories attempting to explain the anatamofunctional basis of these disorders, as well as the efficacy of stereotactic neuromodulatory treatments. Neuroimaging now plays a central and ever-expanding role in the neurosurgical management of psychiatric disorders, by influencing the determination of surgical candidates, allowing individualized surgical targeting and planning, and identifying network-level changes in the brain following surgery. In this review, we aim to describe the coevolution of psychiatric neurosurgery and neuroimaging, including ways in which neuroimaging has proved useful in elucidating the therapeutic mechanisms of neuromodulatory procedures. We focus on ablative over stimulation-based procedures given their historical precedence and the greater opportunity they afford for post-operative re-imaging, but also discuss important contributions from the deep brain stimulation (DBS) literature. We conclude with a discussion of how neuroimaging will transition the field of psychiatric neurosurgery into the era of precision medicine. PMID:27445706

  9. Advances in neuroimaging in frontotemporal dementia.

    PubMed

    Gordon, Elizabeth; Rohrer, Jonathan D; Fox, Nick C

    2016-08-01

    Frontotemporal dementia (FTD) is a clinically and neuroanatomically heterogeneous neurodegenerative disorder with multiple underlying genetic and pathological causes. Whilst initial neuroimaging studies highlighted the presence of frontal and temporal lobe atrophy or hypometabolism as the unifying feature in patients with FTD, more detailed studies have revealed diverse patterns across individuals, with variable frontal or temporal predominance, differing degrees of asymmetry, and the involvement of other cortical areas including the insula and cingulate, as well as subcortical structures such as the basal ganglia and thalamus. Recent advances in novel imaging modalities including diffusion tensor imaging, resting-state functional magnetic resonance imaging and molecular positron emission tomography imaging allow the possibility of investigating alterations in structural and functional connectivity and the visualisation of pathological protein deposition. This review will cover the major imaging modalities currently used in research and clinical practice, focusing on the key insights they have provided into FTD, including the onset and evolution of pathological changes and also importantly their utility as biomarkers for disease detection and staging, differential diagnosis and measurement of disease progression. Validating neuroimaging biomarkers that are able to accomplish these tasks will be crucial for the ultimate goal of powering upcoming clinical trials by correctly stratifying patient enrolment and providing sensitive markers for evaluating the effects and efficacy of disease-modifying therapies. This review describes the key insights provided by research into the major neuroimaging modalities currently used in research and clinical practice, including what they tell us about the onset and evolution of FTD and how they may be used as biomarkers for disease detection and staging, differential diagnosis and measurement of disease progression. This article is

  10. Clinical and neuroimaging differences between posterior cortical atrophy and typical amnestic Alzheimer’s disease patients at an early disease stage

    PubMed Central

    Peng, Guoping; Wang, Jianqin; Feng, Zhan; Liu, Ping; Zhang, Yafei; He, Fangping; Chen, Zhongqin; Zhao, Kui; Luo, Benyan

    2016-01-01

    To identify clinical and neuroimaging characteristics between posterior cortical atrophy (PCA) and typical amnestic Alzheimer’s disease (tAD) patients at an early disease stage, 16 PCA and 13 age-matched tAD patients were enrolled. Compared with tAD patients, PCA patients showed higher mean recognition and recall test scores, and lower mean calculation, spatial attention, shape discrimination, and writing test scores. Mean right hippocampal volume was larger in PCA patients compared with tAD patients, while cortical gray matter (GM) volume of bilateral parietal and occipital lobes was smaller in PCA patients. Further, when compared with tAD patients, significant hypometabolism was observed in bilateral parietal and occipital lobes, particularly the right occipitotemporal junction in PCA patients. Additionally, there were significant positive correlations in recognition and recall scores with hippocampal volumes. In PCA patients, calculation and visuospatial ability scores are positively associated with GM volume of parietal and occipital lobes. And only spatial attention and shape discrimination scores are positively associated with regional glucose metabolism of parietal and occipital lobes. Therefore, PCA patients display better recognition and recall scores, which are associated with larger hippocampal volumes and poorer performance in visual spatial tasks because of marked GM atrophy and hypometabolism of parietal and occipital lobes. PMID:27377199

  11. Clinical neuroimaging

    SciTech Connect

    Gilman, S.; Mazziotta, J.C.

    1989-01-01

    Designed for practicing neurologists and neurosurgeons, this reference focuses on the newest techniques in computed assisted tomography. Text material covers basic principles of computed tomography, as well as the clinical advantages and disadvantages of each modality. The anatomical and/or physiological processes measured by XCT, PET, SPECT and MRI are first discussed in terms of the normal patient, and then applied to the diagnosis and treatment of patients with neurological disease (primarily of the brain). Emphasis is placed on areas of difficult diagnosis, such as differentiating recurrent tumor from radiation necrosis, early diagnosis of dementia, selection of patients for extracranial-intracranial bypass procedures, and localization of epileptic foci.

  12. [Pediatric neuroimaging emergencies].

    PubMed

    Adamsbaum, C; Rolland, Y; Husson, B

    2004-09-01

    The notion of emergency with regards to pediatric neuroimaging requires a strong knowledge of clinical indications. In children under 2 years of age, head trauma requires a CT scan in case of repeated or prolonged or rapidly increasing vomiting, focal signs, loss of consciousness, unusual behavior, seizures, clinical signs of skull fracture or polytrauma. The "shaken baby syndrome" is usually suspected in case of loss of consciousness or seizures before 8 months of age. The hematomas that are observed are subdural in location, diffuse and deeply located. Imaging is only mandatory for headache suggesting underlying space occupying lesion: permanent or increasing pain, nocturnal headache, headache during postural changes or efforts, associated to seizures or abnormal neurological examination. No imaging is indicated in case of first epileptic seizure associated to normal neurological examination and without any particular context. The presence of trauma, intracranial hypertension, persisting disturbances of consciousness or associated focal sign necessitates urgent neuroimaging. No imaging is indicated in case of typical febrile seizures, i.e. generalized, brief and occurring between 1 and 5 years of age. Spinal cord symptoms require immediate MRI evaluation. The most frequent tumor is neuroblastoma. In the absence of spinal tumor, brain abnormalities must be excluded (inflammatory disease). In neonates, CT scan or MRI must be readily performed in case of seizures or loss of consciousness to exclude ischemic, traumatic or infectious lesions.

  13. Initial Staging of Hodgkin’s Disease

    PubMed Central

    Chiaravalloti, Agostino; Danieli, Roberta; Caracciolo, Cristiana Ragano; Travascio, Laura; Cantonetti, Maria; Gallamini, Andrea; Guazzaroni, Manlio; Orlacchio, Antonio; Simonetti, Giovanni; Schillaci, Orazio

    2014-01-01

    Abstract The objective of this study was to compare the diagnostic accuracy of positron emission tomography/low-dose computed tomography (PET/ldCT) versus the same technique implemented by contrast-enhanced computed tomography (ceCT) in staging Hodgkin’s disease (HD). Forty patients (18 men and 22 women, mean age 30 ± 9.6) with biopsy-proven HD underwent a PET/ldCT study for initial staging including an unenhanced low-dose computed tomography for attenuation correction with positron emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT scan, in the same exam session. A detailed datasheet was generated for illness locations for separate imaging modality comparison and then merged in order to compare the separate imaging method results (PET/ldCT and ceCT) versus merged results positron emission tomography/contrast-enhanced computed tomography (PET/ceCT). The nodal and extranodal lesions detected by each technique were then compared with follow-up data that served as the reference standard. No significant differences were found at staging between PET/ldCT and PET/ceCT in our series. One hundred and eighty four stations of nodal involvement have been found with no differences in both modalities. Extranodal involvement was identified in 26 sites by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences concerning the stage (Ann Arbor). Our study shows a good concordance and conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the initial staging of HD, suggesting that PET/ldCT could suffice in most of these patients. PMID:25121354

  14. [Neuroimaging in psychiatry: multivariate analysis techniques for diagnosis and prognosis].

    PubMed

    Kambeitz, J; Koutsouleris, N

    2014-06-01

    Multiple studies successfully applied multivariate analysis to neuroimaging data demonstrating the potential utility of neuroimaging for clinical diagnostic and prognostic purposes. Summary of the current state of research regarding the application of neuroimaging in the field of psychiatry. Literature review of current studies. Results of current studies indicate the potential application of neuroimaging data across various diagnoses, such as depression, schizophrenia, bipolar disorder and dementia. Potential applications include disease classification, differential diagnosis and prediction of disease course. The results of the studies are heterogeneous although some studies report promising findings. Further multicentre studies are needed with clearly specified patient populations to systematically investigate the potential utility of neuroimaging for the clinical routine.

  15. Structural brain network constrained neuroimaging marker identification for predicting cognitive functions.

    PubMed

    De, Wang; Nie, Feiping; Huang, Heng; Yan, Jingwen; Risacher, Shannon L; Saykin, Andrew J; Shen, Li

    2013-01-01

    Neuroimaging markers have been widely used to predict the cognitive functions relevant to the progression of Alzheimer's disease (AD). Most previous studies identify the imaging markers without considering the brain structural correlations between neuroimaging measures. However, many neuroimaging markers interrelate and work together to reveal the cognitive functions, such that these relevant markers should be selected together as the phenotypic markers. To solve this problem, in this paper, we propose a novel network constrained feature selection (NCFS) model to identify the neuroimaging markers guided by the structural brain network, which is constructed by the sparse representation method such that the interrelations between neuroimaging features are encoded into probabilities. Our new methods are evaluated by the MRI and AV45-PET data from ADNI-GO and ADNI-2 (Alzheimer's Disease Neuroimaging Initiative). In all cognitive function prediction tasks, our new NCFS method outperforms other state-of-the-art regression approaches. Meanwhile, we show that the new method can select the correlated imaging markers, which are ignored by the competing approaches.

  16. Neural Circuit Modulation During Deep Brain Stimulation at the Subthalamic Nucleus for Parkinson's Disease: What Have We Learned from Neuroimaging Studies?

    PubMed Central

    Albaugh, Daniel L.

    2014-01-01

    Abstract Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) represents a powerful clinical tool for the alleviation of many motor symptoms that are associated with Parkinson's disease. Despite its extensive use, the underlying therapeutic mechanisms of STN-DBS remain poorly understood. In the present review, we integrate and discuss recent literature examining the network effects of STN-DBS for Parkinson's disease, placing emphasis on neuroimaging findings, including functional magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. These techniques enable the noninvasive detection of brain regions that are modulated by DBS on a whole-brain scale, representing a key experimental strength given the diffuse and far-reaching effects of electrical field stimulation. By examining these data in the context of multiple hypotheses of DBS action, generally developed through clinical and physiological observations, we define a multitude of consistencies and inconsistencies in the developing literature of this rapidly moving field. PMID:24147633

  17. Functional Neuroimaging: A Physiological Perspective

    PubMed Central

    Lin, Ai-Ling; Gao, Jia-Hong; Duong, Timonthy Q.; Fox, Peter T.

    2010-01-01

    Metabolic physiology and functional neuroimaging have played important and complementary roles over the past two decades. In particular, investigations of the mechanisms underlying functional neuroimaging signals have produced fundamental new insights into hemodynamic and metabolic regulation. However, controversies were also raised as regards the metabolic pathways (oxidative vs. non-oxidative) for meeting the energy demand and driving the increases in cerebral blood flow (CBF) during brain activation. In a recent study, with the concurrent functional MRI-MRS measurements, we found that task-evoked energy demand was predominately met through oxidative metabolism (approximately 98%), despite a small increase in cerebral metabolic rate of oxygen (12–17%). In addition, the task-induced increases in CBF were most likely mediated by anaerobic glycolysis rather than oxygen demand. These observations and others from functional neuroimaging support the activation-induced neuron-astrocyte interactions portrayed by the astrocyte-neuron lactate shuttle model. The concurrent developments of neuroimaging methods and metabolic physiology will also pave the way for the future investigation of cerebral hemodynamics and metabolism in disease states. PMID:20725632

  18. COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), a global--clinical evaluations, serum biomarkers, genetic studies and neuroimaging--prospective, multicenter, non-interventional, long-term study on Parkinson's disease progression.

    PubMed

    Santos-García, Diego; Mir, Pablo; Cubo, Esther; Vela, Lydia; Rodríguez-Oroz, Mari Cruz; Martí, Maria José; Arbelo, José Matías; Infante, Jon; Kulisevsky, Jaime; Martínez-Martín, Pablo

    2016-02-25

    Parkinson's disease (PD) is a progressive neurodegenerative disorder causing motor and non-motor symptoms that can affect independence, social adjustment and the quality of life (QoL) of both patients and caregivers. Studies designed to find diagnostic and/or progression biomarkers of PD are needed. We describe here the study protocol of COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015), an integral PD project based on four aspects/concepts: 1) PD as a global disease (motor and non-motor symptoms); 2) QoL and caregiver issues; 3) Biomarkers; 4) Disease progression. Observational, descriptive, non-interventional, 5-year follow-up, national (Spain), multicenter (45 centers from 15 autonomous communities), evaluation study. Specific goals: (1) detailed study (clinical evaluations, serum biomarkers, genetic studies and neuroimaging) of a population of PD patients from different areas of Spain, (2) comparison with a control group and (3) follow-up for 5 years. COPPADIS-2015 has been specifically designed to assess 17 proposed objectives. approximately 800 non-dementia PD patients, 600 principal caregivers and 400 control subjects. Study evaluations: (1) baseline includes motor assessment (e.g., Unified Parkinson's Disease Rating Scale part III), non-motor symptoms (e.g., Non-Motor Symptoms Scale), cognition (e.g., Parkinson's Disease Cognitive Rating Scale), mood and neuropsychiatric symptoms (e.g., Neuropsychiatric Inventory), disability, QoL (e.g., 39-item Parkinson's disease Quality of Life Questionnaire Summary-Index) and caregiver status (e.g., Zarit Caregiver Burden Inventory); (2) follow-up includes annual (patients) or biannual (caregivers and controls) evaluations. Serum biomarkers (S-100b protein, TNF-α, IL-1, IL-2, IL-6, vitamin B12, methylmalonic acid, homocysteine, uric acid, C-reactive protein, ferritin, iron) and brain MRI (volumetry, tractography and MTAi [Medial Temporal Atrophy Index]), at baseline and at the end of follow

  19. The Interleukin-1 Balance During Encephalitis Is Associated With Clinical Severity, Blood-Brain Barrier Permeability, Neuroimaging Changes, and Disease Outcome.

    PubMed

    Michael, Benedict Daniel; Griffiths, Michael J; Granerod, Julia; Brown, David; Keir, Geoff; Wnęk, Gosia; Cox, Daniel J; Vidyasagar, Rishma; Borrow, Ray; Parkes, Laura M; Solomon, Tom

    2016-05-15

    Encephalitis is parenchymal brain inflammation, commonly due to herpes simplex virus (HSV). Key host inflammatory mediators and their relationship to blood-brain barrier (BBB) permeability, neuroimaging changes, and disease outcome are poorly understood. We measured levels of 38 mediators in serum (n = 78) and cerebrospinal fluid (n = 37) specimens from patients with encephalitis, including 17 with disease due to HSV infection. Outcome measures were Glasgow coma and outcome scores; CSF to serum albumin ratio, reflecting BBB permeability; and, in patients with HSV infection, magnetic resonance imaging-based temporal lobe volume. Serum interleukin 1 receptor antagonist (IL-1RA) levels were elevated in patients with a good outcome (P= .004). Among patients infected with HSV, the ratio of CSF IL-1β to IL-1RA was associated with a worse outcome (P= .009); a ratio of ≥0.55 pg/mL had high specificity and sensitivity for a poor outcome (100% and 83%;P= .015). Temporal lobe volume had a negative correlation with serum IL-1RA level (P= .012) and a positive correlation with serum IL-1α level (P= .0003) and CSF IL-1β level (P= .007). A normal coma score was associated with an elevated interleukin 10 (IL-10) level in serum specimens from HSV-infected patients (P= .007) and CSF specimens from all patients (P= .016); the IL-10 level correlated inversely with BBB permeability (P= .005). A proinflammatory cytokine response is associated with greater clinical severity, BBB permeability, and neuroimaging damage during encephalitis. IL-1 antagonists should be investigated as adjunctive treatment in encephalitis. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  20. Neuroimaging of Infections

    PubMed Central

    Kastrup, Oliver; Wanke, Isabel; Maschke, Matthias

    2005-01-01

    Summary: Neuroimaging plays a crucial role in the diagnosis and therapeutic decision making in infectious diseases of the nervous system. The review summarizes imaging findings and recent advances in the diagnosis of pyogenic brain abscess, ventriculitis, viral disease including exotic and emergent viruses, and opportunistic disease. For each condition, the ensuing therapeutic steps are presented. In cases of uncomplicated meningitis, cranial computed tomography (CT) appears to be sufficient for clinical management to exclude acute brain edema, hydrocephalus, and pathology of the base of skull. Magnetic resonance imaging (MRI) is superior in depicting complications like sub-/epidural empyema and vasculitic complications notably on FLAIR (fluid-attenuated inversion recovery)-weighted images. The newer technique of diffusion-weighted imaging (DWI) shows early parenchymal complications of meningitis earlier and with more clarity and is of help in differentiation of pyogenic abscess (PA) from ring enhancing lesions of other etiology. Proton magnetic resonance spectroscopy (PMRS) seems to produce specific peak patterns in cases of abscess. The presence of lactate cytosolic amino acids and absence of choline seems to indicate PA. Also in cases of suspected opportunistic infection due to toxoplasma DWI may be of help in the differentiation from lymphoma, showing no restriction of water diffusion. In patients with herpes simplex and more exotic viruses like West Nile and Murray Valley virus DWI allows earlier lesion detection and therapeutic intervention with virustatic drugs. PMID:15897953

  1. Pitfalls in the Neuroimaging of Glioblastoma in the Era of Antiangiogenic and Immuno/Targeted Therapy – Detecting Illusive Disease, Defining Response

    PubMed Central

    Huang, Raymond Y.; Neagu, Martha R.; Reardon, David A.; Wen, Patrick Y.

    2015-01-01

    Glioblastoma, the most common malignant primary brain tumor in adults is a devastating diagnosis with an average survival of 14–16 months using the current standard of care treatment. The determination of treatment response and clinical decision making is based on the accuracy of radiographic assessment. Notwithstanding, challenges exist in the neuroimaging evaluation of patients undergoing treatment for malignant glioma. Differentiating treatment response from tumor progression is problematic and currently combines long-term follow-up using standard magnetic resonance imaging (MRI), with clinical status and corticosteroid-dependency assessments. In the clinical trial setting, treatment with gene therapy, vaccines, immunotherapy, and targeted biologicals similarly produces MRI changes mimicking disease progression. A neuroimaging method to clearly distinguish between pseudoprogression and tumor progression has unfortunately not been found to date. With the incorporation of antiangiogenic therapies, a further pitfall in imaging interpretation is pseudoresponse. The Macdonald criteria that correlate tumor burden with contrast-enhanced imaging proved insufficient and misleading in the context of rapid blood–brain barrier normalization following antiangiogenic treatment that is not accompanied by expected survival benefit. Even improved criteria, such as the RANO criteria, which incorporate non-enhancing disease, clinical status, and need for corticosteroid use, fall short of definitively distinguishing tumor progression, pseudoresponse, and pseudoprogression. This review focuses on advanced imaging techniques including perfusion MRI, diffusion MRI, MR spectroscopy, and new positron emission tomography imaging tracers. The relevant image analysis algorithms and interpretation methods of these promising techniques are discussed in the context of determining response and progression during treatment of glioblastoma both in the standard of care and in clinical trial

  2. The Interleukin-1 Balance During Encephalitis Is Associated With Clinical Severity, Blood-Brain Barrier Permeability, Neuroimaging Changes, and Disease Outcome

    PubMed Central

    Michael, Benedict Daniel; Griffiths, Michael J.; Granerod, Julia; Brown, David; Keir, Geoff; Wnęk, Gosia; Cox, Daniel J.; Vidyasagar, Rishma; Borrow, Ray; Parkes, Laura M.; Solomon, Tom

    2016-01-01

    Background. Encephalitis is parenchymal brain inflammation, commonly due to herpes simplex virus (HSV). Key host inflammatory mediators and their relationship to blood-brain barrier (BBB) permeability, neuroimaging changes, and disease outcome are poorly understood. Methods. We measured levels of 38 mediators in serum (n = 78) and cerebrospinal fluid (n = 37) specimens from patients with encephalitis, including 17 with disease due to HSV infection. Outcome measures were Glasgow coma and outcome scores; CSF to serum albumin ratio, reflecting BBB permeability; and, in patients with HSV infection, magnetic resonance imaging–based temporal lobe volume. Results. Serum interleukin 1 receptor antagonist (IL-1RA) levels were elevated in patients with a good outcome (P = .004). Among patients infected with HSV, the ratio of CSF IL-1β to IL-1RA was associated with a worse outcome (P = .009); a ratio of ≥0.55 pg/mL had high specificity and sensitivity for a poor outcome (100% and 83%; P = .015). Temporal lobe volume had a negative correlation with serum IL-1RA level (P = .012) and a positive correlation with serum IL-1α level (P = .0003) and CSF IL-1β level (P = .007). A normal coma score was associated with an elevated interleukin 10 (IL-10) level in serum specimens from HSV-infected patients (P = .007) and CSF specimens from all patients (P = .016); the IL-10 level correlated inversely with BBB permeability (P = .005). Conclusions. A proinflammatory cytokine response is associated with greater clinical severity, BBB permeability, and neuroimaging damage during encephalitis. IL-1 antagonists should be investigated as adjunctive treatment in encephalitis. PMID:26712949

  3. Multiple comparison procedures for neuroimaging genomewide association studies.

    PubMed

    Hua, Wen-Yu; Nichols, Thomas E; Ghosh, Debashis

    2015-01-01

    Recent research in neuroimaging has focused on assessing associations between genetic variants that are measured on a genomewide scale and brain imaging phenotypes. A large number of works in the area apply massively univariate analyses on a genomewide basis to find single nucleotide polymorphisms that influence brain structure. In this paper, we propose using various dimensionality reduction methods on both brain structural MRI scans and genomic data, motivated by the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. We also consider a new multiple testing adjustment method and compare it with two existing false discovery rate (FDR) adjustment methods. The simulation results suggest an increase in power for the proposed method. The real-data analysis suggests that the proposed procedure is able to find associations between genetic variants and brain volume differences that offer potentially new biological insights. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Neuroimaging of the Philadelphia neurodevelopmental cohort.

    PubMed

    Satterthwaite, Theodore D; Elliott, Mark A; Ruparel, Kosha; Loughead, James; Prabhakaran, Karthik; Calkins, Monica E; Hopson, Ryan; Jackson, Chad; Keefe, Jack; Riley, Marisa; Mentch, Frank D; Sleiman, Patrick; Verma, Ragini; Davatzikos, Christos; Hakonarson, Hakon; Gur, Ruben C; Gur, Raquel E

    2014-02-01

    The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale, NIMH funded initiative to understand how brain maturation mediates cognitive development and vulnerability to psychiatric illness, and understand how genetics impacts this process. As part of this study, 1445 adolescents ages 8-21 at enrollment underwent multimodal neuroimaging. Here, we highlight the conceptual basis for the effort, the study design, and the measures available in the dataset. We focus on neuroimaging measures obtained, including T1-weighted structural neuroimaging, diffusion tensor imaging, perfusion neuroimaging using arterial spin labeling, functional imaging tasks of working memory and emotion identification, and resting state imaging of functional connectivity. Furthermore, we provide characteristics regarding the final sample acquired. Finally, we describe mechanisms in place for data sharing that will allow the PNC to become a freely available public resource to advance our understanding of normal and pathological brain development. © 2013 Elsevier Inc. All rights reserved.

  5. Parkinson's disease: initial treatment of motor disorders.

    PubMed

    2015-09-01

    Parkinson's disease is characterised by three main symptoms: slowness and paucity of movements, rigidity, and resting tremor. Rapid improvement in these symptoms after levodopa administration supports the diagnosis of Parkinson's disease. It is important to inform the patient tactfully, allowing him or her to control the pace at which information on the diagnosis, symptoms and prognosis is conveyed. Patients with minimal discomfort or mild disability derive little benefit from drug therapy. Physiotherapy and physical exercises are sometimes useful. Previously untreated patients with marked functional impairment should receive medication. The choice is essentially between levodopa and ropinirole, and mainly depends on the patient's age.

  6. FUNCTIONAL NEUROIMAGING IN GERIATRIC DEPRESSION

    PubMed Central

    Gunning, Faith M.; Smith, Gwenn S.

    2012-01-01

    Synopsis Abnormalities in specific cerebral networks likely confer vulnerability that increases the susceptibility for development of geriatric depression and impact the course of symptoms. Functional neuroimaging enables the in vivo identification of alterations in cerebral function that not only characterize disease vulnerability, but also may contribute to variability in depressive symptoms and antidepressant response. Judicious use of functional neuroimaging tools can advance pathophysiological models of geriatric depression. Furthermore, due to the age-related vulnerability of specific brain systems that have been implicated in mood disorders, geriatric depression provides a logical context within which to study the role of specific functional abnormalities in both antidepressant response and key behavioral and cognitive abnormalities of mood disorders. PMID:21536165

  7. A New Approach to Investigate the Association between Brain Functional Connectivity and Disease Characteristics of Attention-Deficit/Hyperactivity Disorder: Topological Neuroimaging Data Analysis.

    PubMed

    Kyeong, Sunghyon; Park, Seonjeong; Cheon, Keun-Ah; Kim, Jae-Jin; Song, Dong-Ho; Kim, Eunjoo

    2015-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is currently diagnosed by a diagnostic interview, mainly based on subjective reports from parents or teachers. It is necessary to develop methods that rely on objectively measureable neurobiological data to assess brain-behavior relationship in patients with ADHD. We investigated the application of a topological data analysis tool, Mapper, to analyze the brain functional connectivity data from ADHD patients. To quantify the disease severity using the neuroimaging data, the decomposition of individual functional networks into normal and disease components by the healthy state model (HSM) was performed, and the magnitude of the disease component (MDC) was computed. Topological data analysis using Mapper was performed to distinguish children with ADHD (n = 196) from typically developing controls (TDC) (n = 214). In the topological data analysis, the partial clustering results of patients with ADHD and normal subjects were shown in a chain-like graph. In the correlation analysis, the MDC showed a significant increase with lower intelligence scores in TDC. We also found that the rates of comorbidity in ADHD significantly increased when the deviation of the functional connectivity from HSM was large. In addition, a significant correlation between ADHD symptom severity and MDC was found in part of the dataset. The application of HSM and topological data analysis methods in assessing the brain functional connectivity seem to be promising tools to quantify ADHD symptom severity and to reveal the hidden relationship between clinical phenotypic variables and brain connectivity.

  8. Neuroimaging of epilepsy

    PubMed Central

    Cendes, Fernando; Theodore, William H.; Brinkmann, Benjamin H.; Sulc, Vlastimil; Cascino, Gregory D.

    2017-01-01

    Imaging is pivotal in the evaluation and management of patients with seizure disorders. Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, low-grade glial neoplasms and malformations of cortical development has been demonstrated. Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment. This chapter highlights neuroimaging developments and innovations, and provides a comprehensive overview of the imaging strategies used to improve the care and management of people with epilepsy. PMID:27430454

  9. Neuroimaging of epilepsy.

    PubMed

    Cendes, Fernando; Theodore, William H; Brinkmann, Benjamin H; Sulc, Vlastimil; Cascino, Gregory D

    2016-01-01

    Imaging is pivotal in the evaluation and management of patients with seizure disorders. Elegant structural neuroimaging with magnetic resonance imaging (MRI) may assist in determining the etiology of focal epilepsy and demonstrating the anatomical changes associated with seizure activity. The high diagnostic yield of MRI to identify the common pathological findings in individuals with focal seizures including mesial temporal sclerosis, vascular anomalies, low-grade glial neoplasms and malformations of cortical development has been demonstrated. Positron emission tomography (PET) is the most commonly performed interictal functional neuroimaging technique that may reveal a focal hypometabolic region concordant with seizure onset. Single photon emission computed tomography (SPECT) studies may assist performance of ictal neuroimaging in patients with pharmacoresistant focal epilepsy being considered for neurosurgical treatment. This chapter highlights neuroimaging developments and innovations, and provides a comprehensive overview of the imaging strategies used to improve the care and management of people with epilepsy. © 2016 Elsevier B.V. All rights reserved.

  10. Functional neuroimaging in psychiatry.

    PubMed Central

    Fu, C H; McGuire, P K

    1999-01-01

    Functional neuroimaging is one of the most powerful means available for investigating the pathophysiology of psychiatric disorders. In this review, we shall focus on the different ways that it can be employed to this end, describing the major findings in the field in the context of different methodological approaches. We will also discuss practical issues that are particular to studying psychiatric disorders and the potential contribution of functional neuroimaging to future psychiatric research. PMID:10466156

  11. [Mixed states and neuroimaging].

    PubMed

    Kaladjian, A; Belzeaux, R; Micoulaud-Franchi, J A; Cermolacce, M; Fakra, E; Azorin, J-M

    2013-12-01

    Despite the growing number of neuroimaging studies in bipolar disorder over the past years, the brain regions involved in mood dysregulation in this disease are still poorly understood. If some neurofunctional abnormalities seem to be independent of mood state, others were preferentially associated with mania or depression, involving the amygdala and other limbic regions as well as ventral frontal regions, with a likely hemispheric lateralization of these abnormalities according to the thymic state that was examined. Very few imaging studies became interested in bipolar patients in a mixed state, making it harder to connect brain malfunction to a given mood state. However, data obtained so far support the hypothesis of a lateralization of brain abnormalities in relation to bipolar symptomatology, suggesting that neurofonctional abnormalities preferentially located in the right ventral frontal and limbic areas may underlie the depressive component, associated with abnormalities of the left similar regions for the manic component. Identification of brain dysfunctions that may explain the emergence of mixed symptoms will likely provide useful information to better understand the respective roles of each hemisphere in the pathophysiology of bipolar disorder. Copyright © 2013 Sociedade Brasileira de Farmacognosia. Published by Elsevier Masson SAS.. All rights reserved.

  12. Neuroimaging in Cockayne syndrome.

    PubMed

    Koob, M; Laugel, V; Durand, M; Fothergill, H; Dalloz, C; Sauvanaud, F; Dollfus, H; Namer, I J; Dietemann, J-L

    2010-10-01

    CS is an autosomal recessive multisystem disorder, which is mainly characterized by neurologic and sensory impairment, cachectic dwarfism, and photosensitivity. We describe the neuroimaging features (MR imaging, ¹H-MR spectroscopy, and CT) in the various clinical subtypes of CS from a cohort of genetically and biochemically proved cases. Hypomyelination, calcifications, and brain atrophy were the main imaging features. Calcifications were typically found in the putamen and less often in the cortex and dentate nuclei. Severe progressive atrophy was seen in the supratentorial white matter, the cerebellum, the corpus callosum, and the brain stem. Patients with early-onset disease displayed more severe hypomyelination and prominent calcifications in the sulcal depth of the cerebral cortex, but atrophy was less severe in late-onset patients. On proton MR spectroscopy, lactate was detected and Cho and NAA values were decreased. These combined neuroradiologic findings can help in the differential diagnosis of CS, distinguishing it from other leukoencephalopathies and/or cerebral calcifications in childhood.

  13. Human neuroimaging as a "Big Data" science.

    PubMed

    Van Horn, John Darrell; Toga, Arthur W

    2014-06-01

    The maturation of in vivo neuroimaging has led to incredible quantities of digital information about the human brain. While much is made of the data deluge in science, neuroimaging represents the leading edge of this onslaught of "big data". A range of neuroimaging databasing approaches has streamlined the transmission, storage, and dissemination of data from such brain imaging studies. Yet few, if any, common solutions exist to support the science of neuroimaging. In this article, we discuss how modern neuroimaging research represents a multifactorial and broad ranging data challenge, involving the growing size of the data being acquired; sociological and logistical sharing issues; infrastructural challenges for multi-site, multi-datatype archiving; and the means by which to explore and mine these data. As neuroimaging advances further, e.g. aging, genetics, and age-related disease, new vision is needed to manage and process this information while marshalling of these resources into novel results. Thus, "big data" can become "big" brain science.

  14. The Road Ahead to Cure Alzheimer’s Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations

    PubMed Central

    Cavedo, E.; Lista, S.; Khachaturian, Z.; Aisen, P.; Amouyel, P.; Herholz, K.; Jack, C.R.; Sperling, R.; Cummings, J.; Blennow, K.; O’Bryant, S.; Frisoni, G.B.; Khachaturian, A.; Kivipelto, M.; Klunk, W.; Broich, K.; Andrieu, S.; de Schotten, M. Thiebaut; Mangin, J.-F.; Lammertsma, A.A.; Johnson, K.; Teipel, S.; Drzezga, A.; Bokde, A.; Colliot, O.; Bakardjian, H.; Zetterberg, H.; Dubois, B.; Vellas, B.; Schneider, L.S.; Hampel, H.

    2015-01-01

    Alzheimer’s disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group’s revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard (“core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aβ1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1-40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for “prodromal AD” and “mild cognitive impairment due to AD” include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis

  15. Basics of Multivariate Analysis in Neuroimaging Data

    PubMed Central

    Habeck, Christian Georg

    2010-01-01

    data set from the Alzheimer s Disease Neuroimaging Initiative (ADNI), clearly demonstrating the superior performance of the multivariate approach. PMID:20689509

  16. Familial Creutzfeldt-Jakob disease with the E200K mutation: longitudinal neuroimaging from asymptomatic to symptomatic CJD.

    PubMed

    Cohen, Oren S; Chapman, Joab; Korczyn, Amos D; Nitsan, Zeev; Appel, Shmuel; Hoffmann, Chen; Rosenmann, Hanna; Kahana, Esther; Lee, Hedok

    2015-03-01

    Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. While carriers are born with this mutation, they usually remain asymptomatic until middle age. Early detection of conversion is crucial for understanding and eventually for the treatment of the disease. The aim of this study was to report longitudinal MRI data in E200K individuals who eventually converted from healthy mutation carriers to clinically symptomatic CJD. As a part of a prospective study, asymptomatic E200K mutation carriers were scanned annually until their conversion to symptomatic disease. Standardized diffusion and anatomical MR sequences were performed before and after clinical conversion in the subjects and those were compared to 15 non-carrier siblings ("healthy controls"). Blinded radiological readings and region of interest analyses were performed. Radiological readings of individual cases failed to detect characteristic changes in the scans taken before the conversion. Region of interest analysis of diffusion changes in pre-symptomatic stage was inconclusive; however, ADC reduction was found in early and late stages of the disease. Computerized volumetric analysis revealed monotonic volume reductions in thalamus, putamen and caudate following conversion, and the lateral ventricles showed dilatation of up to 62 % after clinical conversion. Although the clinical manifestations at disease onset are variable, the diffusion abnormalities and/or volume changes in the thalamus and basal ganglia during conversion may indicate early involvement of the thalamostriatal neuronal circuit.

  17. A review of neuroimaging studies of stressor-evoked blood pressure reactivity: Emerging evidence for a brain-body pathway to coronary heart disease risk

    PubMed Central

    Gianaros, Peter J.; Sheu, Lei K.

    2009-01-01

    An individual's tendency to show exaggerated or otherwise dysregulated cardiovascular reactions to acute stressors has long been associated with increased risk for clinical and preclinical endpoints of coronary heart disease (CHD). However, the ‘brain-body’ pathways that link stressor-evoked cardiovascular reactions to CHD risk remain uncertain. This review summarizes emerging neuroimaging research indicating that individual differences in stressor-evoked blood pressure reactivity (a particular form of cardiovascular reactivity) are associated with activation patterns in corticolimbic brain areas that are jointly involved in processing stressors and regulating the cardiovascular system. As supported empirically by activation likelihood estimates derived from a meta-analysis, these corticolimbic areas include divisions of the cingulate cortex, insula, and amygdala—as well as networked cortical and subcortical areas involved in mobilizing hemodynamic and metabolic support for stress-related behavioral responding. Contextually, the research reviewed here illustrates how behavioral medicine and health neuroscience methods can be integrated to help characterize the ‘brain-body’ pathways that mechanistically link stressful experiences with CHD risk. PMID:19410652

  18. The Receiver Operational Characteristic for Binary Classification with Multiple Indices and Its Application to the Neuroimaging Study of Alzheimer’s Disease

    PubMed Central

    Wu, Xia; Li, Juan; Ayutyanont, Napatkamon; Protas, Hillary; Jagust, William; Fleisher, Adam; Reiman, Eric; Yao, Li; Chen, Kewei

    2014-01-01

    Given a single index, the receiver operational characteristic (ROC) curve analysis is routinely utilized for characterizing performances in distinguishing two conditions/groups in terms of sensitivity and specificity. Given the availability of multiple data sources (referred to as multi-indices), such as multimodal neuroimaging data sets, cognitive tests, and clinical ratings and genomic data in Alzheimer’s disease (AD) studies, the single-index-based ROC underutilizes all available information. For a long time, a number of algorithmic/analytic approaches combining multiple indices have been widely used to simultaneously incorporate multiple sources. In this study, we propose an alternative for combining multiple indices using logical operations, such as “AND,” “OR,” and “at least n” (where n is an integer), to construct multivariate ROC (multiV-ROC) and characterize the sensitivity and specificity statistically associated with the use of multiple indices. With and without the “leave-one-out” cross-validation, we used two data sets from AD studies to showcase the potentially increased sensitivity/specificity of the multiV-ROC in comparison to the single-index ROC and linear discriminant analysis (an analytic way of combining multi-indices). We conclude that, for the data sets we investigated, the proposed multiV-ROC approach is capable of providing a natural and practical alternative with improved classification accuracy as compared to univariate ROC and linear discriminant analysis. PMID:23702553

  19. Neuroimaging diagnosis for cerebral infarction

    PubMed Central

    Du, Yan; Yang, Xiaoxia; Song, Hong; Chen, Bo; Li, Lin; Pan, Yue; Wu, Qiong; Li, Jia

    2012-01-01

    Objective: To identify global research trends in neuroimaging diagnosis for cerebral infarction using a bibliometric analysis of the Web of Science. Data Retrieval: We performed a bibliometric analysis of data retrieval for neuroimaging diagnosis for cerebral infarction containing the key words “CT, magnetic resonance imaging, MRI, transcranial Doppler, transvaginal color Doppler, digital subtraction angiography, and cerebral infarction” using the Web of Science. Selection Criteria: Inclusion criteria were: (a) peer-reviewed articles on neuroimaging diagnosis for cerebral infarction which were published and indexed in the Web of Science; (b) original research articles and reviews; and (c) publication between 2004–2011. Exclusion criteria were: (a) articles that required manual searching or telephone access; and (b) corrected papers or book chapters. Main Outcome Measures: (1) Annual publication output; (2) distribution according to country; (3) distribution according to institution; (4) top cited publications; (5) distribution according to journals; and (6) comparison of study results on neuroimaging diagnosis for cerebral infarction. Results: Imaging has become the predominant method used in diagnosing cerebral infarction. The most frequently used clinical imaging methods were digital subtraction angiography, CT, MRI, and transcranial color Doppler examination. Digital subtraction angiography is used as the gold standard. However, it is a costly and time-consuming invasive diagnosis that requires some radiation exposure, and is poorly accepted by patients. As such, it is mostly adopted in interventional therapy in the clinic. CT is now accepted as a rapid, simple, and reliable non-invasive method for use in diagnosis of cerebrovascular disease and preoperative appraisal. Ultrasonic Doppler can be used to reflect the hardness of the vascular wall and the nature of the plaque more clearly than CT and MRI. Conclusion: At present, there is no unified standard of

  20. Exploring yawning with neuroimaging.

    PubMed

    Nahab, Fatta B

    2010-01-01

    The neural mechanisms responsible for spontaneous yawning as well as contagious yawning are not well characterized. Neuroimaging is an essential tool for helping to identify the seminal neural structures and their inter-related functions to carry out this complex stereotyped motor program. Studies to date have explored the structural neural correlates of yawning through a series of lesion-based case reports and identified participatory structures at various levels of the central nervous system. Functional neuroimaging methods like fMRI have also shed led on the genesis of contagious yawning, though cohesive models explaining the neural mechanisms of contagious motor programs such as yawning remain limited.

