Browsing by Author "Quaid, Kimberly A."
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Item [(11)C]PiB PET in Gerstmann-Sträussler-Scheinker disease(e-Century Publishing Corporation, 2016) Deters, Kacie D.; Risacher, Shannon L.; Yoder, Karmen K.; Oblak, Adrian L.; Unverzagt, Frederick W.; Murrell, Jill R.; Epperson, Francine; Tallman, Eileen F.; Quaid, Kimberly A.; Farlow, Martin R.; Saykin, Andrew J.; Ghetti, Bernardino; Department of Pathology & Laboratory Medicine, IU School of MedicineGerstmann-Sträussler-Scheinker Disease (GSS) is a familial neurodegenerative disorder characterized clinically by ataxia, parkinsonism, and dementia, and neuropathologically by deposition of diffuse and amyloid plaques composed of prion protein (PrP). The purpose of this study was to evaluate if [(11)C]Pittsburgh Compound B (PiB) positron emission tomography (PET) is capable of detecting PrP-amyloid in PRNP gene carriers. Six individuals at risk for GSS and eight controls underwent [(11)C]PiB PET scans using standard methods. Approximately one year after the initial scan, each of the three asymptomatic carriers (two with PRNP P102L mutation, one with PRNP F198S mutation) underwent a second [(11)C]PiB PET scan. Three P102L carriers, one F198S carrier, and one non-carrier of the F198S mutation were cognitively normal, while one F198S carrier was cognitively impaired during the course of this study. No [(11)C]PiB uptake was observed in any subject at baseline or at follow-up. Neuropathologic study of the symptomatic individual revealed PrP-immunopositive plaques and tau-immunopositive neurofibrillary tangles in cerebral cortex, subcortical nuclei, and brainstem. PrP deposits were also numerous in the cerebellar cortex. This is the first study to investigate the ability of [(11)C]PiB PET to bind to PrP-amyloid in GSS F198S subjects. This finding suggests that [(11)C]PiB PET is not suitable for in vivo assessment of PrP-amyloid plaques in patients with GSS.Item Benchmarks for ethically credible partnerships between industry and academic health centers: beyond disclosure of financial conflicts of interest(Springer (Biomed Central Ltd.), 2015-12) Meslin, Eric M.; Rager, Joshua B.; Schwartz, Peter H.; Quaid, Kimberly A.; Gaffney, Margaret M.; Duke, Jon; Tierney, William H.; Department of Philosophy, IU School of Liberal ArtsRelationships between industry and university-based researchers have been commonplace for decades and have received notable attention concerning the conflicts of interest these relationships may harbor. While new efforts are being made to update conflict of interest policies and make industry relationships with academia more transparent, the development of broader institutional partnerships between industry and academic health centers challenges the efficacy of current policy to effectively manage these innovative partnerships. In this paper, we argue that existing strategies to reduce conflicts of interest are not sufficient to address the emerging models of industry-academic partnerships because they focus too narrowly on financial matters and are not comprehensive enough to mitigate all ethical risk. Moreover, conflict-of-interest strategies are not designed to promote best practices nor the scientific and social benefits of academic-industry collaboration. We propose a framework of principles and benchmarks for "ethically credible partnerships" between industry and academic health centers and describe how this framework may provide a practical and comprehensive approach for designing and evaluating such partnerships.Item Characterizing neurodegeneration in the human connectome: a network science study of hereditary diffuse leukoencephalopathy with spheroids(Office of the Vice Chancellor for Research, 2015-04-17) Contreras, Joey; Rishacher, Shannon L.; West, John D.; Wu, Yu-Chien; Wang, Yang; Murrell, Jill R.; Dzemidzic, Mario; Farlow, Martin R.; Unverzagt, Frederik; Ghetti, Bernardino; Matthews, Brandy R.; Quaid, Kimberly A.; Sporns, Olaf; Saykin, Andrew J.; Goñi, JoaquínAbstract The effect of white matter neurodegeneration on the human connectome and its functional implications is an important topic with clinical applicability of advanced brain network analysis. The aim of this study was to evaluate integration and segregation changes in structural connectivity (SC) that arise as consequence of white matter lesions in hereditary diffuse leukoencephalopathy with spheroids (HDLS). Also, we assessed the relationship between HDLS induced structural changes and changes in restingstate functional connectivity (rsFC). HDLS is a rare autosomal dominant neurodegenerative disorder caused by mutations in the CSF1R gene. HDLS is characterized by severe white matter damage leading to prominent subcortical lesions detectable by structural MRI. Spheroids, an important feature of HDLS, are axonal swellings indicating damage. HDLS causes progressive motor and cognitive decline. The clinical symptoms of HDLS are often mistaken for other diseases such as Alzheimer’s disease, frontotemporal dementia, atypical Parkinsonism