  1. Computer-assisted initial diagnosis of rare diseases

    PubMed Central

    Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert

    2016-01-01

    Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient’s symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers. PMID:27547534

  2. Computer-assisted initial diagnosis of rare diseases.

    PubMed

    Alves, Rui; Piñol, Marc; Vilaplana, Jordi; Teixidó, Ivan; Cruz, Joaquim; Comas, Jorge; Vilaprinyo, Ester; Sorribas, Albert; Solsona, Francesc

    2016-01-01

    Introduction. Most documented rare diseases have genetic origin. Because of their low individual frequency, an initial diagnosis based on phenotypic symptoms is not always easy, as practitioners might never have been exposed to patients suffering from the relevant disease. It is thus important to develop tools that facilitate symptom-based initial diagnosis of rare diseases by clinicians. In this work we aimed at developing a computational approach to aid in that initial diagnosis. We also aimed at implementing this approach in a user friendly web prototype. We call this tool Rare Disease Discovery. Finally, we also aimed at testing the performance of the prototype. Methods. Rare Disease Discovery uses the publicly available ORPHANET data set of association between rare diseases and their symptoms to automatically predict the most likely rare diseases based on a patient's symptoms. We apply the method to retrospectively diagnose a cohort of 187 rare disease patients with confirmed diagnosis. Subsequently we test the precision, sensitivity, and global performance of the system under different scenarios by running large scale Monte Carlo simulations. All settings account for situations where absent and/or unrelated symptoms are considered in the diagnosis. Results. We find that this expert system has high diagnostic precision (≥80%) and sensitivity (≥99%), and is robust to both absent and unrelated symptoms. Discussion. The Rare Disease Discovery prediction engine appears to provide a fast and robust method for initial assisted differential diagnosis of rare diseases. We coupled this engine with a user-friendly web interface and it can be freely accessed at http://disease-discovery.udl.cat/. The code and most current database for the whole project can be downloaded from https://github.com/Wrrzag/DiseaseDiscovery/tree/no_classifiers.

  3. Comparison of neuroimaging modalities for the prediction of conversion from mild cognitive impairment to Alzheimer's dementia.

    PubMed

    Trzepacz, Paula T; Yu, Peng; Sun, Jia; Schuh, Kory; Case, Michael; Witte, Michael M; Hochstetler, Helen; Hake, Ann

    2014-01-01

    In this study we compared Pittsburgh compound-B (PIB) positron emission tomography (PET) amyloid imaging, fluorodeoxyglucose PET for metabolism, and magnetic resonance imaging (MRI) for structure to predict conversion from amnestic mild cognitive impairment (MCI) to Alzheimer's dementia using data from the Alzheimer's Disease Neuroimaging Initiative cohort. Numeric neuroimaging variables generated by the Alzheimer's Disease Neuroimaging Initiative-funded laboratories for each neuroimaging modality along with apolipoprotein-E genotype (n = 29) were analyzed. Performance of these biomarkers for predicting conversion from MCI to Alzheimer's dementia at 2 years was evaluated in 50 late amnestic MCI subjects, 20 of whom converted. Multivariate modeling found that among individual modalities, MRI had the highest predictive accuracy (67%) which increased by 9% to 76% when combined with PIB-PET, producing the highest accuracy among any biomarker combination. Individually, PIB-PET generated the best sensitivity, and fluorodeoxyglucose PET had the lowest. Among individual brain regions, the temporal cortex was found to be most predictive for MRI and PIB-PET. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Teaching video neuroimages: gelastic cataplexy as the first neurologic manifestation of Niemann-Pick disease type C.

    PubMed

    Pedroso, José Luiz; Fusão, Eduardo Ferracioli; Ladeia-Frota, Carol; Arita, Juliana Harumi; Barsottini, Orlando G; Masruha, Marcelo Rodrigues; Vilanova, Luiz Celso Pereira

    2012-11-27

    A 10-year-old boy presented to our hospital with a 3-year history of fall attacks triggered by laughing, leading to a generalized loss of muscle tone without loss of consciousness (video). One year later, motor delayed skills started. Examination showed ataxia, moderate cognitive impairment, and vertical gaze palsy. EEG revealed diffuse slowing and disorganization of background rhythms. Molecular analysis disclosed heterozygosis p.P1007A and p.A1035V mutations, diagnostic of Niemann-Pick disease type C (NPC).

  5. Neuroimaging and Fetal Alcohol Spectrum Disorders

    ERIC Educational Resources Information Center

    Norman, Andria L.; Crocker, Nicole; Mattson, Sarah N.; Riley, Edward P.

    2009-01-01

    The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimaging studies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and…

  6. Neuroimaging and Fetal Alcohol Spectrum Disorders

    ERIC Educational Resources Information Center

    Norman, Andria L.; Crocker, Nicole; Mattson, Sarah N.; Riley, Edward P.

    2009-01-01

    The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimaging studies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and…

  7. Neuroimaging in psychiatry: an update on neuroimaging in the clinical setting.

    PubMed

    Power, Brian D; Nguyen, T; Hayhow, B; Looi, Jcl

    2016-04-01

    We offered guidance on the role of structural and functional neuroimaging modalities for the general psychiatrist and for trainees in the clinical setting. We outlined the utility of neuroimaging modalities in the clinical setting, specifically with a view to understanding the pathophysiology of manifestations of disease. Both structural and functional neuroimaging modalities have a clear role in diagnostic evaluation in the spectrum of neurodegenerative disorders. Whilst the role of neuroimaging in patients with mood, anxiety and psychotic disorders is less clear, structural and functional imaging modalities have utility in the clinical setting in the form of diagnostic refinement and in understanding the pathophysiology of disorders, towards explaining manifestations and planning treatment. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  8. Neuroimaging and Psychopharmacology

    ERIC Educational Resources Information Center

    Semrud-Clikeman, Margaret; Pliszka, Steve R.

    2005-01-01

    This review presents the most recent research concerning neuroimaging in developmental disabilities. Changes in structure and activation have been found in children with ADHD and learning disabilities, following intervention. For the children with learning disabilities changes in activation have been found following intensive behavioral and…

  9. Introduction to neuroimaging

    SciTech Connect

    Orrison, W.W.

    1989-01-01

    The author focuses on neuroradiology with emphasis on the current imaging modalities. There are chapters on angiography, myelography, nuclear medicine, ultrasonography, computer tomography (CT), and magnetic resonance (MR) imaging. The other chapters are dedicated to the spine, skull, head and neck, and pediatric neuroimaging.

  10. Neuroimaging and Psychopharmacology

    ERIC Educational Resources Information Center

    Semrud-Clikeman, Margaret; Pliszka, Steve R.

    2005-01-01

    This review presents the most recent research concerning neuroimaging in developmental disabilities. Changes in structure and activation have been found in children with ADHD and learning disabilities, following intervention. For the children with learning disabilities changes in activation have been found following intensive behavioral and…

  11. Neuroimaging in Epilepsy.

    PubMed

    Middlebrooks, Erik H; Ver Hoef, Lawrence; Szaflarski, Jerzy P

    2017-04-01

    In recent years, the field of neuroimaging has undergone dramatic development. Specifically, of importance for clinicians and researchers managing patients with epilepsies, new methods of brain imaging in search of the seizure-producing abnormalities have been implemented, and older methods have undergone additional refinement. Methodology to predict seizure freedom and cognitive outcome has also rapidly progressed. In general, the image data processing methods are very different and more complicated than even a decade ago. In this review, we identify the recent developments in neuroimaging that are aimed at improved management of epilepsy patients. Advances in structural imaging, diffusion imaging, fMRI, structural and functional connectivity, hybrid imaging methods, quantitative neuroimaging, and machine-learning are discussed. We also briefly summarize the potential new developments that may shape the field of neuroimaging in the near future and may advance not only our understanding of epileptic networks as the source of treatment-resistant seizures but also better define the areas that need to be treated in order to provide the patients with better long-term outcomes.

  12. Neuroimaging and Aggression.

    ERIC Educational Resources Information Center

    Mills, Shari; Raine, Adrian

    1994-01-01

    Brain imaging research allows direct assessment of structural and functional brain abnormalities, and thereby provides an improved methodology for studying neurobiological factors predisposing to violent and aggressive behavior. This paper reviews 20 brain imaging studies using four different types of neuroimaging techniques that were conducted in…

  13. Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer's disease: A behavioral and neuroimaging study.

    PubMed

    Joubert, Sven; Vallet, Guillaume T; Montembeault, Maxime; Boukadi, Mariem; Wilson, Maximiliano A; Laforce, Robert Jr; Rouleau, Isabelle; Brambati, Simona M

    2017-07-01

    The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer's disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Neuroimaging and biomarkers in addiction treatment.

    PubMed

    Garrison, Kathleen A; Potenza, Marc N

    2014-12-01

    Neuroimaging studies have made a significant contribution to the efforts to identify measurable indices, or biomarkers, of addictions and their treatments. Biomarkers in addiction treatment are needed to provide targets for treatment, detect treatment subgroups, predict treatment response, and broadly improve outcomes. Neuroimaging is important to biomarkers research as it relates neural circuits to both molecular mechanisms and behavior. A focus of recent efforts in neuroimaging in addiction has been to elucidate the neural correlates associated with dimensions of functioning in substance-use and related disorders, such as cue-reactivity, impulsivity, and cognitive control, among others. These dimensions of functioning have been related to addiction treatment outcomes and relapse, and therefore, a better understanding of these dimensions and their neural correlates may help to identify brain-behavior biomarkers of treatment response. This paper reviews recent neuroimaging studies that report potential biomarkers in addiction treatment related to cue-reactivity, impulsivity, and cognitive control, as well as recent advances in neuroimaging that may facilitate efforts to determine reliable biomarkers. This important initial work has begun to identify possible mediators and moderators of treatment response, and multiple promising indices are being tested.

  15. Neuroimaging and Fetal Alcohol Spectrum Disorders

    PubMed Central

    Norman, Andria L.; Crocker, Nicole; Mattson, Sarah N.; Riley, Edward P.

    2012-01-01

    The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimaging studies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and central nervous system (CNS) disorganization, with specific structural abnormalities of the corpus callosum, cerebellum, caudate, and hippocampus. Advances in neuroimaging techniques have allowed detection of regional increases in cortical thickness and gray matter volume along with decreased volume and disorganization of white matter in individuals with FASD. In addition, functional imaging studies have found functional and neurochemical differences in those prenatally exposed to alcohol. Behavioral alterations noted in individuals with FASD are consistent with the findings noted in the brain imaging studies. Continued neuroimaging studies are needed to further advance understanding of the neuroteratogenic effects of alcohol. PMID:19731391

  16. Differentiating symptomatic Parkin mutations carriers from patients with idiopathic Parkinson's disease: contribution of automated segmentation neuroimaging method.

    PubMed

    Bilgic, Basar; Bayram, Ali; Arslan, Ali Bilgin; Hanagasi, Hasmet; Dursun, Burcu; Gurvit, Hakan; Emre, Murat; Lohmann, Ebba

    2012-06-01

    Parkin (PARK2) gene mutations are the predominant cause of autosomal recessive parkinsonism. Characteristic features include: early onset symptoms with slow clinical course, good response to low doses of levodopa, and frequently treatment-induced dyskinesia. Studies using a voxel-based morphometry approach showed a decrease in the gray matter volume of the basal ganglia in mutation carriers during the symptomatic stages. A bilateral, presumably compensatory increase of basal ganglia gray matter value was recently demonstrated in asymptomatic Parkin mutation carriers. Behavioral disorders including: anxiety, psychosis, panic attacks, depression, disturbed sexual, behavioral and obsessive-compulsive disorders have been reported in these patients. A total of 28 Parkinson's Disease (PD) patients consisting of 10 Young-Onset without Parkin mutations (YOPD), 9 Young-Onset with Parkin mutations (YOPD-p), 9 Late-Onset without Parkin mutations (LOPD) and 32 healthy control subjects were studied with an automated volumetric assessment method to quantify subcortical atrophy. Patients but not controls also underwent a neuropsychological and neuropsychiatric assessment. Results revealed a reduction of bilateral caudate nuclei volumes in YOPD-p patients compared to the YOPD patients while there were no statistically significant differences between other groups. YOPD-p patients showed similar results to other patient groups on neuropsychiatric and neuropsychological evaluation measures. YOPD-p and YOPD patients showed a different pattern of volume changes in basal ganglia. Despite its relatively benign clinical course, carrying the Parkin mutation seems to be associated with greater atrophy in subcortical structures. Failure of compensatory mechanisms, different mutation types and pathophysiologic processes may underlie this diverse pattern of subcortical brain changes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Alzheimer Disease: Quantitative Structural Neuroimaging for Detection and Prediction of Clinical and Structural Changes in Mild Cognitive Impairment

    PubMed Central

    McEvoy, Linda K.; Fennema-Notestine, Christine; Roddey, J. Cooper; Hagler, Donald J.; Holland, Dominic; Karow, David S.; Pung, Christopher J.; Brewer, James B.; Dale, Anders M.

    2009-01-01

    Purpose: To use structural magnetic resonance (MR) images to identify a pattern of regional atrophy characteristic of mild Alzheimer disease (AD) and to investigate whether presence of this pattern prospectively can aid prediction of 1-year clinical decline and increased structural loss in mild cognitive impairment (MCI). Materials and Methods: The study was conducted with institutional review board approval and compliance with HIPAA regulations. Written informed consent was obtained from each participant. High-throughput volumetric segmentation and cortical surface reconstruction methods were applied to MR images from 84 subjects with mild AD, 175 with MCI, and 139 healthy control (HC) subjects. Stepwise linear discriminant analysis was used to identify regions that best can aid discrimination of HC subjects from subjects with AD. A classifier trained on data from HC subjects and those with AD was applied to data from subjects with MCI to determine whether presence of phenotypic AD atrophy at baseline was predictive of clinical decline and structural loss. Results: Atrophy in mesial and lateral temporal, isthmus cingulate, and orbitofrontal areas aided discrimination of HC subjects from subjects with AD, with fully cross-validated sensitivity of 83% and specificity of 93%. Subjects with MCI who had phenotypic AD atrophy showed significantly greater 1-year clinical decline and structural loss than those who did not and were more likely to have progression to probable AD (annual progression rate of 29% for subjects with MCI who had AD atrophy vs 8% for those who did not). Conclusion: Semiautomated, individually specific quantitative MR imaging methods can be used to identify a pattern of regional atrophy in MCI that is predictive of clinical decline. Such information may aid in prediction of patient prognosis and increase the efficiency of clinical trials. © RSNA, 2009 PMID:19201945

  18. Development of Alzheimer-disease neuroimaging-biomarkers using mouse models with amyloid-precursor protein-transgene expression.

    PubMed

    Teipel, Stefan J; Buchert, Ralph; Thome, Johannes; Hampel, Harald; Pahnke, Jens

    2011-12-01

    There are important recent developments in Alzheimer's disease (AD) translational research, especially with respect to the imaging of amyloid pathology in vivo using MRI and PET technologies. Here we exploit the most widely used transgenic mouse models of amyloid pathology in order to relate the imaging findings to our knowledge about the histopathological phenotype of these models. The development of new diagnostic criteria of AD necessitates the use of biological markers to diagnose AD even in the absence of overt dementia or early symptomatic mild cognitive impairment. The validity of the diagnosis will depend on the availability of an in vivo marker to reflect underlying neurobiological changes of AD. Transgenic models with essential features of AD pathology and mechanisms provide a test setting for the development and evaluation of new biological imaging markers. Among the best established imaging markers of amyloid pathology in transgenic animals are high-field MRI of brain atrophy, proton spectroscopy of neurochemical changes, high-field MRI of amyloid plaque load, and in vivo plaque imaging using radio-labelled ligands with PET. We discuss the implications of the findings as well as the methodological limitations and the specific requirements of these technologies. We furthermore outline future directions of transgene-imaging research. Transgene imaging is an emerging area of translational research that implies strong multi- and interdisciplinary collaborations. It will become ever more valuable with the introduction of new diagnostic standards and novel treatment approaches which will require valid and reliable biological markers to improve the diagnosis and early treatment of AD patients.

  19. The Relationship Between Parkinson's Disease and Essential Tremor: Review of Clinical, Epidemiologic, Genetic, Neuroimaging and Neuropathological Data, and Data on the Presence of Cardinal Signs of Parkinsonism in Essential Tremor

    PubMed Central

    Jiménez-Jiménez, Félix Javier; Alonso-Navarro, Hortensia; García-Martín, Elena; Agúndez, José A. G.

    2012-01-01

    Background The possible relationship between essential tremor (ET) and Parkinson's disease (PD) has been controversial since the first description of PD. However, there is increasing evidence suggesting an overlap between these two disorders. The aim of this review is to examine the relationship between PD and ET, focusing on clinical, epidemiologic, genetic, neuroimaging, and neuropathological data, and the presence of cardinal parkinsonism symptoms in ET. Methods We conducted a PubMed search for articles published between 1966 and November 2011 regarding the relationship between ET and PD and the presence of postural tremor in PD patients; the presence of rest tremor, rigidity, and slowed movements in ET patients is reviewed. Results Clinical series, follow-up studies of ET patients, and case–control and genetic epidemiological studies indicate that ET is associated with increased risk for PD. Some neuroimaging studies and neuropathological reports suggest an association between the two diseases. ET patients show high prevalence of rest tremor, and at least seven studies described slowed movements (possibly related to cerebellar dysfunction and/or bradykinesia) in patients with ET. Discussion There is reasonable epidemiological and clinical evidence to support a link between ET and PD, although it is not clear what factors predict ET patient risk for developing PD or, more rarely, of PD patients developing ET. Future multicentric and multidisciplinary studies including epidemiological, clinical, neuroimaging, genetic, and neuropathological assessments are required to understand these associations. PMID:23439992

  20. Longitudinal change of neuroimaging and clinical markers in autosomal dominant Alzheimer’s disease: a prospective cohort study

    PubMed Central

    Yau, Wai-Ying Wendy; Tudorascu, Dana L.; McDade, Eric M.; Ikonomovic, Snezana; James, Jeffrey A.; Minhas, Davneet; Mowrey, Wenzhu; Sheu, Lei K.; Snitz, Beth E.; Weissfeld, Lisa; Gianaros, Peter J.; Aizenstein, Howard J.; Price, Julie C.; Mathis, Chester A.; Lopez, Oscar L.; Klunk, William E.

    2015-01-01

    Background The biomarker model of Alzheimer’s disease (AD) hypothesizes a dynamic sequence of amyloidosis, neurodegeneration, and cognitive decline, as an individual progresses from preclinical AD to dementia. Despite supportive evidence from cross-sectional studies, verification with long-term within-individual data is needed. Methods Autosomal dominant AD (ADAD) mutation carriers, aged 21 years or older (no cognitive restrictions), were recruited from across the United States via referral by colleagues or ADAD families themselves. Sixteen individuals with mutations in PSEN1, PSEN2 or APP, aged 28 to 56, were assessed longitudinally every one to two years, between March 23, 2003 and August 1, 2014. Participants completed two to eight assessments (total=83), over a period of two to eleven years. We measured global amyloid-beta load with Pittsburgh Compound-B PET, posterior cortical metabolism with [18F]fluorodeoxyglucose PET, hippocampal volume (age-, and gender-corrected) with T1 MRI, verbal memory with 10-item delayed word recall, and general cognition with Mini Mental State Exam. We estimated overall biomarker trajectories across estimated years from symptom onset (EYO) using linear mixed models, and compared ADAD estimates to cross-sectional data from cognitively normal, older controls selected to be negative for amyloidosis, hypometabolism, and hippocampal atrophy. In seven individuals with the longest follow-up (seven/eight assessments spanning six to eleven years), we further examined the within-individual progression of amyloidosis, metabolism, hippocampal volume, and cognition, to identify progressive within-individual change in these markers (increase/decrease of greater than two Z-scores standardized to controls). Findings Significant differences in ADAD compared to controls (p<0·01) were detected in the following order: increased amyloidosis (−7.5 EYO), decreased metabolism (0 EYO), decreased hippocampal volume and verbal memory (+7.5 EYO

  1. Neuroimaging in anxiety disorders.

    PubMed

    Engel, Kirsten; Bandelow, Borwin; Gruber, Oliver; Wedekind, Dirk

    2009-06-01

    Neuroimaging studies have gained increasing importance in validating neurobiological network hypotheses for anxiety disorders. Functional imaging procedures and radioligand binding studies in healthy subjects and in patients with anxiety disorders provide growing evidence of the existence of a complex anxiety network, including limbic, brainstem, temporal, and prefrontal cortical regions. Obviously, "normal anxiety" does not equal "pathological anxiety" although many phenomena are evident in healthy subjects, however to a lower extent. Differential effects of distinct brain regions and lateralization phenomena in different anxiety disorders are mentioned. An overview of neuroimaging investigations in anxiety disorders is given after a brief summary of results from healthy volunteers. Concluding implications for future research are made by the authors.

  2. Excessive blinking as an initial manifestation of juvenile Huntington's disease.

    PubMed

    Xing, Shihui; Chen, Ling; Chen, Xi; Pei, Zhong; Zeng, Jinsheng; Li, Jinru

    2008-09-01

    Juvenile Huntington's disease (JHD) is mostly characterized by rigidity, myoclonus, bradykinesia, dystonia and seizure. We report a 9-year-old male JHD patient presenting excessive blinking as the initial symptom two years prior to typical JHD symptoms. Genetic analysis revealed expansion of 108 CAG repeats and magnetic resonance imaging showed caudate atrophy with lateral ventricular enlargement.

  3. Psychotherapy and Neuroimaging

    PubMed Central

    Fournier, Jay C.; Price, Rebecca B.

    2014-01-01

    Technological advances in neuroimaging have enabled researchers to examine, in vivo, the relationship between psychotherapeutic interventions and markers of brain activity. This review focuses on two kinds of neuroimaging studies in psychotherapy: those that examine the patterns of brain activity associated with response to treatments and those that examine the changes that occur in brain activity during treatment. A general, hypothetical neural model of psychotherapy is presented, and support for the model is evaluated across anxiety disorders and major depression. Neuroimaging studies are broadly consistent in observing associations between response to psychotherapy and baseline activity in several key regions within the prefrontal cortex, basal ganglia, and limbic areas. These regions are involved in the generation and regulation of emotion, fear responding, and response to reward. Pre-post examinations of change following psychotherapy also typically observe that psychological treatments for anxiety and depression can affect neural activity in these regions. Despite general consensus that activity in these regions is associated with psychotherapy, substantial discrepancy persists regarding the precise direction of the observed relationships. Methodological challenges of the existing literature are considered, and future directions are discussed. PMID:25346646

  4. Late recurrences of Cushing's disease after initial successful transsphenoidal surgery.

    PubMed

    Patil, Chirag G; Prevedello, Daniel M; Lad, Shivanand P; Vance, Mary Lee; Thorner, Michael O; Katznelson, Laurence; Laws, Edward R

    2008-02-01

    Few studies have systematically analyzed the long-term recurrence rates of Cushing's disease after initial successful transsphenoidal surgery. This was a retrospective review of patients treated at the University of Virginia Medical Center. A total of 215 subjects with Cushing's disease who underwent initial transsphenoidal surgery for resection of a presumed pituitary microadenoma from 1992-2006 were included. Remission and recurrence rates of Cushing's disease were examined. Recurrence was defined as an elevated 24-h urine free cortisol with clinical symptoms consistent with Cushing's disease. Of the 215 patients who underwent transsphenoidal surgery for Cushing's disease, surgical remission was achieved in 184 (85.6%). The mean length of follow-up was 45 months. Actuarial recurrence rates of Cushing's disease after initially successful transsphenoidal surgery at 1, 2, 3, and 5 yr were 0.5, 6.7, 10.8, and 25.5%, respectively. Among the 184 patients who achieved remission, 32 (17.4%) patients followed for more than 6 months ultimately had a recurrence of Cushing's disease. The median time to recurrence was 39 months. Immediate postoperative hypocortisolemia (serum cortisol < or = 2 microg/dl within 72-h surgery) was achieved in 97 (45.1%) patients. Patients who had postoperative serum cortisol of more than 2 microg/dl were 2.5 times more likely to have a recurrence than patients who had serum cortisol less than or equal to 2 microg/dl (odds ratio = 2.5; 95% confidence interval 1.12-5.52; P = 0.022). A quarter of the patients with Cushing's disease who achieve surgical remission after transsphenoidal surgery, recur with long-term follow-up. This finding emphasizes the need for continued biochemical and clinical follow-up to ensure remission after surgery.

  5. Retrospective study on structural neuroimaging in first-episode psychosis

    PubMed Central

    Silva-dos-Santos, Amilcar; Talina, Miguel Cotrim

    2016-01-01

    Background. No consensus between guidelines exists regarding neuroimaging in first-episode psychosis. The purpose of this study is to assess anomalies found in structural neuroimaging exams (brain computed tomography (CT) and magnetic resonance imaging (MRI)) in the initial medical work-up of patients presenting first-episode psychosis. Methods. The study subjects were 32 patients aged 18–48 years (mean age: 29.6 years), consecutively admitted with first-episode psychosis diagnosis. Socio-demographic and clinical data and neuroimaging exams (CT and MRI) were retrospectively studied. Diagnostic assessments were made using the Operational Criteria Checklist +. Neuroimaging images (CT and MRI) and respective reports were analysed by an experienced consultant psychiatrist. Results. None of the patients had abnormalities in neuroimaging exams responsible for psychotic symptoms. Thirty-seven percent of patients had incidental brain findings not causally related to the psychosis (brain atrophy, arachnoid cyst, asymmetric lateral ventricles, dilated lateral ventricles, plagiocephaly and falx cerebri calcification). No further medical referral was needed for any of these patients. No significant differences regarding gender, age, diagnosis, duration of untreated psychosis, in-stay and cannabis use were found between patients who had neuroimaging abnormalities versus those without. Discussion. This study suggests that structural neuroimaging exams reveal scarce abnormalities in young patients with first-episode psychosis. Structural neuroimaging is especially useful in first-episode psychosis patients with neurological symptoms, atypical clinical picture and old age. PMID:27257547

  6. Initiation of acute graft-versus-host disease by angiogenesis.

    PubMed

    Riesner, Katarina; Shi, Yu; Jacobi, Angela; Kraeter, Martin; Kalupa, Martina; McGearey, Aleixandria; Mertlitz, Sarah; Cordes, Steffen; Schrezenmeier, Jens-Florian; Mengwasser, Jörg; Westphal, Sabine; Perez-Hernandez, Daniel; Schmitt, Clemens; Dittmar, Gunnar; Guck, Jochen; Penack, Olaf

    2017-01-17

    The inhibition of inflammation-associated angiogenesis ameliorates inflammatory diseases by reducing the recruitment of tissue infiltrating leukocytes. However, it is not known if angiogenesis has an active role during the initiation of inflammation or if it is merely a secondary effect occurring in response to stimuli by tissue infiltrating leukocytes. Here we show that angiogenesis precedes leukocyte infiltration in experimental models of inflammatory bowel disease and acute graft-versus-host disease (GVHD). We found that angiogenesis occurred as early as day+2 after allogeneic transplantation mainly in GVHD typical target organs skin, liver and intestines whereas no angiogenic changes appeared due to conditioning or syngeneic transplantation. The initiation phase of angiogenesis was not associated to classical endothelial cell (EC) activation signs, such as Vegfa/VEGFR1+2 upregulation or increased adhesion molecule expression. During early GVHD at day+2, we found significant metabolic and cytoskeleton changes in target organ ECs in gene array- and proteomic analyses. These modifications have significant functional consequences as indicated by profoundly higher deformation in Real-time deformability cytometry. Our results demonstrate that metabolic changes trigger alterations in cell mechanics leading to enhanced migratory and proliferative potential of ECs during the initiation of inflammation. Our study adds evidence to the hypothesis that angiogenesis is involved in the initiation of tissue inflammation during GVHD.

  7. [Interstitial lung disease as an initial manifestation of dermatomyositis].

    PubMed

    Shen, Min; Gong, Yulin; Zeng, Xiaofeng; Zhang, Fengchun; Tang, Fulin

    2014-11-25

    To explore the clinical features and prognosis of dermatomyositis patients with interstitial lung disease (ILD) as an initial manifestation. Medical records of 184 dermatomyositis inpatients complicated with ILD, admitted into Peking Union Medical College Hospital from January 1999 to January 2013, were retrospectively analyzed. The clinical features, biochemical parameters, positive rates of autoantibodies, radiology, pulmonary function tests, pathology, treatments and prognosis were compared between two subgroups of ILD-initial and non-ILD-initial dermatomyositis. The incidence of ILD of dermatomyositis inpatients was 17%. The average age was 48 ± 12 years and the gender ratio of male-to-female was 63: 121. Eighty eight (47.8%) dermatomyositis patients had ILD as an initial manifestation, including (n = 42, 22.8%) of ILD concomitant dermatomyositis (within 1 month) and (n = 46, 25.0%) of ILD before dermatomyositis with an average ahead time of (11 ± 3) months. Patients of ILD-initial dermatomyositis had a higher incidence of dyspnea on exertion, cough and lung crackles, but there were lower incidences of heliotrope rash, chest V area rash, shawl sign and joint involvement than non-ILD-initial dermatomyositis (P < 0.05). The positive rate of anti-Jo-1 antibodies of ILD-initial dermatomyositis group was 13.6%. The main performances of ILD-initial dermatomyositis on pulmonary function tests were diffusing and restrictive ventilation impairment. And there was a lower diffusing rate of carbon monoxide than non-ILD-initial dermatomyositis group (P < 0.01). Organic and non-specific interstitial pneumonias were the major clinical pathology types of ILD-initial dermatomyositis. The mortality rate of ILD-initial dermatomyositis patients was 19.3% and there was no significant difference from non-ILD-initial dermatomyositis (P > 0.05). The main course of ILD-initial dermatomyositis was respiratory failure due to progressive ILD (n = 13, 76.5%). ILD as an initial

  8. Giardia and Cryptosporidium join the 'Neglected Diseases Initiative'.

    PubMed

    Savioli, L; Smith, H; Thompson, A

    2006-05-01

    Giardia and Cryptosporidium are ubiquitous enteric protozoan pathogens that infect humans, domestic animals and wildlife worldwide. Both pathogens are significant causes of diarrhea and nutritional disorders in institutional and community settings. They are also significant waterborne pathogens. In developing regions of the world, Giardia and Cryptosporidium constitute part of the complex group of parasitic, bacterial and viral diseases that impair the ability to achieve full potential and impair development and socio-economic improvements. All diseases included in the WHO Neglected Diseases Initiative have a common link with poverty and, as the current view is to take a comprehensive approach to all these diseases, both Giardia and Cryptosporidium were included in 2004. Our current state of knowledge of Giardia and Cryptosporidium is summarized here, and some important questions are raised that need to be addressed if control strategies are to be effective.

  9. Structural neuroimaging correlates of cognitive status in older adults: A person-oriented approach.

    PubMed

    Malpas, Charles B

    2016-08-01

    Person-oriented approaches to clinical research aim to uncover subgroups of patients with different patterns of clinically relevant variables. Such approaches, however, are not yet widely employed in clinical neuroimaging research. This paper demonstrates an accessible approach to person-oriented research using model-based clustering in high-dimensional structural neuroimaging data. Cortical thickness measurements for 369 older adults (182 women, 187 men) were obtained from the Alzheimer's Disease Neuroimaging Initiative. Model-based cluster analysis was performed on these imaging variables and then validated using variables that were not used in the clustering process. Variable selection identified two specific regions that contributed to cluster formation: the left and right entorhinal cortices. Two subgroups were uncovered: a "typical" cluster with higher entorhinal thickness (M=3.59mm, 95% confidence interval=3.57, 3.62), and an "atypical" cluster with relatively lower thickness (M=2.84mm, 95% confidence interval=2.75, 2.92). Members of the atypical cluster also had lower hippocampal volumes, memory scores, and executive function scores, and were also more likely to be clinically classified as cognitively impaired. These findings demonstrate the utility of model-based clustering of structural neuroimaging data in studies of ageing. The role of the entorhinal cortices in cluster formation is consistent with the known pathological substrate of Alzheimer's disease. The entorhinal cortices are implicated in the early genesis of the disease and atrophy of these regions is strongly associated with the cognitive phenotype. Overall, this approach can be readily applied to future neuroimaging investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. A probabilistic functional atlas of the VIM nucleus constructed from pre-, intra- and postoperative electrophysiological and neuroimaging data acquired during the surgical treatment of Parkinson's disease patients.

    PubMed

    Nowinski, Wieslaw L; Belov, Dmitry; Thirunavuukarasuu, A; Benabid, Alim Louis

    2005-01-01

    We have previously introduced a concept of a probabilistic functional atlas (PFA) to overcome limitations of the current electronic stereotactic brain atlases: anatomical nature, spatial sparseness, inconsistency and lack of population information. The PFA for the STN has already been developed. This work addresses construction of the PFA for the ventrointermediate nucleus (PFA-VIM). The PFA-VIM is constructed from pre-, intra- and postoperative electrophysiological and neuroimaging data acquired during the surgical treatment of Parkinson's disease patients. The data contain the positions of the chronically implanted electrodes and their best contacts. For each patient, the intercommissural distance, height of the thalamus and width of the third ventricle were measured. An algorithm was developed to convert these data into the PFA-VIM, and to present them on axial, coronal and sagittal planes and in 3-D. The PFA-VIM gives a spatial distribution of the best contacts, and its probability is proportional to best contact concentration in a given location. The region with the highest probability corresponds to the best target. The PFA-VIM is calculated with 0.25-mm3 resolution from 107 best contacts in two situations: with and without lateral compensation against the width of the third ventricle. For the PFA-VIM compensated laterally, the anterior, lateral and dorsal coordinates of the mean value are (in mm) 6.24, 13.83, 1.68 for the left VIM and 6.54, -13.84, 2.10 for the right VIM. The coordinates of the mean value of the highest probability region along with the highest number of the best contacts (P) are: 6.25, 14.25, 1.75, P = 16, for the left VIM, and 6.0, -14.0, 1.00, P = 18, for the right VIM. The coordinate system origin is at the posterior commissure. For the PFA-VIM not compensated laterally, the coordinates of the mean value are 6.24, 13.99, 1.68 for the left VIM and 6.53, -14.13, 2.10 for the right VIM. The coordinates of the mean value of the highest

  11. Systematic Redaction for Neuroimage Data

    PubMed Central

    Matlock, Matt; Schimke, Nakeisha; Kong, Liang; Macke, Stephen; Hale, John

    2013-01-01

    In neuroscience, collaboration and data sharing are undermined by concerns over the management of protected health information (PHI) and personal identifying information (PII) in neuroimage datasets. The HIPAA Privacy Rule mandates measures for the preservation of subject privacy in neuroimaging studies. Unfortunately for the researcher, the management of information privacy is a burdensome task. Wide scale data sharing of neuroimages is challenging for three primary reasons: (i) A dearth of tools to systematically expunge PHI/PII from neuroimage data sets, (ii) a facility for tracking patient identities in redacted datasets has not been produced, and (iii) a sanitization workflow remains conspicuously absent. This article describes the XNAT Redaction Toolkit—an integrated redaction workflow which extends a popular neuroimage data management toolkit to remove PHI/PII from neuroimages. Quickshear defacing is also presented as a complementary technique for deidentifying the image data itself. Together, these tools improve subject privacy through systematic removal of PII/PHI. PMID:24179597

  12. Multiple lymphadenopathy as an initial sign of extramammary Paget disease.

    PubMed

    Hirakawa, S; Tanemura, A; Mori, H; Katayama, I; Hashimoto, K

    2011-01-01

    Extramammary Paget disease (EMPD) often develops in external genitalia. Paget cells can, however, adopt an invasive phenotype and metastasize to regional lymph nodes and beyond, leading to poor patient outcomes. Based on this clinical observation, multiple lymphadenopathy may represent an initial sign of EMPD. To address the potential significance of multiple lymph node swelling in EMPD, we report two patients with cutaneous primary EMPD who showed multiple lymphadenopathy as an initial sign during the clinical course of the disease as well as tumour metastasis. Significantly, marked lymphatic vessel growth was observed in regional lymph nodes that underwent massive tumour cell invasion. Therefore, nodal lymphangiogenesis may promote tumour cell invasion and metastasis to distant organs, including the lymph nodes, emphasizing the clinical relevance of multiple lymphadenopathy.

  13. Preeclampsia or initial diagnosis of chronic renal disease during pregnancy.

    PubMed

    Iavazzo, C; Kalmantis, K; Bozemberg, T; Ntziora, F; Ioakeimidis, A; Paschalinopoulos, D

    2008-01-01

    An unusual case of early nephrotic syndrome without hypertension which slightly resolved after delivery is documented. Renal biopsy was performed postpartum and the diagnosis was focal and segmental glomerulosclerosis with moderate chronic renal changes. It is questioned whether the case was due to preeclampsia or was the initial diagnosis of chronic renal disease which was made during pregnancy. The role of renal biopsy in such cases is briefly discussed (Tab. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

  14. Neuroimaging of Cognition

    PubMed Central

    Dolan, R.J.

    2009-01-01

    Neuroimaging, particularly that based upon functional magnetic resonance (fMRI), has become a dominant tool in cognitive neuroscience. This review provides a personal and selective perspective on its past, present, and future. Two trends currently characterize the field that broadly reflect a pursuit of “where”- and “how”-type questions. The latter addresses basic mechanisms related to the expression of task-induced neural activity and is likely to be an increasingly important theme in the future. This trend entails an enhanced symbiosis among investigators pursuing similar questions in fields such as computational and theoretical neuroscience as well as through the detailed analysis of microcircuitry. PMID:18995825

  15. Motor initiation versus execution in normal and Parkinson's disease subjects.

    PubMed

    Montgomery, E B; Gorman, D S; Nuessen, J

    1991-09-01

    We studied motor initiation and execution using wrist extension movements to changing target locations in eight normal subjects and nine Parkinson's disease (PD) patients before and after medications. Late changes resulted in double trajectories, indicating commitment to the initial target acquisition program followed by a correcting movement. There was compensation for earlier changes, even after onset of agonist muscle activity, resulting in a single trajectory, implying that the original trajectory had not yet been specified. However, movements were slowed in PD patients implying an abnormality in the content of the target acquisition program but not in the timing of its specification. In PD patients, the timing of the second movement onset correlated best with the timing of target location change and did not depend on initial movement completion. Thus, PD patients were able to program the second movement while the first movement was under way.

  16. Clinical applications of neuroimaging in patients with Alzheimer's disease: a review from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012

    PubMed Central

    2013-01-01

    In May 2012, the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia brought together in Montreal experts from around Canada to update Canadian recommendations for the diagnosis and management of patients with neurodegenerative conditions associated with deterioration of cognition. Multiple topics were discussed. The present paper is a highly condensed version of those recommendations that were produced to support discussions in the field of neuroimaging for clinical diagnosis of those conditions. PMID:24565260

  17. Neuroimaging Study Designs, Computational Analyses and Data Provenance Using the LONI Pipeline

    PubMed Central

    Dinov, Ivo; Lozev, Kamen; Petrosyan, Petros; Liu, Zhizhong; Eggert, Paul; Pierce, Jonathan; Zamanyan, Alen; Chakrapani, Shruthi; Van Horn, John; Parker, D. Stott; Magsipoc, Rico; Leung, Kelvin; Gutman, Boris; Woods, Roger; Toga, Arthur

    2010-01-01

    Modern computational neuroscience employs diverse software tools and multidisciplinary expertise to analyze heterogeneous brain data. The classical problems of gathering meaningful data, fitting specific models, and discovering appropriate analysis and visualization tools give way to a new class of computational challenges—management of large and incongruous data, integration and interoperability of computational resources, and data provenance. We designed, implemented and validated a new paradigm for addressing these challenges in the neuroimaging field. Our solution is based on the LONI Pipeline environment [3], [4], a graphical workflow environment for constructing and executing complex data processing protocols. We developed study-design, database and visual language programming functionalities within the LONI Pipeline that enable the construction of complete, elaborate and robust graphical workflows for analyzing neuroimaging and other data. These workflows facilitate open sharing and communication of data and metadata, concrete processing protocols, result validation, and study replication among different investigators and research groups. The LONI Pipeline features include distributed grid-enabled infrastructure, virtualized execution environment, efficient integration, data provenance, validation and distribution of new computational tools, automated data format conversion, and an intuitive graphical user interface. We demonstrate the new LONI Pipeline features using large scale neuroimaging studies based on data from the International Consortium for Brain Mapping [5] and the Alzheimer's Disease Neuroimaging Initiative [6]. User guides, forums, instructions and downloads of the LONI Pipeline environment are available at http://pipeline.loni.ucla.edu. PMID:20927408

  18. Pretibial myxedema without ophthalmopathy: an initial presentation of Graves' disease.

    PubMed

    Lohiya, Sheela; Lohiya, Vipin; Stahl, Elizabeth J

    2013-07-01

    To report a rare case of Graves' disease without ophthalmopathy presenting with pretibial myxedema (PM) as an initial presentation. We present the clinical history, physical findings, laboratory studies and biopsy data of a 62-year-old man with a history of uncontrolled type 2 diabetes (DM2) presenting with arm and leg skin lesions in the absence of other physical findings. Histopathology confirmed PM. Graves' disease and its association with PM without Graves' ophthalmopathy and the pertinent literature are reviewed. A 60-year-old man with a history of uncontrolled DM2 presented for glycemic management. He described symptoms of anxiety, insomnia and fatigue for the last 5 to 6 months. He described diffuse chest pain, occasionally associated with palpitations, and a 50-pound weight loss. He also complained of severe itching and burning of his arms and legs for the past several months. Subsequent thyroid studies revealed hyperthyroidism suggestive of Graves' disease. In the interim, he was hospitalized for atrial flutter and was cardioverted. After being started on methimazole, his symptoms abated. His skin lesions were biopsied, and the leg biopsy was consistent with PM. He however had no lid lag or proptosis characteristic of Graves' disease. He subsequently underwent radioiodine ablation. His hyperglycemia was better control led after treatment of his hyperthyroidism. PM is an autoimmune manifestation of Graves' disease. Almost all cases of thyroid dermopathy are associated with relatively severe ophthalmopathy. Usually ophthalmopathy appears first and dermopathy much later. However, this case represents a rare initial presentation of Graves' disease with PM without ophthalmologic symptoms or findings. Hyperthyroidism is typically associated with worsening glycemic control and increased insulin requirements. In patients with diabetes having hyperthyroidism, deterioration in glycemic control should be anticipated and treatment should be adjusted accordingly

  19. [Pedophilia: contribution of neurology and neuroimaging techniques].

    PubMed

    Fonteille, V; Cazala, F; Moulier, V; Stoléru, S

    2012-12-01

    Pedophilia is characterized by a persistent sexual interest of an adult for prepubescent children. The development of neuroimaging techniques such as functional Magnetic Resonance Imaging (fMRI) is starting to clarify the cerebral basis of disorders of sexual behavior such as pedophilia, which had been previously suggested by case studies. To review structural and functional neuroimaging studies of pedophilia. An exhaustive consultation of PubMed and Ovid databases was conducted. We obtained 19 articles presented in the present review of the literature. Case studies have demonstrated various changes of sexual behavior in relation to brain lesions, including the late appearance in adults of a sexual attraction to prepubescent children. In most cases of pedophilia associated with brain lesions, these lesions were located in frontal or in temporal regions. Structural neuroimaging studies have compared pedophiles with healthy subjects and tried to relate pedophilia to anatomical differences between these two groups. The location of structural changes is inconsistent across studies. Recent functional neuroimaging studies have also attempted to investigate the cerebral correlates of pedophilia. Results suggest that the activation pattern found in pedophiles in response to pictures of prepubescent nude girls or boys is similar to the pattern observed in healthy subjects in response to pictures of adult nude women or men. However, regions that become more activated in patients than in healthy controls in response to the presentation of pictures of children vary across studies. Studies that have begun to investigate the cerebral correlates of pedophilia demonstrate that it is possible to explore them through neuroimaging techniques. These initial results have to be confirmed by new studies backed with objective measurements of sexual arousal such as phallometry. Copyright © 2012 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  20. 4-Repeat Tauopathy Neuroimaging Initiative - Cycle 2

    ClinicalTrials.gov

    2016-11-15

    Corticobasal Degeneration (CBD); Corticobasal Syndrome (CBS); Cortical-basal Ganglionic Degeneration (CBGD); Progressive Supranuclear Palsy (PSP); Nonfluent Variant Primary Progressive Aphasia (nfvPPA); Oligosymptomatic/Variant Progressive Supranuclear Palsy (o/vPSP)

  1. Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis.

    PubMed

    Menke, Ricarda A L; Agosta, Federica; Grosskreutz, Julian; Filippi, Massimo; Turner, Martin R

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative, clinically heterogeneous syndrome pathologically overlapping with frontotemporal dementia. To date, therapeutic trials in animal models have not been able to predict treatment response in humans, and the revised ALS Functional Rating Scale, which is based on coarse disability measures, remains the gold-standard measure of disease progression. Advances in neuroimaging have enabled mapping of functional, structural, and molecular aspects of ALS pathology, and these objective measures may be uniquely sensitive to the detection of propagation of pathology in vivo. Abnormalities are detectable before clinical symptoms develop, offering the potential for neuroprotective intervention in familial cases. Although promising neuroimaging biomarker candidates for diagnosis, prognosis, and disease progression have emerged, these have been from the study of necessarily select patient cohorts identified in specialized referral centers. Further multicenter research is now needed to establish their validity as therapeutic outcome measures.

  2. Provenance in Neuroimaging

    PubMed Central

    MacKenzie-Graham, Allan J.; Van Horn, John D.; Woods, Roger P.; Crawford, Karen L.

    2008-01-01

    Provenance, the description of the history of a set of data, has grown more important with the proliferation of research consortia-related efforts in neuroimaging. Knowledge about the origin and history of an image is crucial for establishing data and results quality; detailed information about how it was processed, including the specific software routines and operating systems that were used, is necessary for proper interpretation, high fidelity replication and re-use. We have drafted a mechanism for describing provenance in a simple and easy to use environment, alleviating the burden of documentation from the user while still providing a rich description of an image’s provenance. This combination of ease of use and highly descriptive metadata should greatly facilitate the collection of provenance and subsequent sharing of data. PMID:18519166

  3. [Initial deficits in Alzheimer's disease: 3 practical examples].

    PubMed

    Jódar-Vicente, M

    The aim of the first studies to determine the neuropsychological features of Alzheimer's disease (AD) were based on the concept of the disease as an homogeneous entity. However, clinical observations and the most recent research studies have demonstrated that Alzheimer's disease may present several other neuropsychological deficits on its clinical onset. in the initial process of cognitive function loss, memory deficits are seen as a consequence of hippocampal degeneration; however, a great interindividual variability is observed in the appearance of other cortical deficits. In addiction, new advances in epidemiology, neurochemistry and neuropathology support the idea that AD represents a neuropsychologically heterogeneous disorder. In AD three different subgroups have been established: patients with initial deficits in visuospatial abilities, patients with a major deterioration of linguistic abilities, and a third group with altered visuospatial and linguistic abilities. The most sensitive neuropsychological tests capable of distinguish among these differences were The Boston Naming Test (BNT) and the copy of a drawing. These results have been confirmed with single photon emission computed tomography (SPECT) images, and has been observed that patients with a pattern of a elevated right-hemispheric deterioration presented also a higher right-hipofunctionality. At the same time, patients with an elevated linguistic deficit showed a higher hipofunctionality image in the left hemisphere. In this work we present three patients from a prospective study in course, who have similar background, education, gender and disease evolution, but with an onset of the illness corresponding to each of the patterns previously described All three patients were explored with an extense neuropsychological battery of tests specially chosen for this study.

  4. How the EUCERD Joint Action supported initiatives on Rare Diseases.

    PubMed

    Lynn, Stephen; Hedley, Victoria; Atalaia, Antonio; Evangelista, Teresinha; Bushby, Kate

    2017-03-01

    Joint Actions are successful initiatives from the European Commission (EC) that have helped to raise awareness and to bring significant benefit to those suffering from a rare disease (RD). In this paper, we will focus on the activities developed by the EUCERD Joint Action (EJA) and by the Orphanet Joint Action ("Orphanet Europe"). EUCERD Joint Action was co-funded by the EC and the Member States between 2012 and 2015 to help to define the activities and policies in the field of RD and foster exchange of experiences amongst Member States. This project is the continuation of previous efforts to turn RD a priority in the EC Health Programmes. "Orphanet Europe" was a Joint Action co-funded by INSERM, the French Directorate General for Health and the EC to address the need for a common portal that would gather the most update information regarding RD. This need was identified in the European Commission report "Rare Diseases: Europe's challenge" and in the Recommendation of the Council for a European RD portal. These joint actions have supported the policy development work of the European Commission, through the support of their committees for rare diseases. In this paper, the authors aim to raise awareness of the work done by the EUCERD Joint Action on behalf of the rare disease community and the policies established.

  5. Sharing neuroimaging studies of human cognition.

    PubMed

    Van Horn, John Darrell; Grafton, Scott T; Rockmore, Daniel; Gazzaniga, Michael S

    2004-05-01

    After more than a decade of collecting large neuroimaging datasets, neuroscientists are now working to archive these studies in publicly accessible databases. In particular, the fMRI Data Center (fMRIDC), a high-performance computing center managed by computer and brain scientists, seeks to catalogue and openly disseminate the data from published fMRI studies to the community. This repository enables experimental validation and allows researchers to combine and examine patterns of brain activity beyond that of any single study. As with some biological databases, early scientific, technical and sociological concerns hindered initial acceptance of the fMRIDC. However, with the continued growth of this and other neuroscience archives, researchers are recognizing the potential of such resources for identifying new knowledge about cognitive and neural activity. Thus, the field of neuroimaging is following the lead of biology and chemistry, mining its accumulating body of knowledge and moving toward a 'discovery science' of brain function.

  6. [The initial symptoms of Alzheimer disease: caregiver perception].

    PubMed

    Cruz, Vítor Tedim; Pais, Joana; Teixeira, Alexandre; Nunes, Belina

    2004-01-01

    Early recognition of Alzheimer's disease (AD) symptoms is crucial to the integration of patient and caregiver in the healthcare system. Family perception of initial cognitive and behavioural symptoms is decisive and has impact on quality of life of both patient and family. To analyse caregiver's perception of initial AD symptoms and characterize the degree of cognitive decline that determines disease recognition. A semi-structured interview was performed including questions about: i) socio-economic characterization of patient and caregiver; ii) disease natural history; iii) DA first symptoms. The interview was applied by phone to a sample of caregivers of patients from two memory clinics. Were included 41 patients (22 M;19 F) with age at onset of 69 years (51-81) and a mean of 14.6 months (2-43) since diagnosis. School level: patients = 3.2 +/- 2.2 and caregivers = 5.37 +/- 3.2 years; leisure activities score: patients = 2.6 +/- 1.9 and caregivers = 2.9 +/- 2. Patients were recognized with involvement of 4-6 cognitive areas in 58.5%; only 12.2% had one cognitive area involved. Women cared by their husbands had less cognitive areas involved at initial perception than men cared by their wives (2.7 +/- 1.5 vs 4 +/- 2.5). Time interval since family perception until reporting to the general practitioner (GP) was 4.16 +/- 5.7 months and to neurological observation 27.7 +/- 13.9. No correlation was found between these intervals and school level or leisure activities. Families have difficulties in the detection of initial dementia symptoms and in adequately transmitting them to GP. The pair of patient and caregiver seemed determinant in dementia recognition: female patients were recognized with less cognitive areas involved, probably in relation with their greater enrollment in household activities. The characterization of the process of perception in dementia is crucial for definition of adequate strategies of detection and intervention in AD.

  7. Investigating motor initiation and inhibition deficits in patients with Parkinson's disease and freezing of gait using a virtual reality paradigm.

    PubMed

    Georgiades, Matthew J; Gilat, Moran; Ehgoetz Martens, Kaylena A; Walton, Courtney C; Bissett, Patrick G; Shine, James M; Lewis, Simon J G

    2016-11-19

    Freezing of gait (FOG) is a common, disabling symptom of Parkinson's disease (PD) that is associated with deficits in motor initiation and inhibition. Understanding of underlying neurobiological mechanisms has been limited by difficulties in eliciting and objectively characterizing such gait phenomena in the clinical setting. However, recent work suggests that virtual reality (VR) techniques might offer the potential to study motor control. This study utilized a VR paradigm to explore deficits in motor initiation and stopping performance, including stop failure in PD patients with (Freezers, 31) and without (Non-Freezers, 23) FOG, and healthy age-matched Controls (15). The VR task required subjects to respond to a series of start and stop cues while navigating a corridor using ankle flexion/extension movements on foot pedals. We found that Freezers experienced slower motor output initiation and more frequent start hesitations (SHs) (initiations greater than twice a subject's usual initiation latency) compared to Non-Freezers and Controls. Freezers also showed more marked inhibitory impairments, taking significantly longer to execute motor inhibition, and experiencing an increased frequency of failed stopping in response to stop cues compared to Non-Freezers and Controls. Stopping impairments were exacerbated by stop cues requiring additional cognitive processing. These results suggest that PD patients with FOG have marked impairments in motor initiation and inhibition that are not prominent in patients without FOG, nor healthy controls. Future work combining such VR paradigms with neuroimaging techniques and intra-operative deep brain recordings may increase our understanding of these phenomena, promoting the development of novel technologies and therapeutic approaches. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Neuroimaging studies of word reading.

    PubMed

    Fiez, J A; Petersen, S E

    1998-02-03

    This review discusses how neuroimaging can contribute to our understanding of a fundamental aspect of skilled reading: the ability to pronounce a visually presented word. One contribution of neuroimaging is that it provides a tool for localizing brain regions that are active during word reading. To assess the extent to which similar results are obtained across studies, a quantitative review of nine neuroimaging investigations of word reading was conducted. Across these studies, the results converge to reveal a set of areas active during word reading, including left-lateralized regions in occipital and occipitotemporal cortex, the left frontal operculum, bilateral regions within the cerebellum, primary motor cortex, and the superior and middle temporal cortex, and medial regions in the supplementary motor area and anterior cingulate. Beyond localization, the challenge is to use neuroimaging as a tool for understanding how reading is accomplished. Central to this challenge will be the integration of neuroimaging results with information from other methodologies. To illustrate this point, this review will highlight the importance of spelling-to-sound consistency in the transformation from orthographic (word form) to phonological (word sound) representations, and then explore results from three neuroimaging studies in which the spelling-to-sound consistency of the stimuli was deliberately varied. Emphasis is placed on the pattern of activation observed within the left frontal cortex, because the results provide an example of the issues and benefits involved in relating neuroimaging results to behavioral results in normal and brain damaged subjects, and to theoretical models of reading.

  9. Neuroimaging evaluation of patients with headaches.

    PubMed

    Diamond, S

    1984-11-01

    As discussed in the introduction, the rote laboratory and neuroimaging evaluation of a patient with headache but without other neurologic symptoms or signs is often unrewarding. Such evaluations are dictated by the clinical history and examination, hence rely on the diagnostic acumen of the physician. In the case of patients during their initial visit, it is frequently useful to proceed with skull radiographs and, if the symptoms warrant, contrast-enhanced CT scanning. In the future, as NMR imaging becomes more widely available, it may prove useful for these initial clinical evaluations. More invasive procedures, such as angiography, are undertaken only if specific indications, such as those summarized in Table 1, are present.

  10. Neuroimaging distinction between neurological and psychiatric disorders†

    PubMed Central

    Crossley, Nicolas A.; Scott, Jessica; Ellison-Wright, Ian; Mechelli, Andrea

    2015-01-01

    Background It is unclear to what extent the traditional distinction between neurological and psychiatric disorders reflects biological differences. Aims To examine neuroimaging evidence for the distinction between neurological and psychiatric disorders. Method We performed an activation likelihood estimation meta-analysis on voxel-based morphometry studies reporting decreased grey matter in 14 neurological and 10 psychiatric disorders, and compared the regional and network-level alterations for these two classes of disease. In addition, we estimated neuroanatomical heterogeneity within and between the two classes. Results Basal ganglia, insula, sensorimotor and temporal cortex showed greater impairment in neurological disorders; whereas cingulate, medial frontal, superior frontal and occipital cortex showed greater impairment in psychiatric disorders. The two classes of disorders affected distinct functional networks. Similarity within classes was higher than between classes; furthermore, similarity within class was higher for neurological than psychiatric disorders. Conclusions From a neuroimaging perspective, neurological and psychiatric disorders represent two distinct classes of disorders. PMID:26045351

  11. Acute disseminated encephalomyelitis complicating dengue infection with neuroimaging mimicking multiple sclerosis: A report of two cases.

    PubMed

    Viswanathan, S; Botross, N; Rusli, B N; Riad, A

    2016-11-01

    Acute disseminated encephalomyelitis (ADEM) complicating dengue infection is still exceedingly rare even in endemic countries such as Malaysia. Here we report two such cases, the first in an elderly female patient and the second in a young man. Both presented with encephalopathy, brainstem involvement and worsening upper and lower limb weakness. Initial magnetic resonance imaging (MRI) of the brain was normal in the first case. Serum for dengue Ig M and NS-1 was positive in both cases. Cerebrospinal fluid (CSF) showed pleocytosis in both with Dengue IgM and NS-1 positive in the second case but not done in the first. MRI brain showed changes of perpendicular subcortical palisading white matter, callosal and brainstem disease mimicking multiple sclerosis (MS) in both patients though in the former case there was a lag between the onset of clinical symptoms and MRI changes which was only clarified on reimaging. The temporal evolution and duration of the clinical symptoms, CSF changes and neuroimaging were more suggestive of Dengue ADEM rather than an encephalitis though initially the first case began as dengue encephalitis. Furthermore in dengue encephalitis neuroimaging is usually normal or rarely edema, haemorrhage, brainstem, thalamic or focal lesions are seen. Therefore, early recognition of ADEM as a sequelae of dengue infection with neuroimaging mimicking MS and repeat imaging helped in identifying these two cases. Treatment with intravenous steroids followed by maintenance oral steroids produced good outcome in both patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Functional neuroimaging of extraversion-introversion.

    PubMed

    Lei, Xu; Yang, Tianliang; Wu, Taoyu

    2015-12-01

    Neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography have provided an unprecedented neurobiological perspective for research on personality traits. Evidence from task-related neuroimaging has shown that extraversion is associated with activations in regions of the anterior cingulate cortex, dorsolateral prefrontal cortex, middle temporal gyrus and the amygdala. Currently, resting-state neuroimaging is being widely used in cognitive neuroscience. Initial exploration of extraversion has revealed correlations with the medial prefrontal cortex, anterior cingulate cortex, insular cortex, and the precuneus. Recent research work has indicated that the long-range temporal dependence of the resting-state spontaneous oscillation has high test-retest reliability. Moreover, the long-range temporal dependence of the resting-state networks is highly correlated with personality traits, and this can be used for the prediction of extraversion. As the long-range temporal dependence reflects real-time information updating in individuals, this method may provide a new approach to research on personality traits.

  13. Traumatic brain injury, neuroimaging, and neurodegeneration

    PubMed Central

    Bigler, Erin D.

    2012-01-01

    Depending on severity, traumatic brain injury (TBI) induces immediate neuropathological effects that in the mildest form may be transient but as severity increases results in neural damage and degeneration. The first phase of neural degeneration is explainable by the primary acute and secondary neuropathological effects initiated by the injury; however, neuroimaging studies demonstrate a prolonged period of pathological changes that progressively occur even during the chronic phase. This review examines how neuroimaging may be used in TBI to understand (1) the dynamic changes that occur in brain development relevant to understanding the effects of TBI and how these relate to developmental stage when the brain is injured, (2) how TBI interferes with age-typical brain development and the effects of aging thereafter, and (3) how TBI results in greater frontotemporolimbic damage, results in cerebral atrophy, and is more disruptive to white matter neural connectivity. Neuroimaging quantification in TBI demonstrates degenerative effects from brain injury over time. An adverse synergistic influence of TBI with aging may predispose the brain injured individual for the development of neuropsychiatric and neurodegenerative disorders long after surviving the brain injury. PMID:23964217

  14. Neuroimaging of Wernicke's encephalopathy and Korsakoff's syndrome.

    PubMed

    Jung, Young-Chul; Chanraud, Sandra; Sullivan, Edith V

    2012-06-01

    There is considerable evidence that neuroimaging findings can improve the early diagnosis of Wernicke's encephalopathy (WE) in clinical settings. The most distinctive neuroimaging finding of acute WE are cytotoxic edema and vasogenic edema, which are represented by bilateral symmetric hyperintensity alterations on T2-weighted MR images in the periphery of the third ventricle, periaqueductal area, mammillary bodies and midbrain tectal plate. An initial bout of WE can result in Korsakoff's syndrome (KS), but repeated bouts in conjunction with its typical comorbidity, chronic alcoholism, can result in signs of tissue degeneration in vulnerable brain regions. Chronic abnormalities identified with neuroimaging enable examination of brain damage in living patients with KS and have expanded the understanding of the neuropsychological deficits resulting from thiamine deficiency, alcohol neurotoxicity, and their comorbidity. Brain structure and functional studies indicate that the interactions involving the thalamus, mammillary bodies, hippocampus, frontal lobes, and cerebellum are crucial for memory formation and executive functions, and the interruption of these circuits by WE and chronic alcoholism can contribute substantially to the neuropsychological deficits in KS.

  15. [Modern neuroimaging of brain plasticity].

    PubMed

    Kasprian, G; Seidel, S

    2010-02-01

    Modern neuroimaging methods offer new insights into the plasticity of the human brain. As the techniques of functional MRI and diffusion tensor imaging are increasingly being applied in a clinical setting, the examiner is now frequently confronted with the interpretation of imaging findings related to regenerative processes in response to lesions of the central and also of the peripheral nervous system. In this article individual results of modern neuroimaging studies are discussed in the context of structural and functional plasticity of the CNS.

  16. Molecular neuroimaging in degenerative dementias.

    PubMed

    Jiménez Bonilla, J F; Carril Carril, J M

    2013-01-01

    In the context of the limitations of structural imaging, brain perfusion and metabolism using SPECT and PET have provided relevant information for the study of cognitive decline. The introduction of the radiotracers for cerebral amyloid imaging has changed the diagnostic strategy regarding Alzheimer's disease, which is currently considered to be a "continuum." According to this new paradigm, the increasing amyloid load would be associated to the preclinical phase and mild cognitive impairment. It has been possible to observe "in vivo" images using 11C-PIB and PET scans. The characteristics of the 11C-PIB image include specific high brain cortical area retention in the positive cases with typical distribution pattern and no retention in the negative cases. This, in combination with 18F-FDG PET, is the basis of molecular neuroimaging as a biomarker. At present, its prognostic value is being evaluated in longitudinal studies. 11C-PIB-PET has become the reference radiotracer to evaluate the presence of cerebral amyloid. However, its availability is limited due to the need for a nearby cyclotron. Therefore, 18F labeled radiotracers are being introduced. Our experience in the last two years with 11C-PIB, first in the research phase and then as being clinically applied, has shown the utility of the technique in the clinical field, either alone or in combination with FDG. Thus, amyloid image is a useful tool for the differential diagnosis of dementia and it is a potentially useful method for early diagnosis and evaluation of future treatments.

  17. Deep Vein Thrombosis as Initial Manifestation of Whipple Disease

    PubMed Central

    Henriques, Mônica Souza de Miranda; da Paz, Alexandre Rolim; Gaertner, Ana Beatriz Person; Melo, Cibelle Ingrid Stephen; Filgueiras, Priscyanne Lins; Jerome, Rafaella Alencar

    2016-01-01

    Introduction Wipple disease (WD) is a rare chronic disease caused by the bacillus Tropheryma whipplei. Constitutive, rheumatologic, gastrointestinal, cardiac, cerebral, lymphatic, cutaneous, and ophthalmological signs are possible systemic symptoms. However, thrombotic manifestations are rarely described as “stroke-like syndrome” or arterial thrombosis. Diagnosis is based on clinical manifestations and pathological examination. Laboratory findings may include anemia, leukocytosis, and thrombocytosis. Objective We report a case of venous thrombosis as initial manifestation of WD. Case Report We describe the case of a 53-year-old male with iliofemoral vein thrombosis followed by intermittent diarrhea, loss of appetite, abdominal distension, and bloating. A mild malnutrition state with a weight loss of 13 kg, pallor (+/4 +), presence of lower-limb edema (+/4 +), and hypertympanic distended abdomen occurred. Laboratory tests on admission revealed anemia, positive inflammatory activity tests, and normal coagulation. Endoscopic examination showed villous edema with white dotted infiltrates in the second duodenal portion and intestinal lymphangiectasia in the terminal ileum. Pathological examination revealed numerous macrophages with positive periodic acid-Schiff inclusions. Venous Doppler ultrasound showed extensive deep thrombosis on the left lower limb and recanalization of the femoral vein in the right lower limb. The patient was treated with ceftriaxone and enoxaparin sodium, which led to an improvement of gastrointestinal and thrombosis symptoms. Comments Hypercoagulability, endothelial damage, vasculitis, and blood stasis are present in T. whipplei infection, which are associated with the activation of inflammatory mechanisms as well as procoagulant and thromboembolic events. WD should be part of the differential diagnosis of diseases that cause venous thrombosis of unknown origin. PMID:27920655

  18. [Neuroimaging in corticobasal syndrome].

    PubMed

    Shinotoh, Hitoshi; Hirano, Shigeki

    2013-01-01

    Recently, several attempts have been made to characterize the clinical symptoms and brain atrophy patterns in pathology-proven corticobasal degeneration (CBD) and corticobasal syndrome (CBS) with known histopathology. CBS is a term which was proposed to characterize the constellation of clinical features initially considered the defining characteristics of CBD. Voxel-based morphometry (VBM) analyses of MRI revealed that frontal lobe involvement is characteristic of CBD. The pathologic substrates for clinical CBS were found to be CBD, Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein (TDP) inclusions. CBS was associated with perirolandic atrophy, irrespective of underlying pathology. In CBS due to FTLD, atrophy extended into the prefrontal cortex, striatum, and brainstem, whereas in CBS due to AD, atrophy extended into the temporoparietal cortex and precuneus. No functional imaging studies in pathology-proven CBD or CBS with known histopathology have yet been published. PET and SPECT studies have demonstrated decreased glucose metabolism and cerebral blood flow in the fronto-parietal cortex, particularly contralateral to the dominant symptoms in CBS patients. A PET study showed decreased acetylcholinesterase (AChE) activity in the fronto-parietal cortex, as well as a correlation between cortical AChE activity and mini-mental state examination score in CBS patients, suggesting that cholinergic stimulant therapy may be effective for dementia in CBS. Additionally, [18F] 6-fluorodopa PET and dopamine transporter SPECT studies have demonstrated nigrostriatal dopaminergic dysfunction in CBS. Antemortem prediction of CBD will remain challenging until sensitive, specific biomarkers are identified.

  19. Development of a disease registry for autoimmune bullous diseases: initial analysis of the pemphigus vulgaris subset.

    PubMed

    Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A

    2015-01-01

    Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation.

  20. Human Neuroimaging as a “Big Data” Science

    PubMed Central

    Van Horn, John Darrell; Toga, Arthur W.

    2013-01-01

    The maturation of in vivo neuroimaging has lead to incredible quantities of digital information about the human brain. While much is made of the data deluge in science, neuroimaging represents the leading edge of this onslaught of “big data”. A range of neuroimaging databasing approaches has streamlined the transmission, storage, and dissemination of data from such brain imaging studies. Yet few, if any, common solutions exist to support the science of neuroimaging. In this article, we discuss how modern neuroimaging research represents a mutifactorial and broad ranging data challenge, involving the growing size of the data being acquired; sociologial and logistical sharing issues; infrastructural challenges for multi-site, multi-datatype archiving; and the means by which to explore and mine these data. As neuroimaging advances further, e.g. aging, genetics, and age-related disease, new vision is needed to manage and process this information while marshalling of these resources into novel results. Thus, “big data” can become “big” brain science. PMID:24113873

  1. Neuroimaging findings in pediatric sports-related concussion.

    PubMed

    Ellis, Michael J; Leiter, Jeff; Hall, Thomas; McDonald, Patrick J; Sawyer, Scott; Silver, Norm; Bunge, Martin; Essig, Marco

    2015-09-01

    The goal in this review was to summarize the results of clinical neuroimaging studies performed in patients with sports-related concussion (SRC) who were referred to a multidisciplinar ypediatric concussion program. The authors conducted a retrospective review of medical records and neuroimaging findings for all patients referred to a multidisciplinary pediatric concussion program between September 2013 and July 2014. Inclusion criteria were as follows: 1) age ≤ 19 years; and 2) physician-diagnosed SRC. All patients underwent evaluation and follow-up by the same neurosurgeon. The 2 outcomes examined in this review were the frequency of neuroimaging studies performed in this population (including CT and MRI) and the findings of those studies. Clinical indications for neuroimaging and the impact of neuroimaging findings on clinical decision making were summarized where available. This investigation was approved by the local institutional ethics review board. A total of 151 patients (mean age 14 years, 59% female) were included this study. Overall, 36 patients (24%) underwent neuroimaging studies, the results of which were normal in 78% of cases. Sixteen percent of patients underwent CT imaging; results were normal in 79% of cases. Abnormal CT findings included the following: arachnoid cyst (1 patient), skull fracture (2 patients), suspected intracranial hemorrhage (1 patient), and suspected hemorrhage into an arachnoid cyst (1 patient). Eleven percent of patients underwent MRI; results were normal in 75% of cases. Abnormal MRI findings included the following: intraparenchymal hemorrhage and sylvian fissure arachnoid cyst (1 patient); nonhemorrhagic contusion (1 patient); demyelinating disease (1 patient); and posterior fossa arachnoid cyst, cerebellar volume loss, and nonspecific white matter changes (1 patient). Results of clinical neuroimaging studies are normal in the majority of pediatric patients with SRC. However, in selected cases neuroimaging can provide

  2. Chinese patients with Huntington's disease initially presenting with spinocerebellar ataxia.

    PubMed

    Dong, Y; Sun, Y-M; Liu, Z-J; Ni, W; Shi, S-S; Wu, Z-Y

    2013-04-01

    Recent studies have described Huntington's disease (HD) patients with atypical onset of ataxia. Symptoms in these patients can overlap with those of spinocerebellar ataxia (SCA). We retrospectively examined clinical data for 82 HD probands and found 7 had initially been clinically diagnosed as SCA cases. Clinical features in these patients were further investigated and the number of CAG repeats in the huntingtin (HTT) gene was determined by direct sequencing. Genetic screenings for SCAs in the 7 patients were all negative. By contrast, HTT was heterozygous in each patient. The distribution of CAG number in the 7 patients was statistically the same as that in the other 75 patients. Each of 7 HD patients had presented with atypical onset of ataxia. The mean time from onset to HTT genetic testing was 5.6 ± 5.52 years. Three of the patients developed chorea, but the others did not. Our observations confirm the clinical heterogeneity of HD in Han Chinese. Based on these findings, testing for HTT expansions should be considered for clinically diagnosed SCA patients who test negatively in genetic screening of SCA genes.

  3. PET neuroimaging studies of [18F]CABS13 in a double transgenic mouse model of Alzheimer’s disease and non-human primates

    PubMed Central

    Liang, Steven H.; Holland, Jason P.; Stephenson, Nickeisha A.; Kassenbrock, Alina; Rotstein, Benjamin H.; Daignault, Cory P.; Lewis, Rebecca; Collier, Lee; Hooker, Jacob M.; Vasdev, Neil

    2016-01-01

    Fluorine-18 labeled 2-fluoro-8-hydroxyquinoline ([18F]CABS13) is a promising positron emission tomography (PET) radiopharmaceutical based on a metal chelator developed to probe the “metal hypothesis of Alzheimer’s disease”. Herein, a practical radiosynthesis of [18F]CABS13 was achieved by radiofluorination followed by deprotection of an O-benzyloxymethyl group. Automated production and formulation of [18F]CABS13 resulted in 19 ± 5% uncorrected radiochemical yield, relative to starting [18F]fluoride, with ≥95% chemical and radiochemical purities, and high specific activity (>2.5 Ci/μmol) within 80 minutes. Temporal PET neuroimaging studies were carried out in female transgenic B6C3- Tg(APPswe,PSEN1dE9)85Dbo/J (APP/PS1) and age-matched wild-type (WT) B6C3F1/J control mice at 3, 7 and 10 months of age. [18F]CABS13 showed an overall higher uptake and retention of radioactivity in the central nervous system of APP/PS1 mice versus WT mice with increasing age. However, PET/magnetic resonance imaging in normal non-human primates revealed that the tracer had low uptake in the brain and rapid formation of a hydrophilic radiometabolite. Identification of more metabolically stable 18F-hydroxyquinolines that can be readily accessed by the radiochemical strategy presented herein is underway. PMID:25776827

  4. Neuroimaging findings in primary insomnia.

    PubMed

    O'Byrne, J N; Berman Rosa, M; Gouin, J-P; Dang-Vu, T T

    2014-10-01

    State-of-the-art neuroimaging techniques have accelerated progress in the study and understanding of sleep in humans. Neuroimaging studies in primary insomnia remain relatively few, considering the important prevalence of this disorder in the general population. This review examines the contribution of functional and structural neuroimaging to our current understanding of primary insomnia. Functional studies during sleep provided support for the hyperarousal theory of insomnia. Functional neuroimaging also revealed abnormalities in cognitive and emotional processing in primary insomnia. Results from structural studies suggest neuroanatomical alterations in primary insomnia, mostly in the hippocampus, anterior cingulate cortex and orbitofrontal cortex. However, these results are not well replicated across studies. A few magnetic resonance spectroscopy studies revealed abnormalities in neurotransmitter concentrations and bioenergetics in primary insomnia. The inconsistencies among neuroimaging findings on insomnia are likely due to clinical heterogeneity, differences in imaging and overall diversity of techniques and designs employed. Larger samples, replication, as well as innovative methodologies are necessary for the progression of this perplexing, yet promising area of research. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. LSTGEE: longitudinal analysis of neuroimaging data

    NASA Astrophysics Data System (ADS)

    Li, Yimei; Zhu, Hongtu; Chen, Yasheng; An, Hongyu; Gilmore, John; Lin, Weili; Shen, Dinggang

    2009-02-01

    Longitudinal imaging studies are essential to understanding the neural development of neuropsychiatric disorders, substance use disorders, and normal brain. Using appropriate image processing and statistical tools to analyze the imaging, behavioral, and clinical data is critical for optimally exploring and interpreting the findings from those imaging studies. However, the existing imaging processing and statistical methods for analyzing imaging longitudinal measures are primarily developed for cross-sectional neuroimaging studies. The simple use of these cross-sectional tools to longitudinal imaging studies will significantly decrease the statistical power of longitudinal studies in detecting subtle changes of imaging measures and the causal role of time-dependent covariate in disease process. The main objective of this paper is to develop longitudinal statistics toolbox, called LSTGEE, for the analysis of neuroimaging data from longitudinal studies. We develop generalized estimating equations for jointly modeling imaging measures with behavioral and clinical variables from longitudinal studies. We develop a test procedure based on a score test statistic and a resampling method to test linear hypotheses of unknown parameters, such as associations between brain structure and function and covariates of interest, such as IQ, age, gene, diagnostic groups, and severity of disease. We demonstrate the application of our statistical methods to the detection of the changes of the fractional anisotropy across time in a longitudinal neonate study. Particularly, our results demonstrate that the use of longitudinal statistics can dramatically increase the statistical power in detecting the changes of neuroimaging measures. The proposed approach can be applied to longitudinal data with multiple outcomes and accommodate incomplete and unbalanced data, i.e., subjects with different number of measurements.

  6. Heart Rate and Initial Presentation of Cardiovascular Diseases (Caliber)

    ClinicalTrials.gov

    2013-09-17

    Abdominal Aortic Aneurysm; Coronary Heart Disease NOS; Unheralded Coronary Death; Intracerebral Haemorrhage; Heart Failure; Ischemic Stroke; Myocardial Infarction; Stroke; Peripheral Arterial Disease; Stable Angina Pectoris; Subarachnoid Haemorrhage; Transient Ischemic Attack; Unstable Angina; Cardiac Arrest, Sudden Cardiac Death

  7. Efficient, Distributed and Interactive Neuroimaging Data Analysis Using the LONI Pipeline

    PubMed Central

    Dinov, Ivo D.; Van Horn, John D.; Lozev, Kamen M.; Magsipoc, Rico; Petrosyan, Petros; Liu, Zhizhong; MacKenzie-Graham, Allan; Eggert, Paul; Parker, Douglas S.; Toga, Arthur W.

    2009-01-01

    The LONI Pipeline is a graphical environment for construction, validation and execution of advanced neuroimaging data analysis protocols (Rex et al., 2003). It enables automated data format conversion, allows Grid utilization, facilitates data provenance, and provides a significant library of computational tools. There are two main advantages of the LONI Pipeline over other graphical analysis workflow architectures. It is built as a distributed Grid computing environment and permits efficient tool integration, protocol validation and broad resource distribution. To integrate existing data and computational tools within the LONI Pipeline environment, no modification of the resources themselves is required. The LONI Pipeline provides several types of process submissions based on the underlying server hardware infrastructure. Only workflow instructions and references to data, executable scripts and binary instructions are stored within the LONI Pipeline environment. This makes it portable, computationally efficient, distributed and independent of the individual binary processes involved in pipeline data-analysis workflows. We have expanded the LONI Pipeline (V.4.2) to include server-to-server (peer-to-peer) communication and a 3-tier failover infrastructure (Grid hardware, Sun Grid Engine/Distributed Resource Management Application API middleware, and the Pipeline server). Additionally, the LONI Pipeline provides three layers of background-server executions for all users/sites/systems. These new LONI Pipeline features facilitate resource-interoperability, decentralized computing, construction and validation of efficient and robust neuroimaging data-analysis workflows. Using brain imaging data from the Alzheimer's Disease Neuroimaging Initiative (Mueller et al., 2005), we demonstrate integration of disparate resources, graphical construction of complex neuroimaging analysis protocols and distributed parallel computing. The LONI Pipeline, its features, specifications

  8. Disease progression in non-erosive reflux disease (NERD): impact of initial esophageal acid exposure.

    PubMed

    Chen, C L; Liu, T T; Yi, C H

    2010-11-01

    We investigated the 5-year clinical course in a cohort of patients with typical reflux symptoms and negative endoscopy. Prospective follow-up was conducted in patients with non-erosive reflux disease (NERD) for at least 5 years after initial evaluation with esophageal pH monitoring and upper gastrointestinal endoscopy. Within the last year of follow-up, reflux symptoms occurred in 27 of the 30 patients (90%). Twenty-five of twenty-seven symptomatic patients (93%) were on acid suppression therapy. The majority of our patients (70%) remained unchanged regarding their endoscopic status over 5 years. Progression to erosive esophagitis occurred in four patients with Los Angeles (LA) A (13%), three patients with LA B (10%), and two patients with LA C (7%). The presence of pathological acid exposure did not alter the presence of reflux symptoms over 5 years. Disease progression to erosive esophagitis occurred more frequently in patients with pathological acid exposure than those without pathological acid exposure (P= 0.025). Most NERD patients have symptoms and require acid suppression therapy 5 years after their initial diagnosis. Initial pathological acid exposure does not influence the use of acid suppression; however, it does influence the progression of NERD within 5 years of follow-up.

  9. Neuroimaging evaluation in refractory epilepsy

    PubMed Central

    Granados, Ana M; Orejuela, Juan F

    2015-01-01

    Purpose To describe the application of neuroimaging analysis, compared to neuropsychological tests and video-electroencephalogram, for the evaluation of refractory epilepsy in a reference centre in Cali, Colombia. Methods Between March 2013 and November 2014, 29 patients, 19 men and 10 women, aged 9–65 years and with refractory epilepsy, were assessed by structural and functional magnetic resonance imaging while performing tasks related to language, verbal and non-verbal memory. Also, volumetric evaluation was performed. A 1.5 Tesla magnetic resonance imaging scanner was used in all cases. Results Neuroimaging evaluation identified 13 patients with mesial temporal sclerosis. The remaining patients were classified as: 10 patients with neoplastic masses, two patients with cortical atrophy, two patients with scarring lesions and two patients with non-structural aetiology. Among patients with mesial temporal sclerosis, comparison between techniques for lateralising the epileptogenic foci was made; the κ index between functional magnetic resonance imaging and hippocampi volumetry was κ = 1.00, agreement between neuroimaging and video-electroencephalogram was good (κ = 0.78) and comparison with a neuropsychological test was mild (κ = 0.24). Conclusions Neuroimaging studies allow the assessment of functional and structural damage related to epileptogenic lesions and foci, and are helpful to select surgical treatment, conduct intraoperative neuronavigation techniques, predict surgical deficits and evaluate patient recovery. PMID:26427897

  10. Neuroimaging training among neuropsychologists: A survey of the state of current training and recommendations for trainees

    PubMed Central

    Benitez, Andreana; Hassenstab, Jason; Bangen, Katherine J.