or multiple sclerosis. Our study is focused on the follow-up of two siblings, one being a healthy control (HC) and the other one being an HDLS patient. In this study, deterministic fiber-tractography of diffusion MRI with multi-tensor modeling was used in order to obtain reliable and reproducible SC matrices. Integration changes were measured by means of SC shortest-paths (including distance and number of edges), whereas segregation and community organization were measured by means of a multiplex modularity analysis on the SC matrices. Additionally, rsFC was modeled using state of the art preprocessing methods including motion regressors and scrubbing. This allowed us to characterize functional changes associated to the disease. Major integration disruption involved superior frontal (L,R), caudal middle frontal (R), precentral (L,R), inferior parietal (R), insula (R) and paracentral (L) regions. Major segregation changes were characterized by the disruption of a large bilateral module that was observed in the HC that includes the frontal pole (L,R), medial orbitofrontal (L,R), rostral middle frontal (L), superior frontal (L,R), precentral (L,R), paracentral (L,R), rostral anterior cingulate (L,R), caudal anterior cingulate (L,R), posterior cingulate (L,R), postcentral (L), precuneus (L,R), lateral orbitofrontal (R) and parsorbitalis (R). The combination of tractography and network analysis permitted the detection and characterization of profound cortical to cortical changes in integration and segregation associated with HDLS white matter lesions and its relationship with rsFC. Our preliminary findings suggest that advanced network analytic approaches show promising sensitivity to known white matter pathology and progression. Further Indiana Alzheimer Disease Center Symposium. March 6, 2015. research is needed to address the specificity of network profiles for differentiation among white matter pathologies and diseases.Item Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer's disease(SpringerNature, 2017-04-27) Müller, Stephan; Preische, Oliver; Sohrabi, Hamid R.; Gräber, Susanne; Jucker, Mathias; Dietzsch, Janko; Ringman, Ralph N.; Martins, Ralph N.; McDade, Eric; Schofield, Peter R.; Ghetti, Bernardino; Rossor, Martin; Graff-Radford, Neill R.; Levin, Johannes; Galasko, Douglas; Quaid, Kimberly A.; Salloway, Stephen; Xiong, Chengjie; Benzinger, Tammie; Buckles, Virginia; Masters, Colin L.; Sperling, Reisa; Bateman, Randall J.; Morris, John C.; Laske, Christoph; Department of Pathology and Laboratory Medicine, School of MedicineThe relationship between body-mass index (BMI) and Alzheimer´s disease (AD) has been extensively investigated. However, BMI alterations in preclinical individuals with autosomal dominant AD (ADAD) have not yet been investigated. We analyzed cross-sectional data from 230 asymptomatic members of families with ADAD participating in the Dominantly Inherited Alzheimer Network (DIAN) study including 120 preclinical mutation carriers (MCs) and 110 asymptomatic non-carriers (NCs). Differences in BMI and their relation with cerebral amyloid load and episodic memory as a function of estimated years to symptom onset (EYO) were analyzed. Preclinical MCs showed significantly lower BMIs compared to NCs, starting 11.2 years before expected symptom onset. However, the BMI curves begun to diverge already at 17.8 years before expected symptom onset. Lower BMI in preclinical MCs was significantly associated with less years before estimated symptom onset, higher global Aβ brain burden, and with lower delayed total recall scores in the logical memory test. The study provides cross-sectional evidence that weight loss starts one to two decades before expected symptom onset of ADAD. Our findings point toward a link between the pathophysiology of ADAD and disturbance of weight control mechanisms. Longitudinal follow-up studies are warranted to investigate BMI changes over time.Item Erratum to: Benchmarks for ethically credible partnerships between industry and academic health centers: beyond disclosure of financial conflicts of interest.(Springer, 2016) Meslin, Eric M.; Rager, Joshua B.; Schwartz, Peter H.; Quaid, Kimberly A.; Gaffney, Margaret M.; Duke, Jon; Tierney, William M.; Department of Philosophy, IU School of Liberal ArtsItem Factors related to genetic testing in adults at risk for Huntington disease: the prospective Huntington at-risk observational study (PHAROS)(Wiley, 2017-06) Quaid, Kimberly A.; Eberly, Shirley W.; Kayson-Rubin, Elise; Oakes, David; Shoulson, Ira; Huntington Study Group PHAROS Investigators; Medical and Molecular Genetics, School of MedicineHuntington disease (HD) is a late onset ultimately fatal neurodegenerative disorder caused by a cytosine-adenine-guanine ( CAG) triplet repeat expansion in the Huntingtin gene which was discovered in 1993. The PHAROS study is a unique observational study of 1001 individuals at risk for HD who had not been previously tested for HD and who had no plans to do so. In this cohort, 104 (10%) individuals changed their minds and chose to be tested