    2013-01-01

    Neuroimaging has gained widespread use in neuropsychological research and practice. However, there are neither established guidelines on how neuropsychologists might become competent researchers or consumers of neuroimaging data, nor any published studies describing the state of neuroimaging training among neuropsychologists. We report the results of two online surveys, one of 13 expert neuropsychologist-neuroimagers, whose responses informed the formulation of a second, larger survey to neuropsychologists-at-large that were a random selection of a third of the members of the International Neuropsychological Society and American Academy of Clinical Neuropsychology. 237 doctoral-level neuropsychologists, or 15.3% of potential participants, provided complete responses. Most respondents (69.2%) received training in neuroimaging, mostly at the post-doctoral level, largely through independent study, clinical conferences, instruction by clinical supervisors, and individualized mentoring, on topics such as neuroimaging modalities in neurology, neuroanatomy, and the appropriate information to glean from neuroradiology reports. Of the remaining respondents who did not receive training in neuroimaging, 64.4% indicated that such training would be very or extremely beneficial to one’s career as a neuropsychologist. Both neuropsychologist-neuroimagers and neuropsychologists-at-large provided specific recommendations for training. Findings from this initial effort will guide trainees who seek to develop competence in neuroimaging, and inform future formulations of neuropsychological training. PMID:24215451

  11. Neuroimaging training among neuropsychologists: a survey of the state of current training and recommendations for trainees.

    PubMed

    Benitez, Andreana; Hassenstab, Jason; Bangen, Katherine J

    2014-01-01

    Neuroimaging has gained widespread use in neuropsychological research and practice. However, there are neither established guidelines on how neuropsychologists might become competent researchers or consumers of neuroimaging data, nor any published studies describing the state of neuroimaging training among neuropsychologists. We report the results of two online surveys, one of 13 expert neuropsychologist-neuroimagers whose responses informed the formulation of a second, larger survey to neuropsychologists-at-large that were a random selection of a third of the members of the International Neuropsychological Society and American Academy of Clinical Neuropsychology. A total of 237 doctoral-level neuropsychologists, or 15.3% of potential participants, provided complete responses. Most respondents (69.2%) received training in neuroimaging, mostly at the post-doctoral level, largely through independent study, clinical conferences, instruction by clinical supervisors, and individualized mentoring, on topics such as neuroimaging modalities in neurology, neuroanatomy, and the appropriate information to glean from neuroradiology reports. Of the remaining respondents who did not receive training in neuroimaging, 64.4% indicated that such training would be very or extremely beneficial to one's career as a neuropsychologist. Both neuropsychologist-neuroimagers and neuropsychologists-at-large provided specific recommendations for training. Findings from this initial effort will guide trainees who seek to develop competence in neuroimaging, and inform future formulations of neuropsychological training.

  12. Vitamin D and Risk of Neuroimaging Abnormalities.

    PubMed

    Littlejohns, Thomas J; Kos, Katarina; Henley, William E; Lang, Iain A; Annweiler, Cedric; Beauchet, Olivier; Chaves, Paulo H M; Kestenbaum, Bryan R; Kuller, Lewis H; Langa, Kenneth M; Lopez, Oscar L; Llewellyn, David J

    2016-01-01

    Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer's disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25-50 nmol/L) were 0.76 (0.35-1.66) and 1.09 (0.76-1.55) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OH)D deficient and deficient were 0.49 (0.20-1.19) and 1.12 (0.79-1.59) compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OH)D deficient and deficient were 1.95 (0.84-4.54) and 0.73 (0.47-1.95) compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with the development of

  13. Building better biomarkers: brain models in translational neuroimaging.

    PubMed

    Woo, Choong-Wan; Chang, Luke J; Lindquist, Martin A; Wager, Tor D

    2017-02-23

    Despite its great promise, neuroimaging has yet to substantially impact clinical practice and public health. However, a developing synergy between emerging analysis techniques and data-sharing initiatives has the potential to transform the role of neuroimaging in clinical applications. We review the state of translational neuroimaging and outline an approach to developing brain signatures that can be shared, tested in multiple contexts and applied in clinical settings. The approach rests on three pillars: (i) the use of multivariate pattern-recognition techniques to develop brain signatures for clinical outcomes and relevant mental processes; (ii) assessment and optimization of their diagnostic value; and (iii) a program of broad exploration followed by increasingly rigorous assessment of generalizability across samples, research contexts and populations. Increasingly sophisticated models based on these principles will help to overcome some of the obstacles on the road from basic neuroscience to better health and will ultimately serve both basic and applied goals.

  14. Disease management. A global cost-containing initiative?

    PubMed

    Bloor, K; Maynard, A

    2000-06-01

    Disease management has been marketed by healthcare industry providers as a way of improving resource allocation in healthcare and containing costs. However, to achieve improved efficiency in healthcare requires the guidelines and protocols in the disease management process to be based on sound evidence of effectiveness and cost effectiveness. This has not always been the case. The approach itself has an inadequate evidence base in terms of randomised controlled trials, other rigorous methods of evaluation and the results of economic evaluation. Disease management can be viewed as an attempt by pharmaceutical companies to undertake forward vertical integration into other parts of the healthcare process. This could reduce uncertainty for purchasers and reduce transaction costs, thereby potentially facilitating both healthcare expenditure control and efficiency. However, such cost savings may be outweighed by a concentration of power in disease management (pharmaceutical) companies, and the exploitation of such power to inflate expenditure and misallocate resources. Disease management must be appraised with care.

  15. Echocardiography Criteria for Structural Heart Disease in Patients With End-Stage Renal Disease Initiating Hemodialysis.

    PubMed

    Hickson, LaTonya J; Negrotto, Sara M; Onuigbo, Macaulay; Scott, Christopher G; Rule, Andrew D; Norby, Suzanne M; Albright, Robert C; Casey, Edward T; Dillon, John J; Pellikka, Patricia A; Pislaru, Sorin V; Best, Patricia J M; Villarraga, Hector R; Lin, Grace; Williams, Amy W; Nkomo, Vuyisile T

    2016-03-15

    Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for structural heart disease (SHD) in dialysis patients. The association of SHD with important patient outcomes is not well defined. This study sought to determine prevalence of ECHO-determined SHD and its association with survival among incident HD patients. We analyzed patients who began chronic HD from 2001 to 2013 who underwent ECHO ≤1 month prior to or ≤3 months following initiation of HD (n = 654). Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and sex-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LVEF) ≤45% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.20 to 1.83) and right ventricular (RV) systolic dysfunction (HR: 1.68; CI: 1.35 to 2.07). An additive of higher death risk included LVEF ≤45% and RV systolic dysfunction rather than neither (HR: 2.04; CI: 1.57 to 2.67; p = 0.53 for test for interaction). Following adjustment for age, sex, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR: 1.66; CI 1.34 to 2.06; p < 0.001). SHD was common in our HD study population, and RV systolic dysfunction independently predicted mortality. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  16. 78 FR 17412 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-21

    ... Diseases in Africa, FOA GH13-002, initial review. In accordance with Section 10(a)(2) of the Federal... and Evaluation of Programs for the Elimination and Control of Neglected Tropical Diseases in...

  17. The Spanish biology/disease initiative within the human proteome project: Application to rheumatic diseases.

    PubMed

    Ruiz-Romero, Cristina; Calamia, Valentina; Albar, Juan Pablo; Casal, José Ignacio; Corrales, Fernando J; Fernández-Puente, Patricia; Gil, Concha; Mateos, Jesús; Vivanco, Fernando; Blanco, Francisco J

    2015-09-08

    The Spanish Chromosome 16 consortium is integrated in the global initiative Human Proteome Project, which aims to develop an entire map of the proteins encoded following a gene-centric strategy (C-HPP) in order to make progress in the understanding of human biology in health and disease (B/D-HPP). Chromosome 16 contains many genes encoding proteins involved in the development of a broad range of diseases, which have a significant impact on the health care system. The Spanish HPP consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. Proteomics strategies have enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. In this manuscript we describe how the Spanish HPP-16 consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. We show how the Proteomic strategy has enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. This article is part of a Special Issue entitled: HUPO 2014. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Advanced Neuroimaging of Tinnitus.

    PubMed

    Raghavan, Prashant; Steven, Andrew; Rath, Tanya; Gandhi, Dheeraj

    2016-05-01

    Although tinnitus may originate in damage to the peripheral auditory apparatus, its perception and distressing symptomatology are consequences of alterations to auditory, sensory, and limbic neural networks. This has been described in several studies, some using advanced structural MR imaging techniques such as diffusion tensor imaging. An understanding of these complex changes could enable development of targeted treatment. New MR imaging techniques enabling detailed depiction of the labyrinth may be useful when diagnosis of Meniere disease is equivocal. Advances in computed tomography and MR imaging have enabled noninvasive diagnosis of dural arteriovenous fistulae.

  19. High-dose thiamine as initial treatment for Parkinson's disease

    PubMed Central

    Costantini, Antonio; Pala, Maria Immacolata; Compagnoni, Laura; Colangeli, Marco

    2013-01-01

    Parkinson's disease (PD) is a systemic disease with motor and non-motor deficits. We recruited three patients with newly diagnosed PD. They were not under anti-Parkinson's therapy. Plasmatic thiamine was within healthy reference range. We performed the Unified Parkinson's Disease Rating Scale (UPDRS) and started a parenteral therapy with high doses of thiamine. The therapy led to a considerable improvement in the motor part of the UPDRS ranging from 31.3% to 77.3%. From this clinical observation, it is reasonable to infer that a focal, severe thiamine deficiency due to a dysfunction of thiamine metabolism could cause a selective neuronal damage in the centres that are typically hit in this disease. Injection of high doses of thiamine was effective in reversing the symptoms, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23986125

  20. 78 FR 60878 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... and Disease Prevention Research Centers, Funding Opportunity Announcement (FOA) DP14-001, initial... Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Times And Dates 8...

  1. 78 FR 60878 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... and Disease Prevention Research Centers, Funding Opportunity Announcement (FOA) DP14-001, initial... Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting: Times and Dates 8...

  2. Neuroimaging of Plasmacytoma

    PubMed Central

    Agarwal, Ajay

    2014-01-01

    Summary This pictorial review describes the spectrum of CT/MR imaging findings of solitary extramedullary and bone plasmacytomas in different locations related to neuroradiology. Plasmacytoma is considered a counterpart of multiple myeloma that is described as a solitary and discrete mass of monoclonal neoplastic plasma cells. It may arise from osseous (medullary) or extramedullary sites. Isolated extramedullary plasmacytoma is very rare and comprises less than 4% of all plasma cellular diseases of which more than 80% are localized to the submucosal lymphoid tissue of the nasopharynx, nasal cavity and paranasal sinuses. We will demonstrate imaging findings in ten histopathologically proven plasmacytomas in different locations related to neuroradiology. Extramedullary and osseous plasmacytoma show nonspecific CT and MR imaging findings. MR is the preferred modality for evaluation due to better soft tissue contrast. Features that may suggest the diagnosis of plasmacytoma are bulky soft tissue mass and relatively isointense signal on T2-weighted MR images due to high cellularity. PMID:25196616

  3. Neuroimaging for psychotherapy research: Current trends

    PubMed Central

    WEINGARTEN, CAROL P.; STRAUMAN, TIMOTHY J.

    2014-01-01

    Objective This article reviews neuroimaging studies that inform psychotherapy research. An introduction to neuroimaging methods is provided as background for the increasingly sophisticated breadth of methods and findings appearing in psychotherapy research. Method We compiled and assessed a comprehensive list of neuroimaging studies of psychotherapy outcome, along with selected examples of other types of studies that also are relevant to psychotherapy research. We emphasized magnetic resonance imaging (MRI) since it is the dominant neuroimaging modality in psychological research. Results We summarize findings from neuroimaging studies of psychotherapy outcome, including treatment for depression, obsessive-compulsive disorder (OCD), and schizophrenia. Conclusions The increasing use of neuroimaging methods in the study of psychotherapy continues to refine our understanding of both outcome and process. We suggest possible directions for future neuroimaging studies in psychotherapy research. PMID:24527694

  4. Neuroimaging for psychotherapy research: current trends.

    PubMed

    Weingarten, Carol P; Strauman, Timothy J

    2015-01-01

    This article reviews neuroimaging studies that inform psychotherapy research. An introduction to neuroimaging methods is provided as background for the increasingly sophisticated breadth of methods and findings appearing in psychotherapy research. We compiled and assessed a comprehensive list of neuroimaging studies of psychotherapy outcome, along with selected examples of other types of studies that also are relevant to psychotherapy research. We emphasized magnetic resonance imaging (MRI) since it is the dominant neuroimaging modality in psychological research. We summarize findings from neuroimaging studies of psychotherapy outcome, including treatment for depression, obsessive compulsive disorder (OCD), and schizophrenia. The increasing use of neuroimaging methods in the study of psychotherapy continues to refine our understanding of both outcome and process. We suggest possible directions for future neuroimaging studies in psychotherapy research.

  5. Dracunculiasis (Guinea worm disease) and the eradication initiative.

    PubMed

    Cairncross, Sandy; Muller, Ralph; Zagaria, Nevio

    2002-04-01

    Dracunculiasis, also known as guinea worm disease, is caused by the large female of the nematode Dracunculus medinensis, which emerges painfully and slowly from the skin, usually on the lower limbs. The disease can infect animals, and sustainable animal cycles occur in North America and Central Asia but do not act as reservoirs of human infection. The disease is endemic across the Sahel belt of Africa from Mauritania to Ethiopia, having been eliminated from Asia and some African countries. It has a significant socioeconomic impact because of the temporary disability that it causes. Dracunculiasis is exclusively caught from drinking water, usually from ponds. A campaign to eradicate the disease was launched in the 1980s and has made significant progress. The strategy of the campaign is discussed, including water supply, health education, case management, and vector control. Current issues including the integration of the campaign into primary health care and the mapping of cases by using geographic information systems are also considered. Finally, some lessons for other disease control and eradication programs are outlined.

  6. Dracunculiasis (Guinea Worm Disease) and the Eradication Initiative

    PubMed Central

    Cairncross, Sandy; Muller, Ralph; Zagaria, Nevio

    2002-01-01

    Dracunculiasis, also known as guinea worm disease, is caused by the large female of the nematode Dracunculus medinensis, which emerges painfully and slowly from the skin, usually on the lower limbs. The disease can infect animals, and sustainable animal cycles occur in North America and Central Asia but do not act as reservoirs of human infection. The disease is endemic across the Sahel belt of Africa from Mauritania to Ethiopia, having been eliminated from Asia and some African countries. It has a significant socioeconomic impact because of the temporary disability that it causes. Dracunculiasis is exclusively caught from drinking water, usually from ponds. A campaign to eradicate the disease was launched in the 1980s and has made significant progress. The strategy of the campaign is discussed, including water supply, health education, case management, and vector control. Current issues including the integration of the campaign into primary health care and the mapping of cases by using geographic information systems are also considered. Finally, some lessons for other disease control and eradication programs are outlined. PMID:11932231

  7. Neuroimaging features of Cornelia de Lange syndrome.

    PubMed

    Whitehead, Matthew T; Nagaraj, Usha D; Pearl, Phillip L

    2015-07-01

    Cornelia de Lange syndrome is a rare genetic disease characterized by distinctive facial dysmorphia and dwarfism. Multiple organ system involvement is typical. Various central nervous system (CNS) aberrations have been described in the pathology literature; however, the spectrum of neuroimaging manifestations is less well documented. To present neuroimaging findings from a series of eight patients with Cornelia de Lange syndrome. The CT/MR database at a single academic children's hospital was searched for the terms "Cornelia," "Brachmann" and "de Lange." The search yielded 18 exams from 16 patients. Two non-CNS and six exams without available images were excluded. Ten exams from eight patients were evaluated by a board-certified neuroradiologist. All patients had skull base dysplasia, most with an unusual coronal basioccipital cleft (7/8). All brain MR exams showed microcephaly, volume loss and gyral simplification (5/5). Six patients had an absent massa intermedia. Four patients had small globe anterior segments; three had optic pathway hypoplasia. Basilar artery fenestration was present in two patients; vertebrobasilar hypoplasia was present in one patient. The inner ear vestibules were dysplastic in two patients. One patient had pachymeningeal thickening. Spinal anomalies included scoliosis, segmentation anomalies, endplate irregularities, basilar invagination, foramen magnum stenosis and tethered spinal cord. Typical imaging manifestations of Cornelia de Lange syndrome include skull base dysplasia with coronal clival cleft, cerebral and brainstem volume loss, and gyral simplification. Membranous labyrinth dysplasia, anterior segment and optic pathway hypoplasia, basilar artery fenestration, absent massa intermedia and spinal anomalies may also be present.

  8. Gray Matter Pathology in MS: Neuroimaging and Clinical Correlations

    PubMed Central

    Honce, Justin Morris

    2013-01-01

    It is abundantly clear that there is extensive gray matter pathology occurring in multiple sclerosis. While attention to gray matter pathology was initially limited to studies of autopsy specimens and biopsies, the development of new MRI techniques has allowed assessment of gray matter pathology in vivo. Current MRI techniques allow the direct visualization of gray matter demyelinating lesions, the quantification of diffuse damage to normal appearing gray matter, and the direct measurement of gray matter atrophy. Gray matter demyelination (both focal and diffuse) and gray matter atrophy are found in the very earliest stages of multiple sclerosis and are progressive over time. Accumulation of gray matter damage has substantial impact on the lives of multiple sclerosis patients; a growing body of the literature demonstrates correlations between gray matter pathology and various measures of both clinical disability and cognitive impairment. The effect of disease modifying therapies on the rate accumulation of gray matter pathology in MS has been investigated. This review focuses on the neuroimaging of gray matter pathology in MS, the effect of the accumulation of gray matter pathology on clinical and cognitive disability, and the effect of disease-modifying agents on various measures of gray matter damage. PMID:23878736

  9. [Correlation between EEG and neuroimaging].

    PubMed

    Tobimatsu, Shozo

    2012-01-01

    The present state of knowledge of physiological mechanisms underlying nonepileptiform EEG abnormalities is reviewed to clarify the correlation between EEG and neuroimaging. Focal and widespread slow waves, background abnormalities, and bursts of rhythmic slow activity are discussed. EEG phenomena were correlated with lesion size, location, type (white matter vs. gray matter, high density vs. low density), and mass effect. Clinical and experimental accumulated over the past five decades suggest that polymorphic slow activity is generated in cerebral cortex by layers of pyramidal cells and is probably due to partial deafferentation from subcortical areas. Unilateral background activity changes are probably thalamic dysfunction, and bilateral paroxysmal slow activity is due to abnormal thalamocortical circuits combined with cortical pathology. Paroxysmal discharges indicate the presence of epilepsy with possible brain lesion(s). The EEG is a functional test and provides us complementary information to neuroimaging studies.

  10. Initial studies on "six months disease" in sheep.

    PubMed

    Pyakural, S; Singh, N B

    1976-01-17

    Enterotoxaemia in sheep due to Clostridium welchii type D was indicated by field and laboratory investigations in Nepal. Morphological, cultural, biochemical, biological and toxin-producing characteristics observed were used to type the isolates. In anaerobic meat medium, all isolates produced pinkish discoloration of meat. All the strains fermented lactose, maltose, dextrose and sucrose whereas, salicine was fermented only by 17 strains. All but five strains were MR negative. Out of 200 isolated, 166 produced both alpha and epsilon toxins and the remaining 34 non-toxogenic strains are likely to be variants which have lost their toxogenicity. Epidemiologically the local name "Six months disease" and enterotoxaemia are considered to be identical diseases.

  11. [Neuroimaging in corticobasal syndrome].

    PubMed

    Shinotoh, Hitoshi

    2013-01-01

    Recently, several attempts have been made to characterize clinical symptoms and brain atrophy patterns in pathology-proven corticobasal degeneration (CBD) and corticobasal syndrome (CBS). Voxel-based morphometry (VBM) analysis of MRI revealed that frontal lobe involvement is characteristic of CBD. CBS was associated with perirolandic atrophy irrespective of underlying pathology. In CBS due to frontotemporal lobar degeneration (FTLD), atrophy extended into prefrontal cortex, striatum, and brainstem, whereas in CBS due to Alzheimer's disease (AD), atrophy extended into temporoparietal cortex and precuneus.No functional imaging study in pathology-proven CBD or CBS with known histopathology has been published today. PET and SPECT studies demonstrated that decreased glucose metabolism and cerebral blood flow in the fronto-parietal cortex, especially contralateral to the dominant symptoms in patients with CBS. [(18)F]6-fluorodopa PET and dopamine transporter SPECT studies demonstrated dysfunction of nigrostriatal dopaminergic function in CBS. A PET study showed decreased acetylcholinesterase activity (AChE) in the fronto-parietal cortex, and a correlation between cortical AChE activity and mini-mental state examination score in patients with CBS.Amyloid imaging agent is useful for detection of AD pathology in CBS. The recent development of tau imaging agent has made it possible to image distribution of neurofibrillary tangles in the brain in vivo.

  12. Can neuroimaging disentangle bipolar disorder?

    PubMed

    Hozer, Franz; Houenou, Josselin

    2016-05-01

    Bipolar disorder heterogeneity is large, leading to difficulties in identifying neuropathophysiological and etiological mechanisms and hindering the formation of clinically homogeneous patient groups in clinical trials. Identifying markers of clinically more homogeneous groups would help disentangle BD heterogeneity. Neuroimaging may aid in identifying such groups by highlighting specific biomarkers of BD subtypes or clinical dimensions. We performed a systematic literature search of the neuroimaging literature assessing biomarkers of relevant BD phenotypes (type-I vs. II, presence vs. absence of psychotic features, suicidal behavior and impulsivity, rapid cycling, good vs. poor medication response, age at onset, cognitive performance and circadian abnormalities). Consistent biomarkers were associated with suicidal behavior, i.e. frontal/anterior alterations (prefrontal and cingulate grey matter, prefrontal white matter) in patients with a history of suicide attempts; and with cognitive performance, i.e. involvement of frontal and temporal regions, superior and inferior longitudinal fasciculus, right thalamic radiation, and corpus callosum in executive dysfunctions. For the other dimensions and sub-types studied, no consistent biomarkers were identified. Studies were heterogeneous both in methodology and outcome. Though theoretically promising, neuroimaging has not yet proven capable of disentangling subtypes and dimensions of bipolar disorder, due to high between-study heterogeneity. We issue recommendations for future studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. [Obstructive uropathy as initial manifestation of Crohn disease].

    PubMed

    Hernández Jaras, J; García-Samaniego Rey, J; Paraiso Cuevas, V; Castaños-Mollor Penalva, R; Pajares García, J M; Traver Aguilar, J A

    1990-10-01

    A patient with renal colicky pain caused by urinary tract obstruction, as a result of psoas abscess, is presented. It was the first manifestation of Crohn's disease. A Gram negative bacteria was isolated from the abscess. The CT images performed to evaluate the abscess suggested this etiology, even though there were no previous symptoms.

  14. [Alzheimer's disease and geolocation: initial results of the Estima study].

    PubMed

    Rialle, Vincent; Ollivet, Catherine; Brissonneau, Christophe; Leard, Franck; Barth, Iwan; Extra, Jocelyne; Sablier, Juliette

    2012-01-01

    Geolocation devices for patients suffering from Alzheimer's disease constitute an improvement in their care. However, this system arouses debate. The Estima study offers a series of results and recommendations concerning the use of these devices. It consists of three complementary sections: a sociological study, an observational retrospective study and an ethical analysis.

  15. 25 years of neuroimaging in amyotrophic lateral sclerosis

    PubMed Central

    Foerster, Bradley R.; Welsh, Robert C.; Feldman, Eva L.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which a precise cause has not yet been identified. Standard CT or MRI evaluation does not demonstrate gross structural nervous system changes in ALS, so conventional neuroimaging techniques have provided little insight into the pathophysiology of this disease. Advanced neuroimaging techniques—such as structural MRI, diffusion tensor imaging and proton magnetic resonance spectroscopy—allow evaluation of alterations of the nervous system in ALS. These alterations include focal loss of grey and white matter and reductions in white matter tract integrity, as well as changes in neural networks and in the chemistry, metabolism and receptor distribution in the brain. Given their potential for investigation of both brain structure and function, advanced neuroimaging methods offer important opportunities to improve diagnosis, guide prognosis, and direct future treatment strategies in ALS. In this article, we review the contributions made by various advanced neuroimaging techniques to our understanding of the impact of ALS on different brain regions, and the potential role of such measures in biomarker development. PMID:23917850

  16. 25 years of neuroimaging in amyotrophic lateral sclerosis.

    PubMed

    Foerster, Bradley R; Welsh, Robert C; Feldman, Eva L

    2013-09-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which a precise cause has not yet been identified. Standard CT or MRI evaluation does not demonstrate gross structural nervous system changes in ALS, so conventional neuroimaging techniques have provided little insight into the pathophysiology of this disease. Advanced neuroimaging techniques--such as structural MRI, diffusion tensor imaging and proton magnetic resonance spectroscopy--allow evaluation of alterations of the nervous system in ALS. These alterations include focal loss of grey and white matter and reductions in white matter tract integrity, as well as changes in neural networks and in the chemistry, metabolism and receptor distribution in the brain. Given their potential for investigation of both brain structure and function, advanced neuroimaging methods offer important opportunities to improve diagnosis, guide prognosis, and direct future treatment strategies in ALS. In this article, we review the contributions made by various advanced neuroimaging techniques to our understanding of the impact of ALS on different brain regions, and the potential role of such measures in biomarker development.

  17. INITIAL EXPERIENCE WITH TRANSPUPILLARY DIODE LASER PHOTOCOAGULATION FOR RETINAL DISEASES.

    PubMed

    Uhumwangho, O M; Iyiriaro, Iao

    2014-01-01

    Lasers are an invaluable treatment modality for the management of some retinovascular diseases. One of these lasers is the diode laser which is easy to procure and maintain. To review the outcomes of diode laser photocoagulation in patients with a variety of retinal conditions. A retrospective case series of all patients who had retinal laser photocoagulation between July 2012 and June 2014 with the semiconductor infrared diode laser was performed. Demographic and clinical data collected included age, sex, eye involved, visual acuity, diagnosis, associated systemic and ocular diseases, intra and post treatment findings, laser treatment parameters and follow up. A total of 22 eyes of 15 patients had diode laser treatment during the period under review comprising 8(53.3%) males and 7(46.7%) females with a mean age at presentation of 53.4±8.9 years. The indications for treatment were proliferative diabetic retinopathy in 18(81.8%) eyes of 11 patients, retinal vein occlusion in 2(9.1%) eyes of 2 patients and retinal breaks with lattice in 2(9.1%) eyes of 2 patients with fellow eye retinal detachment. Visual acuity in eyes with diabetic retinopathy improved in 9(50%) eyes, worsened in 3(16.7%) eyes and was unchanged/ stable in 6(33.3%) eyes. Regression of neovascularization was achieved in 2(100%) eyes with retinal vein occlusion. The retina of the 2(100%) eyes with breaks following retinopexy remained attached during the follow up period. The follow up period ranged from 2 days to 2 years with a mean duration of 13.5±15.8 months. The diode laser is an effective and beneficial treatment modality in the management of proliferative retinopathies and some retinal diseases.

  18. The role of air pollutants in initiating liver disease.

    PubMed

    Kim, Jong Won; Park, Surim; Lim, Chae Woong; Lee, Kyuhong; Kim, Bumseok

    2014-06-01

    Recent episodes of severe air pollution in eastern Asia have been reported in the scientific literature and news media. Therefore, there is growing concern about the systemic effects of air pollution on human health. Along with the other well-known harmful effects of air pollution, recently, several animal models have provided strong evidence that air pollutants can induce liver toxicity and act to accelerate liver inflammation and steatosis. This review briefly describes examples where exposure to air pollutants was involved in liver toxicity, focusing on how particulate matter (PM) or carbon black (CB) may be translocated from lung to liver and what liver diseases are closely associated with these air pollutants.

  19. Overview of Coronary Heart Disease Risk Initiatives in South Asia.

    PubMed

    Kalra, Ankur; Bhatt, Deepak L; Rajagopalan, Sanjay; Suri, Kunal; Mishra, Sundeep; Iqbal, Romaina; Virani, Salim S

    2017-06-01

    Cardiovascular disease (CVD) is now the leading cause of morbidity and mortality worldwide. Industrialization and economic growth have led to an unprecedented increment in the burden of CVD and their risk factors in less industrialized regions of the world. While there are abundant data on CVD and their risk factors from longitudinal cohort studies done in the West, good-quality data from South Asia are lacking. Several multi-institutional, observational, prospective registries, and epidemiologic cohorts in South Asia have been established to systematically evaluate the burden of CVD and their risk factors. The PINNACLE (Practice Innovation and Clinical Excellence) India Quality Improvement Program (PIQIP), the Kerala Acute Coronary Syndrome (ACS), and Trivandrum Heart Failure registries have focused on secondary prevention of CVD and performance measurement in both outpatient and inpatient settings, respectively. The Prospective Urban and Rural Epidemiology (PURE), Centre for Cardiometabolic Risk Reduction in South Asia (CARRS), and other epidemiologic and genetic studies have focused on primary prevention of CVD and evaluated variables such as environment, smoking, physical activity, health systems, food and nutrition policy, dietary consumption patterns, socioeconomic factors, and healthy neighborhoods. The international cardiovascular community has been responsive to a burgeoning cardiovascular disease burden in South Asia. Several collaborations have formed between the West (North America in particular) and South Asia to catalyze evidence-based and data-driven changes in the federal health policy in this part of the world to promote cardiovascular health and mitigate cardiovascular risk.

  20. 77 FR 31018 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ...] [FR Doc No: 2012-12675] DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial.... 92-463), the Centers for Disease Control and Prevention (CDC) announces the aforementioned meeting...

  1. 77 FR 5026 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Occupational... Section 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control...

  2. 78 FR 66938 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review Notice of Cancellation: This notice concerns.... Department of Health and Human Services, Centers for Disease Control and Prevention, from October 1-16,...

  3. 78 FR 66937 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Capacity...), the Centers for Disease Control and Prevention (CDC) announces the aforementioned SEP: Times and...

  4. 78 FR 66937 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Occupational... 10(a)(2) of the Federal Advisory Committee Act (Pub. L. 92-463), the Centers for Disease Control...

  5. 78 FR 66937 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-07

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review Notice of Cancellation: This notice concerns.... Department of Health and Human Services, Centers for Disease Control and Prevention, from October 1-16,...

  6. Testing for association with multiple traits in generalized estimation equations, with application to neuroimaging data.

    PubMed

    Zhang, Yiwei; Xu, Zhiyuan; Shen, Xiaotong; Pan, Wei

    2014-08-01

    There is an increasing need to develop and apply powerful statistical tests to detect multiple traits-single locus associations, as arising from neuroimaging genetics and other studies. For example, in the Alzheimer's Disease Neuroimaging Initiative (ADNI), in addition to genome-wide single nucleotide polymorphisms (SNPs), thousands of neuroimaging and neuropsychological phenotypes as intermediate phenotypes for Alzheimer's disease, have been collected. Although some classic methods like MANOVA and newly proposed methods may be applied, they have their own limitations. For example, MANOVA cannot be applied to binary and other discrete traits. In addition, the relationships among these methods are not well understood. Importantly, since these tests are not data adaptive, depending on the unknown association patterns among multiple traits and between multiple traits and a locus, these tests may or may not be powerful. In this paper we propose a class of data-adaptive weights and the corresponding weighted tests in the general framework of generalized estimation equations (GEE). A highly adaptive test is proposed to select the most powerful one from this class of the weighted tests so that it can maintain high power across a wide range of situations. Our proposed tests are applicable to various types of traits with or without covariates. Importantly, we also analytically show relationships among some existing and our proposed tests, indicating that many existing tests are special cases of our proposed tests. Extensive simulation studies were conducted to compare and contrast the power properties of various existing and our new methods. Finally, we applied the methods to an ADNI dataset to illustrate the performance of the methods. We conclude with the recommendation for the use of the GEE-based Score test and our proposed adaptive test for their high and complementary performance. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. The Human Connectome Project's neuroimaging approach.

    PubMed

    Glasser, Matthew F; Smith, Stephen M; Marcus, Daniel S; Andersson, Jesper L R; Auerbach, Edward J; Behrens, Timothy E J; Coalson, Timothy S; Harms, Michael P; Jenkinson, Mark; Moeller, Steen; Robinson, Emma C; Sotiropoulos, Stamatios N; Xu, Junqian; Yacoub, Essa; Ugurbil, Kamil; Van Essen, David C

    2016-08-26

    Noninvasive human neuroimaging has yielded many discoveries about the brain. Numerous methodological advances have also occurred, though inertia has slowed their adoption. This paper presents an integrated approach to data acquisition, analysis and sharing that builds upon recent advances, particularly from the Human Connectome Project (HCP). The 'HCP-style' paradigm has seven core tenets: (i) collect multimodal imaging data from many subjects; (ii) acquire data at high spatial and temporal resolution; (iii) preprocess data to minimize distortions, blurring and temporal artifacts; (iv) represent data using the natural geometry of cortical and subcortical structures; (v) accurately align corresponding brain areas across subjects and studies; (vi) analyze data using neurobiologically accurate brain parcellations; and (vii) share published data via user-friendly databases. We illustrate the HCP-style paradigm using existing HCP data sets and provide guidance for future research. Widespread adoption of this paradigm should accelerate progress in understanding the brain in health and disease.

  8. The Role of Air Pollutants in Initiating Liver Disease

    PubMed Central

    Kim, Jong Won; Park, Surim; Lim, Chae Woong; Lee, Kyuhong

    2014-01-01

    Recent episodes of severe air pollution in eastern Asia have been reported in the scientific literature and news media. Therefore, there is growing concern about the systemic effects of air pollution on human health. Along with the other well-known harmful effects of air pollution, recently, several animal models have provided strong evidence that air pollutants can induce liver toxicity and act to accelerate liver inflammation and steatosis. This review briefly describes examples where exposure to air pollutants was involved in liver toxicity, focusing on how particulate matter (PM) or carbon black (CB) may be translocated from lung to liver and what liver diseases are closely associated with these air pollutants. PMID:25071914

  9. Tinnitus: perspectives from human neuroimaging.

    PubMed

    Elgoyhen, Ana Belén; Langguth, Berthold; De Ridder, Dirk; Vanneste, Sven

    2015-10-01

    Tinnitus is the perception of phantom sound in the absence of a corresponding external source. It is a highly prevalent disorder, and most cases are caused by cochlear injury that leads to peripheral deafferentation, which results in adaptive changes in the CNS. In this article we critically assess the recent neuroimaging studies in individuals with tinnitus that suggest that the disorder is accompanied by functional and structural brain abnormalities in distributed auditory and non-auditory brain regions. Moreover, we consider how the identification of the neuronal mechanisms underlying the different forms of tinnitus would benefit from larger studies, replication and comprehensive clinical assessment of patients.

  10. A transformation similarity constraint for groupwise nonlinear registration in longitudinal neuroimaging studies

    NASA Astrophysics Data System (ADS)

    Fleishman, Greg M.; Gutman, Boris A.; Fletcher, P. Thomas; Thompson, Paul

    2015-03-01

    Patients with Alzheimer's disease and other brain disorders often show a similar spatial distribution of volume change throughout the brain over time, but this information is not yet used in registration algorithms to refine the quantification of change. Here, we develop a mathematical basis to incorporate that prior information into a longitudinal structural neuroimaging study. We modify the canonical minimization problem for non-linear registration to include a term that couples a collection of registrations together to enforce group similarity. More specifically, throughout the computation we maintain a group-level representation of the transformations and constrain updates to individual transformations to be similar to this representation. The derivations necessary to produce the Euler-Lagrange equations for the coupling term are presented and a gradient descent algorithm based on the formulation was implemented. We demonstrate using 57 longitudinal image pairs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) that longitudinal registration with such a groupwise coupling prior is more robust to noise in estimating change, suggesting such change maps may have several important applications.

  11. Neuroimaging Endophenotypes in Autism Spectrum Disorder

    PubMed Central

    Mahajan, Rajneesh; Mostofsky, Stewart H.

    2015-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has a strong genetic basis, and is heterogeneous in its etiopathogenesis and clinical presentation. Neuroimaging studies, in concert with neuropathological and clinical research, have been instrumental in delineating trajectories of development in children with ASD. Structural neuroimaging has revealed ASD to be a disorder with general and regional brain enlargement, especially in the frontotemporal cortices, while functional neuroimaging studies have highlighted diminished connectivity, especially between frontal-posterior regions. The diverse and specific neuroimaging findings may represent potential neuroendophenotypes, and may offer opportunities to further understand the etiopathogenesis of ASD, predict treatment response and lead to the development of new therapies. PMID:26234701

  12. Cognitive and neuroimaging predictors of instrumental activities of daily living.

    PubMed

    Cahn-Weiner, Deborah A; Farias, Sarah Tomaszewski; Julian, Laura; Harvey, Danielle J; Kramer, Joel H; Reed, Bruce R; Mungas, Dan; Wetzel, Margaret; Chui, Helena

    2007-09-01

    Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.

  13. Cognitive and neuroimaging predictors of instrumental activities of daily living

    PubMed Central

    Cahn-Weiner, Deborah A.; Farias, Sarah Tomaszewski; Julian, Laura; Harvey, Danielle J.; Kramer, Joel H.; Reed, Bruce R.; Mungas, Dan; Wetzel, Margaret; Chui, Helena

    2010-01-01

    Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis. PMID:17521485

  14. A review of neuroimaging findings in repetitive brain trauma.

    PubMed

    Koerte, Inga K; Lin, Alexander P; Willems, Anna; Muehlmann, Marc; Hufschmidt, Jakob; Coleman, Michael J; Green, Isobel; Liao, Huijun; Tate, David F; Wilde, Elisabeth A; Pasternak, Ofer; Bouix, Sylvain; Rathi, Yogesh; Bigler, Erin D; Stern, Robert A; Shenton, Martha E

    2015-05-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease confirmed at postmortem. Those at highest risk are professional athletes who participate in contact sports and military personnel who are exposed to repetitive blast events. All neuropathologically confirmed CTE cases, to date, have had a history of repetitive head impacts. This suggests that repetitive head impacts may be necessary for the initiation of the pathogenetic cascade that, in some cases, leads to CTE. Importantly, while all CTE appears to result from repetitive brain trauma, not all repetitive brain trauma results in CTE. Magnetic resonance imaging has great potential for understanding better the underlying mechanisms of repetitive brain trauma. In this review, we provide an overview of advanced imaging techniques currently used to investigate brain anomalies. We also provide an overview of neuroimaging findings in those exposed to repetitive head impacts in the acute/subacute and chronic phase of injury and in more neurodegenerative phases of injury, as well as in military personnel exposed to repetitive head impacts. Finally, we discuss future directions for research that will likely lead to a better understanding of the underlying mechanisms separating those who recover from repetitive brain trauma vs. those who go on to develop CTE.

  15. CSF biomarkers associated with disease heterogeneity in early Parkinson's disease: the Parkinson's Progression Markers Initiative study.

    PubMed

    Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S; Toledo, Jon B; Weintraub, Daniel; Galasko, Douglas R; Irwin, David J; Van Deerlin, Vivianna; Chen-Plotkin, Alice S; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W; Chowdhury, Sohini; Trojanowski, John Q; Shaw, Leslie M

    2016-06-01

    The development of biomarkers to predict the progression of Parkinson's disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson's Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1-42 (Aβ1-42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1-42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1-42, or highest t-tau/Aβ1-42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1-42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance.

  16. Neuroimaging findings in late-onset schizophrenia and bipolar disorder.

    PubMed

    Hahn, Changtae; Lim, Hyun Kook; Lee, Chang Uk

    2014-03-01

    In recent years, there has been an increasing interest in late-onset mental disorders. Among them, geriatric schizophrenia and bipolar disorder are significant health care risks and major causes of disability. We discussed whether late-onset schizophrenia (LOS) and late-onset bipolar (LOB) disorder can be a separate entity from early-onset schizophrenia (EOS) and early-onset bipolar (EOB) disorder in a subset of late-life schizophrenia or late-life bipolar disorder through neuroimaging studies. A literature search for imaging studies of LOS or LOB was performed in the PubMed database. Search terms used were "(imaging OR MRI OR CT OR SPECT OR DTI OR PET OR fMRI) AND (schizophrenia or bipolar disorder) AND late onset." Articles that were published in English before October 2013 were included. There were a few neuroimaging studies assessing whether LOS and LOB had different disease-specific neural substrates compared with EOS and EOB. These researches mainly observed volumetric differences in specific brain regions, white matter hyperintensities, diffusion tensor imaging, or functional neuroimaging to explore the differences between LOS and LOB and EOS and EOB. The aim of this review was to highlight the neural substrates involved in LOS and LOB through neuroimaging studies. The exploration of neuroanatomical markers may be the key to the understanding of underlying neurobiology in LOS and LOB.

  17. Neuroimaging Week: A Novel, Engaging, and Effective Curriculum for Teaching Neuroimaging to Junior Psychiatric Residents

    ERIC Educational Resources Information Center

    Downar, Jonathan; Krizova, Adriana; Ghaffar, Omar; Zaretsky, Ari

    2010-01-01

    Objective: Neuroimaging techniques are increasingly important in psychiatric research and clinical practice, but few postgraduate psychiatry programs offer formal training in neuroimaging. To address this need, the authors developed a course to prepare psychiatric residents to use neuroimaging techniques effectively in independent practice.…

  18. Neuroimaging Week: A Novel, Engaging, and Effective Curriculum for Teaching Neuroimaging to Junior Psychiatric Residents

    ERIC Educational Resources Information Center

    Downar, Jonathan; Krizova, Adriana; Ghaffar, Omar; Zaretsky, Ari

    2010-01-01

    Objective: Neuroimaging techniques are increasingly important in psychiatric research and clinical practice, but few postgraduate psychiatry programs offer formal training in neuroimaging. To address this need, the authors developed a course to prepare psychiatric residents to use neuroimaging techniques effectively in independent practice.…

  19. A simple tool for neuroimaging data sharing

    PubMed Central

    Haselgrove, Christian; Poline, Jean-Baptiste; Kennedy, David N.

    2014-01-01

    Data sharing is becoming increasingly common, but despite encouragement and facilitation by funding agencies, journals, and some research efforts, most neuroimaging data acquired today is still not shared due to political, financial, social, and technical barriers to sharing data that remain. In particular, technical solutions are few for researchers that are not a part of larger efforts with dedicated sharing infrastructures, and social barriers such as the time commitment required to share can keep data from becoming publicly available. We present a system for sharing neuroimaging data, designed to be simple to use and to provide benefit to the data provider. The system consists of a server at the International Neuroinformatics Coordinating Facility (INCF) and user tools for uploading data to the server. The primary design principle for the user tools is ease of use: the user identifies a directory containing Digital Imaging and Communications in Medicine (DICOM) data, provides their INCF Portal authentication, and provides identifiers for the subject and imaging session. The user tool anonymizes the data and sends it to the server. The server then runs quality control routines on the data, and the data and the quality control reports are made public. The user retains control of the data and may change the sharing policy as they need. The result is that in a few minutes of the user’s time, DICOM data can be anonymized and made publicly available, and an initial quality control assessment can be performed on the data. The system is currently functional, and user tools and access to the public image database are available at http://xnat.incf.org/. PMID:24904398

  20. Neuroimaging of Freezing of Gait

    PubMed Central

    Fasano, Alfonso; Herman, Talia; Tessitore, Alessandro; Strafella, Antonio P.; Bohnen, Nicolaas I.

    2015-01-01

    Abstract Functional brain imaging techniques appear ideally suited to explore the pathophysiology of freezing of gait (FOG). In the last two decades, techniques based on magnetic resonance or nuclear medicine imaging have found a number of structural changes and functional disconnections between subcortical and cortical regions of the locomotor network in patients with FOG. FOG seems to be related in part to disruptions in the “executive-attention” network along with regional tissue loss including the premotor area, inferior frontal gyrus, precentral gyrus, the parietal and occipital areas involved in visuospatial functions of the right hemisphere. Several subcortical structures have been also involved in the etiology of FOG, principally the caudate nucleus and the locomotor centers in the brainstem. Maladaptive neural compensation may present transiently in the presence of acute conflicting motor, cognitive or emotional stimulus processing, thus causing acute network overload and resulting in episodic impairment of stepping. In this review we will summarize the state of the art of neuroimaging research for FOG. We will also discuss the limitations of current approaches and delineate the next steps of neuroimaging research to unravel the pathophysiology of this mysterious motor phenomenon. PMID:25757831

  1. What's new in neuroimaging methods?

    PubMed Central

    Bandettini, Peter A.

    2009-01-01

    The rapid advancement of neuroimaging methodology and availability has transformed neuroscience research. The answers to many questions that we ask about how the brain is organized depend on the quality of data that we are able to obtain about the locations, dynamics, fluctuations, magnitudes, and types of brain activity and structural changes. In this review, an attempt is made to take a snapshot of the cutting edge of a small component of the very rapidly evolving field of neuroimaging. For each area covered, a brief context is provided along with a summary of a few of the current developments and issues. Then, several outstanding papers, published in the past year or so, are described, providing an example of the directions in which each area is progressing. The areas covered include functional MRI (fMRI), voxel based morphometry (VBM), diffusion tensor imaging (DTI), electroencephalography (EEG), magnetoencephalography (MEG), optical imaging, and positron emission tomography (PET). More detail is included on fMRI, as subsections include: functional MRI interpretation, new functional MRI contrasts, MRI technology, MRI paradigms and processing, and endogenous oscillations in functional MRI. PMID:19338512

  2. Neuroimaging in repetitive brain trauma.

    PubMed

    Ng, Thomas Sc; Lin, Alexander P; Koerte, Inga K; Pasternak, Ofer; Liao, Huijun; Merugumala, Sai; Bouix, Sylvain; Shenton, Martha E

    2014-01-01

    Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report.

  3. Neuroimaging in repetitive brain trauma

    PubMed Central

    2014-01-01

    Sports-related concussions are one of the major causes of mild traumatic brain injury. Although most patients recover completely within days to weeks, those who experience repetitive brain trauma (RBT) may be at risk for developing a condition known as chronic traumatic encephalopathy (CTE). While this condition is most commonly observed in athletes who experience repetitive concussive and/or subconcussive blows to the head, such as boxers, football players, or hockey players, CTE may also affect soldiers on active duty. Currently, the only means by which to diagnose CTE is by the presence of phosphorylated tau aggregations post-mortem. Non-invasive neuroimaging, however, may allow early diagnosis as well as improve our understanding of the underlying pathophysiology of RBT. The purpose of this article is to review advanced neuroimaging methods used to investigate RBT, including diffusion tensor imaging, magnetic resonance spectroscopy, functional magnetic resonance imaging, susceptibility weighted imaging, and positron emission tomography. While there is a considerable literature using these methods in brain injury in general, the focus of this review is on RBT and those subject populations currently known to be susceptible to RBT, namely athletes and soldiers. Further, while direct detection of CTE in vivo has not yet been achieved, all of the methods described in this review provide insight into RBT and will likely lead to a better characterization (diagnosis), in vivo, of CTE than measures of self-report. PMID:25031630

  4. Finger movement improves ankle control for gait initiation in patients with Parkinson's disease.

    PubMed

    Hiraoka, K; Kamata, N; Iwata, A; Minamida, F; Abe, K

    2008-01-01

    The purpose of this study was to investigate the effect of finger movement on ankle control for gait initiation in patients with Parkinson's disease (PD patients). The subjects were 13 PD patients and 6 age-matched healthy adults. The subjects moved fingers before or after gait initiation, or initiated gait without finger movement. Ankle joint movement in the stance leg was recorded to estimate the duration of ankle dorsiflexion (DIF duration), which reflects the degree of disturbance in ankle control for gait initiation in PD patients. In the PD patients with prolonged D/F duration, finger movement that preceded gait initiation shortened the D/F duration, but in the PD patients without prolonged D/F duration and in healthy subjects, the effect was not found. Accordingly, finger movement that precedes gait initiation improves ankle control for gait initiation in PD patients who suffer disturbance in ankle control for gait initiation.

  5. Effects of cognitive task on gait initiation in Parkinson disease: evidence of motor prioritization?

    PubMed

    Nocera, Joe R; Roemmich, Ryan; Elrod, Jonathan; Altmann, Lori J P; Hass, Chris J

    2013-01-01

    While much is known about the effects of dual tasking on cyclical and continuous motor performance (e.g., locomotion), there is a paucity of information on the effect of dual tasking on the initiation of movement. Therefore, the purpose of this study was to investigate the effect of a concurrent cognitive task on gait initiation in three groups: patients with Parkinson disease, healthy older adults, and healthy young adults. We examined the anticipatory postural adjustment displacements and velocities during single-task gait initiation as well as two dual-task conditions: (1) 0-back + gait initiation and (2) 2-back + gait initiation. The Parkinson disease group exhibited less anticipatory postural adjustment displacement and velocity than their aged-matched healthy peers and young adults during the single- and dual-task gait initiation settings (p < 0.05). Of interest was the finding of no additional effect on anticipatory postural adjustment displacement or velocity of gait initiation during the dual-task conditions in any group, including the Parkinson disease group. More traditionally studied gait/balance dual-task paradigms have demonstrated both motor and cognitive decline. Therefore, our results may suggest a prioritization of more "intentional" movement task (e.g., gait initiation) while dual tasking in Parkinson disease.

  6. Intergenerational Neuroimaging of Human Brain Circuitry.

    PubMed

    Ho, Tiffany C; Sanders, Stephan J; Gotlib, Ian H; Hoeft, Fumiko

    2016-10-01

    Neuroscientists are increasingly using advanced neuroimaging methods to elucidate the intergenerational transmission of human brain circuitry. This new line of work promises to shed light on the ontogeny of complex behavioral traits, including psychiatric disorders, and possible mechanisms of transmission. Here we highlight recent intergenerational neuroimaging studies and provide recommendations for future work.

  7. Neuroimaging and Research into Second Language Acquisition

    ERIC Educational Resources Information Center

    Sabourin, Laura

    2009-01-01

    Neuroimaging techniques are becoming not only more and more sophisticated but are also coming to be increasingly accessible to researchers. One thing that one should take note of is the potential of neuroimaging research within second language acquisition (SLA) to contribute to issues pertaining to the plasticity of the adult brain and to general…

  8. Neuroimaging and Research into Second Language Acquisition

    ERIC Educational Resources Information Center

    Sabourin, Laura

    2009-01-01

    Neuroimaging techniques are becoming not only more and more sophisticated but are also coming to be increasingly accessible to researchers. One thing that one should take note of is the potential of neuroimaging research within second language acquisition (SLA) to contribute to issues pertaining to the plasticity of the adult brain and to general…

  9. Neuroimaging of Cognitive Load in Instructional Multimedia

    ERIC Educational Resources Information Center

    Whelan, Robert R.

    2007-01-01

    This paper reviews research literature on cognitive load measurement in learning and neuroimaging, and describes a mapping between the main elements of cognitive load theory and findings in functional neuroanatomy. It is argued that these findings may lead to the improved measurement of cognitive load using neuroimaging. The paper describes how…

  10. 77 FR 22326 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... World Trade Center Health Registry (U50) Request for Applications (RFA), OH12-001, initial review. In... evaluation of applications received in response to ``Extension of the World Trade Center Health Registry (U50... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and...

  11. 78 FR 9926 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... Research Agreements Related to the World Trade Center Health Program (U01) PAR 12-126, initial review... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and... 6329. The place should read as follows: Place: Atlanta Marriott Century Center, 2000 Century Boulevard...

  12. 77 FR 44618 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-30

    ... in response to ``World Trade Center Health Program Outreach and Education Plan RFA-OH12-1201... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns the World Trade...

  13. 78 FR 6329 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... Research Agreements Related to the World Trade Center Health Program (U01) PAR 12-126, initial review. In... Trade Center Health Program (U01) PAR 12-126.'' Contact Person for More Information: Nina Turner, Ph.D... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and...

  14. 77 FR 291 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-04

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns National HIV...., February 29, 2012 (Closed). Contact Person For More Information: Amy Yang, Ph.D., Scientific Review Officer...

  15. 77 FR 34045 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-08

    ... HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel: Initial Review The meeting announced below concerns Cooperative Research... Control and Prevention (CDC) announces the aforementioned meeting: Times and Dates: 8 a.m.-5 p.m., July 17...

  16. 78 FR 78966 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review The meeting announced below concerns Capacity Building Assistance for High Impact...

  17. Commentary: Applications of functional neuroimaging to civil litigation of mild traumatic brain injury.

    PubMed

    Granacher, Robert P

    2008-01-01

    The current definition of mild traumatic brain injury (MTBI) is in flux. Presently, there are at least three working definitions of this disorder in the United States, with no clear consensus. Functional neuroimaging, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), initially showed promise in their ability to improve the diagnostic credibility of MTBI. Over the past decade, that promise has not been fulfilled and there is a paucity of quality studies or standards for the application of functional neuroimaging to traumatic brain injury, particularly in litigation. The legal profession is ahead of the science in this matter. The emergence of neurolaw is driving a growing use of functional neuroimaging, as a sole imaging modality, used by lawyers in an attempt to prove MTBI at trial. The medical literature on functional neuroimaging and its applications to MTBI is weak scientifically, sparse in quality publications, lacking in well-designed controlled studies, and currently does not meet the complete standards of Daubert v. Merrell Dow Pharmaceuticals, Inc., for introduction of scientific evidence at trial. At the present time, there is a clear lack of clinical correlation between functional neuroimaging of MTBI and behavioral, neuropsychological, or structural neuroimaging deficits. The use of SPECT or PET, without concurrent clinical correlation with structural neuroimaging (CT or MRI), is not recommended to be offered as evidence of MTBI in litigation.

  18. Structural neuroimaging in sport-related concussion.

    PubMed

    Bigler, Erin D

    2017-09-12

    Structural neuroimaging of athletes who have sustained a sports-related concussion (SRC) can be viewed as either standard clinical imaging or with advanced neuroimaging methods that quantitatively assess brain structure. Negative findings from conventional computed tomography (CT) or magnetic resonance imaging (MRI) are the norm in SRC. Nonetheless, these conventional measures remain the first line of neuroimaging of the athlete as they do detect clinically significant pathologies, when present, such as hemorrhagic abnormalities in the form of hematomas, contusions and mircobleeds along with regions of focal encephalomalacia or other signal abnormalities, with CT best capable of detecting skull fractures. However, advanced neuroimaging techniques hold particular promise in detecting subtle neuropathology in the athlete which standard clinical neuroimaging cannot. To best understand what conventional as well as quantitative neuroimaging methods are detecting in SRC, this review begins by covering basic neuroanatomical principles associated with mild traumatic brain injury (mTBI) and the brain regions most vulnerable to injury from SRC, as these regions define where advanced neuroimaging methods most likely detect abnormalities. Advanced MRI techniques incorporate quantitative metrics that include volume, shape, thickness along with diffusion parameters that provide a more fine-grained analysis of brain structure. With advancements in image analysis, multiple quantitative neuroimaging metrics now can be utilized in assessing SRC. Such multimodality approaches are particularly relevant and important for assessing white matter and network integrity of the brain following injury, including SRC. This review focuses just on the structural side of neuroimaging in SRC, but these techniques also are being integrated with functional neuroimaging, where the combination of the two approaches may provide superior methods in assessing the pathological effects of SRC. Copyright

  19. Neuroimaging of classic neuralgic amyotrophy.

    PubMed

    Lieba-Samal, Doris; Jengojan, Suren; Kasprian, Gregor; Wöber, Christian; Bodner, Gerd

    2016-12-01

    Neuralgic amyotrophy (NA) often imposes diagnostic problems. Recently, MRI and high-resolution ultrasound (HRUS) have proven useful in diagnosing peripheral nerve disorders. We performed a chart and imaging review of patients who were examined using neuroimaging and who were referred because of clinically diagnosed NA between March 1, 2014 and May 1, 2015. Six patients were included. All underwent HRUS, and 5 underwent MRI. Time from onset to evaluation ranged from 2 weeks to 6 months. HRUS showed segmental swelling of all clinically affected nerves/trunks. Atrophy of muscles was detected in those assessed >1 month after onset. MRI showed T2-weighted hyperintensity in all clinically affected nerves, except for the long thoracic nerve, and denervation edema of muscles. HRUS and MRI are valuable diagnostic tools in NA. This could change the diagnostic approach from one now focused on excluding other disorders to confirming NA through imaging markers. Muscle Nerve 54: 1079-1085, 2016. © 2016 Wiley Periodicals, Inc.

  20. Vitamin D deficiency and the lung: disease initiator or disease modifier?

    PubMed

    Foong, Rachel E; Zosky, Graeme R

    2013-07-26

    Vitamin D deficiency is a global public health problem and has been associated with an increased incidence and severity of many diseases including diseases of the respiratory system. These associations have largely been demonstrated epidemiologically and have formed the basis of the justification for a large number of clinical supplementation trials with a view to improving disease outcomes. However, the trials that have been completed to date and the ongoing experimental studies that have attempted to demonstrate a mechanistic link between vitamin D deficiency and lung disease have been disappointing. This observation raises many questions regarding whether vitamin D deficiency is truly associated with disease pathogenesis, is only important in the exacerbation of disease or is simply an indirect biomarker of other disease mechanisms? In this review, we will briefly summarize our current understanding of the role of vitamin D in these processes with a focus on lung disease.

  1. Degree of host susceptibility in the initial disease outbreak influences subsequent epidemic spread.

    PubMed

    Severns, Paul M; Estep, Laura K; Sackett, Kathryn E; Mundt, Christopher C

    2014-12-01

    Disease epidemics typically begin as an outbreak of a relatively small, spatially explicit population of infected individuals (focus), in which disease prevalence increases and rapidly spreads into the uninfected, at-risk population. Studies of epidemic spread typically address factors influencing disease spread through the at-risk population, but the initial outbreak may strongly influence spread of the subsequent epidemic.We initiated wheat stripe rust Puccinia striiformis f. sp. tritici epidemics to assess the influence of the focus on final disease prevalence when the degree of disease susceptibility differed between the at-risk and focus populations.When the focus/at-risk plantings consisted of partially genetic resistant and susceptible cultivars, final disease prevalence was statistically indistinguishable from epidemics produced by the focus cultivar in monoculture. In these experimental epidemics, disease prevalence was not influenced by the transition into an at-risk population that differed in disease susceptibility. Instead, the focus appeared to exert a dominant influence on the subsequent epidemic.Final disease prevalence was not consistently attributable to either the focus or the at-risk population when focus/at-risk populations were planted in a factorial set-up with a mixture (~28% susceptible and 72% resistant) and susceptible individuals. In these experimental epidemics, spatial heterogeneity in disease susceptibility within the at-risk population appeared to counter the dominant influence of the focus.Cessation of spore production from the focus (through fungicide/glyphosate application) after 1.3 generations of stripe rust spread did not reduce final disease prevalence, indicating that the focus influence on disease spread is established early in the epidemic.Synthesis and applications. Our experiments indicated that outbreak conditions can be highly influential on epidemic spread, even when disease resistance in the at-risk population is

  2. Neuroimaging Craving: Urge Intensity Matters

    PubMed Central

    Wilson, Stephen J.; Sayette, Michael A.

    2015-01-01

    Functional neuroimaging has become an increasingly common tool for studying drug craving. Furthermore, functional neuroimaging studies, which have addressed an incredibly diverse array of questions regarding the nature and treatment of craving, have had a substantial impact on theoretical models of addiction. Here, we offer three points related to this sizeable and influential body of research. First, we assert that the craving most investigators seek to study represents not just a desire but a strong desire to use drugs, consistent with prominent theoretical and clinical descriptions of craving. Second, we highlight that, despite the clear conceptual and clinical emphasis on craving as an intense desire, brain imaging studies often have been explicitly designed in a way that reduces the ability to generate powerful cravings. We illustrate this point by reviewing the peak urge levels endorsed by participants in functional magnetic resonance imaging (fMRI) studies of cigarette craving in nicotine-deprived versus nondeprived smokers. Third, we suggest that brain responses measured during mild states of desire (such as following satiety) differ in fundamental ways from those measured during states of overpowering desire (i.e., craving) to use drugs. We support this position by way of a meta-analysis revealing that fMRI cue exposure studies using nicotine-deprived smokers have produced different patterns of brain activation than those using nondeprived smokers. Regarding brain imaging studies of craving, intensity of the urges matter, and more explicit attention to urge intensity in future work has the potential to yield valuable information about the nature of craving. PMID:25073979

  3. Neuroimaging craving: urge intensity matters.

    PubMed

    Wilson, Stephen J; Sayette, Michael A

    2015-02-01

    Functional neuroimaging has become an increasingly common tool for studying drug craving. Furthermore, functional neuroimaging studies, which have addressed an incredibly diverse array of questions regarding the nature and treatment of craving, have had a substantial impact on theoretical models of addiction. Here, we offer three points related to this sizeable and influential body of research. First, we assert that the craving most investigators seek to study represents not just a desire but a strong desire to use drugs, consistent with prominent theoretical and clinical descriptions of craving. Secondly, we highlight that, despite the clear conceptual and clinical emphasis on craving as an intense desire, brain imaging studies often have been designed explicitly in a way that reduces the ability to generate powerful cravings. We illustrate this point by reviewing the peak urge levels endorsed by participants in functional magnetic resonance imaging (fMRI) studies of cigarette craving in nicotine-deprived versus non-deprived smokers. Thirdly, we suggest that brain responses measured during mild states of desire (such as following satiety) differ in fundamental ways from those measured during states of overpowering desire (i.e. craving) to use drugs. We support this position by way of a meta-analysis revealing that fMRI cue exposure studies using nicotine-deprived smokers have produced different patterns of brain activation to those using non-deprived smokers. Regarding brain imaging studies of craving, intensity of the urges matter, and more explicit attention to urge intensity in future work has the potential to yield valuable information about the nature of craving. © 2014 Society for the Study of Addiction.

  4. Effects of auditory cues on gait initiation and turning in patients with Parkinson's disease.

    PubMed

    Gómez-González, J; Martín-Casas, P; Cano-de-la-Cuerda, R

    2016-12-08

    To review the available scientific evidence about the effectiveness of auditory cues during gait initiation and turning in patients with Parkinson's disease. We conducted a literature search in the following databases: Brain, PubMed, Medline, CINAHL, Scopus, Science Direct, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Library Plus, CENTRAL, Trip Database, PEDro, DARE, OTseeker, and Google Scholar. We included all studies published between 2007 and 2016 and evaluating the influence of auditory cues on independent gait initiation and turning in patients with Parkinson's disease. The methodological quality of the studies was assessed with the Jadad scale. We included 13 studies, all of which had a low methodological quality (Jadad scale score≤2). In these studies, high-intensity, high-frequency auditory cues had a positive impact on gait initiation and turning. More specifically, they 1) improved spatiotemporal and kinematic parameters; 2) decreased freezing, turning duration, and falls; and 3) increased gait initiation speed, muscle activation, and gait speed and cadence in patients with Parkinson's disease. We need studies of better methodological quality to establish the Parkinson's disease stage in which auditory cues are most beneficial, as well as to determine the most effective type and frequency of the auditory cue during gait initiation and turning in patients with Parkinson's disease. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. How Can Functional Neuroimaging Inform Cognitive Theories?

    PubMed

    Coltheart, Max

    2013-01-01

    Work on functional neuroimaging of cognition falls into two categories. The first aims at localizing specific cognitive subsystems in specific brain regions. In this research, the cognitive subsystems in question need to be defined independently of the neuroimaging data because the interpretation of the data requires such definition; so functional neuroimaging is informed by cognitive theories rather than informing them. The second category uses neuroimaging data to test cognitive theories. As cognitive theories are expressed in cognitive terms, such theories have to be embellished by explicit proposals about relationships between cognition and the brain if they are to become capable of generating predictions about the results of experiments that use functional neuroimaging. Whether functional neuroimaging can succeed in informing a cognitive theory depends critically upon the plausibility of such supplementary proposals. It is also critical to avoid the "consistency fallacy." When neuroimaging data from an experiment are consistent with predictions from a particular cognitive theory, this cannot be offered as evidence in support of that theory unless it can be shown that there were possible other outcomes of the experiment that are inconsistent with the theory-outcomes that would have falsified predictions from the theory had they been obtained. © The Author(s) 2013.

  6. Visual Attention and the Neuroimage Bias

    PubMed Central

    Baker, D. A.; Schweitzer, N. J.; Risko, Evan F.; Ware, Jillian M.

    2013-01-01

    Several highly-cited experiments have presented evidence suggesting that neuroimages may unduly bias laypeople’s judgments of scientific research. This finding has been especially worrisome to the legal community in which neuroimage techniques may be used to produce evidence of a person’s mental state. However, a more recent body of work that has looked directly at the independent impact of neuroimages on layperson decision-making (both in legal and more general arenas), and has failed to find evidence of bias. To help resolve these conflicting findings, this research uses eye tracking technology to provide a measure of attention to different visual representations of neuroscientific data. Finding an effect of neuroimages on the distribution of attention would provide a potential mechanism for the influence of neuroimages on higher-level decisions. In the present experiment, a sample of laypeople viewed a vignette that briefly described a court case in which the defendant’s actions might have been explained by a neurological defect. Accompanying these vignettes was either an MRI image of the defendant’s brain, or a bar graph depicting levels of brain activity–two competing visualizations that have been the focus of much of the previous research on the neuroimage bias. We found that, while laypeople differentially attended to neuroimagery relative to the bar graph, this did not translate into differential judgments in a way that would support the idea of a neuroimage bias. PMID:24040251

  7. Neuroimaging week: a novel, engaging, and effective curriculum for teaching neuroimaging to junior psychiatric residents.

    PubMed

    Downar, Jonathan; Krizova, Adriana; Ghaffar, Omar; Zaretsky, Ari

    2010-01-01

    Neuroimaging techniques are increasingly important in psychiatric research and clinical practice, but few postgraduate psychiatry programs offer formal training in neuroimaging. To address this need, the authors developed a course to prepare psychiatric residents to use neuroimaging techniques effectively in independent practice. The authors present the format and curriculum of a highly interactive, 5-day intensive neuroimaging course, taught by psychiatry, neurology, radiology, nuclear medicine, and sleep medicine staff, covering psychiatrically oriented neuroanatomy; neuroimaging techniques and principles; clinical skills, including interpretation of computed tomography and MRI in neuropsychiatric cases; and formal approaches to critiquing neuroimaging research and applying its findings to clinical practice. Detailed questionnaires assessed the subjective and objective impact of the course on residents' knowledge of, and attitudes toward, neuroimaging in psychiatry before and after the course. Twenty-five first-year residents completed the questionnaires. Participants were enthusiastic about the content and interested in improving their skills in interpreting clinical neuroimaging studies. By the end of the course, residents also reported large gains in subjective comfort level with neuroimaging literature appraisal and functional neuroanatomy and believed that the course was effective in meeting their own specific learning objectives. Objective measures showed significant gains in most areas of the curriculum. This short, intensive course effectively teaches clinically oriented neuroimaging principles to psychiatric residents and can be readily adapted to other postgraduate programs or continuing medical education.

  8. Second-opinion interpretations of neuroimaging studies by oncologic neuroradiologists can help reduce errors in cancer care.

    PubMed

    Hatzoglou, Vaios; Omuro, Antonio M; Haque, Sofia; Khakoo, Yasmin; Ganly, Ian; Oh, Jung Hun; Shukla-Dave, Amita; Fatovic, Robin; Gaal, Joshua; Holodny, Andrei I

    2016-09-01

    The purpose of this study was to investigate the utility and clinical impact of second-opinion interpretations of outside neuroimaging studies by oncologic neuroradiologists at a National Cancer Institute-designated cancer center. We performed a retrospective analysis of initial outside and second-opinion radiology reports from 300 computed tomography and magnetic resonance imaging studies and identified cases with discrepancies between the two reports. An adult neuro-oncologist, pediatric neuro-oncologist, and head and neck surgeon reviewed each pair of discrepant reports based on their area of expertise, patient age, and the type of study performed. The clinicians were blinded to the origin of each report and recorded whether the differences in the reports would have led to a change in patient management and/or disease staging. Histopathologic analysis, clinical assessment, and/or minimum 3-month imaging follow-up served as the reference standards to establish which of the 2 reports was correct. Among the 283 cases that met our study criteria, there were 55 neuroimaging studies with disagreements (19%) between the initial outside report and second-opinion interpretation. Patient management and/or disease stage would have been altered in 42 of 283 cases (15%) based on report differences as determined by the 2 neuro-oncologists and the surgeon participating in the study. Sufficient follow-up was available in 35 of 42 cases (83%). The second-opinion interpretation was correct 100% of the time (35/35). Second-opinion interpretations of neuroimaging studies by subspecialized oncologic neuroradiologists provide added value by reducing error and optimizing the care of cancer patients. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2708-2714. © 2016 American Cancer Society. © 2016 American Cancer Society.

  9. Burning Tongue as Initial Presentation of Celiac Disease in an Elderly Woman: A Case Report.

    PubMed

    Sherman, Andrea; Zamulko, Alla

    2016-06-01

    There are few reports in the literature where celiac disease presents with tongue manifestations, although atypical presentations of celiac disease are not uncommon. This case report highlights an atypical presentation of celiac disease in an elderly female. Our patient presented to clinic with complaints of a burning tongue for the past two years as well as occasional loose stools and fatigue. Work-up revealed iron deficiency anemia, zinc deficiency and an abnormal celiac panel. Complete symptom improvement was noted by 10 weeks into the initiation of a gluten free diet. Celiac disease can present at any age and should be considered as a differential in findings of malabsorption and gastrointestinal symptoms.

  10. Homocystinuria: Diagnosis and Neuroimaging Findings of Iranian Pediatric patients.

    PubMed

    Karimzadeh, Parvaneh; Jafari, Narjes; Alai, MohammadReza; Jabbehdari, Sayena; Nejad Biglari, Habibeh

    2015-01-01

    Homocystinuria is a neurometabolic diseases characterized by symptoms include Neurodevelopmental delay, lens dislocation, long limbs and thrombosis. The patients who were diagnosed as homocystinuria marfaniod habits, seizure in the Neurology Department of Mofid Children's Hospital in Tehran, Iran between 2004 and 2014 were included in our study. The disorder was confirmed by clinical andneuroimaging findings along withneurometabolic and genetic assessment fromreference laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 20 patients with homocystinuria. A total of 75% of patients were offspring from consanguineous marriages. A total of 95% of patients had a history of developmental delay and 40% had developmental regression. A total of 75% had seizures from these 45% showed refractory seizures. Seizures among 13 patients werecontrolled with suitable homocystinuria treatment. The patients with homocystinuriawere followed for approximately 10 years and the follow-ups showed that the patients with an early diagnosis and treatment had more favorable clinical responses for growth index, controlled refractory seizures, neurodevelopmental status, and neuroimaging findings. Neuroimaging findings include brain atrophy and/or white matter involvement. According to the results of this study, we suggest that early assessment and detectionplayan important role in the prevention of disease progression and clinical signs. Homocystinuria in patients with a positive family history, developmental delays, or regression, refractory, or recurrent seizures should take precedence over other causes.

  11. Homocystinuria: Diagnosis and Neuroimaging Findings of Iranian Pediatric patients

    PubMed Central

    KARIMZADEH, Parvaneh; JAFARI, Narjes; ALAI, MohammadReza; JABBEHDARI, Sayena; NEJAD BIGLARI, Habibeh

    2015-01-01

    Objective Homocystinuria is a neurometabolic diseases characterized by symptoms include Neurodevelopmental delay, lens dislocation, long limbs and thrombosis. Materials & Methods The patients who were diagnosed as homocystinuria marfaniod habits, seizure in the Neurology Department of Mofid Children’s Hospital in Tehran, Iran between 2004 and 2014 were included in our study. The disorder was confirmed by clinical andneuroimaging findings along withneurometabolic and genetic assessment fromreference laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 20 patients with homocystinuria. Results A total of 75% of patients were offspring from consanguineous marriages. A total of 95% of patients had a history of developmental delay and 40% had developmental regression. A total of 75% had seizures from these 45% showed refractory seizures. Seizures among 13 patients werecontrolled with suitable homocystinuria treatment. The patients with homocystinuriawere followed for approximately 10 years and the follow-ups showed that the patients with an early diagnosis and treatment had more favorable clinical responses for growth index, controlled refractory seizures, neurodevelopmental status, and neuroimaging findings. Neuroimaging findings include brain atrophy and/or white matter involvement. Conclusion According to the results of this study, we suggest that early assessment and detectionplayan important role in the prevention of disease progression and clinical signs. Homocystinuria in patients with a positive family history, developmental delays, or regression, refractory, or recurrent seizures should take precedence over other causes. PMID:25767545

  12. The role of neuroimaging in the diagnosis of headache disorders

    PubMed Central

    Obermann, Mark

    2013-01-01

    Headache is a common clinical feature in patients in the emergency room and in general neurology clinics. For physicians not experienced in headache disorders it might be difficult sometimes to decide in which patients neuroimaging is necessary to diagnose an underlying brain pathology and in which patients cerebral imaging is unnecessary. Most patients presenting to the primary-care physician with a nonacute headache and no further neurological signs or symptoms will not be suffering from an underlying serious condition. This review focuses on the main primary headache diseases, including migraine, tension-type headache and cluster headache, as well as frequent secondary headache entities with common clinical presentation and appropriate diagnostic and therapeutic algorithms to help guide the decision on the utilization of neuroimaging in the diagnostic workup. PMID:24228072

  13. The prenatal origin of hemispheric asymmetry: an in utero neuroimaging study.

    PubMed

    Kasprian, Gregor; Langs, Georg; Brugger, Peter C; Bittner, Mario; Weber, Michael; Arantes, Mavilde; Prayer, Daniela

    2011-05-01

    Anatomical and functional hemispheric lateralization originates from differential gene expression and leads to asymmetric structural brain development, which initially appears in the perisylvian regions by 26 gestational weeks (GWs). In this in vivo neuroimaging study, we demonstrated a predominant pattern of temporal lobe (TL) asymmetry in a large cohort of human fetuses between 18 and 37 GWs. Over two-thirds of fetuses showed a larger, left-sided TL, combined with the earlier appearance of the right superior temporal sulcus by 23 GWs (vs. 25 GWs on the left side), which was also deeper than its left counterpart in the majority of cases (94.2%). Shape analysis detected highly significant differences in the contour of the right and left TLs by 20 GWs. Thus, fetal hemispheric asymmetry can be detected in utero, opening new diagnostic possibilities for the assessment of diseases that are believed to be linked to atypical hemispheric lateralization.

  14. Workflow-based approaches to neuroimaging analysis.

    PubMed

    Fissell, Kate

    2007-01-01

    Analysis of functional and structural magnetic resonance imaging (MRI) brain images requires a complex sequence of data processing steps to proceed from raw image data to the final statistical tests. Neuroimaging researchers have begun to apply workflow-based computing techniques to automate data analysis tasks. This chapter discusses eight major components of workflow management systems (WFMSs): the workflow description language, editor, task modules, data access, verification, client, engine, and provenance, and their implementation in the Fiswidgets neuroimaging workflow system. Neuroinformatics challenges involved in applying workflow techniques in the domain of neuroimaging are discussed.

  15. Predicting Meningioma Consistency on Preoperative Neuroimaging Studies

    PubMed Central

    Shiroishi, Mark S.; Cen, Steven Y.; Tamrazi, Benita; D'Amore, Francesco; Lerner, Alexander; King, Kevin S.; Kim, Paul E.; Law, Meng; Hwang, Darryl H.; Boyko, Orest B.; Liu, C. Jason

    2016-01-01

    Synopsis This article provides an overview of the neuroimaging literature focused on pre-operative prediction of meningioma consistency. A validated, non-invasive neuroimaging method to predict tumor consistency can provide valuable information regarding neurosurgical planning and patient counseling. Most of the neuroimaging literature indicates conventional MRI using T2-weighted imaging (T2WI) may be helpful to predict meningioma consistency, however, further rigorous validation is necessary. Much less is known about advanced MRI techniques such as diffusion MRI, MR elastography (MRE) and MR spectroscopy (MRS). Of these methods, MRE and DTI appear particularly promising. PMID:27012379

  16. How can neuroimaging facilitate the diagnosis and stratification of patients with psychosis?

    PubMed Central

    Kempton, Matthew J.; McGuire, Philip

    2015-01-01

    Early diagnosis and treatment of patients with psychosis are associated with improved outcome in terms of future functioning, symptoms and treatment response. Identifying neuroimaging biomarkers for illness onset and treatment response would lead to immediate clinical benefits. In this review we discuss if neuroimaging may be utilised to diagnose patients with psychosis, predict those who will develop the illness in those at high risk, and stratify patients. State-of-the-art developments in the field are critically examined including multicentre studies, longitudinal designs, multimodal imaging and machine learning as well as some of the challenges in utilising future neuroimaging biomarkers in clinical trials. As many of these developments are already being applied in neuroimaging studies of Alzheimer׳s disease, we discuss what lessons have been learned from this field and how they may be applied to research in psychosis. PMID:25092428

  17. How can neuroimaging facilitate the diagnosis and stratification of patients with psychosis?

    PubMed

    Kempton, Matthew J; McGuire, Philip

    2015-05-01

    Early diagnosis and treatment of patients with psychosis are associated with improved outcome in terms of future functioning, symptoms and treatment response. Identifying neuroimaging biomarkers for illness onset and treatment response would lead to immediate clinical benefits. In this review we discuss if neuroimaging may be utilised to diagnose patients with psychosis, predict those who will develop the illness in those at high risk, and stratify patients. State-of-the-art developments in the field are critically examined including multicentre studies, longitudinal designs, multimodal imaging and machine learning as well as some of the challenges in utilising future neuroimaging biomarkers in clinical trials. As many of these developments are already being applied in neuroimaging studies of Alzheimer's disease, we discuss what lessons have been learned from this field and how they may be applied to research in psychosis. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Predictors of time to initiation of symptomatic therapy in early Parkinson's disease.

    PubMed

    Simuni, Tanya; Long, Jeffrey D; Caspell-Garcia, Chelsea; Coffey, Christopher S; Lasch, Shirley; Tanner, Caroline M; Jennings, Danna; Kieburtz, Karl D; Marek, Kenneth

    2016-07-01

    To determine clinical and biological variables that predict time to initiation of symptomatic therapy in de novo Parkinson's disease patients. Parkinson's Progression Markers Initiative is a longitudinal case-control study of de novo, untreated Parkinson's disease participants at enrolment. Participants contribute a wide range of motor and non-motor measures, including biofluids and imaging biomarkers. The machine learning method of random survival forests was used to examine the ability of baseline variables to predict time to initiation of symptomatic therapy since study enrollment (baseline). There were 423 PD participants enrolled in PPMI and 33 initial baseline variables. Cross-validation results showed that the three-predictor subset of disease duration (time from diagnosis to enrollment), the modified Schwab and England activities of daily living scale, and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score modestly predicted time to initiation of symptomatic therapy (C = 0.70, pseudo-R (2) = 0.13). Prediction using the three variables was similar to using the entire set of 33. None of the biological variables increased accuracy of the prediction. A prognostic index for time to initiation of symptomatic therapy was created using the linear and nonlinear effects of the three top variables based on a post hoc Cox model. Our findings using a novel machine learning method support previously reported clinical variables that predict time to initiation of symptomatic therapy. However, the inclusion of biological variables did not increase prediction accuracy. Our prognostic index constructed, based on the group-level survival curve can provide an indication of the risk of initiation of ST for PD patients based on functions of the three top predictors.

  19. The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep phenotyping of Alzheimer’s disease biomarkers in down syndrome

    PubMed Central

    Rafii, Michael S.; Wishnek, Hannah; Brewer, James B.; Donohue, Michael C.; Ness, Seth; Mobley, William C.; Aisen, Paul S.; Rissman, Robert A.

    2015-01-01

    To gain further knowledge on the preclinical phase of Alzheimer’s disease (AD), we sought to characterize cognitive performance, neuroimaging and plasma-based AD biomarkers in a cohort of non-demented adults with down syndrome (DS). The goal of the down syndrome biomarker Initiative (DSBI) pilot is to test feasibility of this approach for future multicenter studies. We enrolled 12 non-demented participants with DS between the ages of 30–60 years old. Participants underwent extensive cognitive testing, volumetric MRI, amyloid positron emission tomography (PET; 18F-florbetapir), fluorodeoxyglucose (FDG) PET (18F-fluorodeoxyglucose) and retinal amyloid imaging. In addition, plasma beta-amyloid (Aβ) species were measured and Apolipoprotein E (ApoE) genotyping was performed. Results from our multimodal analysis suggest greater hippocampal atrophy with amyloid load. Additionally, we identified an inverse relationship between amyloid load and regional glucose metabolism. Cognitive and functional measures did not correlate with amyloid load in DS but did correlate with regional FDG PET measures. Biomarkers of AD can be readily studied in adults with DS as in other preclinical AD populations. Importantly, all subjects in this feasibility study were able to complete all test procedures. The data indicate that a large, multicenter longitudinal study is feasible to better understand the trajectories of AD biomarkers in this enriched population. This trial is registered with ClinicalTrials.gov, number NCT02141971. PMID:26441570

  20. Developments in functional neuroimaging techniques

    SciTech Connect

    Aine, C.J.