during the course of the study but outside of the study protocol. Baseline behavioral scores, especially apathy, were more strongly associated with later genetic testing than motor and chorea scores, particularly among subjects with expanded CAG repeat length. In the CAG expanded group, those choosing to be tested were older and had more chorea and higher scores on the behavioral section of the unified Huntington's disease rating scale at baseline than those not choosing to be tested. Following genetic testing, 56% of subjects with CAG < 37 had less depression when compared to prior to testing, but depression generally stayed the same or increased for 64% of subjects in the expanded group. This finding suggests that approaches to testing must continue to be cautious, with appropriate medical, psychological and social support.Item Final Summary Report: Review of Merck-Regenstrief Partnership(Indiana University Center for Bioethics, 2014) Meslin, Eric M.; Gaffney, Margaret M.; Quaid, Kimberly A.; Schwartz, Peter H.; Pitt, Avril Rua; Rager, Joshua B.Item HDQLIFE: development and assessment of health-related quality of life in Huntington disease (HD)(Springer, 2016-10) Carlozzi, N. E.; Schilling, S. G.; Lai, J.-S.; Paulsen, J. S.; Hahn, E. A.; Perlmutter, J. S.; Ross, C. A.; Downing, N. R.; Kratz, A. L.; McCormack, M. K.; Nance, M. A.; Quaid, Kimberly A.; Stout, J. C.; Gershon, R. C.; Ready, R. E.; Miner, J. A.; Barton, S. K.; Perlman, S. L.; Rao, S. M.; Frank, S.; Shoulson, I.; Marin, H.; Geschwind, M. D.; Dayalu, P.; Goodnight, S. M.; Cella, D.; Department of Medicine, IU School of MedicinePurpose Huntington disease (HD) is a chronic, debilitating genetic disease that affects physical, emotional, cognitive, and social health. Existing patient-reported outcomes (PROs) of health-related quality of life (HRQOL) used in HD are neither comprehensive, nor do they adequately account for clinically meaningful changes in function. While new PROs examining HRQOL (i.e., Neuro-QoL—Quality of Life in Neurological Disorders and PROMIS—Patient-Reported Outcomes Measurement Information System) offer solutions to many of these shortcomings, they do not include HD-specific content, nor have they been validated in HD. HDQLIFE addresses this by validating 12 PROMIS/Neuro-QoL domains in individuals with HD and by using established PROMIS methodology to develop new, HD-specific content. Methods New item pools were developed using cognitive debriefing with individuals with HD, and expert, literacy, and translatability reviews. Existing item banks and new item pools were field tested in 536 individuals with prodromal, early-, or late-stage HD. Results Moderate to strong relationships between Neuro-QoL/PROMIS measures and generic self-report measures of HRQOL, and moderate relationships between Neuro-QoL/PROMIS and clinician-rated measures of similar constructs supported the validity of Neuro-QoL/PROMIS in individuals with HD. Exploratory and confirmatory factor analysis, item response theory, and differential item functioning analyses were utilized to develop new item banks for Chorea, Speech Difficulties, Swallowing Difficulties, and Concern with Death and Dying, with corresponding six-item short forms. A four-item short form was developed for Meaning and Purpose. Conclusions HDQLIFE encompasses both validated Neuro-QoL/PROMIS measures, as well as five new scales in order to provide a comprehensive assessment of HRQOL in HD.Item Seizures as an early symptom of autosomal dominant Alzheimer's disease(Elsevier, 2019-04) Vöglein, Jonathan; Noachtar, Soheyl; McDade, Eric; Quaid, Kimberly A.; Salloway, Stephen; Ghetti, Bernardino; Noble, James; Berman, Sarah; Chhatwal, Jasmeer; Mori, Hiroshi; Fox, Nick; Allegri, Ricardo; Masters, Colin L.; Buckles, Virginia; Ringman, John M.; Rossor, Martin; Schofield, Peter R.; Sperling, Reisa; Jucker, Mathias; Laske, Christoph; Paumier, Katrina; Morris, John C.; Bateman, Randall J.; Levin, Johannes; Danek, Adrian; Medical and Molecular Genetics, School of MedicineOur objective was to assess the reported history of seizures in cognitively asymptomatic mutation carriers for autosomal dominant Alzheimer's disease (ADAD) and the predictive value of seizures for mutation carrier status in cognitively asymptomatic first-degree relatives of ADAD patients. Seizure occurrence in the Dominantly Inherited Alzheimer Network observational study was correlated with mutation carrier status in cognitively asymptomatic subjects. Of 276 cognitively asymptomatic individuals, 11 (4%) had experienced seizures, and nine of these carried an ADAD mutation. Thus, in the Dominantly Inherited Alzheimer Network population, seizure frequency in mutation carriers was significantly higher than in noncarriers (p = 0.04), and the positive predictive value of seizures for the presence of a pathogenic mutation was 81.8%. Among cognitively asymptomatic ADAD family members, the occurrence of seizures increases the a priori risk of 50% mutation-positive status to about 80%. This finding suggests that ADAD mutations increase the risk of seizures.