    1995-03-01

    A recent review of neuroimaging techniques indicates that new developments have primarily occurred in the area of data acquisition hardware/software technology. For example, new pulse sequences on standard clinical imagers and high-powered, rapidly oscillating magnetic field gradients used in echo planar imaging (EPI) have advanced MRI into the functional imaging arena. Significant developments in tomograph design have also been achieved for monitoring the distribution of positron-emitting radioactive tracers in the body (PET). Detector sizes, which pose a limit on spatial resolution, have become smaller (e.g., 3--5 mm wide) and a new emphasis on volumetric imaging has emerged which affords greater sensitivity for determining locations of positron annihilations and permits smaller doses to be utilized. Electromagnetic techniques have also witnessed growth in the ability to acquire data from the whole head simultaneously. EEG techniques have increased their electrode coverage (e.g., 128 channels rather than 16 or 32) and new whole-head systems are now in use for MEG. But the real challenge now is in the design and implementation of more sophisticated analyses to effectively handle the tremendous amount of physiological/anatomical data that can be acquired. Furthermore, such analyses will be necessary for integrating data across techniques in order to provide a truly comprehensive understanding of the functional organization of the human brain.

  1. Functional near-infrared neuroimaging.

    PubMed

    Izzetoglu, Kurtulus; Bunce, Scott; Izzetoglu, Meltem; Onaral, Banu; Pourrezaei, Kambiz

    2004-01-01

    Functional near-infrared (fNIR) spectroscopy is a wearable neuroimaging device that enables the continuous, non-invasive, and portable monitoring of changes in blood oxygen and blood volume related to human brain function. Over the last three years, studies in the laboratory and under field conditions have established the positive correlation between a participant's performance and oxygenation responses as a function of task load. Our findings indicate that fNIR can effectively monitor attention and working memory in real-life situations. These experimental outcomes compare favorably with functional magnetic resonance imaging (fMRI) studies, and in particular, with the blood oxygenation level dependent (BOLD) signal. The capacity to monitor brain hemodynamics with a wearable device holds promise for the use of fNIR in the creation of a symbiotic relationship between the user and his/her everyday environment. Moreover, under operational conditions, the fNIR system is amenable to integration with other established physiological and neurobehavioral measures, including EEG, eye tracking, pupil reflex, heart rate variability, respiration and electrodermal activity.

  2. Molecular Neuroimaging in Posttraumatic Stress Disorder

    PubMed Central

    Im, Jooyeon Jamie; Namgung, Eun; Choi, Yejee; Kim, Jung Yoon; Rhie, Sandy Jeong

    2016-01-01

    Over the past decade, an increasing number of neuroimaging studies have provided insight into the neurobiological mechanisms of posttraumatic stress disorder (PSTD). In particular, molecular neuroimaging techniques have been employed in examining metabolic and neurochemical processes in PTSD. This article reviews molecular neuroimaging studies in PTSD and focuses on findings using three imaging modalities including positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS). Although there were some inconsistences in the findings, patients with PTSD showed altered cerebral metabolism and perfusion, receptor bindings, and metabolite profiles in the limbic regions, medial prefrontal cortex, and temporal cortex. Studies that have investigated brain correlates of treatment response are also reviewed. Lastly, the limitations of the molecular neuroimaging studies and potential future research directions are discussed. PMID:28035179

  3. Ethics of neuroimaging after serious brain injury

    PubMed Central

    2014-01-01

    Background Patient outcome after serious brain injury is highly variable. Following a period of coma, some patients recover while others progress into a vegetative state (unresponsive wakefulness syndrome) or minimally conscious state. In both cases, assessment is difficult and misdiagnosis may be as high as 43%. Recent advances in neuroimaging suggest a solution. Both functional magnetic resonance imaging and electroencephalography have been used to detect residual cognitive function in vegetative and minimally conscious patients. Neuroimaging may improve diagnosis and prognostication. These techniques are beginning to be applied to comatose patients soon after injury. Evidence of preserved cognitive function may predict recovery, and this information would help families and health providers. Complex ethical issues arise due to the vulnerability of patients and families, difficulties interpreting negative results, restriction of communication to “yes” or “no” answers, and cost. We seek to investigate ethical issues in the use of neuroimaging in behaviorally nonresponsive patients who have suffered serious brain injury. The objectives of this research are to: (1) create an approach to capacity assessment using neuroimaging; (2) develop an ethics of welfare framework to guide considerations of quality of life; (3) explore the impact of neuroimaging on families; and, (4) analyze the ethics of the use of neuroimaging in comatose patients. Methods/Design Our research program encompasses four projects and uses a mixed methods approach. Project 1 asks whether decision making capacity can be assessed in behaviorally nonresponsive patients. We will specify cognitive functions required for capacity and detail their assessment. Further, we will develop and pilot a series of scenarios and questions suitable for assessing capacity. Project 2 examines the ethics of welfare as a guide for neuroimaging. It grounds an obligation to explore patients’ interests, and we

  4. Ethics of neuroimaging after serious brain injury.

    PubMed

    Weijer, Charles; Peterson, Andrew; Webster, Fiona; Graham, Mackenzie; Cruse, Damian; Fernández-Espejo, Davinia; Gofton, Teneille; Gonzalez-Lara, Laura E; Lazosky, Andrea; Naci, Lorina; Norton, Loretta; Speechley, Kathy; Young, Bryan; Owen, Adrian M

    2014-05-20

    Patient outcome after serious brain injury is highly variable. Following a period of coma, some patients recover while others progress into a vegetative state (unresponsive wakefulness syndrome) or minimally conscious state. In both cases, assessment is difficult and misdiagnosis may be as high as 43%. Recent advances in neuroimaging suggest a solution. Both functional magnetic resonance imaging and electroencephalography have been used to detect residual cognitive function in vegetative and minimally conscious patients. Neuroimaging may improve diagnosis and prognostication. These techniques are beginning to be applied to comatose patients soon after injury. Evidence of preserved cognitive function may predict recovery, and this information would help families and health providers. Complex ethical issues arise due to the vulnerability of patients and families, difficulties interpreting negative results, restriction of communication to "yes" or "no" answers, and cost. We seek to investigate ethical issues in the use of neuroimaging in behaviorally nonresponsive patients who have suffered serious brain injury. The objectives of this research are to: (1) create an approach to capacity assessment using neuroimaging; (2) develop an ethics of welfare framework to guide considerations of quality of life; (3) explore the impact of neuroimaging on families; and, (4) analyze the ethics of the use of neuroimaging in comatose patients. Our research program encompasses four projects and uses a mixed methods approach. Project 1 asks whether decision making capacity can be assessed in behaviorally nonresponsive patients. We will specify cognitive functions required for capacity and detail their assessment. Further, we will develop and pilot a series of scenarios and questions suitable for assessing capacity. Project 2 examines the ethics of welfare as a guide for neuroimaging. It grounds an obligation to explore patients' interests, and we explore conceptual issues in the

  5. Neonatal Neuroimaging Findings in Inborn Errors of Metabolism

    PubMed Central

    Poretti, Andrea; Blaser, Susan I.; Lequin, Maarten H.; Fatemi, Ali; Meoded, Avner; Northington, Frances J.; Boltshauser, Eugen; Huisman, Thierry A.G.M.

    2014-01-01

    Individually, metabolic disorders are rare, but overall they account for a significant number of neonatal disorders affecting the central nervous system. The neonatal clinical manifestations of inborn errors of metabolism (IEMs) are characterized by nonspecific systemic symptoms that may mimic more common acute neonatal disorders like sepsis, severe heart insufficiency, or neonatal hypoxic-ischemic encephalopathy. Certain IEMs presenting in the neonatal period may also be complicated by sepsis and cardiomyopathy. Early diagnosis is mandatory to prevent death and permanent long-term neurological impairments. Although neuroimaging findings are rarely specific, they play a key role in suggesting the correct diagnosis, limiting the differential diagnosis, and may consequently allow early initiation of targeted metabolic and genetic laboratory investigations and treatment. Neuroimaging may be especially helpful to distinguish metabolic disorders from other more common causes of neonatal encephalopathy, as a newborn may present with an IEM prior to the availability of the newborn screening results. It is therefore important that neonatologists, pediatric neurologists, and pediatric neuroradiologists are familiar with the neuroimaging findings of metabolic disorders presenting in the neonatal time period. PMID:22566357

  6. Neuroimaging of Fear-Associated Learning

    PubMed Central

    Greco, John A; Liberzon, Israel

    2016-01-01

    Fear conditioning has been commonly used as a model of emotional learning in animals and, with the introduction of functional neuroimaging techniques, has proven useful in establishing the neurocircuitry of emotional learning in humans. Studies of fear acquisition suggest that regions such as amygdala, insula, anterior cingulate cortex, and hippocampus play an important role in acquisition of fear, whereas studies of fear extinction suggest that the amygdala is also crucial for safety learning. Extinction retention testing points to the ventromedial prefrontal cortex as an essential region in the recall of the safety trace, and explicit learning of fear and safety associations recruits additional cortical and subcortical regions. Importantly, many of these findings have implications in our understanding of the pathophysiology of psychiatric disease. Recent studies using clinical populations have lent insight into the changes in regional activity in specific disorders, and treatment studies have shown how pharmaceutical and other therapeutic interventions modulate brain activation during emotional learning. Finally, research investigating individual differences in neurotransmitter receptor genotypes has highlighted the contribution of these systems in fear-associated learning. PMID:26294108

  7. Neuroimaging of Fear-Associated Learning.

    PubMed

    Greco, John A; Liberzon, Israel

    2016-01-01

    Fear conditioning has been commonly used as a model of emotional learning in animals and, with the introduction of functional neuroimaging techniques, has proven useful in establishing the neurocircuitry of emotional learning in humans. Studies of fear acquisition suggest that regions such as amygdala, insula, anterior cingulate cortex, and hippocampus play an important role in acquisition of fear, whereas studies of fear extinction suggest that the amygdala is also crucial for safety learning. Extinction retention testing points to the ventromedial prefrontal cortex as an essential region in the recall of the safety trace, and explicit learning of fear and safety associations recruits additional cortical and subcortical regions. Importantly, many of these findings have implications in our understanding of the pathophysiology of psychiatric disease. Recent studies using clinical populations have lent insight into the changes in regional activity in specific disorders, and treatment studies have shown how pharmaceutical and other therapeutic interventions modulate brain activation during emotional learning. Finally, research investigating individual differences in neurotransmitter receptor genotypes has highlighted the contribution of these systems in fear-associated learning.

  8. Neuroimaging characteristics of dementia with Lewy bodies.

    PubMed

    Mak, Elijah; Su, Li; Williams, Guy B; O'Brien, John T

    2014-01-01

    This review summarises the findings and applications from neuroimaging studies in dementia with Lewy bodies (DLB), highlighting key differences between DLB and other subtypes of dementia. We also discuss the increasingly important role of imaging biomarkers in differential diagnosis and outline promising areas for future research in DLB. DLB shares common clinical, neuropsychological and pathological features with Parkinson's disease dementia and other dementia subtypes, such as Alzheimer's disease. Despite the development of consensus diagnostic criteria, the sensitivity for differential diagnosis of DLB in clinical practice remains low and many DLB patients will be misdiagnosed. The importance of developing accurate imaging markers in dementia is highlighted by the potential for treatments targeting specific molecular abnormalities as well as the responsiveness to cholinesterase inhibitors and marked neuroleptic sensitivity of DLB. We review various brain imaging techniques that have been applied to investigate DLB, including the characteristic nigrostriatal degeneration in DLB using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers. Dopamine transporter loss has proven to reliably differentiate DLB from other dementias and has been incorporated into the revised clinical diagnostic criteria for DLB. To date, this remains the 'gold standard' for diagnostic imaging of DLB. Regional cerebral blood flow, 18 F-fluorodeoxygluclose-PET and SPECT have also identified marked deficits in the occipital regions with relative sparing of the medial temporal lobe when compared to Alzheimer's disease. In addition, structural, diffusion, and functional magnetic resonance imaging techniques have shown alterations in structure, white matter integrity, and functional activity in DLB. We argue that the multimodal identification of DLB-specific biomarkers has the potential to improve ante-mortem diagnosis and contribute to our

  9. [Neuroimaging findings in autism: a brief review].

    PubMed

    Ulay, Halime Tuna; Ertuğrul, Aygün

    2009-01-01

    Many structural and functional neuroimaging studies have investigated the neuroanatomical changes and possible pathophysiological pathways in autism. In this review the objective was to assess, with an integrative perspective, recent neuroimaging studies that have contributed to the explanation of the possible pathophysiological pathways in autism. Relevant attainable studies published between 1997 and 2007 were included in this retrospective literature review. The PubMed search engine and the keywords, autism, autistic spectrum disorders, neuroimaging, computerized tomography, magnetic resonance imaging, functional magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography, single photon emission computed tomography, and diffusion tensor imaging were used. Structural neuroimaging studies reported an increase in total cerebral volume, both in grey and white matter, mostly in the frontal, temporal and parietal lobes. These global volumetric changes are suggested to indicate a diffuse disturbance in neural networks during early development. In functional neuroimaging studies, activation abnormalities were observed in the temporal lobes and amygdala, which are involved in language and social cognition. An increase in visual activity cortex was also reported. Clinical observations and results from neuroimaging studies were gathered to hypothize and explain the pathophysiology of autism. Yet, it is still very early to conclude with certainty the neurobiological process responsible for autism.

  10. Design and rationale for examining neuroimaging genetics in ischemic stroke

    PubMed Central

    Giese, Anne-Katrin; Schirmer, Markus D.; Donahue, Kathleen L.; Cloonan, Lisa; Irie, Robert; Winzeck, Stefan; Bouts, Mark J.R.J.; McIntosh, Elissa C.; Mocking, Steven J.; Dalca, Adrian V.; Sridharan, Ramesh; Xu, Huichun; Frid, Petrea; Giralt-Steinhauer, Eva; Holmegaard, Lukas; Roquer, Jaume; Wasselius, Johan; Cole, John W.; McArdle, Patrick F.; Broderick, Joseph P.; Jimenez-Conde, Jordi; Jern, Christina; Kissela, Brett M.; Kleindorfer, Dawn O.; Lemmens, Robin; Lindgren, Arne; Meschia, James F.; Rundek, Tatjana; Sacco, Ralph L.; Schmidt, Reinhold; Sharma, Pankaj; Slowik, Agnieszka; Thijs, Vincent; Woo, Daniel; Worrall, Bradford B.; Kittner, Steven J.; Mitchell, Braxton D.; Rosand, Jonathan; Golland, Polina; Wu, Ona

    2017-01-01

    Objective: To describe the design and rationale for the genetic analysis of acute and chronic cerebrovascular neuroimaging phenotypes detected on clinical MRI in patients with acute ischemic stroke (AIS) within the scope of the MRI–GENetics Interface Exploration (MRI-GENIE) study. Methods: MRI-GENIE capitalizes on the existing infrastructure of the Stroke Genetics Network (SiGN). In total, 12 international SiGN sites contributed MRIs of 3,301 patients with AIS. Detailed clinical phenotyping with the web-based Causative Classification of Stroke (CCS) system and genome-wide genotyping data were available for all participants. Neuroimaging analyses include the manual and automated assessments of established MRI markers. A high-throughput MRI analysis pipeline for the automated assessment of cerebrovascular lesions on clinical scans will be developed in a subset of scans for both acute and chronic lesions, validated against gold standard, and applied to all available scans. The extracted neuroimaging phenotypes will improve characterization of acute and chronic cerebrovascular lesions in ischemic stroke, including CCS subtypes, and their effect on functional outcomes after stroke. Moreover, genetic testing will uncover variants associated with acute and chronic MRI manifestations of cerebrovascular disease. Conclusions: The MRI-GENIE study aims to develop, validate, and distribute the MRI analysis platform for scans acquired as part of clinical care for patients with AIS, which will lead to (1) novel genetic discoveries in ischemic stroke, (2) strategies for personalized stroke risk assessment, and (3) personalized stroke outcome assessment. PMID:28852707

  11. 76 FR 33305 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-08

    ..., initial review.'' Contact Person for More Information: J. Felix Rogers, Ph.D., M.P.H., Scientific Review...: Time and Date: 8 a.m.--5 p.m., July 11, 2011 (Closed). Place: Intercontinental Hotel Buckhead, 3315... for Disease Control and Prevention. BILLING CODE 4163-18-P...

  12. 77 FR 5257 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... Indonesia, FOA CK12-002, initial review.'' Contact Person for More Information: Greg Anderson, M.P.H., M.S... Date: 1 p.m.-5 p.m., March 26, 2012 (Closed). Place: Teleconference. Status: The meeting will be closed... Office, Centers for Disease Control and Prevention. BILLING CODE 4163-18-P...

  13. Dietary patterns are associated with disease risk among participants in the women's health initiative observational study

    USDA-ARS?s Scientific Manuscript database

    Coronary heart disease (CHD) is the leading cause of death in women. A nested case-control study tested whether dietary patterns predicted CHD events among 1224 participants in the Women’s Health Initiative-Observational Study (WHI-OS) with centrally confirmed CHD, fatal or nonfatal myocardial infar...

  14. Visual systems for interactive exploration and mining of large-scale neuroimaging data archives.

    PubMed

    Bowman, Ian; Joshi, Shantanu H; Van Horn, John D

    2012-01-01

    While technological advancements in neuroimaging scanner engineering have improved the efficiency of data acquisition, electronic data capture methods will likewise significantly expedite the populating of large-scale neuroimaging databases. As they do and these archives grow in size, a particular challenge lies in examining and interacting with the information that these resources contain through the development of compelling, user-driven approaches for data exploration and mining. In this article, we introduce the informatics visualization for neuroimaging (INVIZIAN) framework for the graphical rendering of, and dynamic interaction with the contents of large-scale neuroimaging data sets. We describe the rationale behind INVIZIAN, detail its development, and demonstrate its usage in examining a collection of over 900 T1-anatomical magnetic resonance imaging (MRI) image volumes from across a diverse set of clinical neuroimaging studies drawn from a leading neuroimaging database. Using a collection of cortical surface metrics and means for examining brain similarity, INVIZIAN graphically displays brain surfaces as points in a coordinate space and enables classification of clusters of neuroanatomically similar MRI images and data mining. As an initial step toward addressing the need for such user-friendly tools, INVIZIAN provides a highly unique means to interact with large quantities of electronic brain imaging archives in ways suitable for hypothesis generation and data mining.

  15. Visual Systems for Interactive Exploration and Mining of Large-Scale Neuroimaging Data Archives

    PubMed Central

    Bowman, Ian; Joshi, Shantanu H.; Van Horn, John D.

    2012-01-01

    While technological advancements in neuroimaging scanner engineering have improved the efficiency of data acquisition, electronic data capture methods will likewise significantly expedite the populating of large-scale neuroimaging databases. As they do and these archives grow in size, a particular challenge lies in examining and interacting with the information that these resources contain through the development of compelling, user-driven approaches for data exploration and mining. In this article, we introduce the informatics visualization for neuroimaging (INVIZIAN) framework for the graphical rendering of, and dynamic interaction with the contents of large-scale neuroimaging data sets. We describe the rationale behind INVIZIAN, detail its development, and demonstrate its usage in examining a collection of over 900 T1-anatomical magnetic resonance imaging (MRI) image volumes from across a diverse set of clinical neuroimaging studies drawn from a leading neuroimaging database. Using a collection of cortical surface metrics and means for examining brain similarity, INVIZIAN graphically displays brain surfaces as points in a coordinate space and enables classification of clusters of neuroanatomically similar MRI images and data mining. As an initial step toward addressing the need for such user-friendly tools, INVIZIAN provides a highly unique means to interact with large quantities of electronic brain imaging archives in ways suitable for hypothesis generation and data mining. PMID:22536181

  16. Neuroimaging essentials in essential tremor: A systematic review

    PubMed Central

    Sharifi, Sarvi; Nederveen, Aart J.; Booij, Jan; van Rootselaar, Anne-Fleur

    2014-01-01

    Background Essential tremor is regarded to be a disease of the central nervous system. Neuroimaging is a rapidly growing field with potential benefits to both diagnostics and research. The exact role of imaging techniques with respect to essential tremor in research and clinical practice is not clear. A systematic review of the different imaging techniques in essential tremor is lacking in the literature. Methods We performed a systematic literature search combining the terms essential tremor and familial tremor with the following keywords: imaging, MRI, VBM, DWI, fMRI, PET and SPECT, both in abbreviated form as well as in full form. We summarize and discuss the quality and the external validity of each study and place the results in the context of existing knowledge regarding the pathophysiology of essential tremor. Results A total of 48 neuroimaging studies met our search criteria, roughly divided into 19 structural and 29 functional and metabolic studies. The quality of the studies varied, especially concerning inclusion criteria. Functional imaging studies indicated cerebellar hyperactivity during rest and during tremor. The studies also pointed to the involvement of the thalamus, the inferior olive and the red nucleus. Structural studies showed less consistent results. Discussion and conclusion Neuroimaging techniques in essential tremor give insight into the pathophysiology of essential tremor indicating the involvement of the cerebellum as the most consistent finding. GABAergic dysfunction might be a major premise in the pathophysiological hypotheses. Inconsistencies between studies can be partly explained by the inclusion of heterogeneous patient groups. Improvement of scientific research requires more stringent inclusion criteria and application of advanced analysis techniques. Also, the use of multimodal neuroimaging techniques is a promising development in movement disorders research. Currently, the role of imaging techniques in essential tremor in daily

  17. Neuroimaging essentials in essential tremor: a systematic review.

    PubMed

    Sharifi, Sarvi; Nederveen, Aart J; Booij, Jan; van Rootselaar, Anne-Fleur

    2014-01-01

    Essential tremor is regarded to be a disease of the central nervous system. Neuroimaging is a rapidly growing field with potential benefits to both diagnostics and research. The exact role of imaging techniques with respect to essential tremor in research and clinical practice is not clear. A systematic review of the different imaging techniques in essential tremor is lacking in the literature. We performed a systematic literature search combining the terms essential tremor and familial tremor with the following keywords: imaging, mri, vbm, dwi, fmri, pet and spect, both in abbreviated form as well as in full form. We summarize and discuss the quality and the external validity of each study and place the results in the context of existing knowledge regarding the pathophysiology of essential tremor. A total of 48 neuroimaging studies met our search criteria, roughly divided into 19 structural and 29 functional and metabolic studies. The quality of the studies varied, especially concerning inclusion criteria. Functional imaging studies indicated cerebellar hyperactivity during rest and during tremor. The studies also pointed to the involvement of the thalamus, the inferior olive and the red nucleus. Structural studies showed less consistent results. Neuroimaging techniques in essential tremor give insight into the pathophysiology of essential tremor indicating the involvement of the cerebellum as the most consistent finding. GABAergic dysfunction might be a major premise in the pathophysiological hypotheses. Inconsistencies between studies can be partly explained by the inclusion of heterogeneous patient groups. Improvement of scientific research requires more stringent inclusion criteria and application of advanced analysis techniques. Also, the use of multimodal neuroimaging techniques is a promising development in movement disorders research. Currently, the role of imaging techniques in essential tremor in daily clinical practice is limited.

  18. Source counting in MEG neuroimaging

    NASA Astrophysics Data System (ADS)

    Lei, Tianhu; Dell, John; Magee, Ralphy; Roberts, Timothy P. L.

    2009-02-01

    Magnetoencephalography (MEG) is a multi-channel, functional imaging technique. It measures the magnetic field produced by the primary electric currents inside the brain via a sensor array composed of a large number of superconducting quantum interference devices. The measurements are then used to estimate the locations, strengths, and orientations of these electric currents. This magnetic source imaging technique encompasses a great variety of signal processing and modeling techniques which include Inverse problem, MUltiple SIgnal Classification (MUSIC), Beamforming (BF), and Independent Component Analysis (ICA) method. A key problem with Inverse problem, MUSIC and ICA methods is that the number of sources must be detected a priori. Although BF method scans the source space on a point-to-point basis, the selection of peaks as sources, however, is finally made by subjective thresholding. In practice expert data analysts often select results based on physiological plausibility. This paper presents an eigenstructure approach for the source number detection in MEG neuroimaging. By sorting eigenvalues of the estimated covariance matrix of the acquired MEG data, the measured data space is partitioned into the signal and noise subspaces. The partition is implemented by utilizing information theoretic criteria. The order of the signal subspace gives an estimate of the number of sources. The approach does not refer to any model or hypothesis, hence, is an entirely data-led operation. It possesses clear physical interpretation and efficient computation procedure. The theoretical derivation of this method and the results obtained by using the real MEG data are included to demonstrates their agreement and the promise of the proposed approach.

  19. Yield of Emergent Neuroimaging in Children with New-Onset Seizure and Status Epilepticus

    PubMed Central

    Lyons, Todd W.; Johnson, Kara B.; Michelson, Kenneth A.; Nigrovic, Lise E.; Loddenkemper, Tobias; Prabhu, Sanjay P.; Kimia MD, Amir A.

    2017-01-01

    PURPOSE To determine the yield of emergent neuroimaging among children with new-onset seizures presenting with status epilepticus. METHOD We performed a cross-sectional study of children seen at a single ED between 1995–2012 with new-onset seizure presenting with status epilepticus. We defined status epilepticus as a single seizure or multiple seizures without regaining consciousness lasting 30 minutes or longer. Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging. We categorized neuroimaging results as emergent if they would have changed acute management as assessed by a blinded neuroradiologist and neurologist. To ensure abnormalities were not missed, we review neuroimaging results for 30 days following the initial episode of SE. RESULTS We included 177 children presenting with new-onset seizure with status epilepticus, of whom 170 (96%) had neuroimaging performed. Abnormal findings were identified on neuroimaging in 64/177 (36%, 95% confidence interval 29–43%) children with 15 (8.5%, 95% confidence interval 5.2–14%) children having urgent or emergent pathology. Four (27%) of the 15 children with urgent or emergent findings had a normal non-contrast computed tomography scan and a subsequently abnormal magnetic resonance image. Longer seizure duration and older age were associated with urgent or emergent intracranial pathology. CONCLUSION A substantial minority of children with new-onset seizures presenting with status epilepticus have urgent or emergent intracranial pathology identified on neuroimaging. Clinicians should strongly consider emergent neuroimaging in these children. Magnetic resonance imaging is the preferred imaging modality when available and safe. PMID:26773658

  20. Yield of emergent neuroimaging in children with new-onset seizure and status epilepticus.

    PubMed

    Lyons, Todd W; Johnson, Kara B; Michelson, Kenneth A; Nigrovic, Lise E; Loddenkemper, Tobias; Prabhu, Sanjay P; Kimia, Amir A

    2016-02-01

    To determine the yield of emergent neuroimaging among children with new-onset seizures presenting with status epilepticus. We performed a cross-sectional study of children seen at a single ED between 1995 and 2012 with new-onset seizure presenting with status epilepticus. We defined status epilepticus as a single seizure or multiple seizures without regaining consciousness lasting 30 min or longer. Our primary outcome was urgent or emergent intracranial pathology identified on neuroimaging. We categorized neuroimaging results as emergent if they would have changed acute management as assessed by a blinded neuroradiologist and neurologist. To ensure abnormalities were not missed, we review neuroimaging results for 30 days following the initial episode of SE. We included 177 children presenting with new-onset seizure with status epilepticus, of whom 170 (96%) had neuroimaging performed. Abnormal findings were identified on neuroimaging in 64/177 (36%, 95% confidence interval 29-43%) children with 15 (8.5%, 95% confidence interval 5.2-14%) children having urgent or emergent pathology. Four (27%) of the 15 children with urgent or emergent findings had a normal non-contrast computed tomography scan and a subsequently abnormal magnetic resonance image. Longer seizure duration and older age were associated with urgent or emergent intracranial pathology. A substantial minority of children with new-onset seizures presenting with status epilepticus have urgent or emergent intracranial pathology identified on neuroimaging. Clinicians should strongly consider emergent neuroimaging in these children. Magnetic resonance imaging is the preferred imaging modality when available and safe. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  1. Chronic granulomatous otitis externa as an initial presentation of cutaneous Crohn disease.

    PubMed

    Raynor, Eileen M

    2014-08-01

    In the limited number of Crohn disease cases involving the head and neck, there is a predilection for mucosal surfaces and rare reports of involvement in the postauricular region. To our knowledge, in all previously reported cases involving the head and neck, the patients had a known diagnosis of Crohn disease. This case describes a 10-year-old boy with a history of psoriasis and psoriasiform dermatitis who presented with bilateral chronic granulomatous otitis externa, obliteration of the external auditory canal, and fissuring, resulting in separation of the lobule from the preauricular skin. Pathologic examination results were consistent with granulomatous dermatitis concerning for cutaneous Crohn disease, and a subsequent gastroenterologic workup confirmed the diagnosis of Crohn disease. This is a report of chronic granulomatous otitis as the initial presentation of cutaneous Crohn disease in a child.

  2. Building chronic disease management capacity in General Practice: The South Australian GP Plus Practice Nurse Initiative.

    PubMed

    Fuller, Jeffrey; Koehne, Kristy; Verrall, Claire C; Szabo, Natalie; Bollen, Chris; Parker, Sharon

    2015-01-01

    This paper draws on the implementation experience of the South Australian GP Plus Practice Nurse Initiative in order to establish what is needed to support the development of the chronic disease management role of practice nurses. The Initiative was delivered between 2007 and 2010 to recruit, train and place 157 nurses across 147 General Practices in Adelaide. The purpose was to improve chronic disease management in General Practice, by equipping nurses to work as practice nurses who would coordinate care and establish chronic disease management systems. Secondary analysis of qualitative data contained in the Initiative evaluation report, specifically drawing on quarterly project records and four focus groups conducted with practice nurses, practice nurse coordinators and practice nurse mentors. As evidenced by the need to increase the amount of support provided during the implementation of the Initiative, nurses new to General Practice faced challenges in their new role. Nurses described a big learning curve as they dealt with role transition to a new work environment and learning a range of new skills while developing chronic disease management systems. Informants valued the skills development and support offered by the Initiative, however the ongoing difficulties in implementing the role suggested that change is also needed at the level of the Practice. While just over a half of the placement positions were retained, practice nurses expressed concern with having to negotiate the conditions of their employment. In order to advance the role of practice nurses as managers of chronic disease support is needed at two levels. At one level support is needed to assist practice nurses to build their own skills. At the level of the Practice, and in the wider health workforce system, support is also needed to ensure that Practices are organisationally ready to include the practice nurse within the practice team.

  3. Analysis of residual disease following preoperative radiotherapy versus initial surgery in endometrial carcinoma

    SciTech Connect

    Chung, C.K.; Stryker, J.A.; Nahhas, W.A.; Cunningham, D.E.; Mortel, R.

    1982-02-01

    A clinicopathologic study of residual disease following pre-operative radiotherapy (RT) in 67 patients and initial surgery in 40 patients with early invasive endometrial carcinoma is presented. In 10%, extrauterine spread was found at operation. In 10% of patients, the histologic type, and in 19% the grade of tumor, differed between the curettage and hysterectomy specimens. Pre-op RT altered the depth of myometrial invasion and frequency of vascular invasion, but there was no evidence that irradiation itself affected the histologic type or grade of tumor. The patients with residual tumor after pre-op RT had significantly more cancer-related deaths than those without residual disease. The high risk factors were deep myometrial invasion and residual disease outside the uterus. Vascular invasion did not affect the prognosis in this series. The importance of surgical-pathologic staging by initial surgery is discussed.

  4. Neuroimaging in pediatric leukemia and lymphoma: differential diagnosis.

    PubMed

    Vázquez, Elida; Lucaya, Javier; Castellote, Amparo; Piqueras, Joaquim; Sainz, Pilar; Olivé, Teresa; Sánchez-Toledo, José; Ortega, Juan J

    2002-01-01

    Recent advances in therapy for pediatric hematologic neoplasms have greatly improved the prognosis but have resulted in an increased incidence of associated complications and toxic effects. The main neuroimaging features in pediatric patients with leukemia or lymphoma treated with chemotherapy or radiation therapy were retrospectively reviewed. To simplify the approach and facilitate differential diagnosis, the neuroimaging features have been classified into three main categories: central nervous system manifestations of primary disease, side effects of therapeutic procedures (radiation therapy, chemotherapy, bone marrow transplantation), and complications due to immunosuppression, particularly infections. Manifestations of primary disease include cerebrovascular complications (hemorrhage, cerebral infarction) and central nervous system involvement (infiltration of the meninges, parenchyma, bone marrow, orbit, and spine). Effects of radiation therapy include white matter disease, mineralizing microangiopathy, parenchymal brain volume loss, radiation-induced cryptic vascular malformations, and second neoplasms. Effects of chemotherapy and bone marrow transplantation include hemorrhage, dural venous thrombosis, white matter disease, reversible posterior leukoencephalopathy syndrome, and anterior lumbosacral radiculopathy. Both the underlying malignancy and antineoplastic therapy can cause immunosuppression. Fungi are the most frequent causal microorganisms in immunosuppressed patients with infection. Familiarity with the imaging findings is essential for proper diagnosis of neurologic symptoms in pediatric patients with oncohematologic disease. Copyright RSNA, 2002

  5. Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

    PubMed Central

    Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

    2016-01-01

    Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

  6. Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases.

    PubMed

    Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

    2016-01-01

    There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and "others"). We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and "true" effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. The differences in reliability between biological psychiatry, neurology and somatic

  7. Integrating gut microbiota immaturity and disease-discriminatory taxa to diagnose the initiation and severity of shrimp disease.

    PubMed

    Xiong, Jinbo; Zhu, Jinyong; Dai, Wenfang; Dong, Chunming; Qiu, Qiongfen; Li, Chenghua

    2017-04-01

    Increasing evidence has emerged a tight link among the gut microbiota, host age and health status. This osculating interplay impedes the definition of gut microbiome features associated with host health from that in developmental stages. Consequently, gut microbiota-based prediction of health status is promising yet not well established. Here we firstly tracked shrimp gut microbiota (N = 118) over an entire cycle of culture; shrimp either stayed healthy or progressively transitioned into severe disease. The results showed that the gut microbiota were significantly distinct over shrimp developmental stages and disease progression. Null model and phylogenetic-based mean nearest taxon distance (MNTD) analyses indicated that deterministic processes that governed gut community became less important as the shrimp aged and disease progressed. The predicted gut microbiota age (using the profiles of age-discriminatory bacterial species as independent variables) fitted well (r = 0.996; P < 0.001) with the age of healthy subjects, while this defined trend was disrupted by disease. Microbiota-for-age Z-scores (MAZ, here defined as immaturity) were relative stable among healthy shrimp, but sharply decreased when disease emerged. By distinguishing between age- and disease- discriminatory taxa, we developed a model, bacterial indicators of shrimp health status, to diagnose disease from healthy subjects with 91.5% accuracy. Notably, the relative abundances of the bacterial indicators were indicative for shrimp disease severity. These findings, in aggregate, add our understanding on the gut community assembly patterns over shrimp developmental stages and disease progression. In addition, shrimp disease initiation and severity can be accurately diagnosed using gut microbiota immaturity and bacterial indicators. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  8. Modified boron neutron capture therapy for malignant gliomas performed using epithermal neutron and two boron compounds with different accumulation mechanisms: an efficacy study based on findings on neuroimages.

    PubMed

    Miyatake, Shin-Ichi; Kawabata, Shinji; Kajimoto, Yoshinaga; Aoki, Atsushi; Yokoyama, Kunio; Yamada, Makoto; Kuroiwa, Toshihiko; Tsuji, Motomu; Imahori, Yoshio; Kirihata, Mitsunori; Sakurai, Yoshinori; Masunaga, Shin-Ichiro; Nagata, Kenji; Maruhashi, Akira; Ono, Koji

    2005-12-01

    To improve the effectiveness of boron neutron capture therapy (BNCT) for malignant gliomas, the authors used epithermal rather than thermal neutrons for deep penetration and two boron compounds-sodium borocaptate (BSH) and boronophenylalanine (BPA)-with different accumulation mechanisms to increase the boron level in tumors while compensating for each other's faults. Thirteen patients, 10 of whom harbored a glioblastoma multiforme (GBM), one a gliosarcoma, one an anaplastic astrocytoma, and one an anaplastic oligoastrocytoma, were treated using this modified BNCT between January 2002 and December 2003. Postoperatively, neuroimaging revealed that only one patient with a GBM had no lesion enhancement postoperatively. The patients underwent 18F-BPA positron emission tomography, if available, to assess the accumulation and distribution of BPA before neutron radiotherapy. The neutron fluence rate was estimated using the Simulation Environments for Radiotherapy Applications dose-planning system before irradiation. The patients' volume assessments were performed using magnetic resonance (MR) imaging or computerized tomography (CT) scanning. Improvements in the disease as seen on neuroimages were assessed between 2 and 7 days after irradiation to determine the initial effects of BNCT; its maximal effects were also analyzed on serial neuroimages. The mean tumor volume before BNCT was 42.3 cm3. Regardless of the pre-BNCT tumor volume, in every patient harboring an assessable lesion, improvements on MR or CT images were recognized both at the initial assessment (range of volume reduction rate 17.4-71%, mean rate 46.4%) and at follow-up assessments (range of volume reduction rates 30.3-87.6%, mean rate 58.5%). More than 50% of the contrast-enhanced lesions disappeared in eight of the 12 patients during the follow-up period. This modified BNCT produced a good improvement in malignant gliomas, as seen on neuroimages.

  9. Tobacco-related disease burden and preventive initiatives in China. Global health and the chronic diseases: perspective, policy and practice.

    PubMed

    Niu, Bolin

    2011-06-01

    The burden of chronic diseases in global health is a surging area of research. The Global Health Initiative at the National Heart, Lung, and Blood Institute brings together investigators from developing countries with those from the developed world to study these diseases. In China, approximately 83 percent of all deaths in 2000 were attributed to chronic illnesses, which are the research focuses of the Chinese center of the Global Health Initiative. Tobacco use as well as passive smoking are modifiable risk factors in a large number of such chronic conditions. The prevalence of smoking in China is extensive and has inseparable ties to the economy, with tobacco taxes making up a large portion of government revenue in poorer provinces. Methods of smoking prevention have been piloted in some Chinese schools, which have mitigated the increase in smoking rate but have not resulted in a primary preventive effect. Efforts by the Yale Global Health Initiative and the Yale-China Association are bringing researchers together to address chronic disease in China as Yale School of Medicine enters its 200th year.

  10. Side and Type of Initial Motor Symptom Influences Visuospatial Functioning in Parkinson’s Disease

    PubMed Central

    Seichepine, Daniel R.; Neargarder, Sandy; Davidsdottir, Sigurros; Reynolds, Gretchen O.; Cronin-Golomb, Alice

    2015-01-01

    Background/Objectives Visuospatial problems are common in Parkinson’s disease (PD) and likely stem from dysfunction in dopaminergic pathways and consequent disruption of cortical functioning. Characterizing the motor symptoms at disease onset provides a method of observing how dysfunction in these pathways influences visuospatial cognition. We examined two types of motor characteristics: body side (left or right) and type of initial symptom (tremor or symptom other than tremor). Methods 31 non-demented patients with PD, 16 with left-side onset (LPD) and 15 with right-side onset (RPD), as well as 17 healthy control participants (HC). The PD group was also divided by type of initial motor symptom, 15 having tremor as the initial symptom and 16 having an initial symptom other than tremor. Visuospatial function was assessed with the Clock Drawing Test. Results Of the four Clock Drawing scoring methods used, the Rouleau method showed sensitivity to subgroup differences. As predicted, the LPD and non-tremor subgroups, but not the other subgroups, performed more poorly than the HC group. Conclusion The findings provide further evidence for differences in cognition between these subtypes of PD and highlight the importance of considering disease subtypes when examining cognition. PMID:25311203

  11. Residual Tumor Cells That Drive Disease Relapse after Chemotherapy Do Not Have Enhanced Tumor Initiating Capacity

    PubMed Central

    Hegde, Ganapati V.; de la Cruz, Cecile; Eastham-Anderson, Jeffrey; Zheng, Yanyan; Sweet-Cordero, E. Alejandro; Jackson, Erica L.

    2012-01-01

    Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC) to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs). We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell’s ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell’s ability to drive disease recurrence. PMID:23115623

  12. Neuroimaging overuse is more common in Medicare compared with the VA.

    PubMed

    Burke, James F; Kerr, Eve A; McCammon, Ryan J; Holleman, Rob; Langa, Kenneth M; Callaghan, Brian C

    2016-08-23

    To inform initiatives to reduce overuse, we compared neuroimaging appropriateness in a large Medicare cohort with a Department of Veterans Affairs (VA) cohort. Separate retrospective cohorts were established in Medicare and in VA for headache and neuropathy from 2004 to 2011. The Medicare cohorts included all patients enrolled in the Health and Retirement Study (HRS) with linked Medicare claims (HRS-Medicare; n = 1,244 for headache and 998 for neuropathy). The VA cohorts included all patients receiving services in the VA (n = 93,755 for headache and 183,642 for neuropathy). Inclusion criteria were age over 65 years and an outpatient visit for incident neuropathy or a primary headache. Neuroimaging use was measured with Current Procedural Terminology codes and potential overuse was defined using published criteria for use with administrative data. Increasingly specific appropriateness criteria excluded nontarget conditions for which neuroimaging may be appropriate. For both peripheral neuropathy and headache, potentially inappropriate imaging was more common in HRS-Medicare compared with the VA. Forty-nine percentage of all headache patients received neuroimaging in HRS-Medicare compared with 22.1% in the VA (p < 0.001) and differences persist when analyzing more specific definitions of overuse. A total of 23.7% of all HRS-Medicare incident neuropathy patients received neuroimaging compared with 9.0% in the VA (p < 0.001), and the difference persisted after excluding nontarget conditions. Overuse of neuroimaging is likely less common in the VA than in a Medicare population. Better understanding the reasons for the more selective use of neuroimaging in the VA could help inform future initiatives to reduce overuse of diagnostic testing. © 2016 American Academy of Neurology.

  13. Gene Interactions and Structural Brain Change in Early-Onset Alzheimer's Disease Subjects Using the Pipeline Environment

    PubMed Central

    Dinov, Ivo D.; Zamanyan, Alen; Shi, Ran; Genco, Alex; Hobel, Sam; Thompson, Paul M.; Toga, Arthur W.

    2015-01-01

    Objective This article investigates subjects aged 55 to 65 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to broaden our understanding of early-onset (EO) cognitive impairment using neuroimaging and genetics biomarkers. Methods Nine of the subjects had EO-AD (Alzheimer's disease) and 27 had EO-MCI (mild cognitive impairment). The 15 most important neuroimaging markers were extracted with the Global Shape Analysis (GSA) Pipeline workflow. The 20 most significant single nucleotide polymorphisms (SNPs) were chosen and were associated with specific neuroimaging biomarkers. Results We identified associations between the neuroimaging phenotypes and genotypes for a total of 36 subjects. Our results for all the subjects taken together showed the most significant associations between rs7718456 and L_hippocampus (volume), and between rs7718456 and R_hippocampus (volume). For the 27 MCI subjects, we found the most significant associations between rs6446443 and R_superior_frontal_gyrus (volume), and between rs17029131 and L_Precuneus (volume). For the nine AD subjects, we found the most significant associations between rs16964473 and L_rectus gyrus (surface area), and between rs12972537 and L_rectus_gyrus (surface area). Conclusion We observed significant correlations between the SNPs and the neuroimaging phenotypes in the 36 EO subjects in terms of neuroimaging genetics. However, larger sample sizes are needed to ensure that the effects will be detectable for a reasonable false-positive error rate using the GSA and Plink Pipeline workflows. PMID:25670955

  14. Hairy cell leukemia presenting initially with symptoms of Behçet's disease.

    PubMed

    Oksuz, Mustafa Ferhat; Coskun, Belkis Nihan; Tufan, Ayse Nur; Orucoglu, Nurdan; Dalkilic, Ediz; Oztürk Nazlıoğlu, Hülya; Pehlivan, Yavuz

    2014-07-01

    Vasculitis is relatively uncommon in lymphoproliferative disease and may predate the diagnosis of lymphoproliferative disease. Many vasculitides have been associated with hairy cell leukemia (HCL), including polyarteritis nodosa (PAN) and leukocytoclastic vasculitis. We herein report a case whose initial presentation was like Behçet's disease (BD) (arthritis, oral and genital ulcerations, papulopustular skin lesions) in addition to pancytopenia, but turned out to have HCL. Because of the overlap between their symptoms, like oral ulcerations, skin lesions, arthritis and constitutional findings, HCL and BD may mimic each other. We should keep in mind other reasons for vasculitis such as lymphoproliferative disease, especially whose who have hematological abnormalities such as pancytopenia. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  15. Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

    PubMed

    Ioset, Jean-Robert; Chang, Shing

    2011-09-01

    The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

  16. Cardiac lesions and initial laboratory data in Kawasaki disease: a nationwide survey in Japan.

    PubMed

    Kuwabara, Masanari; Yashiro, Mayumi; Kotani, Kazuhiko; Tsuboi, Satoshi; Ae, Ryusuke; Nakamura, Yosikazu; Yanagawa, Hiroshi; Kawasaki, Tomisaku

    2015-01-01

    Cardiac lesions, such as coronary dilatation, aneurysms, narrowing, myocardial infarction, and valvular lesions, sometimes occur in Kawasaki disease, but most studies have only evaluated cardiac lesions in the later phase of the disease. This study was undertaken to clarify the related factors between cardiac lesions and laboratory data in the initial phase of Kawasaki disease. We conducted a cross-sectional study using data for 26 691 patients from the 22nd nationwide survey of Kawasaki disease in Japan, the observation period of which was from January 2011 through December 2012. We excluded patients with recurrent Kawasaki disease and who were more than seven days from the start of symptoms at admission. We analyzed 23 155 cases (13 353 boys; mean age: 923 ± 734 days) with available laboratory data for white blood cell count, platelet count, serum albumin, and C-reactive protein (CRP). Cardiac lesions were detected in 984 cases (656 boys and 328 girls); lesions were classified as coronary dilatation (764 cases), coronary aneurysm (40), giant coronary aneurysm (6), coronary narrowing (3), and valvular lesions (204). The significant related factors of initial coronary dilatation were male sex (odds ratio [OR] 1.73), older age (OR per 100 days increase 1.03), higher platelet count (OR per 10 000 cells/µL increase 1.006), lower albumin (OR per 1 g/dL increase 0.66), and higher CRP (OR per 1 mg/dL increase 1.02). The factors related to coronary aneurysm were higher platelet count (OR 1.01) and lower albumin (OR 0.34). No factors were significantly related to giant coronary aneurysm. The related factors of valvular lesions were age (OR 0.98), and higher CRP (OR 1.05). Clinicians should consider male sex, older age, higher platelet count, lower albumin levels, and higher CRP levels when assessing risk of cardiac lesions in the initial phase of Kawasaki disease.

  17. Adolescence and Later Life Disease Burden: Quantifying the Contribution of Adolescent Tobacco Initiation From Longitudinal Cohorts.

    PubMed

    Viner, Russell M; Hargreaves, Dougal S; Motta, Janaina Vieira Dos Santos; Horta, Bernardo; Mokdad, Ali H; Patton, George

    2017-08-01

    Adolescence is a time of initiation of behaviors leading to noncommunicable diseases (NCDs). We use tobacco to illustrate a novel method for assessing the contribution of adolescence to later burden. Data on initiation of regular smoking during adolescence (10-19 years) and current adult smoking were obtained from the 1958 British Birth Cohort, the U.S. National Longitudinal Study of Adolescent Health (Add Health), the Pelotas 1982 Birth Cohort, and the Victorian Adolescent Health Cohort Study. We estimated an "adolescent attributable fraction" (AAF) by calculating the proportion of persisting adult daily smoking initiated < age 20 years. We used findings to estimate AAFs for >155 countries using contemporary surveillance data. In the 1958 British Birth Cohort, 81.6% of daily smokers at age 50 years initiated < age 20 years, with a risk ratio of 6.1 for adult smoking related to adolescent initiation. The adjusted AAF was 69.1. Proportions of smokers initiating <20 years, risk ratio, and AAFs were 83.3%, 7.0%, and 70.4% for Add Health; 75.5%, 3.7%, and 50.2% in Victorian Adolescent Health Cohort Study; and 70.9%, 5.8%, and 56.9% in Pelotas males and 89.9%, 6.4%, and 75.9% in females. Initiation <16 years resulted in the highest AAFs. Estimated AAFs globally ranged from 35% in China to 76% in Argentina. The contribution of adolescent smoking initiation to adult smoking burden is high, suggesting a need to formulate and implement effective actions to reduce smoking initiation in adolescents. Similar trends in other NCD risks suggest that adolescents will be central to future efforts to control NCDs. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  18. Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.

    PubMed

    Holloway, Robert G; Shoulson, Ira; Fahn, Stanley; Kieburtz, Karl; Lang, Anthony; Marek, Kenneth; McDermott, Michael; Seibyl, John; Weiner, William; Musch, Bruno; Kamp, Cornelia; Welsh, Mickie; Shinaman, Aileen; Pahwa, Rajesh; Barclay, Lynn; Hubble, Jean; LeWitt, Peter; Miyasaki, Janis; Suchowersky, Oksana; Stacy, Mark; Russell, David S; Ford, Blair; Hammerstad, John; Riley, David; Standaert, David; Wooten, Frederick; Factor, Stewart; Jankovic, Joseph; Atassi, Farah; Kurlan, Roger; Panisset, Michel; Rajput, Ali; Rodnitzky, Robert; Shults, Cliff; Petsinger, Giselle; Waters, Cheryl; Pfeiffer, Ronald; Biglan, Kevin; Borchert, Leona; Montgomery, Amy; Sutherland, Laura; Weeks, Carolyn; DeAngelis, Maryan; Sime, Elspeth; Wood, Susan; Pantella, Carol; Harrigan, Mary; Fussell, Barbara; Dillon, Sandra; Alexander-Brown, Barbara; Rainey, Pamela; Tennis, Marsha; Rost-Ruffner, Elke; Brown, Diane; Evans, Sharon; Berry, Debra; Hall, Jean; Shirley, Theresa; Dobson, Judith; Fontaine, Deborah; Pfeiffer, Brenda; Brocht, Alicia; Bennett, Susan; Daigneault, Susan; Hodgeman, Karen; O'Connell, Carolynn; Ross, Tori; Richard, Karen; Watts, Arthur

    2004-07-01

    The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. Multicenter, parallel-group, double-blind, randomized controlled trial. Academic movement disorders clinics at 22 sites in the United States and Canada. Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001. Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events. Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months

  19. Utilization of Emergent Neuroimaging for Thrombolysis-Eligible Stroke Patients.

    PubMed

    Sanossian, Nerses; Fu, Katherine A; Liebeskind, David S; Starkman, Sidney; Hamilton, Scott; Villablanca, J Pablo; Burgos, Adrian M; Conwit, Robin; Saver, Jeffrey L

    2017-01-01

    Advances in diagnostic imaging of stroke include multimodal techniques such as noninvasive angiography and perfusion imaging. We aimed to characterize trends in neuroimaging utilization among acute stroke patients. Utilization of multimodal imaging for acute stroke in the community has remained largely uncharacterized despite its increased adoption at academic medical centers. We quantified neuroimaging utilization in the emergency department (ED) for 1,700 hyperacute stroke patients presenting <2 hours after symptom onset who participated in the National Institutes of Health Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study throughout Los Angeles and Orange Counties. FAST-MAG provided no recommendation as to imaging utilization. A total of 1,700 cases were imaged a median (interquartile range [IQR]) of 92 (74-120) minutes after last known well time and 28 (19-41) minutes after ED arrival. The initial scanner used in the ED was computed tomography (CT) in a preponderance of cases (N = 1,612, 95%), with magnetic resonance imaging (MRI) in 88 cases (5%). CT angiography (CTA) was obtained in 192 (11%) and perfusion CT (CTP) in 91 (5.4%) cases. MRI imaging was universally obtained using diffusion-weighted images, 60% with MR angiography and 33% included perfusion imaging. Rates of concomitant CTA or CTP use increased in the later years of the study from 4% in 2005-2006, 2% in 2007-2008, 8% in 2009-2010, and 26% in 2011-2012 (P for trend < .001). Among acute stroke patients, noncontrast CT was the most common initial imaging strategy in clinical practice in the 2005-2012 time period, though use of concomitant CTA grew to one-quarter of cases, suggestive of an upward trend. Copyright © 2016 by the American Society of Neuroimaging.

  20. Neuroimaging Coordination Dynamics in the Sport Sciences

    PubMed Central

    Jantzen, Kelly J.; Oullier, Olivier; Kelso, J.A. Scott

    2008-01-01

    Key methodological issues for designing, analyzing, and interpreting neuroimaging experiments are presented from the perspective of the framework of Coordination Dynamics. To this end, a brief overview of Coordination Dynamics is introduced, including the main concepts of control parameters and collective variables, theoretical modeling, novel experimental paradigms, and cardinal empirical findings. Basic conceptual and methodological issues for the design and implementation of coordination experiments in the context of neuroimaging are discussed. The paper concludes with a presentation of neuroimaging findings central to understanding the neural basis of coordination and addresses their relevance for the sport sciences. The latter include but are not restricted to learning and practice-related issues, the role of mental imagery, and the recovery of function following brain injury. PMID:18602998

  1. Molecular neuroimaging of emotional decision-making.

    PubMed

    Takahashi, Hidehiko

    2013-04-01

    With the dissemination of non-invasive human neuroimaging techniques such as fMRI and the advancement of cognitive science, neuroimaging studies focusing on emotions and social cognition have become established. Along with this advancement, behavioral economics taking emotional and social factors into account for economic decisions has been merged with neuroscientific studies, and this interdisciplinary approach is called neuroeconomics. Past neuroeconomics studies have demonstrated that subcortical emotion-related brain structures play an important role in "irrational" decision-making. The research field that investigates the role of central neurotransmitters in this process is worthy of further development. Here, we provide an overview of recent molecular neuroimaging studies to further the understanding of the neurochemical basis of "irrational" or emotional decision-making and the future direction, including clinical implications, of the field.

  2. Conceptual issues in psychiatric neuroimaging: an update.

    PubMed

    Stoyanov, D; Stanghellini, G; Broome, M

    2012-01-01

    In this paper, we provide an update on the conceptual issues of psychiatric neuroimaging, especially in the light of the current reductive claims of the eliminative physicalism. our argument is developed on three stages. The first is to highlight the crucial importance of phenomenological psychopathology and person-centered approach, which remains underestimated; the second is to bring forward the view that functional neuroimaging is relevant to the area of 'translation' in the mind-brain debate. The third point is to present a critical analysis of the shortcomings in structural and functional neuroimaging from methodological and epistemological perspectives. a novel paradigm for translational cross-validation among neuroscience, psychopathology and clinical psychology is presented.

  3. Methodological Approaches in Developmental Neuroimaging Studies

    PubMed Central

    Luna, Beatriz; Velanova, Katerina; Geier, Charles F.

    2010-01-01

    Pediatric neuroimaging is increasingly providing insights into the neural basis of cognitive development. Indeed, we have now arrived at a stage where we can begin to identify optimal methodological and statistical approaches to the acquisition and analysis of developmental imaging data. In this article, we describe a number of these approaches and how their selection impacts the ability to examine and interpret developmental effects. We describe preferred approaches to task selection, definition of age groups, selection of fMRI designs, definition of regions of interest (ROI), optimal baseline measures, and treatment of timecourse data. Consideration of these aspects of developmental neuroimaging reveals that unlike single-group neuroimaging studies, developmental studies pose unique challenges that impact study planning, task design, data analysis, and the interpretation of findings. PMID:20496377

  4. Multimodal neuroimaging computing: the workflows, methods, and platforms.

    PubMed

    Liu, Sidong; Cai, Weidong; Liu, Siqi; Zhang, Fan; Fulham, Michael; Feng, Dagan; Pujol, Sonia; Kikinis, Ron

    The last two decades have witnessed the explosive growth in the development and use of noninvasive neuroimaging technologies that advance the research on human brain under normal and pathological conditions. Multimodal neuroimaging has become a major driver of current neuroimaging research due to the recognition of the clinical benefits of multimodal data, and the better access to hybrid devices. Multimodal neuroimaging computing is very challenging, and requires sophisticated computing to address the variations in spatiotemporal resolution and merge the biophysical/biochemical information. We review the current workflows and methods for multimodal neuroimaging computing, and also demonstrate how to conduct research using the established neuroimaging computing packages and platforms.

  5. Multimodal neuroimaging computing: the workflows, methods, and platforms.

    PubMed

    Liu, Sidong; Cai, Weidong; Liu, Siqi; Zhang, Fan; Fulham, Michael; Feng, Dagan; Pujol, Sonia; Kikinis, Ron

    2015-09-01

    The last two decades have witnessed the explosive growth in the development and use of noninvasive neuroimaging technologies that advance the research on human brain under normal and pathological conditions. Multimodal neuroimaging has become a major driver of current neuroimaging research due to the recognition of the clinical benefits of multimodal data, and the better access to hybrid devices. Multimodal neuroimaging computing is very challenging, and requires sophisticated computing to address the variations in spatiotemporal resolution and merge the biophysical/biochemical information. We review the current workflows and methods for multimodal neuroimaging computing, and also demonstrate how to conduct research using the established neuroimaging computing packages and platforms.

  6. Proliferation-Independent Initiation of Biliary Cysts in Polycystic Liver Diseases.

    PubMed

    Beaudry, Jean-Bernard; Cordi, Sabine; Demarez, Céline; Lepreux, Sébastien; Pierreux, Christophe E; Lemaigre, Frédéric P

    2015-01-01

    Biliary cysts in adult patients affected by polycystic liver disease are lined by cholangiocytes that proliferate, suggesting that initiation of cyst formation depends on proliferation. Here, we challenge this view by analyzing cyst-lining cell proliferation and differentiation in Cpk mouse embryos and in livers from human fetuses affected by Autosomal Recessive Polycystic Kidney Disease (ARPKD), at early stages of cyst formation. Proliferation of fetal cholangiocyte precursors, measured by immunostaining in human and mouse livers, was low and did not differ between normal and ARPKD or Cpk livers, excluding excessive proliferation as an initiating cause of liver cysts. Instead, our analyses provide evidence that the polycystic livers exhibit increased and accelerated differentiation of hepatoblasts into cholangiocyte precursors, eventually coalescing into large biliary cysts. Lineage tracing experiments, performed in mouse embryos, indicated that the cholangiocyte precursors in Cpk mice generate cholangiocytes and periportal hepatocytes, like in wild-type animals. Therefore, contrary to current belief, cyst formation in polycystic liver disease does not necessarily depend on overproliferation. Combining our prenatal data with available data from adult livers, we propose that polycystic liver can be initiated by proliferation-independent mechanisms at a fetal stage, followed by postnatal proliferation-dependent cyst expansion.

  7. The Influence of Movement Initiation Deficits on the Quantification of Retention in Parkinson’s Disease

    PubMed Central

    Pendt, Lisa K.; Maurer, Heiko; Müller, Hermann

    2012-01-01

    In patients with an impaired motor system, like Parkinson’s disease (PD), deficits in motor learning are expected and results of various studies seem to confirm these expectations. However, most studies in this regard are behaviorally based and quantify learning by performance changes between at least two points in time, e.g., baseline and retention. But, performance in a retention test is also dependent on other factors than learning. Especially in patients, the functional capacity of the control system might be altered unspecific to a certain task and learning episode. The aim of the study is to test whether characteristic temporal deficits exist in PD patients that affect retention performance. We tested the confounding effects of typical PD motor control deficits, here movement initiation deficits, on retention performance in the motor learning process. 12 PD patients and 16 healthy control participants practiced a virtual throwing task over 3 days with 24 h rest between sessions. Retention was tested comparing performance before rest with performance after rest. Movement initiation deficits were quantified by the timing of throwing release that should be affected by impairments in movement initiation. To scrutinize the influence of the initiation deficits on retention performance we gave participants a specific initiation intervention prior to practice on one of the three practice days. We found that only for the PD patients, post-rest performance as well as release timing was better with intervention as compared to without intervention. Their performance could be enhanced through a tuning of release initiation. Thus, we suggest that in PD patients, performance decline after rest that might be easily interpreted as learning deficits could rather result from disease-related deficiencies in motor control. PMID:22870067

  8. Neuroimaging in the Diagnostic Evaluation of Eye Pain.

    PubMed

    Szatmáry, Gabriella

    2016-09-01

    Ocular or eye pain is a frequent complaint encountered not only by eye care providers but neurologists. Isolated eye pain is non-specific and non-localizing; therefore, it poses significant differential diagnostic problems. A wide range of neurologic and ophthalmic disorders may cause pain in, around, or behind the eye. These include ocular and orbital diseases and primary and secondary headaches. In patients presenting with an isolated and chronic eye pain, neuroimaging is usually normal. However, at the beginning of a disease process or in low-grade disease, the eye may appear "quiet," misleading a provider lacking familiarity with underlying disorders and high index of clinical suspicion. Delayed diagnosis of some neuro-ophthalmic causes of eye pain could result in significant neurologic and ophthalmic morbidity, conceivably even mortality. This article reviews some recent advances in imaging of the eye, the orbit, and the brain, as well as research in which neuroimaging has advanced the discovery of the underlying pathophysiology and the complex differential diagnosis of eye pain.

  9. Neuroimaging and Recovery of Language in Aphasia

    PubMed Central

    Thompson, Cynthia K.; den Ouden, Dirk-Bart

    2010-01-01

    The use of functional neuroimaging techniques has advanced what is known about the neural mechanisms used to support language processing in aphasia resulting from brain damage. This paper highlights recent findings derived from neuroimaging studies focused on neuroplasticity of language networks, the role of the left and right hemispheres in this process, and studies examining how treatment affects the neurobiology of recovery. We point out variability across studies as well as factors related to this variability, and we emphasize challenges that remain for research. PMID:18957184

  10. Model-based neuroimaging for cognitive computing.

    PubMed

    Poznanski, Roman R

    2009-09-01

    The continuity of the mind is suggested to mean the continuous spatiotemporal dynamics arising from the electrochemical signature of the neocortex: (i) globally through volume transmission in the gray matter as fields of neural activity, and (ii) locally through extrasynaptic signaling between fine distal dendrites of cortical neurons. If the continuity of dynamical systems across spatiotemporal scales defines a stream of consciousness then intentional metarepresentations as templates of dynamic continuity allow qualia to be semantically mapped during neuroimaging of specific cognitive tasks. When interfaced with a computer, such model-based neuroimaging requiring new mathematics of the brain will begin to decipher higher cognitive operations not possible with existing brain-machine interfaces.

  11. [Functional neuroimaging in the diagnosis of patients with Parkinsonism: Update and recommendations for clinical use].

    PubMed

    Arbizu, J; Luquin, M R; Abella, J; de la Fuente-Fernández, R; Fernandez-Torrón, R; García-Solís, D; Garrastachu, P; Jiménez-Hoyuela, J M; Llaneza, M; Lomeña, F; Lorenzo-Bosquet, C; Martí, M J; Martinez-Castrillo, J C; Mir, P; Mitjavila, M; Ruiz-Martínez, J; Vela, L

    2014-01-01

    Functional Neuroimaging has been traditionally used in research for patients with different Parkinsonian syndromes. However, the emergence of commercial radiotracers together with the availability of single photon emission computed tomography (SPECT) and, more recently, positron emission tomography (PET) have made them available for clinical practice. Particularly, the development of clinical evidence achieved by functional neuroimaging techniques over the past two decades have motivated a progressive inclusion of several biomarkers in the clinical diagnostic criteria for neurodegenerative diseases that occur with Parkinsonism. However, the wide range of radiotracers designed to assess the involvement of different pathways in the neurodegenerative process underlying Parkinsonian syndromes (dopaminergic nigrostriatal pathway integrity, basal ganglia and cortical neuronal activity, myocardial sympathetic innervation), and the different neuroimaging techniques currently available (scintigraphy, SPECT and PET), have generated some controversy concerning the best neuroimaging test that should be indicated for the differential diagnosis of Parkinsonism. In this article, a panel of nuclear medicine and neurology experts has evaluated the functional neuroimaging techniques emphazising practical considerations related to the diagnosis of patients with uncertain origin parkinsonism and the assessment Parkinson's disease progression.

  12. [Treatment and outcome of Crohn's disease without initial complications. Results of a retrospective, multicenter Tunisian study].

    PubMed

    Cheikh, Imed; Ben Ammar, Ahmed; Essid, Mejda; Azzouz, Messadak; Ettahri, Nabil; Krichene, Mohamed; Bouzaidi, Slim; Ennajar, Taoufik

    2002-04-01

    The purpose of this study was to estimate and achieve the factors that have an influence on the evolution of the Chron's disease. This study was done in 124 patients reaching the diagnosis of Chron's disease between 1988 and 1997. The evolution of this disease was achieved in 87 patients. The Chron's disease was inactive among 31 patients (35-6%)--with discontinous evolution in 42 patients (48.3%) and active chronic in 14 patients (16-1%). The active chronic form of Chron's disease was twice more frequent among the smokers and the patients with age above 40 years--but this difference has no statistical significance. The indication of surgical treatment was realised in 21 patients and it takes place as result of failure of medical treatment in 16 patients (76-2%)--an abcess in 2 patents (9-5%) and iatrogenic perforation in 1 patient (4-8%). The age-sexe-smoke--the intensity of the initial attack and the nature of the treatment had no influence in the need of the surgical interfference. The Chron's disease showed the less severe evolution in this study--the age above 40 years and the consumption of smoke increased the frequency of active chronic form.

  13. Carpal spasm in a girl as initial presentation of celiac disease: a case report.

    PubMed

    Ramosaj-Morina, Atifete; Keka-Sylaj, A; Hasbahta, V; Baloku-Zejnullahu, A; Azemi, M; Zunec, R

    2017-09-04

    Celiac disease is an immune-mediated disorder elicited by ingestion of gluten in genetically susceptible persons. This disorder is characterized by specific histological changes of the small intestine mucosa resulting in malabsorption. This case was written up as it was an unusual and dramatic presentation of celiac disease. We report the case of a 3-year-old Albanian girl who presented at our clinic with carpal spasms and hand paresthesia. A physical examination at admission revealed a relatively good general condition and body weight of 10.5 kg (10 percentile). Carpal spasms and paresthesias of her extremities were present. Neuromuscular irritability was demonstrated by positive Chvostek and Trousseau signs. Blood tests showed severe hypocalcemia with a total serum calcium of 1.2 mmol/L (normal range 2.12 to 2.55 mmol/L), ionized calcium of 0.87 (normal range 1.11 to 1.30 mmol/L), and 24-hour urine calcium excretion of 9.16 mmol (normal range female <6.2 mmol/day). Among other tests, screening for celiac disease was performed: antigliadin immunoglobulin A, anti-tissue transglutaminase, and anti-endomysial immunoglobulin A antibodies were positive. A duodenal biopsy revealed lymphocyte infiltration, crypt hyperplasia, and villous atrophy compatible with celiac disease grade IIIb according to the Marsh classification. Following the diagnosis of celiac disease, human leukocyte antigen typing was performed, giving a definite diagnosis of celiac disease. She was started on a gluten-free diet. Due to failure to follow a gluten-free diet, episodes of carpal spasms appeared again. Unfortunately, at the age of 7 years she presents with delayed psychophysical development. Although hypocalcemia is a common finding in celiac disease, hypocalcemic carpal spasm is a rare initial manifestation of the disease. Therefore, the possibility of celiac disease should be considered in patients with repeated carpal spasms that seem unduly difficult to treat. This should be

  14. Attenuation of disease phenotype through alternative translation initiation in low-penetrance retinoblastoma.

    PubMed

    Sánchez-Sánchez, Francisco; Ramírez-Castillejo, Carmen; Weekes, Daniel B; Beneyto, Magdalena; Prieto, Félix; Nájera, Carmen; Mittnacht, Sibylle

    2007-02-01

    Hereditary predisposition to retinoblastoma (RB) is caused by germline mutations in the retinoblastoma 1 (RB1) gene and transmits as an autosomal dominant trait. In the majority of cases disease develops in greater than 90% of carriers. However, reduced penetrance with a large portion of disease-free carrier is seen in some families. Unambiguous identification of the predisposing mutation in these families is important for accurate risk prediction in relatives and their genetic counseling but also provides conceptual information regarding the relationship between the RB1 genotype and the disease phenotype. In this study we report a novel mutation detected in 10 individuals of an extended family, only three of whom are affected by RB disease. The mutation comprises a 23-basepair (bp) duplication in the first exon of RB1 (c.43_65dup) producing a frameshift in exon 1 and premature chain termination in exon 2. Mutations resulting in premature chain termination classically are associated with high penetrance disease, as message translation may not generate functional product and nonsense mediated RNA decay (NMD) frequently eliminates the mutant transcript. However, appreciable NMD does not follow from the mutation described here and transcript expression in tissue culture cells and translation in vitro reveals that alternative in-frame translation start sites involving Met113 and possibly Met233 are used to generate truncated RB1 products (pRB94 and pRB80), known and suspected to exhibit tumor suppressor activity. These results strongly suggest that modulation of disease penetrance in this family is achieved by internal translation initiation. Our observations provide the first example for rescue of a chain-terminating mutation in RB1 through alternative translation initiation.

  15. Cost-sharing and initiation of disease-modifying therapy for multiple sclerosis.

    PubMed

    Romley, John; Goldman, Dana; Eber, Michael; Dastani, Homa; Kim, Edward; Raparla, Swetha

    2012-08-01

    To assess the effects of patient cost sharing on initiation of disease-modifying therapies (DMTs) in multiple sclerosis (MS). Retrospective claims database study of privately insured patients newly diagnosed with MS between 2004 and 2008 from 33 large employers. We assessed the effects of plan-level cost-sharing on DMT initiation during a 2-year follow-up period after diagnosis. Incident cases were identified by 2 or more claims with ICD-9 codes for MS within a year, subsequent to a year with no such claims. Covariates for adjustment included age, gender, relationship to primary beneficiary, comorbid conditions, and calendar year, as well as unobserved factors that did not vary within plans over time. Out of a sample of 3460 patients meeting criteria for inclusion, only 17% initiated a DMT within 2 years of diagnosis. An increase in the cost-sharing rate from zero to the 95th percentile (17.8%) was predicted to decrease initiation within 2 years of diagnosis by 2.9 percentage points, or 12.7% (P = .019). High cost-sharing is associated with delayed initiation of effective MS therapies.

  16. Perturbations of ground support alter posture and locomotion coupling during step initiation in Parkinson's disease.

    PubMed

    Rogers, Mark W; Hilliard, Marjorie Johnson; Martinez, Katherine M; Zhang, Yunhui; Simuni, Tanya; Mille, Marie-Laure

    2011-02-01

    During the initiation of stepping, anticipatory postural adjustments (APAs) for lateral weight transfer and propulsion normally precede the onset of locomotion. In Parkinson's disease (PD), impaired step initiation typically involves altered APA ground force production with delayed step onset and deficits in stepping performance. If, as in stance and gait, sensory information about lower limb load is important for the control of stepping, then perturbations influencing loading conditions could affect the step initiation process. This study investigated the influence of changes in lower limb loading during step initiation in patients with PD and healthy control subjects. Participants performed rapid self-triggered step initiation with the impending single stance limb positioned over a pneumatically actuated platform. In perturbation trials, the stance limb ground support surface was either moved vertically downward (DROP) or upward (ELEVATE) by 1.5 cm shortly after the onset of the APA phase. Overall, PD patients demonstrated a longer APA duration, longer time to first step onset, and slower step speed than controls. In both groups, the DROP perturbation reinforced the intended APA kinetic changes for lateral weight transfer and resulted in a significant reduction in APA duration, increase in peak amplitude, and earlier time to first step onset compared with other conditions. During ELEVATE trials that opposed the intended weight transfer forces both groups rapidly adapted their stepping to preserve standing stability by decreasing step length and duration, and increasing step height and foot placement laterally. The findings suggested that sensory information associated with limb load and/or foot pressure modulates the spatial and temporal parameters of posture and locomotion components of step initiation in interaction with a centrally generated feedforward mode of neural control. Moreover, impaired step initiation in PD may at least acutely be enhanced by

  17. Loss of executive function after dialysis initiation in adults with chronic kidney disease.

    PubMed

    Kurella Tamura, Manjula; Vittinghoff, Eric; Hsu, Chi-Yuan; Tam, Karman; Seliger, Stephen L; Sozio, Stephen; Fischer, Michael; Chen, Jing; Lustigova, Eva; Strauss, Louise; Deo, Rajat; Go, Alan S; Yaffe, Kristine

    2017-04-01

    The association of dialysis initiation with changes in cognitive function among patients with advanced chronic kidney disease is poorly described. To better define this, we enrolled participants with advanced chronic kidney disease from the Chronic Renal Insufficiency Cohort in a prospective study of cognitive function. Eligible participants had a glomerular filtration rate of 20 ml/min/1.73m(2) or less, or dialysis initiation within the past two years. We evaluated cognitive function by a validated telephone battery at regular intervals over two years and analyzed test scores as z scores. Of 212 participants, 123 did not transition to dialysis during follow-up, 37 transitioned to dialysis after baseline, and 52 transitioned to dialysis prior to baseline. In adjusted analyses, the transition to dialysis was associated with a significant loss of executive function, but no significant changes in global cognition or memory. The estimated net difference in cognitive z scores at two years for participants who transitioned to dialysis during follow-up compared to participants who did not transition to dialysis was -0.01 (95% confidence interval -0.13, 0.11) for global cognition, -0.24 (-0.51, 0.03) for memory, and -0.33 (-0.60, -0.07) for executive function. Thus, among adults with advanced chronic kidney disease, dialysis initiation was associated with loss of executive function with no change in other aspects of cognition. Larger studies are needed to evaluate cognition during dialysis initiation.

  18. Use of combination antihypertensive therapy initiation in older Americans without prevalent cardiovascular disease.

    PubMed

    Li, Xiaojuan; Camelo Castillo, Wendy; Stürmer, Til; Pate, Virginia; Gray, Christine L; Simpson, Ross J; Setoguchi, Soko; Hanson, Laura C; Jonsson Funk, Michele

    2014-09-01

    To describe new users of antihypertensive medications and identify predictors of combination therapy initiation in older Americans. Retrospective observational cohort study. Population-based study using U.S. Medicare fee-for-service healthcare claims (2007-2010). Medicare beneficiaries aged 65 and older with no recent diagnoses, procedures, or medications for cardiovascular disease who newly initiated an antihypertensive therapy (n = 275,493; 210,605 initiated monotherapy, 64,888 initiated combination therapy). Multivariable Poisson regression was used to assess factors associated with initiation of combination therapy versus monotherapy, including participant characteristics, prescriber characteristics, and participant encounters with the healthcare system. Initiation of combination therapy increased from 21.9% in 2007 to 24.7% in 2010. The most frequently initiated combinations were angiotensin-converting enzyme inhibitors with thiazide (29.7%) and angiotensin II receptor antagonists with thiazide (18.7%). Blacks (prevalence ratio (PR) = 1.48, 95% confidence interval (CI) = 1.45-1.51 vs. whites), individuals seeing a generalist (PR = 1.10, 95% CI = 1.07-1.14), individuals seeing more than one doctor (PR = 3.38, 95% CI = 3.33-3.44), and participants with no pharmacy claims in the previous 6 months (PR = 1.34, 95% CI = 1.30-1.37 vs. ≥3 unique drug classes) were more likely to initiate combination therapy, whereas those who had more outpatient visits in the previous 12 months were less likely to initiate combination therapy (per five visits, PR = 0.82, 95% CI = 0.80-0.83). Nearly one in four new users of antihypertensive medications aged 65 and older started treatment with combination therapy. Blacks, individuals living in the south, and those with fewer outpatient physician office visits were more likely to initiate combination therapy. Further research is needed to determine whether this approach to managing hypertension is being well targeted to individuals who

  19. A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.

    PubMed

    Hampel, H; O'Bryant, S E; Durrleman, S; Younesi, E; Rojkova, K; Escott-Price, V; Corvol, J-C; Broich, K; Dubois, B; Lista, S

    2017-04-01

    After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.

  20. Neuroimaging the brain-gut axis in patients with irritable bowel syndrome

    PubMed Central

    Weaver, Kristen R; Sherwin, LeeAnne B; Walitt, Brian; Melkus, Gail D’Eramo; Henderson, Wendy A

    2016-01-01

    AIM: To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome (IBS). METHODS: A database search for relevant literature was conducted using PubMed, Scopus and Embase in February 2015. Date filters were applied from the year 2009 and onward, and studies were limited to those written in the English language and those performed upon human subjects. The initial search yielded 797 articles, out of which 38 were pulled for full text review and 27 were included for study analysis. Investigations were reviewed to determine study design, methodology and results, and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations. RESULTS: Analysis of study data resulted in the abstraction of four key themes: Neurohormonal differences, anatomic measurements of brain structure and connectivity, differences in functional responsiveness of the brain during rectal distention, and confounding/correlating patient factors. Studies in this review noted alterations of glutamate in the left hippocampus (HIPP), commonalities across IBS subjects in terms of brain oscillation patterns, cortical thickness/gray matter volume differences, and neuroanatomical regions with increased activation in patients with IBS: Anterior cingulate cortex, mid cingulate cortex, amygdala, anterior insula, posterior insula and prefrontal cortex. A striking finding among interventions was the substantial influence that patient variables (e.g., sex, psychological and disease related factors) had upon the identification of neuroanatomical differences in structure and connectivity. CONCLUSION: The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population. PMID:27158548

  1. The open-source neuroimaging research enterprise.

    PubMed

    Marcus, Daniel S; Archie, Kevin A; Olsen, Timothy R; Ramaratnam, Mohana

    2007-11-01

    While brain imaging in the clinical setting is largely a practice of looking at images, research neuroimaging is a quantitative and integrative enterprise. Images are run through complex batteries of processing and analysis routines to generate numeric measures of brain characteristics. Other measures potentially related to brain function - demographics, genetics, behavioral tests, neuropsychological tests - are key components of most research studies. The canonical scanner - PACS - viewing station axis used in clinical practice is therefore inadequate for supporting neuroimaging research. Here, we model the neuroimaging research enterprise as a workflow. The principal components of the workflow include data acquisition, data archiving, data processing and analysis, and data utilization. We also describe a set of open-source applications to support each step of the workflow and the transitions between these steps. These applications include DIGITAL IMAGING AND COMMUNICATIONS IN MEDICINE viewing and storage tools, the EXTENSIBLE NEUROIMAGING ARCHIVE TOOLKIT data archiving and exploration platform, and an engine for running processing/analysis pipelines. The overall picture presented is aimed to motivate open-source developers to identify key integration and communication points for interoperating with complimentary applications.

  2. Advanced Techniques Using Contrast Media in Neuroimaging

    PubMed Central

    Ferré, Jean-Christophe; Shiroishi, Mark S.; Law, Meng

    2012-01-01

    This article presents an overview of advanced MRI techniques using contrast media in neuroimaging, focusing on T2*-weighted dynamic susceptibility contrast MR imaging (DSC-MRI) and T1-weighted dynamic contrast-enhanced MR imaging (DCE-MRI). Image acquisition and data processing methods as well as their clinical application in brain tumors, stroke, dementia and multiple sclerosis are discussed. PMID:23088946

  3. Functional neuroimaging: technical, logical, and social perspectives.

    PubMed

    Aguirre, Geoffrey K

    2014-01-01

    Neuroscientists have long sought to study the dynamic activity of the human brain-what's happening in the brain, that is, while people are thinking, feeling, and acting. Ideally, an inside look at brain function would simultaneously and continuously measure the biochemical state of every cell in the central nervous system. While such a miraculous method is science fiction, a century of progress in neuroimaging technologies has made such simultaneous and continuous measurement a plausible fiction. Despite this progress, practitioners of modern neuroimaging struggle with two kinds of limitations: those that attend the particular neuroimaging methods we have today and those that would limit any method of imaging neural activity, no matter how powerful. In this essay, I consider the liabilities and potential of techniques that measure human brain activity. I am concerned here only with methods that measure relevant physiologic states of the central nervous system and relate those measures to particular mental states. I will consider in particular the preeminent method of functional neuroimaging: BOLD fMRI. While there are several practical limits on the biological information that current technologies can measure, these limits-as important as they are-are minor in comparison to the fundamental logical restraints on the conclusions that can be drawn from brain imaging studies.

  4. Neuroimaging studies of social cognition in schizophrenia.

    PubMed

    Fujiwara, Hironobu; Yassin, Walid; Murai, Toshiya

    2015-05-01

    Impaired social cognition is considered a core contributor to unfavorable psychosocial functioning in schizophrenia. Rather than being a unitary process, social cognition is a collection of multifaceted processes that recruit multiple brain structures, thus structural and functional neuroimaging techniques are ideal methodologies for revealing the underlying pathophysiology of impaired social cognition. Many neuroimaging studies have suggested that in addition to white-matter deficits, schizophrenia is associated with decreased gray-matter volume in multiple brain areas, especially fronto-temporal and limbic regions. However, few schizophrenia studies have examined associations between brain abnormalities and social cognitive disabilities. During the last decade, we have investigated structural brain abnormalities in schizophrenia using high-resolution magnetic resonance imaging, and our findings have been confirmed by us and others. By assessing different types of social cognitive abilities, structural abnormalities in multiple brain regions have been found to be associated with disabilities in social cognition, such as recognition of facial emotion, theory of mind, and empathy. These structural deficits have also been associated with alexithymia and quality of life in ways that are closely related to the social cognitive disabilities found in schizophrenia. Here, we overview a series of neuroimaging studies from our laboratory that exemplify current research into this topic, and discuss how it can be further tackled using recent advances in neuroimaging technology.

  5. Neuroimaging resilience to stress: a review

    PubMed Central

    van der Werff, S. J. A.; van den Berg, S. M.; Pannekoek, J. N.; Elzinga, B. M.; van der Wee, N. J. A.

    2013-01-01

    There is a high degree of intra-individual variation in how individuals respond to stress. This becomes evident when exploring the development of posttraumatic symptoms or stress-related disorders after exposure to trauma. Whether or not an individual develops posttraumatic symptoms after experiencing a traumatic event is partly dependent on a person's resilience. Resilience can be broadly defined as the dynamic process encompassing positive adaptation within the context of significant adversity. Even though research into the neurobiological basis of resilience is still in its early stages, these insights can have important implications for the prevention and treatment of stress-related disorders. Neuroimaging studies contribute to our knowledge of intra-individual variability in resilience and the development of posttraumatic symptoms or other stress-related disorders. This review provides an overview of neuroimaging findings related to resilience. Structural, resting-state, and task-related neuroimaging results associated with resilience are discussed. There are a limited number of studies available and neuroimaging research of resilience is still in its infancy. The available studies point at brain circuitries involved in stress and emotion regulation, with more efficient processing and regulation associated with resilience. PMID:23675330

  6. Functional Neuroimaging Studies of Written Sentence Comprehension

    ERIC Educational Resources Information Center

    Caplan, David

    2004-01-01

    Sentences convey relationships between the meanings of words, such as who is accomplishing an action or receiving it. Functional neuroimaging based on positron-emission tomography and functional magnetic resonance imaging has been used to identify areas of the brain involved in structuring sentences and determining aspects of meaning associated…

  7. Autopsy-confirmed hippocampal-sparing Alzheimer's disease with delusional jealousy as initial manifestation.

    PubMed

    Fujishiro, Hiroshige; Iritani, Shuji; Hattori, Miho; Sekiguchi, Hirotaka; Matsunaga, Shinji; Habuchi, Chikako; Torii, Youta; Umeda, Kentaro; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

    2015-09-01

    Alzheimer's disease (AD) is clinically characterized by gradual onset over years with worsening of cognition. The initial and most prominent cognitive deficit is commonly memory dysfunction. However, a subset of AD cases has less hippocampal atrophy than would be expected relative to the predominance of cortical atrophy. These hippocampal-sparing cases have distinctive clinical features, including the presence of focal cortical clinical syndromes. Given that previous studies have indicated that severe hippocampal atrophy corresponds to prominent loss of episodic memory, it is likely that memory impairment is initially absent in hippocampal-sparing AD cases. Here, we report on a patient with an 8-year history of delusional jealousy with insidious onset who was clinically diagnosed as possible AD and pathologically confirmed to have AD with relatively preserved neurons in the hippocampus. This patient had delusional jealousy with a long pre-dementia stage, which initially was characterized by lack of memory impairment. Head magnetic resonance imaging findings showed preserved hippocampal volume with bilateral enlarged ventricles and mild-to-moderate cortical atrophy. Head single-photon emission computed tomography revealed severely decreased regional cerebral blood flow in the right temporal lobe. The resolution of the delusion was attributed to pharmacotherapy by an acetylcholinesterase inhibitor, suggesting that the occurrence of delusional jealousy was due to the disease process of AD. Although the neural basis of delusional jealousy remains unclear, this hippocampal-sparing AD case may be classified as an atypical presentation of AD. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

  8. Non-infectious environmental antigens as a trigger for the initiation of an autoimmune skin disease.

    PubMed

    Qian, Ye; Culton, Donna A; Jeong, Joseph S; Trupiano, Nicole; Valenzuela, Jesus G; Diaz, Luis A

    2016-09-01

    Pemphigus represents a group of organ specific autoimmune blistering disorders of the skin mediated by pathogenic autoantibodies with well-defined antigenic targets. While most of these diseases are sporadic, endemic forms of disease do exist. The endemic form of pemphigus foliaceus (also known as fogo selvagem, FS) exhibits epidemiological features that suggest exposure to hematophagous insect bites are a possible precipitating factor of this autoimmune disease, and provides a unique opportunity to study how environmental factors contribute to autoimmune disease development. FS patients and healthy individuals from endemic regions show an autoreactive IgM response that starts in early childhood and becomes restricted to IgG4 autoantibodies in FS patients. In searching for triggering environmental antigens, we have found that IgG4 and IgE autoantibodies from FS patients cross-react with a salivary antigen from sand flies. The presence of these cross-reactive antibodies and antibody genetic analysis confirming that these antibodies evolve from the same naïve B cells provides compelling evidence that this non-infectious environmental antigen could be the initial target of the autoantibody response in FS. Consequently, FS serves as an ideal model to study the impact of environmental antigens in the development of autoimmune disease.

  9. Neuroimaging of Lipid Storage Disorders

    ERIC Educational Resources Information Center

    Rieger, Deborah; Auerbach, Sarah; Robinson, Paul; Gropman, Andrea

    2013-01-01

    Lipid storage diseases, also known as the lipidoses, are a group of inherited metabolic disorders in which there is lipid accumulation in various cell types, including the central nervous system, because of the deficiency of a variety of enzymes. Over time, excessive storage can cause permanent cellular and tissue damage. The brain is particularly…

  10. Neuroimaging of Lipid Storage Disorders

    ERIC Educational Resources Information Center

    Rieger, Deborah; Auerbach, Sarah; Robinson, Paul; Gropman, Andrea

    2013-01-01

    Lipid storage diseases, also known as the lipidoses, are a group of inherited metabolic disorders in which there is lipid accumulation in various cell types, including the central nervous system, because of the deficiency of a variety of enzymes. Over time, excessive storage can cause permanent cellular and tissue damage. The brain is particularly…

  11. Multimodal Neuroimaging-Informed Clinical Applications in Neuropsychiatric Disorders.

    PubMed

    O'Halloran, Rafael; Kopell, Brian H; Sprooten, Emma; Goodman, Wayne K; Frangou, Sophia

    2016-01-01

    Recent advances in neuroimaging data acquisition and analysis hold the promise to enhance the ability to make diagnostic and prognostic predictions and perform treatment planning in neuropsychiatric disorders. Prior research using a variety of types of neuroimaging techniques has confirmed that neuropsychiatric disorders are associated with dysfunction in anatomical and functional brain circuits. We first discuss current challenges associated with the identification of reliable neuroimaging markers for diagnosis and prognosis in mood disorders and for neurosurgical treatment planning for deep brain stimulation (DBS). We then present data on the use of neuroimaging for the diagnosis and prognosis of mood disorders and for DBS treatment planning. We demonstrate how multivariate analyses of functional activation and connectivity parameters can be used to differentiate patients with bipolar disorder from those with major depressive disorder and non-affective psychosis. We also present data on connectivity parameters that mediate acute treatment response in affective and non-affective psychosis. We then focus on precision mapping of functional connectivity in native space. We describe the benefits of integrating anatomical fiber reconstruction with brain functional parameters and cortical surface measures to derive anatomically informed connectivity metrics within the morphological context of each individual brain. We discuss how this approach may be particularly promising in psychiatry, given the clinical and etiological heterogeneity of the disorders, and particularly in treatment response prediction and planning. Precision mapping of connectivity is essential for DBS. In DBS, treatment electrodes are inserted into positions near key gray matter nodes within the circuits considered relevant to disease expression. However, targeting white matter tracts that underpin connectivity within these circuits may increase treatment efficacy and tolerability therefore relevant

  12. Multimodal Neuroimaging-Informed Clinical Applications in Neuropsychiatric Disorders

    PubMed Central

    O’Halloran, Rafael; Kopell, Brian H.; Sprooten, Emma; Goodman, Wayne K.; Frangou, Sophia

    2016-01-01

    Recent advances in neuroimaging data acquisition and analysis hold the promise to enhance the ability to make diagnostic and prognostic predictions and perform treatment planning in neuropsychiatric disorders. Prior research using a variety of types of neuroimaging techniques has confirmed that neuropsychiatric disorders are associated with dysfunction in anatomical and functional brain circuits. We first discuss current challenges associated with the identification of reliable neuroimaging markers for diagnosis and prognosis in mood disorders and for neurosurgical treatment planning for deep brain stimulation (DBS). We then present data on the use of neuroimaging for the diagnosis and prognosis of mood disorders and for DBS treatment planning. We demonstrate how multivariate analyses of functional activation and connectivity parameters can be used to differentiate patients with bipolar disorder from those with major depressive disorder and non-affective psychosis. We also present data on connectivity parameters that mediate acute treatment response in affective and non-affective psychosis. We then focus on precision mapping of functional connectivity in native space. We describe the benefits of integrating anatomical fiber reconstruction with brain functional parameters and cortical surface measures to derive anatomically informed connectivity metrics within the morphological context of each individual brain. We discuss how this approach may be particularly promising in psychiatry, given the clinical and etiological heterogeneity of the disorders, and particularly in treatment response prediction and planning. Precision mapping of connectivity is essential for DBS. In DBS, treatment electrodes are inserted into positions near key gray matter nodes within the circuits considered relevant to disease expression. However, targeting white matter tracts that underpin connectivity within these circuits may increase treatment efficacy and tolerability therefore relevant

  13. Neuroimaging findings of Zika virus infection: a review article.

    PubMed

    Zare Mehrjardi, Mohammad; Keshavarz, Elham; Poretti, Andrea; Hazin, Adriano N

    2016-12-01

    Zika virus (ZIKV) is an arbovirus from the Flaviviridae family. It is usually transmitted by mosquito bite. There have been no reports of severe symptoms caused by ZIKV infection up until the last few years. In October 2013 an outbreak was reported in French Polynesia with severe neurological complications in some affected cases. In November 2015, the Ministry of Health of Brazil attributed the increased number of neonatal microcephaly cases in northeastern Brazil to congenital ZIKV infection. The rapid spread of the virus convinced the World Health Organization to announce ZIKV infection as a "Public Health Emergency of International Concern" in February 2016. The main neuroimaging findings in congenital ZIKV infection include microcephaly which is the hallmark of the disease, other malformations of cortical development (e.g., lissencephaly, heterotopia, etc.), parenchymal calcifications, unilateral or bilateral ventriculomegaly, enlarged extra-axial CSF spaces, dysgenesis of the corpus callosum, agenesis of the cavum septum pellucidum, cerebellar and brainstem hypoplasia, and ocular abnormalities. ZIKV infection may also cause Guillain-Barré syndrome and acute disseminated encephalomyelitis in adults. Familiarity with neuroimaging findings of congenital and acquired ZIKV infection is crucial to suspect this disease in residents of endemic regions and travelers to these areas.

  14. Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature.

    PubMed

    Walitt, Brian; Ceko, Marta; Gracely, John L; Gracely, Richard H

    2016-01-01

    Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes. We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes. Evoked sensory paradigms reveal sensory augmentation to both painful and nonpainful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin. However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature. Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes. A defining neuroimaging "signature" cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes. At this time, the existence of "central sensitivity syndromes" is based more soundly on clinical and epidemiological evidence. A coherent picture of a "central sensitization" mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence.

  15. Meningococcal disease in the Asia-Pacific region: Findings and recommendations from the Global Meningococcal Initiative.

    PubMed

    Borrow, Ray; Lee, Jin-Soo; Vázquez, Julio A; Enwere, Godwin; Taha, Muhamed-Kheir; Kamiya, Hajime; Kim, Hwang Min; Jo, Dae Sun

    2016-11-21

    The Global Meningococcal Initiative (GMI) is a global expert group that includes scientists, clinicians, and public health officials with a wide range of specialties. The purpose of the Initiative is to promote the global prevention of meningococcal disease (MD) through education, research, and cooperation. The first Asia-Pacific regional meeting was held in November 2014. The GMI reviewed the epidemiology of MD, surveillance, and prevention strategies, and outbreak control practices from participating countries in the Asia-Pacific region.Although, in general, MD is underreported in this region, serogroup A disease is most prominent in low-income countries such as India and the Philippines, while Taiwan, Japan, and Korea reported disease from serogroups C, W, and Y. China has a mixed epidemiology of serogroups A, B, C, and W. Perspectives from countries outside of the region were also provided to provide insight into lessons learnt. Based on the available data and meeting discussions, a number of challenges and data gaps were identified and, as a consequence, several recommendations were formulated: strengthen surveillance; improve diagnosis, typing and case reporting; standardize case definitions; develop guidelines for outbreak management; and promote awareness of MD among healthcare professionals, public health officials, and the general public.

  16. The impact of birth weight on cardiovascular disease risk in the Women's Health Initiative.

    PubMed

    Smith, C J; Ryckman, K K; Barnabei, V M; Howard, B V; Isasi, C R; Sarto, G E; Tom, S E; Van Horn, L V; Wallace, R B; Robinson, J G

    2016-03-01

    Cardiovascular disease (CVD) is among the leading causes of morbidity and mortality worldwide. Traditional risk factors predict 75-80% of an individual's risk of incident CVD. However, the role of early life experiences in future disease risk is gaining attention. The Barker hypothesis proposes fetal origins of adult disease, with consistent evidence demonstrating the deleterious consequences of birth weight outside the normal range. In this study, we investigate the role of birth weight in CVD risk prediction. The Women's Health Initiative (WHI) represents a large national cohort of post-menopausal women with 63,815 participants included in this analysis. Univariable proportional hazards regression analyses evaluated the association of 4 self-reported birth weight categories against 3 CVD outcome definitions, which included indicators of coronary heart disease, ischemic stroke, coronary revascularization, carotid artery disease and peripheral arterial disease. The role of birth weight was also evaluated for prediction of CVD events in the presence of traditional risk factors using 3 existing CVD risk prediction equations: one body mass index (BMI)-based and two laboratory-based models. Low birth weight (LBW) (<6 lbs.) was significantly associated with all CVD outcome definitions in univariable analyses (HR = 1.086, p = 0.009). LBW was a significant covariate in the BMI-based model (HR = 1.128, p < 0.0001) but not in the lipid-based models. LBW (<6 lbs.) is independently associated with CVD outcomes in the WHI cohort. This finding supports the role of the prenatal and postnatal environment in contributing to the development of adult chronic disease. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  17. The impact of birth weight on cardiovascular disease risk in the Women's Health Initiative

    PubMed Central

    Smith, CJ; Ryckman, KK; Barnabei, Vanessa M.; Howard, Barbara; Isasi, Carmen R.; Sarto, Gloria; Tom, Sarah E.; Van Horn, Linda; Wallace, Robert; Robinson, Jennifer G

    2016-01-01

    Background and Aims Cardiovascular disease (CVD) is among the leading causes of morbidity and mortality worldwide. Traditional risk factors predict 75-80% of an individual's risk of incident CVD. However, the role of early life experiences in future disease risk is gaining attention. The Barker hypothesis proposes fetal origins of adult disease, with consistent evidence demonstrating the deleterious consequences of birth weight outside the normal range. In this study, we investigate the role of birth weight in CVD risk prediction. Methods and Results The Women's Health Initiative (WHI) represents a large national cohort of post-menopausal women with 63 815 participants included in this analysis. Univariable proportional hazards regression analyses evaluated the association of 4 self-reported birth weight categories against 3 CVD outcome definitions, which included indicators of coronary heart disease, ischemic stroke, coronary revascularization, carotid artery disease and peripheral arterial disease. The role of birth weight was also evaluated for prediction of CVD events in the presence of traditional risk factors using 3 existing CVD risk prediction equations: one body mass index (BMI)-based and two laboratory-based models. Low birth weight (LBW) (< 6 lbs.) was significantly associated with all CVD outcome definitions in univariable analyses (HR=1.086, p=0.009). LBW was a significant covariate in the BMI-based model (HR=1.128, p<0.0001) but not in the lipid-based models. Conclusion LBW (<6 lbs.) is independently associated with CVD outcomes in the WHI cohort. This finding supports the role of the prenatal and postnatal environment in contributing to the development of adult chronic disease. PMID:26708645

  18. Indocyanine green angiographic findings in initial-onset acute Vogt-Koyanagi-Harada disease.

    PubMed

    Abouammoh, Marwan A; Gupta, Vishali; Hemachandran, Suhail; Herbort, Carl P; Abu El-Asrar, Ahmed M

    2016-09-01

    To study the features of Indocyanine green angiography (ICGA) in patients with initial-onset acute Vogt-Koyanagi-Harada (VKH) disease. Retrospective cohort study of ICGA performed with the use of Heidelberg scanning laser ophthalmoscope on a consecutive series of patients with initial-onset acute VKH disease. The following signs were analysed: choroidal perfusion inhomogeneity, early hyperfluorescent stromal vessels, hypofluorescent dark dots (HDDs), fuzzy or lost pattern of large stromal choroidal vessels, disc hyperfluorescence, and, diffuse late choroidal hyperfluorescence. In addition, we looked for any new ICGA findings. Thirty-six patients (72 eyes) from a single academic institution were studied. The following findings were identified: HDDs in all eyes (100%), fuzzy or lost pattern of large stromal vessels in all eyes (100%), early hyperfluorescent stromal vessels were seen in 60 eyes (83%), diffuse late choroidal hyperfluorescence was present in 51 eyes (71%), choroidal perfusion inhomogeneity was seen in 44 eyes (61%), disc hyperfluorescence was seen in 25 cases (69%), and choroidal folds were present in only six eyes. New ICGA findings detected in this study were hypofluorescent patches corresponding to areas of exudative retinal detachment in 60 eyes (83%) and 'starry sky' pattern of late widespread punctate choroidal hyperfluorescence in 37 eyes (51%). The most prevalent ICGA findings were HDDs, fuzzy stromal vessels and early hyperfluorescent stromal vessels in patients with initial-onset acute VKH disease. Novel ICGA findings in this group of patients included hypofluorescent patches corresponding to areas of exudative retinal detachment, and late widespread punctate choroidal hyperfluorescence taking on a 'starry sky' pattern. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. Is tree loss associated with cardiovascular-disease risk in the Women's Health Initiative? A natural experiment

    Treesearch

    Geoffrey H. Donovan; Yvonne L. Michael; Demetrios Gatziolis; Jeffrey P. Prestemon; Eric A. Whitsel

    2015-01-01

    Data from the Women's Health Initiative were used to quantify the relationship between the loss of trees to an invasive forest pest—the emerald ash borer—and cardiovascular disease. We estimated semi- parametric Cox proportional hazards model of time to cardiovascular disease, adjusting for confounders. We defined the incidence of cardiovascular disease as acute...

  20. Pulmonary Nodules as an Initial Manifestation of Behçet's Disease

    PubMed Central

    Malekmohammad, M.; Emamifar, A.

    2014-01-01

    Behçet's disease (BD) is a systemic vasculopathy, characterized by recurrent oral aphthae, genital ulcers, uveitis, and skin lesions. Although vascular involvement, including venous and arteries of any size, is a usual manifestation, cases with pulmonary thrombosis as the initial symptom are not common in the absence of pulmonary artery aneurysm (PAA). This report describes a 36-year-old man with recurrent fever, nonmassive hemoptysis, and persistent cough with lung nodules in CT scan who had undergone open lung biopsy. On the basis of morphological findings, BD was suggested and more precise evaluation confirmed the diagnosis. PMID:25436168

  1. Chylothorax and chylopericardium as the initial clinical manifestation of Behcet's disease.

    PubMed

    Moon, H; Lee, Y J; Lee, S I; Yoo, W H

    2008-02-01

    Behcet's disease (BD) is a chronic relapsing systemic vasculitic disorder affecting the arteries, veins, and vessels of any size. Large vein thrombosis in BD is not commonly developed and most commonly observed in the veins in the lower extremities and inferior or superior vena cava. In this report, a 18-year-old male patient with large vein thrombosis involving superior vena cava was presented. He was treated due to chylothorax and chylopericardium with SVC syndrome before diagnosis of BD. SVC thrombosis complicated by chylothorax and chyolpericardium can be a rare presenting initial symptom of BD.

  2. Tubulointerstitial Nephritis as the Initial Presentation of Crohn’s Disease and Successful Treatment with Infliximab

    PubMed Central

    Caza, Tiffany; Huang, Dongmei; Beg, Mirza B.

    2017-01-01

    Tubulointerstitial nephritis (TIN) is not commonly associated in aminosalicylate-naïve patients with Crohn’s disease (CD). Our case describes the initial presentation, diagnosis, and management of an adolescent presenting with TIN and underlying CD. Our case emphasizes that CD should be considered in the differential diagnosis of interstitial nephritis as not only a medication-related effect, but also as an extraintestinal manifestation of CD. We also describe successful management of undiagnosed recurring and symptomatic CD-related TIN with infliximab. PMID:28286790

  3. Heritability and Genetic Association Analysis of Neuroimaging Measures in the Diabetes Heart Study

    PubMed Central

    Raffield, Laura M; Cox, Amanda J; Hugenschmidt, Christina E; Freedman, Barry I; Langefeld, Carl D; Williamson, Jeff D; Hsu, Fang-Chi; Maldjian, Joseph A; Bowden, Donald W

    2014-01-01

    Patients with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Neuroimaging measures such as white matter lesion volume, brain volume, and fractional anisotropy may reflect the pathogenesis of these cognitive declines, and genetic factors may contribute to variability in these measures. This study examined multiple neuroimaging measures in 465 participants from 238 families with extensive genotype data in the type 2 diabetes enriched Diabetes Heart Study-Mind cohort. Heritability of these phenotypes and their association with candidate single nucleotide polymorphisms (SNPs) and SNP data from genome-and exome-wide arrays was explored. All neuroimaging measures analysed were significantly heritable (ĥ2 =0.55–0.99 in unadjusted models). Seventeen candidate SNPs (from 16 genes/regions) associated with neuroimaging phenotypes in prior studies showed no significant evidence of association. A missense variant (rs150706952, A432V) in PLEKHG4B from the exome-wide array was significantly associated with white matter mean diffusivity (p=3.66×10−7) and gray matter mean diffusivity (p=2.14×10−7). This analysis suggests genetic factors contribute to variation in neuroimaging measures in a population enriched for metabolic disease and other associated comorbidities. PMID:25523635

  4. A review of the recent advances in neuroimaging of frontotemporal lobar degeneration.

    PubMed

    D'Agata, Federico; Orsi, Laura; Cicerale, Alessandro; Rubino, Elisa; Rainero, Innocenzo; Bergui, Mauro; Pinessi, Lorenzo

    2017-04-01

    The term "frontotemporal lobar degeneration" (FTLD) includes a large set of neurodegenerative diseases, which are heterogeneous in their genetic, pathologic and clinical aspects. This review will focus on the most recent contribution of neuroimaging tools on the diagnosis, characterization and pathogenesis of FTLD. Scopus, Ovid, PubMed and MEDLINE were searched for articles published from January 2012 up to December 2014. Searches were limited to articles published in English. Frontotemporal lobar degeneration as a key word was always in the search queries in combination with logic AND, and at least one other key word. We found 91 papers of interest and reviewed their contents, finding in particular 4 major topics: the contribution of neuroimaging on the differential diagnosis; patients' functional characterization; new neuroimaging tools under development and pre-symptomatic genetic forms. Neuroimaging techniques have shown to be useful supporting tools in diagnosis, even if not always determinant to reach a conclusive decision, and quite important to identify phenocopies. At the moment, there is not a neuroimaging biomarker that could track the progressive course of dementias and the effect of therapies, but it is possible that in the future Diffusion Tensor Imaging and molecular imaging could fill this void. Monitoring the evolution of the pathology in vivo for at least 5 years is essential, and this would only be possible in a large multicenter study; asymptomatic forms would require even longer observation periods.

  5. Heritability and genetic association analysis of neuroimaging measures in the Diabetes Heart Study.

    PubMed

    Raffield, Laura M; Cox, Amanda J; Hugenschmidt, Christina E; Freedman, Barry I; Langefeld, Carl D; Williamson, Jeff D; Hsu, Fang-Chi; Maldjian, Joseph A; Bowden, Donald W

    2015-03-01

    Patients with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Neuroimaging measures such as white matter lesion volume, brain volume, and fractional anisotropy may reflect the pathogenesis of these cognitive declines, and genetic factors may contribute to variability in these measures. This study examined multiple neuroimaging measures in 465 participants from 238 families with extensive genotype data in the type 2 diabetes enriched Diabetes Heart Study-Mind cohort. Heritability of these phenotypes and their association with candidate single-nucleotide polymorphisms (SNPs), and SNP data from genome- and exome-wide arrays were explored. All neuroimaging measures analyzed were significantly heritable (ĥ(2) = 0.55-0.99 in unadjusted models). Seventeen candidate SNPs (from 16 genes/regions) associated with neuroimaging phenotypes in prior studies showed no significant evidence of association. A missense variant (rs150706952, A432V) in PLEKHG4B from the exome-wide array was significantly associated with white matter mean diffusivity (p = 3.66 × 10(-7)) and gray matter mean diffusivity (p = 2.14 × 10(-7)). This analysis suggests genetic factors contribute to variation in neuroimaging measures in a population enriched for metabolic disease and other associated comorbidities. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Moving Forward with Prisms: Sensory-Motor Adaptation Improves Gait Initiation in Parkinson’s Disease

    PubMed Central

    Bultitude, Janet H.; Rafal, Robert D.; Tinker, Corinne

    2012-01-01

    It is postulated that the decreased walking speed; small, shuffling steps; and “freezing” shown by patients with Parkinson’s disease could stem from an inability to tilt the body forward enough to provide sufficient forward propulsion. In two repeated-measures studies we examined whether adaptation to upward-shifting prisms, resulting in a downward after-effect, could improve gait initiation in healthy participants and patients with Parkinson’s disease. Faster forward stepping followed a brief (5 min) exposure period for patients, and a longer (20 min) exposure period for age-matched controls. Backward stepping was unchanged, and adaptation to downward-shifting prisms with control participants showed no effect on forward or backward stepping. These results suggest that adaptation of arm proprioception in the vertical plane may generalize to anterior-posterior postural control, presenting new possibilities for the treatment of gait disturbance in basal ganglia disorders. PMID:23060852

  7. Moving forward with prisms: sensory-motor adaptation improves gait initiation in Parkinson's disease.

    PubMed

    Bultitude, Janet H; Rafal, Robert D; Tinker, Corinne

    2012-01-01

    It is postulated that the decreased walking speed; small, shuffling steps; and "freezing" shown by patients with Parkinson's disease could stem from an inability to tilt the body forward enough to provide sufficient forward propulsion. In two repeated-measures studies we examined whether adaptation to upward-shifting prisms, resulting in a downward after-effect, could improve gait initiation in healthy participants and patients with Parkinson's disease. Faster forward stepping followed a brief (5 min) exposure period for patients, and a longer (20 min) exposure period for age-matched controls. Backward stepping was unchanged, and adaptation to downward-shifting prisms with control participants showed no effect on forward or backward stepping. These results suggest that adaptation of arm proprioception in the vertical plane may generalize to anterior-posterior postural control, presenting new possibilities for the treatment of gait disturbance in basal ganglia disorders.

  8. Calcium in the initiation, progression and as an effector of Alzheimer’s disease pathology

    PubMed Central

    Green, Kim N

    2009-01-01

    The cause(s) of sporadic Alzheimer’s disease (sAD) are complex and currently poorly understood. They likely result from a combination of genetic, environmental, proteomic and lipidomic factors that crucially occur only in the aged brain. Age-related changes in calcium levels and dynamics have the potential to increase the production and accumulation of both amyloid-β peptide (Aβ) and τ pathologies in the AD brain, although these two pathologies themselves can induce calcium dyshomeostasis, particularly at synaptic membranes. This review discuses the evidence for a role for calcium dyshomeostasis in the initiation of pathology, as well as the evidence for these pathologies themselves disrupting normal calcium homeostasis, which lead to synaptic and neuronal dysfunction, synaptotoxicity and neuronal loss, underlying the dementia associated with the disease. PMID:19650832

  9. Candidate DNA replication initiation regions at human trinucleotide repeat disease loci.

    PubMed

    Nenguke, Taurai; Aladjem, Mirit I; Gusella, James F; Wexler, Nancy S; Arnheim, Norman

    2003-05-01

    The positions of DNA replication initiation regions (IRs) at three human trinucleotide repeat (TNR) disease loci were examined in order to characterize the role played by IRs in explaining the known locus-specific variation in TNR instability levels. Using three different normal cell lines, candidate IRs were identified at the HD, SCA-7 and SBMA loci. At each locus the IR is less than 3.6 kb from the CAG/CTG repeat tract. Preliminary studies with a cell line homozygous for an HD disease mutation indicated no change in the position of the candidate IR in spite of the mutation. Comparison with experimental results from model systems suggests that a complex relationship may exist between instability and the proximity and/or orientation of the repeats with respect to an IR.

  10. Ethnoracial Differences in the Clinical Characteristics of Alzheimer Disease at Initial Presentation at an Urban Alzheimer’s Disease Center

    PubMed Central

    Livney, Melissa Gartenberg; Clark, Christopher M.; Karlawish, Jason H.; Cartmell, Su; Negrón, Mirna; Nuñez-Lopez, Jessica; Xie, Sharon X.; Entenza-Cabrera, Fernando; Vega, Irving E.; Arnold, Steven E.

    2010-01-01

    Objective To compare presentation of Alzheimer disease (AD) at the time of initial evaluation at a university specialty clinic across three ethnoracial groups in order to understand similarities and differences in the demographic, clinical, cognitive, psychiatric, and biologic features. Design Cross-sectional study. Participants A total of 1,341 self-identified African American, Latino (primarily of Caribbean origin), and white non-Hispanic (“WNH”) subjects were recruited from primary care sites or by referral by primary care physicians. Measurements Demographic variables and age of onset of AD, as well as cognitive, functional, and mood impairments at the time of initial presentation and frequencies of apolipoprotein E genotypes, were compared across groups. Results Differences among ethnoracial groups were found for nearly all variables of interest. In particular, the largely immigrant Puerto Rican Latino group had an earlier age of onset of AD, more cognitive impairment, and greater severity of cognitive impairment at the time of initial evaluation in the setting of low average education and socioeconomic status. There was more depression in the Latinos compared with African Americans and WNHs. Greater severity of symptoms was not accounted for by a difference in lag time between onset of symptoms and initial evaluation. The apolipoprotein E-4 genotype was not associated with AD in the Latino cohort. Conclusions Minority groups in Philadelphia, especially Latinos, exhibit a more severe profile of AD at the time of presentation than WNHs. Important potential confounds need to be considered and future research comparing immigrant and nonimmigrant Latino groups will be necessary to elucidate the highly significant differences reported. PMID:21522051

  11. Ethnoracial differences in the clinical characteristics of Alzheimer's disease at initial presentation at an urban Alzheimer's disease center.

    PubMed

    Livney, Melissa Gartenberg; Clark, Christopher M; Karlawish, Jason H; Cartmell, Su; Negrón, Mirna; Nuñez, Jessica; Xie, Sharon X; Entenza-Cabrera, Fernando; Vega, Irving E; Arnold, Steven E

    2011-05-01

    To compare presentation of Alzheimer disease (AD) at the time of initial evaluation at a university specialty clinic across three ethnoracial groups in order to understand similarities and differences in the demographic, clinical, cognitive, psychiatric, and biologic features. Cross-sectional study. A total of 1,341 self-identified African American, Latino (primarily of Caribbean origin), and white non-Hispanic ("WNH") subjects were recruited from primary care sites or by referral by primary care physicians. Demographic variables and age of onset of AD, as well as cognitive, functional, and mood impairments at the time of initial presentation and frequencies of apolipoprotein E genotypes, were compared across groups. Differences among ethnoracial groups were found for nearly all variables of interest. In particular, the largely immigrant Puerto Rican Latino group had an earlier age of onset of AD, more cognitive impairment, and greater severity of cognitive impairment at the time of initial evaluation in the setting of low average education and socioeconomic status. There was more depression in the Latinos compared with African Americans and WNHs. Greater severity of symptoms was not accounted for by a difference in lag time between onset of symptoms and initial evaluation. The apolipoprotein E-4 genotype was not associated with AD in the Latino cohort. Minority groups in Philadelphia, especially Latinos, exhibit a more severe profile of AD at the time of presentation than WNHs. Important potential confounds need to be considered and future research comparing immigrant and nonimmigrant Latino groups will be necessary to elucidate the highly significant differences reported.

  12. Sparse kernel entropy component analysis for dimensionality reduction of neuroimaging data.

    PubMed

    Jiang, Qikun; Shi, Jun

    2014-01-01

    The neuroimaging data typically has extremely high dimensions. Therefore, dimensionality reduction is commonly used to extract discriminative features. Kernel entropy component analysis (KECA) is a newly developed data transformation method, where the key idea is to preserve the most estimated Renyi entropy of the input space data set via a kernel-based estimator. Despite its good performance, KECA still suffers from the problem of low computational efficiency for large-scale data. In this paper, we proposed a sparse KECA (SKECA) algorithm with the recursive divide-and-conquer based solution, and then applied it to perform dimensionality reduction of neuroimaging data for classification of the Alzheimer's disease (AD). We compared the SKECA with KECA, principal component analysis (PCA), kernel PCA (KPCA) and sparse KPCA. The experimental results indicate that the proposed SKECA has most superior performance to all other algorithms when extracting discriminative features from neuroimaging data for AD classification.

  13. Mind-Body Practices and the Adolescent Brain: Clinical Neuroimaging Studies

    PubMed Central

    Sharma, Anup; Newberg, Andrew B

    2016-01-01

    Background Mind-Body practices constitute a large and diverse group of practices that can substantially affect neurophysiology in both healthy individuals and those with various psychiatric disorders. In spite of the growing literature on the clinical and physiological effects of mind-body practices, very little is known about their impact on central nervous system (CNS) structure and function in adolescents with psychiatric disorders. Method This overview highlights findings in a select group of mind-body practices including yoga postures, yoga breathing techniques and meditation practices. Results Mind-body practices offer novel therapeutic approaches for adolescents with psychiatric disorders. Findings from these studies provide insights into the design and implementation of neuroimaging studies for adolescents with psychiatric disorders. Conclusions Clinical neuroimaging studies will be critical in understanding how different practices affect disease pathogenesis and symptomatology in adolescents. Neuroimaging of mind-body practices on adolescents with psychiatric disorders will certainly be an open and exciting area of investigation. PMID:27347478

  14. Spirometry utilisation among Danish adults initiating medication targeting obstructive lung disease.

    PubMed

    Koefoed, Mette Marie

    2015-02-01

    This PhD thesis was written during my employment at the Research Unit of General Practice in Odense, University of Southern Denmark. It comprises an overview and three papers, all published or submitted for publication in international peer-reviewed scientific journals.   Non-infectious dyspnoea, chronic cough and wheezing are common symptoms in the population. Patients often present with these symptoms in general practice and have a high probability of having obstructive lung diseases. However, there is an indication that the majority of these patients are treated empirically with pharmacotherapy targeting obstructive lung disease and only few have additional tests conducted, although the predictive value of respiratory symptoms for diagnosing obstructive lung disease has proven to be low. Spirometry is recommended as the gold standard for confirming obstructive lung disease, and testing can also rule out airway obstruction in patients with respiratory symptoms caused by other illnesses, such as heart failure or lung cancer. Initiating medication for obstructive lung disease without spirometry entails the risk of these patients experiencing unnecessary delay in the diagnostic process and being exposed to unnecessary economic costs and medication risks. The literature has indicated that many users of medication targeting obstructive lung medication have not had spirometry performed and do not actually have obstructive lung disease. This potential quality gap needs to be assessed. Also, in order to target interventions enhancing earlier spirometry utilisation among patients initiating medication targeting obstructive lung disease, improved knowledge on patient and practice factors associated with spirometry testing is needed.   Among first time users of obstructive lung medication we aimed: - To assess to what extent spirometry was performed within the first year of medication use (Study I) - To assess if patient characteristics like socioeconomic and demographic

  15. Initiation and engagement in chronic disease management care for substance dependence.

    PubMed

    Kim, Theresa W; Saitz, Richard; Cheng, Debbie M; Winter, Michael R; Witas, Julie; Samet, Jeffrey H

    2011-05-01

    Substance dependence treatment is often episodic and not well coordinated with healthcare for common comorbidities. Chronic disease/care management (CDM), longitudinal, patient-centered care delivered by multidisciplinary health professionals, may be well suited to treat substance dependence (SD). To examine initiation and engagement with CDM care for SD located in a primary medical setting. We prospectively studied substance dependent participants enrolled in a trial of CDM addiction care. Primary study outcomes, based upon Washington Circle performance measures, were 14-day initiation of CDM care and 30-day engagement with CDM care. Factors associated with these outcomes were determined using multivariable logistic regression models. We also estimated the proportion of participants who eventually attended at least two visits and four visits by the end of the study (Kaplan-Meier method). Of 282 participants, approximately half of the cohort (45%, 95% Confidence Interval [CI] 39-51%) met criteria for 14-day initiation and 23% (95% CI 18-28%) for 30-day engagement with CDM care. Most participants attended two or more (81%, 95% CI 76-85%) and four or more CDM visits (62%, 95% CI 56-68%). Major depressive episode (AOR 2.60, 95% CI 1.39, 4.87) was associated with higher odds of 14-day initiation; younger age, female sex, and higher alcohol addiction severity were associated with lower odds of 30-day engagement with CDM care. People with SD appear to be willing to initiate and engage with CDM care in a primary medical care setting. CDM care has the potential to improve the quality of care for people with addictions. Copyright © 2010. Published by Elsevier Ireland Ltd.

  16. Neuromarketing: the hope and hype of neuroimaging in business.

    PubMed

    Ariely, Dan; Berns, Gregory S

    2010-04-01

    The application of neuroimaging methods to product marketing - neuromarketing - has recently gained considerable popularity. We propose that there are two main reasons for this trend. First, the possibility that neuroimaging will become cheaper and faster than other marketing methods; and second, the hope that neuroimaging will provide marketers with information that is not obtainable through conventional marketing methods. Although neuroimaging is unlikely to be cheaper than other tools in the near future, there is growing evidence that it may provide hidden information about the consumer experience. The most promising application of neuroimaging methods to marketing may come before a product is even released - when it is just an idea being developed.

  17. Initial and Long-Term Costs of Patients Hospitalized with West Nile Virus Disease

    PubMed Central

    Staples, J. Erin; Shankar, Manjunath B.; Sejvar, James J.; Meltzer, Martin I.; Fischer, Marc

    2014-01-01

    There are no published data on the economic burden for specific West Nile virus (WNV) clinical syndromes (i.e., fever, meningitis, encephalitis, and acute flaccid paralysis [AFP]). We estimated initial hospital and lost-productivity costs from 80 patients hospitalized with WNV disease in Colorado during 2003; 38 of these patients were followed for 5 years to determine long-term medical and lost-productivity costs. Initial costs were highest for patients with AFP (median $25,117; range $5,385–$283,381) and encephalitis (median $20,105; range $3,965–$324,167). Long-term costs were highest for patients with AFP (median $22,628; range $624–$439,945) and meningitis (median $10,556; range $0–$260,748). Extrapolating from this small cohort to national surveillance data, we estimated the total cumulative costs of reported WNV hospitalized cases from 1999 through 2012 to be $778 million (95% confidence interval $673 million–$1.01 billion). These estimates can be used in assessing the cost-effectiveness of interventions to prevent WNV disease. PMID:24515937

  18. Functional analysis of the internal translation initiation site of foot-and-mouth disease virus.

    PubMed Central

    Kühn, R; Luz, N; Beck, E

    1990-01-01

    Mutagenesis of the large untranslated sequence at the 5' end of the genome of foot-and-mouth disease virus revealed that a region of approximately 450 nucleotides preceding the open reading frame of the viral polyprotein is involved in the regulation of translation initiation at two internal start sites. Variations in two domains of this region reduced the translation efficiency up to 10-fold, whereas an intermediate segment seemed to be less essential. A pyrimidine-rich sequence precedi